Asian Pacific Journal of Cancer Prevention
Asian Pacific Journal of Cancer Prevention (APOCP)
- Monthly
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
Domain
- Health Sciences > Development of Pharmaceutical
Aim & Scope
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.
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Breast cancer bone metastasis causing severe morbidity is commonly encountered in daily clinical practice. It causes pain, pathologic fractures, spinal cord and other nerve compression syndromes and life threatening hypercalcemia. Breast cancer metastasizes to bone through complicated steps in which numerous molecules play roles. Metastatic cells disrupt normal bone turnover and create a vicious cycle to which treatment efforts should be directed. Bisphosphonates have been used safely for more than two decades. As a group they delay time to first skeletal related event and reduce pain, but do not prevent development of bone metastasis in patients with no bone metastasis, and also do not prolong survival. The receptor activator for nuclear factor
${\kappa}B$ ligand inhibitor denosumab delays time to first skeletal related event and reduces the skeletal morbidity rate. Radionuclides are another treatment option for bone pain. New targeted therapies and radionuclides are still under investigation. In this review we will focus on mechanisms of bone metastasis and its medical treatment in breast cancer patients. -
Zhang, Lei-Lei;Wu, Jiang;Liu, Qiang;Zhang, Yan;Sun, Zhu-Lei;Jing, Hong 1511
Background and Aims: To explore the molecular mechanisms of miR-886-5p in breast cancer., we examined roles in inhibiting growth and migration of MCF-7 cells. Methods: MiR-886-5p mimics and inhibitors were used to express or inhibit MiR-886-5p, respectively, and MTT and clone formation assays were used to determine the survival and proliferation. Hoechst 33342/ PI double staining was applied to detect apoptosis. The expression of caspase-3, caspase-8, caspase-9, MT1-MMP, VEGF-C and VEGF-D was detected by Western blotting, and the levels of MMP2 and MMP9 secreted from MCF-7 cells were assessed by ELISA. MCF-7 cell migration was determined by wound healing and Transwell assays. Results: We found that the growth of MCF-7 cells was inhibited upon decreasing miR-886-5p levels. Inhibiting miR-866-5p also significantly induced apoptosis and decreased the migratory capacity of these cells. The expression of VEGF-C, VEGF-D, MT1-MMP, MMP2, and MMP9 was also found to be decreased as compared to controls. Conclusions: Our data show that downregulation of miR-886-5p expression in MCF-7 cells could significantly inhibit cell growth and migration. This might imply that inhibiting miR-886-5p could be a therapeutic strategy in breast cancer. -
Dang, Ya-Mei;Huang, Gang;Chen, Yi-Rong;Dang, Zhong-Feng;Chen, Cheng;Liu, Feng-Lei;Guo, Ying-Fang;Xie, Xiao-Dong 1517
Aim: To investigate effects of sulforaphane on the BIU87 cell line and underlying mechanisms involving IGFBP-3. Methods: Both BIU87 and IGFBP-3-silenced BIU87 cells were treated with sulforaphane. Cell proliferation was detected by MTT assay. Cell cycle and apoptosis were determined via flow cytometry. Quantitative polymerase chain reaction and Western blotting were applied to analyze the expression of IGFBP-3 and NF-${\kappa}B$ at both mRNA and protein levels. Results: Sulforaphane (80${\mu}M$ ) treatment could inhibit cell proliferation, inducing apoptosis and cell cycle arrest at G2/M phase. All these effects could be antagonized by IGFBP-3 silencing. Furthermore, sulforaphane (80${\mu}M$ ) could down-regulate NF-${\kappa}B$ expression while elevating that of IGFBP-3. Conclusions: Sulforaphane could suppress the proliferation of BIU87 cells via enhancing IGFBP-3 expression, which negatively regulating the NF-${\kappa}B$ signaling pathway. -
Ranjbar, Reza;Saberfar, Esmaiel;Shamsaie, Alireza;Ghasemian, Ehsan 1521
Background: Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide and the association between HPV infection and genital cancers has been well established. This study concerned the possible role of HPV infection in colorectal carcinoma (CRC) in the Iranian population. Materials and Methods: We examined 80 tissues obtained from patients with colorectal cancer consisting of 58 colon cancer samples and 22 rectal cancer samples and 80 tissues from patients with unremarkable pathologic changes as matched controls by sex, study center and anatomical sites. HPV infection and genotypes were detected using nested PCR and sequencing methods, respectively. Results: HPV DNA was detected in 5/80 (6.25%) cases including 1 of 22 (4.54%) patients with rectum cancer and 4 of 58 (6.9%) patients with colon cancer and 1/80 (1.25%) of controls. Furthermore, HPV-18 was detected as the most frequent type and we found no significant correlation between prevalence of HPV infection and anatomical sub- sites. Conclusions: Although a causal relation between human papillomavirus and colorectal cancer was not found through this study, analysis of medical records pointed to a possible role for high- risk types of HPV in increasing the potential of aggressiveness in colorectal cancer. This study shows a particular frequency of HPV genotypes in patients with colorectal cancer in Iran. Since HPV vaccines are limited to a few types of virus, using cohort studies in different geographical zones to screen for patterns of HPV infection in different organs might increase the efficacy and optimization of the current vaccines. -
Meevasana, Vorachart;Suwannarurk, Komsun;Chanthasenanont, Athita;Tanprasertkul, Chamnan;Bhamarapravatana, Kornkarn;Pattaraarchachai, Janya 1527
Background: Time to colposcopy (TC) after abnormal Pap smears was evaluated for influence on cytohistologic correlation (CHC). Materials and Methods: This retrospective study assessed the correlation between TC and CHC of women who had abnormal Pap smears. Colposcopic chart review included participants from 2010-2013 who attended a colposcopic clinic, Thammasat University Hospital, Thailand. Results: Four hundred and sixty cases who had abnormal Pap smears were recruited. Pap reports were atypical smears with low grade squamous intraepithelial lesion (SIL), high grade SIL and cancer at 339, 114 and 7 cases, respectively. One hundred and twenty four patients underwent loop electrosurgical excision procedure (LEEP). A half of the cases were colposcopically examined within 1-2 months after abnormal Pap collection. CHC was 88 percent and not affected at all by TC. Subjects who attended cervical cancer screening from affiliated health providers had shorter TC than those screened in our tertiary hospital. Conclusions: Time to colposcopy with abnormal Pap smears conducted at Thammasat University Hospital had a highest frequency of 42 days, in line with the literature. Length of TC does not affect the correlation between Pap and histopathologic reports. A longer waiting period for colposcopy did not alter progression or regression of the disease. -
Chen, Hua-Xia;Wang, Shuai;Wang, Zhou;Zhang, Zhi-Ping;Shi, Shan-Shan 1531
Runt-related transcription factor 3 (RUNX3) is a tumor suppressor gene whose reduced expression may play an important role in the development and progression of esophageal squamous cell cancer (ESCC). The aim of this study was to investigate the clinical relevance of RUNX3 in ESCC patients and effects of overexpression on biological behaviour of Eca109 cells in vitro and in vivo. Immunohistochemistry was performed to detect the clinical relevance of RUNX3 and lymph node metastasis in 80 ESCC tissues and 40 non-cancerous tissues using the SP method. RT-PCR and Western blotting were applied to assess the RUNX3 level and verify the Eca109 cell line with stable overexpression. Localization of RUNX3 proteins was performed by cell immunofluorescence. CCK-8 and Scrape motility assays were used to determine proliferation and migration and the TUNEL assay to analyze cell apoptosis. Invasive potential was assessed in cell transwell invasion experiments. In nude mice, tumorigenesis in vivo was determined. Results showed decreased expression of RUNX3 in esophageal tissue to be significantly related to lymph node metastasis (LNM) (P<0.01). In addition, construction of a recombinant lentiviral vector and transfection into the human ESCC cell line Eca109 demonstrated that overexpression could inhibit cell proliferation, migration and invasion, and induce apoptosis. The in vivo experiments in mice showed tumorigenicity and invasiveness to be significantly reduced. Taken together, our studies indicate that underexpression of RUNX3 in human ESCC tissue is significantly correlated with progression. Restoration of RUNX3 expression significantly inhibits ESCC cells proliferation, migration, invasion and tumorigenesis. -
Wang, Nan-Ya;Wang, Cong;Li, Wei;Wang, Guan-Jun;Cui, Guo-Zhen;He, Hua;Zhao, Heng-Jun 1539
Purpose: Alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and Golgi protein 73 (GP73) levels have been widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to investigate whether these tumor markers could be used to monitor short-term treatment response and recurrence of HCC in patients undergoing radiofrequency ablation (RFA). Methods: Between July 2012 and July 2013, 53 consecutive patients with newly diagnosed HCC were prospectively enrolled in this study. Among these, 32 patients underwent RFA, after which they were followed up prospectively at the First Hospital of Jilin University in China. Results: AFP, AFP-L3, and GP-73 values pre-RFA were not associated with tumor size, whereas AFP and GP-73 levels tended to be associated with tumor number, the presence of vascular invasion, deterioration of liver function, advanced-stage disease, and a poor performance status. GP-73 levels were dramatically elevated in the patients with hepatitis C-associated HCC. Neither pre-RFA nor 1-month post-RFA tumor marker values were associated with short-term outcome. The short-term recurrence rate of AFP-positive patients measured 1 month post-RFA was obviously higher than that of AFP-negative patients. Conclusions: AFP and GP-73 values were associated with clinical variables representing tumor growth and invasiveness, and the AFP value measured 1 month post-RFA was a strong predictor of short-term recurrence in patients with HCC. -
Background: Published studies on clinical outcome of helical tomotherapy for lung cancer are limited. The purpose of this study was to evaluate clinical outcomes and treatment-related toxicity in inoperable non-small cell lung cancer (NSCLC) patients treated with helical tomotherapy in Korea. Materials and Methods: Twenty-seven patients with NSCLC were included in this retrospective study. Radiotherapy was performed using helical tomotherapy with a daily dose of 2.1-3 Gy delivered at 5 fractions per week resulting in a total dose of 62.5-69.3 Gy. We assessed radiation-related lung and esophageal toxicity, and analyzed overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and prognostic factors for overall survival. Results: The median follow-up period was 28.9 months (range, 10.1-69.4). The median overall survival time was 28.9 months, and 1-, 2-, and 3-year overall survival rates were 96.2%, 92.0%, and 60.0%. The median locoregional recurrence-free survival time was 24.3 months, and 1-, 2-, and 3-year locoregional recurrence-free survival rates were 85.2%, 64.5%, and 50.3%. The median distant metastasis-free survival time was 26.7 months, and 1-, 2-, and 3-year distant metastasis-free survival rates were 92.3%, 83.9%, and 65.3%, respectively. Gross tumor volume was the most significant prognostic factor for overall survival. No grade 4 or more toxicity was observed. Conclusions: Helical tomotherapy in patients with inoperable NSCLC resulted in high survival rates with an acceptable level of toxicity, suggesting it is an effective treatment option in patients with medically inoperable NSCLC.
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Kijpornyongpan, Teeratas;Sereemaspun, Amornpun;Chanchao, Chanpen 1551
Background: Transient receptor potential melastatin 8 (TRPM8), a principle membrane receptor involved in calcium ion influx and cell signal transduction, has been found to be up-regulated in some cancer types, including melanomas. Efficiency of menthol, an agonist of TRPM8, in killing melanoma cancer cells has been reported previously, but the mechanisms remain unclear. We here determined whether in vitro cytotoxic effects of menthol on A-375 human malignant melanoma cells might be related to TRPM8 transcript expression. Materials and Methods: The$PrestoBlue^{(R)}$ cell viability assay was used to assess the in vitro cytotoxic effect of menthol after 24h of treatment. RT-PCR was used to quantify TRPM8 transcript expression levels in normal and menthol-treated cells. Cell morphology was observed under inverted phase contrast light microscopy. Results: TRPM8 transcript expression was found at low levels in A-375 cells and down-regulated in a potentially dose-dependent manner by menthol. Menthol exerted in vitro cytotoxic effects on A-375 cells with an$IC_{50}$ value of 11.8${\mu}M$ , which was at least as effective as 5-fluorouracil ($IC_{50}=120{\mu}M$ ), a commonly applied chemotherapeutic drug. Menthol showed no dose-dependent cytotoxicity on HeLa cells, a TRPM8 non-expressing cell line. Conclusions: The cytotoxic effects on A-375 cells caused by menthol might be related to reduction of the TRPM8 transcript level. This suggests that menthol might activate TRPM8 to increase cytosolic$Ca^{2+}$ levels, which leads to cytosolic$Ca^{2+}$ imbalance and triggers cell death. -
Jafari-Koshki, Tohid;Schmid, Volker Johann;Mahaki, Behzad 1557
Background: Breast cancer is the most frequently diagnosed cancer in women and estimating its relative risks and trends of incidence at the area-level is helpful for health policy makers. However, traditional methods of estimation which do not take spatial heterogeneity into account suffer from drawbacks and their results may be misleading, as the estimated maps of incidence vary dramatically in neighboring areas. Spatial methods have been proposed to overcome drawbacks of traditional methods by including spatial sources of variation in the model to produce smoother maps. Materials and Methods: In this study we analyzed the breast cancer data in Iran during 2004-2008. We used a method proposed to cover spatial and temporal effects simultaneously and their interactions to study trends of breast cancer incidence in Iran. Results: The results agree with previous studies but provide new information about two main issues regarding the trend of breast cancer in provinces of Iran. First, this model discovered provinces with high relative risks of breast cancer during the 5 years of the study. Second, new information was provided with respect to overall trend trends o. East-Azerbaijan, Golestan, North-Khorasan, and Khorasan-Razavi had the highest increases in rates of breast cancer incidence whilst Tehran, Isfahan, and Yazd had the highest incidence rates during 2004-2008. Conclusions: Using spatial methods can provide more accurate and detailed information about the incidence or prevalence of a disease. These models can specify provinces with different health priorities in terms of needs for therapy and drugs or demands for efficient education, screening, and preventive policy into action. -
Long, Qing-Yun;Zhou, Jun;Zhang, Xiao-Long;Cao, Jiang-Hui 1563
Background: Esophageal squamous cell carcinoma (ESCC) accounts for most esophageal cancer in Asia, and is the sixth common cause of cancer-related deaths worldwide. Previous studies indicated HOXB7 is overexpressed in ESCC tissues, but data on prognostic value are limited. Methods: A total of 76 advanced ESCC cases were investigated. Immunohistochemistry (IHC) was used to detect the expression levels of HOXB7 and Kaplan-Meier curves and Cox regression models to determine prognostic significance. Stratified analysis was also performed according to lymph node (LN) status. Results: Kaplan-Meier curve analysis indicated that HOXB7 positive patients had significantly shorter overall survival (OS) than HOXB7 negative patients. Multivariate analysis using the Cox proportional hazards model indicated only TNM stage and HOXB7 expression to be independent predictors of overall survival of advanced ESCC patients. HOXB7 indicated poor OS in both lymph node negative (LN-) and lymph node positive (LN+) patients. Conclusion: HOXB7 predicts poor prognosis of advanced ESCC patients and can be applied as an independent prognostic predictor. -
Deng, Wei;Long, Long;Li, Ji-Lin;Zheng, Dan;Yu, Jia-Hua;Zhang, Chun-Yan;Li, Ke-Zhi;Liu, Hai-Zhou;Huang, Tian-Ren 1567
The incidence and mortality rates of liver and nasopharyngeal cancer in Guangxi province of China have always been among the highest in the world, and cancer is one of the major diseases that pose a threat to the health of residents in Guangxi. However, no systematic study has been performed to evaluate the time trends in the structure of cancer-related deaths and cancer mortality. In this study, we reveal sex, age and geography differences of cancers mortality between three death surveys (1971 to 1973, 1990 to 1992, and 2004 to 2005). The results show that the standardized mortality rate of cancer in Guangxi residents has risen from 43.3/100,000 to 84.2/100,000, the share of cancer deaths in all-cause deaths has increased from 13.3% to 20.7%, and cancer has become the second most common cause of death. The five major cancers, liver cancer, lung cancer, gastric cancer, nasopharyngeal cancer and colorectal cancer, account for 60% of all the cancer deaths. Cancers with growing mortality rates over the past 30 years include lung cancer, colorectal cancer, liver cancer and female breast cancer, of which lung cancer is associated with the sharpest rise in mortality, with a more than 600% rise in both men and women. Cancer death in Guangxi residents occurs mainly in the elderly population above 45 years of age, especially in people over the age of 65. The areas with the highest mortality rates for liver cancer and nasopharyngeal cancer, which feature regional high incidences, include Chongzuo and Wuzhou. Therefore, for major cancers such as liver cancer, lung cancer, gastric cancer, nasopharyngeal cancer and female breast cancer in Guangxi, we can select high-risk age groups as the target population for cancer prevention and control efforts in high-prevalence areas in a bid to achieve the ultimate goal of lowering cancer mortality in Guangxi. -
Basiri, Zeinab;Safaralizadeh, Reza;Bonyadi, Morteza Jabbarpour;Somi, Mohammad Hossein;Mahdavi, Majid;Latifi-Navid, Saeid 1575
Background: There is a close relationship between Helicobacter pylori (H pylori)-specific factors and different gastroduodenal diseases. The present study aimed to investigate the prevalence of vacA d1, d2 genotypes in the H pylori isolates from patients with gastric adenocarcinoma, peptic ulcer disease (PUD) and gastritis in East Azerbaijan region, where the incidence of gastric cancer (GC) is high. Strains isolated from this area are likely to be of European ancestry. Materials and Methods: In this study, genotyping of the vacA d region of 115 isolates obtained from patients with different gastrodoudenal diseases was accomplished by PCR methods. In addition to PCR amplification of H pylori 16S rDNA, rapid urease tests or histological examination were used to confirm the presence of H pylori in biopsy specimens. Data were collected and analyzed using SPSS version 19. Results: Of the total of 83 H pylori isolates, 36 (43.4%) contained the d1 allele and 47 (56.6%) were subtype d2. The results of the multiple linear/logistic regression analysis showed high correlation between allele d1 and gastric adenocarcinoma or PUD. Conclusions: This study suggests that the H pylori vacA d1 genotype helps predict risk for gastric adenocarcinoma and PUD in East Azerbaijan, Iran. -
Demirci, Umut;Coskun, Ugur;Karaca, Halit;Dane, Faysal;Ozdemir, Nuriye Yildirim;Ulas, Arife;Baykara, Meltem;Benekli, Mustafa;Ozkan, Metin;Buyukberber, Suleyman 1581
Background: The overall prognosis for cancers of unknown primary (CUP) is poor, median overall survival (OS) being 6-12 months. We evaluated our multicentric retrospective experience for CUP administered docetaxel and cisplatin combination therapy. Materials and Methods: A total of 29 patients that were pathologically confirmed subtypes of CUP were included in the study. The combination of docetaxel ($75mg/m^2$ , day 1) and cisplatin ($75mg/m^2$ , day 1) was performed as a first line regimen every 21 days. Results: The median age was 51 (range: 27-68). Some 17 patients had multimetastatic disease on the inital diagnosis. Histopathological diagnoses were well-moderate differentiated adenocarcinoma (51.7%), undifferentiated carcinoma (27.6%), squamous cell cancer (13.8%), mucoepidermoid carcinoma (3.4%) and neuroendocrine differentiated carcinoma (3.4%). Median number of cycles was 3 (range: 1-6). Objective response rate was 37.9% and clinical benefit was 58.6%. Median progression free survival (PFS) and overall survival (OS) were 6 months (range: 4.3-7.7 months) and 16 months (range: 8.1-30.9 months), respectively. Fourteen patients (60.8%) were treated in a second line setting. There was no treatment related death. Most common toxicities were nausia-vomiting (44.6%) and fatigue (34.7%), serious cases (grade 3/4) suffering nausia-vomiting (10.3%), neutropenia (13.8%) and febrile neutropenia (n=1). Conclusion: The combination of cisplatin and docetaxel is an effective regimen for selected patients with CUP. -
Binesh, Fariba;Akhavan, Ali;Behniafard, Nasim;Atefi, Aref 1585
Background: Data regarding childhood and adolescent non Hodgkin lymphomas in Iran are limited. The aim of this study was to assess the epidemiological and histomorphological features and survival of affected patients in our center. Materials and Methods: The clinicopathologic features and outcome of 44 children and adolescents with non Hodgkin lymphoma diagnosed during 2004-2012, were investigated retrospectively. The influence of potential prognostic parameters in overall survival was investigated by log-rank test and Cox regression analysis. Results: The mean age at presentation was$13.8{\pm}6.16$ years with a male predilection (M: F=3:1). Malignant lymphoma, not otherwise specified, diffuse large cell lymphoma and Burkitt lymphoma were the three most common histological types observed. The tumors were 36.4% intermediate grade, 27.3% high grade and 34.1% belonged to the malignant lymphoma not otherwise specified group. Immunohistochemistry findings were available in 39 cases. Out of these cases 33 (84.6%) had B cell lineage, 4 (10.25%) T cell lineage and 2 (5.12%) of the cases belonged to miscellaneous group. 3 year and 5 year survivals were 48% and 30% respectively and median survival was 36 months (95%CI=21.7-50.3 months). Overall survival in patients with high grade tumors was 19.5 months, in the intermediate group,79 months, and for malignant lymphomas not otherwise specified it was 33.6 months (p value=0.000). Conclusions: The survival rate for children and adolescents with non Hodgkin lymphomas at our center during 2004-2012 was at a low level. -
Zheng, Chun-Hua;Quan, Yuan;Li, Yi-Yang;Deng, Wei-Guo;Shao, Wen-Jing;Fu, Yan 1589
Objective: Forkhead box C2 (FOXC2) is a member of the winged helix/forkhead box (Fox) family of transcription factors. It has been suggested to regulate tumor vasculature, growth, invasion and metastasis, although it has not been studied in cervical cancer. Here, we analyzed FOXC2 expression in cervical tissues corresponding to different stages of cervical cancer development and examined its correlation with clinicopathological characteristics. In addition, we examined the effects of targeting FOXC2 on the biological behavior of human cervical cancer cells. Methods: The expression of FOXC2 in normal human cervix, CIN I-III and cervical cancer was examined by immunohistochemistry and compared among the three groups and between cervical cancers with different pathological subtypes. Endogenous expression of FOXC2 was transiently knocked down in human Hela and SiHa cervical cells by siRNA, and cell viability and migration were examined by scratch and CCK8 assays, respectively. Results: In normal cervical tissue the frequency of positive staining was 25% (10/40 cases), with a staining intensity (PI) of$0.297{\pm}0.520$ , in CIN was 65% (26/40cases), with a PI of$3.00{\pm}3.29$ , and in cancer was 91.8% (68/74 cases), with a PI of$5.568 {\pm}3.449$ . The frequency was 100% in adenocarcinoma (5/5 cases) and 91.3% in SCCs (63/69 cases). The FOXC2 positive expression rate was 88.5% in patients with cervical SCC stage I and 100% in stage II, showing significant differences compared with normal cervix and CIN. With age, pathologic differentiation degree and tumor size, FOXC2 expression showed no significant variation. On transient transfection of Hela and SiHa cells, FOXC2-siRNA inhibition rates were 76.2% and 75.7%; CCK8 results showed reduced proliferation and relative migration (in Hela cells from$64.5{\pm}3.16$ to$49.5{\pm}9.24$ and in SiHa cells from$60.1{\pm}3.05$ to$44.3{\pm}3.98$ ) (P < 0.05). Conclusion: FOXC2 gene expression increases with malignancy, especially with blood vessel hyperplasia and invasion degree. Targeted silencing was associated with reduced cell proliferation as well as invasion potential. -
Yin, Hang;Lu, Kai;Qiao, Wen-Bo;Zhang, Hai-Yang;Sun, Di;You, Qing-Shan 1597
The purpose of this study was to investigate whether whole-liver radiotherapy plus a tumor-boost dose with concurrent chemotherapy is beneficial for colorectal cancer patients with massive and multiple liver metastases. From January 2007 to December 2012, 19 patients who exhibited massive (with a longest diameter > 5 cm) and invasive liver metastases and multiple metastases were treated with radiotherapy and concurrent chemotherapy. The total radiation dose was 53.4 Gy (range 38.8 Gy-66.3 Gy). All of the patients received a continuous intravenous dose of 5 fluorouracil (5-FU) 225 mg/m2 concurrently with radiation. The median survival time was 19 months. The 1- and 2- year overall survival rates were 78.3% and 14.3%, respectively. Of all of the patients who presented with abdominal pain, 100% experienced a decrease in pain. Decreases in the rates of ascites and jaundice were confirmed by ultrasound and bilirubin levels. No cases of Grade 4 or 5 acute or late toxicity were recorded. There were only two cases of Grade 3 toxicity (elevated bilirubin). These data provide evidence that whole-liver radiotherapy plus a tumor-boost dose with concurrent chemotherapy is beneficial for colorectal cancer patients with massive and multiple liver metastases. -
Zeichner, Simon Blechman;Alghamdi, Sarah;Elhammady, Gina;Poppiti, Robert John;Castellano-Sanchez, Amilcar 1603
Background: The response to treatment and overall survival (OS) of patients with acute myeloid leukemia (AML) is variable, with a median ranging from 6 months to 11.5 years. TP53 is associated with old age, chemotherapy resistance, and worse OS. Using genetic sequencing, we set out to look at our own experience with AML, and hypothesized that both TP53 mutations and SNPs at codon 72 would mimic the literature by occurring in a minority of patients, and conferring a worse OS. Materials and Methods: We performed a pilot study of randomly selected, newly diagnosed AML patients at Mount Sinai Medical Center, diagnosed from 2005-2008 (n=10). TP53 PCR sequencing was performed using DNA from bone marrow smears. Analysis was accomplished using Mutation Surveyor software with confirmation of the variants using the COSMIC and dbSNP databases. Results: Fewer than half of the patients harbored TP53 mutations (40%). There was no significant difference in OS based on gender, AML history, risk-stratified karyotype, or TP53 mutation. There were possible trends toward improved survival among patients less than 60 (11 vs 4 months, p=0.09), Hispanics (8 vs 1 months, p=0.11), and those not harboring SNP P72R (8 vs 2 months, p=0.10). There was a significant improvement in survival among patients with better performance status (28 vs 4 months, p=0.01) and those who did not have a complex karyotype (8 vs 1 months, p=0.03). The most commonly observed TP53 mutation was a missense N310K (40%) and the most commonly observed SNP was P72R (100.0%). Conclusions: Our study confirms previous reports that poor PS and the presence of a complex karyotype are associated with a decreased OS. In our cohort, TP53 mutations were relatively common, occurring more frequently in male patients with an adverse karyotype. Although there was no significant difference in survival between TP53 mutated and un-mutated patients, there was a possible trend toward worse OS among patients with SNP P72R. Larger studies are needed to validate these findings. -
Thumvijit, Tarika;Taya, Sirinya;Punvittayagul, Charatda;Peerapornpisal, Yuwadee;Wongpoomchai, Rawiwan 1611
Spirogyra neglecta, a freshwater green alga, is a local food in the northern and northeastern parts of Thailand. This investigation explored the anticarcinogenicity of S neglecta and its possible cancer chemopreventive mechanisms in rats divided into 14 groups. Groups 1 and 10 served as positive and negative control groups, respectively. Groups 1-9 were intraperitoneally injected with diethylnitrosamine (DEN) once a week for 3 weeks. Groups 10-14 received normal saline instead. One week after the last DEN injection, groups 2-5 were administered for 9 consecutive weeks various doses of S neglecta extract (SNE) and dried S neglecta (SND), mixed with basal diet. Groups 6-9 and 11-14 similarly were administered various doses of SNE and SND starting from the first week of the experiment. Administration of SNE and SND was not associated with formation of glutathione-Stransferase placental form (GST-P) positive foci in rat liver. SNE and SND during initiation phase significantly reduced the number of GST-P positive foci in rats injected with DEN. The number of GST-P also diminished in groups treated with SNE and SND after injection with DEN, except for the low dose extract group. SNE showed stronger anticarcinogenic potency than SND. Furthermore, SNE also decreased the number of Ki-67 positive cells. However, the numbers of TUNEL-positive cells in the liver of the SNE-treated groups were not statistically different from the controls. The GST activity in 50 mg/kg bw of SNE and 1% of SND groups was significantly increased as compared to the positive control. In conclusion, Spirogyra neglecta (Hassall) K$\ddot{u}$ tzing showed cancer chemopreventive properties at the early stages of diethylnitrosamine-induced hepatocarcinogenesis in rats. Possible inhibitory mechanisms include enhancement of the activities of some detoxifying enzymes and/or suppression of precancerous cells. -
Ziaian, Bijan;Saberi, Ali;Ghayyoumi, Mohammad Ali;Safaei, Akbar;Ghaderi, Abbas;Mojtahedi, Zahra 1617
Background: Evidence shows direct link of HER2 to increased glycolysis and over production of lactate dehydrogenase (LDH). HER2 overexpression, high LDH and low glucose pleural levels are associated with poor prognosis in lung cancer. Here, their relationships were investigated. Materials and Methods: HER2 positivity was studied using immunohistochemistry in non-small cell lung cancer. Glucose and LDH levels were measured using commercial colorimetric kits. Results: Of 42 patients (29 adenocarcinoma and 13 squamous cell carcinoma), 28 (66.7%) were HER2-negative, 14 (33.3%) were HER2- positive, including 9 (21.4%) weakly stained (1+) and 5 (11.9%) moderately stained (2+) samples. The relationship between HER2 and glucose and LDH levels were tested in 20 newly diagnosed lung cancer patients who had simultaneous pleural and serum samples. Pleural and serum LDH levels were increased, and pleural glucose levels were decreased with the scale of HER2 positivity, and that the difference in glucose levels between HER2-negative group and HER2-positive patients scored at 2+ reached statistical significance (p=0.02). This latter group all had pleural glucose levels below 40 mg/dl. Conclusions: For the first time, we showed a significant association between low pleural glucose level and overexpression of HER2 in lung cancer. Further investigations are warranted to disclose the association of HER2 with low pleural glucose levels in other populations, with a larger sample size, in malignant pleural effusions caused by other types of cancer, and finally to assess employment as a screening tool for finding HER2-positive cases of lung cancer. -
Wang, Lin-Wei;Yang, Gui-Fang;Chen, Jia-Mei;Yang, Fang;Yuan, Jing-Ping;Sun, Sheng-Rong;Chen, Chuang;Hu, Ming-Bai;Li, Yan 1621
Background: Breast cancer is the most common malignant tumor in females worldwide. Many differences exist in clinico-pathological characteristics of breast cancer patients between China and Western countries. This study aimed to analyze clinico-pathological characteristics of breast cancer from central China. Methods: Clinico-pathological information on breast cancer from three hospitals in central China was collected and analyzed. Results: From 1994 to 2012, 2,525 patients with a median age 50 years were included in this study. The 45-49-year age group and invasive ductal carcinoma not otherwise specified accounted for the highest proportions (19.1%, 480/2,525 and 81.0%, 1,982/2,446). Stages 0-I, II and III accounted for 28.0% (682/2,441), 48.4% (1,180/2,441), and 23.7% (578/2,441), respectively. Distribution of N stage showed that N0 accounted for 53.2% (1,344/2,525), and proportion of N0 rose from 51.1% (157/307) in 30-39-year age group to 64.3% (110/171) in${\geq}$ 70-year age group, with an average increase of 2.1% in each age group. Modified radical mastectomy, radical mastectomy, breast-conserving surgery and simple mastectomy were performed for 71.8% (1,812/2,525), 18.0% (454/2,525), 5.2% (131/2,525) and 2.6% (66/2,525), respectively. Proportions of breast-conserving surgery in age${\leq}$ 44-year group (68/132, 51.5%) and simple mastectomy in age${\geq}$ 60-year group (57/89, 64.0%) were higher than in the other age groups. Breast cancers positive for estrogen receptor accounted for 53.0% (1,107/ 2,112). The comparisons among this study and other reports showed higher proportion of younger patients, lower proportion of breast-conserving surgery and positive estrogen receptor patients in China than western countries. Conclusions: Clinico-pathological characteristics in this study demonstrated clear differences between the center of China than Western countries. Additional classification systems should be developed to guide grading of early breast cancer more accurately, especially for N0 patients. Invasive ductal carcinoma is a focus for intensive research. -
Background: Several studies indicated that the diagnosis season affects the prognosis of some cancers, such as examples in the prostate, colon and breast. This retrospective study aimed to investigate whether the diagnosis and recurrent season impacts the prognosis of epithelial ovarian cancer patients. Methods: From January 2005 to August 2010, 161 epithelial ovarian cancer patients were analyzed and followed up until August 2013. Kaplan-Meier survival curves and the log-rank test were used to make the survival analysis. Multivariate analysis was conducted to identify independent prognostic factors. Results: The prognostic factors of overall survival in epithelial ovarian cancer patients included age, clinical stage, pathological type, histological grade, residual disease after primary surgery, recurrent season and adjuvant chemotherapy cycles. Moreover, clinical stage, histological grade, residual disease after primary surgery, recurrent season and adjuvant chemotherapy cycles also impacted the progression-free survival of epithelial ovarian cancer patients. The diagnosis season did not have a significantly relationship with the survival of operable epithelial ovarian cancer patients. Median overall survival of patients with recurrent month from April to November was 47 months, which was longer (P < 0.001) than that of patients with recurrence month from December to March (19 months). Median progression-free survival of patients with recurrence month from April to November and December to March was 20 and 8 months, respectively (P < 0.001). Conclusion: The recurrence season impacts the survival of epithelial ovarian cancer patients. However, the diagnosed season does not appear to exert a significant influence.
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Ramanathan, Anand;Mahmoud, Hagir Abd Rahman;Hui, Lew Pit;Mei, Ng Yan;Valliappan, Valliammai;Zain, Rosnah Binti 1633
Background: Lymphoma is a malignant neoplasm of lymphoid tissue classified into Hodgkin's and non- Hodgkin's types. It mostly affects lymph nodes although a considerable proportion of Non-Hodgkin's cases occur in extranodal sites. Materials and Methods: Selected cases diagnosed as non-Hodgkin's lymphoma (NHL) during the period of 1980 to 2012 were retrieved from the archives of the Oral Pathology Diagnostic Laboratory, Faculty of Dentistry, University of Malaya. The sections from the formalin-fixed paraffin embedded tissue blocks were stained with H&E as well as with LCA, CD20, and CD3. Results: The mean age was 41.6 years with a male: female ratio of 1.3:1. Out of the forty two cases, nineteen were Malays, eighteen were Chinese, followed by Indians (3) and Indonesians (2). The most common site of involvement was the mandible (22.2%), followed by the maxilla and palate (19.4% each). Most of the lesions presented as a painless progressive swelling. Only thirty six cases were further subdivided into B or T cell types. The majority were B-cell type (26 cases), of these 6 cases were Burkitt's lymphomas. Only ten cases were T-cell lymphoma, with three cases of NK/T-cell lymphoma. Conclusions: In this series of 42 patients diagnosed as extranodal non-Hodgkin's lymphoma, the lesions appeared as painless swellings, mostly in men with the mandible as the most frequent site of involvement. Majority were B-cell lymphomas with Malays and Chinese being equally affected whereas lymphomas were rare in the Indian ethnicity. T-cell lymphomas were found to be common in the Chinese ethnic group. -
Louisa, Melva;Soediro, Tjahjani Mirawati;Suyatna, Frans Dhyanagiri 1639
The multidrug resistance phenotype is one of the major problems in development of cancer cell resistance to chemotherapy. Some natural compounds from medicinal plants have demonstrated promising capacity in enhancing anticancer effects in drug resistant cancer cells. We aimed to investigate whether mangiferin might have an ability to re-sensitize MCF-7 breast cancer cells previously treated with short-term doxorubicin in vitro, through the modulation of efflux transporters, P-glycoprotein (P-gp), MRP1 and BCRP. We exposed MCF-7 breast cancer cells pretreated with doxorubicin for 10 days to mangiferin (10, 25 or 50${\mu}M$ ) for 96 hours. Afterwards, we evaluated influence on cell viability and level of mRNA expression of P-gp, MRP1 and BCRP. Doxorubicin given in combination with mangiferin at low concentrations (10 and 25${\mu}M$ ) failed to give significant reduction in cell viability, while at the highest concentrations, the combination significantly reduced cell viability. The mRNA expression analysis of P-gp, MRP1 and BCRP showed that mangiferin had inhibitory effects on P-gp but no effects on MRP1 and BCRP. In conclusion, we suggest that mangiferin at high concentrations can be used as chemosensitizer for doxorubicin therapy. This effect might be attributed by inhibitory effects of mangiferin on P-glycoprotein expression. -
Chindaprasirt, Jarin;Limpawattana, Panita;Pakkaratho, Pornvaree;Wirasorn, Kosin;Sookprasert, Aumkhae;Kongbunkiat, Kannikar;Sawanyawisuth, Kittisak 1643
Family caregivers of older cancer patients face many challenges in managing illness. The burden impacts physical, emotional, spiritual, and social health. The objective of this study was to identify burden among caregivers of older patients with advanced cancer, and associated factors. Materials and Methods: Caregivers of older cancer patients were randomly interviewed from March-September 2012. Information on baseline characteristics and caregiver burden using the Zarit Burden Inventory (ZBI) was collected. Descriptive statistics were used to analyze baseline data, with univariate and multiple linear regression to analyze factors associated with higher burden. Results: One hundred and fifty participants were assessed. The mean ZBI was$19.2{\pm}12.9$ (95%CI, 17.1, 21.2). Two-thirds of caregivers reported no burden (63%) and the main impact variable on ZBI was guilt. High burdens were associated with single caregiver, relationship with the patient as siblings, presence of migraines, and cancer types of the patients. Conclusions: Caregiver burden of Thai cancer patients is low. This unexpected small number could be the result of the socio-cultural viewpoint. Assessment of caregivers and focusing on related factors should be incorporated into treatment plans. -
Tang, Yun-Hao;Zhu, Wen-Jiang;Wen, Tian-Fu 1649
Background: Clinically significant portal hypertension (PHT) is considered as a contraindication for hepatectomy according to the guidelines of the European Association for Study of Liver and the American Association for Study of Liver Diseases. However, this issue remains controversial. Here we performed a metaanalysis to evaluate the impact of PHT on the results of hepatectomy for hepatocellular carcinoma (HCC). Methods: Cohort studies evaluating the impact of clinically significant PHT, defined as oesophageal varices and/or splenomegaly associated with thrombocytopenia, on the results of hepatectomy for HCC were identified using a predefined search strategy. Summary risk ratios (RRs) and 95% confidence intervals (95% CIs) for PHT and outcomes after hepatectomy for HCC were calculated. Results: Seven cohort studies which including 574 cases with PHT and 1,354 cases without PHT were considered eligible for inclusion. The meta-analysis showed that, in all patients, pooled RRs of post-operative liver failure, post-operative ascites, peri-operative blood transfusion, operative mortality, 3- and 5-year overall survival associated with PHT were 2.23 (95% CI: 1.48-3.34, P=0.0001), 1.77 (95% CI: 1.19-2.64, P=0.005), 1.23 (95% CI: 1.03-1.49, P=0.03), 2.58 (95% CI: 1.12-5.96, P=0.03), 0.82 (95% CI: 0.75-0.88, P<0.00001) and 0.76 (95% CI: 0.69-0.85, P<0.00001), respectively. In subgroup analysis, similar results were found in Child-Pugh class A patients. Conclusion: This meta-analysis suggests that presence of oesophageal varices and/or splenomegaly associated with thrombocytopenia is associated with higher rates of post-operative complications and poor long-term survival after hepatectomy for HCC. -
Chen, Chong;Li, Gang;Liu, Yun-De;Gu, Ya-Jun 1655
Objective: To find a more appropriate alternative to D-dimer cutoff value for the diagnosis of deep vein thrombosis (DVT) in cancer patients. Methods: A total of 711 cancer patients with symptoms suspicious of DVT were included in the study. D-dimer levels were assessed using ELISA. All patients were subjected to imaging procedures. Results: Among 711 patients with cancer, 466 (65.5%) were females and 245 (34.5%) were males, with an average age of$57.3{\pm}13.23$ years. The mean age in the DVT group was significantly higher than in the non-DVT group (P<0.05). The D-dimer levels of the DVT group were significantly higher than those of the non-DVT group (P<0.05). The incidence rate of DVT varied significantly according to cancer type (P<0.05). Increasing age and lung cancer were significantly correlated with D-dimer levels (P<0.05), and a one-year increase in age was associated with a 14.28 ng/ml increase in the D-dimer value. The optimal cutoff point for D-dimer was found to be 981 ng/ml, with a sensitivity of 86.4%, specificity of 79.4%, and accuracy of 82.6%. If the D-dimer cutoff point was set to 981ng/ml, the specificity would increase from 61.8% to 85.5% without loss of sensitivity in patients aged 40 years or younger. In patients aged more than 40 years, the new cutoff almost doubled the specificity with slightly reduced sensitivity. Conclusion: In cancer patients, a new cutoff value of 981 ng/ml effectively improved the exclusion of DVT, especially for patients aged more than 40 years. -
Goyal, Sandeep;Tiwari, Vijay Kumar;Nair, Kesavan Sreekantan;Raj, Sherin 1659
The present study conducted with 100 oral cancer patients at a private tertiary care hospital in Delhidemonstrated that stage III cancer was associated with longer use of tobacco and poor oral hygiene. There was also statistically significant association (p<.05) between consumption of tobacco and alcohol. More than 60% treatment expenditure was on surgery followed by accommodation (9%) and investigations (8%). The effect of tobacco was well known among patients as 76% of the patients knew that common cancer in tobacco chewer is 'oral cancer', 22% of the patients however responded that they did not know which cancer is common in tobacco chewers. 58% said that they learnt about ill effects of tobacco from media while 24% said they learnt from family and friends. Out of 78 tobacco users, 60 (77%) said that they never received help to quit tobacco while 18(23%) have received help to quit. -
Khoshbaten, Manouchehr;Pishahang, Parinaz;Nouri, Mohammad;Lashkari, Alireza;Alizadeh, Mahasti;Rostami-Nejad, Mohammad 1667
Background: Calprotectin in feces seems to be a more sensitive marker for gastrointestinal (GI) cancers than fecal occult blood, but its specificity may be too low for screening average risk populations. This study aims at evaluating the diagnostic value of fecal calprotectin as a screening biomarker for GI malignancies. Materials and Methods: In a case-control study, 100 patients with GI malignancies (50 patients with colorectal cancer and 50 patients with gastric cancer) and 50 controls were recruited in Tabriz Imam Reza and Sina hospitals during a 24-month period. One to two weeks after the last endoscopy/colonoscopy, fecal specimens were collected by the patients and examined by ELISA method for quantitative measurement of calprotectin content. The results were compared between the three groups. Results: The mean fecal calprotectin level was$109.1{\pm}105.3$ (2.3-454.3, median:74),$241.1{\pm}205.2$ (3.4-610.0, median:19.3) and$45.9{\pm}55.1{\mu}g/g$ (1.3-257.1, median:19.3) in gastric cancer, colorectal cancer and control group, respectively, the differences being significant (p<0.001) and remaining after adjustment for age. The optimal cut-off point for fecal calprotectin was${\geq}75.8{\mu}g/g$ for distinguishing colorectal cancer from normal cases (sensitivity and specificity of 80% and 84%, respectively). This value was${\geq}41.9{\mu}g/g$ for distinguishing gastric cancer from normal cases (sensitivity and specificity of 62%). Conclusions: Our results revealed that fecal calprotectin might be a useful and non-invasive biomarker for distinguishing colorectal cancer from non-malignant GI conditions. However, due to low sensitivity and specificity, this biomarker may not help physicians distinguishing gastric cancer cases from healthy subjects. -
Shruthi, Pannayanapalya Suresh;Kalyani, Raju;Lee, Jun Kai;Narayanaswamy, Mariyappa 1671
Background: To study the clinical presentation of cervical carcinoma correlating with histopathological findings in a tertiary hospital situated in the southern part of India catering to rural and semi-urban populations Materials and Methods: 199 cases histopathologically diagnosed as cervical cancer over a period of one year were considered for the study. Clinical details of the patients were noted with the help of semi-structured proforma. The data was analysed by descriptive analysis using SPSS software. Results: Out of 199 patients, 109 had moderately differentiated squamous cell carcinoma, 51 poorly differentiated and 35 well differentiated. Adenocarcinomas numbered only four. 121 cases were in the age group of 40-59 years, 59 in 60-80 years and 19 in 20-39 years. All four cases of adenocarcinoma were seen between 40-59 years. 95 (47.7%) cases were in women who had 4 or more children, 120 presented with white discharge, 89 with bleeding per vagina and 68 had constitutional symptoms. Most of the patients with adenocarcinoma presented with bleeding per vagina. 151 was in stage IIIB, 29 in stage IIB, 14 in stage IVA and 5 in stage IB. Conclusions: Screening of cervical cancer should be emphasised in women with white discharge especially in rural areas for early detection of dysplastic cells and reduce mortality and morbidity in productive age. In addition health education has to be given to women regarding the awareness of hygiene, risk factors and symptoms of cervical cancer. -
Ding, Hui;Wu, Yi-Lin;Wang, Ying-Xia;Zhu, Fu-Fan 1675
Objectives: MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecular mechanisms of metastatic cervical carcinoma by performing miRNA profiling. Methods: Tissue samples were collected from ten cervical squamous cancer patients who underwent hysterectomy and pelvic lymph node (PLN) dissection in our hospital, including four PLN-positive (metastatic) cases and six PLN-negative (non-metastatic) cases. A miRNA microarray platform with 1223 probes was used to determine the miRNA expression profiles of these two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positive and PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAs with tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive and PLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of the miRNAs (27/39) had tumor-associated target genes, and the expression levels of six of those (miR-126, miR-96, miR-144, miR-657, miR-490-5p, and miR-323-3p) were confirmed by quantitative (q)RT-PCR. Conclusions: Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved in cell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. These findings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade by targeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, it is likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or molecular therapy. -
Objective: To investigate interferon (IFN) alpha 2 b for treating patients with JAK2V617F positive polycythemia vera (PV) and essential thrombocytosis (ET). Methods: Interferon alpha 2 b was used to treat patients with JAK2V617F positive PV and ET. In control group, hydroxyurea was used. Endpoint of study was to compare rates of hematological and molecular remission. Results: Patients in the interferon alpha 2 b group achieved higher rates of hematologic and molecular remission than patients in the hydroxyurea group, with a lower incidence of thrombosis. Conclusion: Compared with hydroxyurea, interferon alpha 2 b could reduce JAK2V617F load for patients with PV and ET, and achieve higher molecular remission, improve treatment efficacy and reduce complications.
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Moazzezy, Neda;Farahany, Tahereh Zarnoosheh;Oloomi, Mana;Bouzari, Saeid 1685
Background: CEA and CA 15.3 serum tumor markers are currently used in clinical practice for monitoring therapy. The aim of this study was to evaluate serum level of these markers among healthy females and invasive breast carcinoma (IBC) patients and to determine any relationships with clinicopathological factors. Materials and Methods: 60 Iranian females were enrolled in this study, 30 healthy and 30 diagnosed with breast cancer who had not received any preoperative chemotherapy or hormone therapy. Enzyme linked immunosorbent assays were used for the quantitative determination of the cancer associated antigens, CEA and MUC1 (CA15-3). Results: The serological levels of CEA and CA15-3 ($5.0033{\pm}0.49{\mu}g/L$ and$178.1667{\pm}15.11$ U/ml) in the breast cancer patients were significantly higher (p=0.00) than the serum levels of normal controls ($1.1237{\pm}0.11{\mu}g/L$ and$21.13{\pm}3.058$ U/ml). Regarding the CEA marker, a significant correlation with grade of tumor was shown. Furthermore, there was a low correlation between CA15-3 and CEA marker with correlation coefficient r=0.08. Conclusions: Collectively, markedly high levels of CEA and CA15-3 were found in our patients, pointing to their use as additional tools after clinical diagnosis. -
Acmaz, Gokhan;Aksoy, Huseyin;Unal, Dilek;Ozyurt, Sezin;Cingillioglu, Basak;Aksoy, Ulku;Muderris, Ipek 1689
Background: An easy, reproducible and simple marker is needed to estimate phase of endometrial pathologic lesions such as hyperplasia and endometrial cancer and distinguish from pathologically normal results. We here aimed to clarify associations among neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), endometrial hyperplasia and cancer in patients with abnormal uterine bleeding. Materials and Methods: Patients (n=161) who were admitted with abnormal uterine bleeding and the presence of endometrial cells on cervical cytology or thick endometrium were investigated. The study constituted of three groups according to pathologic diagnosis. Group 1 included endometrial precancerous lesions like hyperplasia (n=63), group 2 included endometrial cancerous lesions (n=38) and group 3 was a pathologically normal group (n=60). Blood samples were obtained just before the curettage procedure and the NLR was defined as the absolute neutrophil count divided by the absolute lymphocyte count; similarly, PLR was defined as the absolute platelet count divided by the absolute lymphocyte count. Results: The white blood cell count was significantly higher in patients with cancer than in those with hyperplasia (p=0.005). The platelet count and neutrophil to lymphocyte ratio were significantly higher in patients with cancer than in control patients, but there was significantly no difference between patients with hyperplasia and other groups (p=0.001 and p=0.025 respectively). PLR was significantly lower in control subjects than in other groups (p<0.001), but there was no significant difference between patients with hyperplasia and those with cancer. Conclusions: PLR was significantly lower in control subjects than in other groups. Thus both hyperplasia and cancer may be differentiated from pathologically normal patients by using PLR. White blood cell count was significantly higher in patients with cancer than in those with hyperplasia and pathologically normal patients. Therefore white blood cell count may be used for discriminate hyperplasia to cancer. By using multiple inflammation parameters, discrimination may be possible among endometrial cancer, endometrial precancerous lesions and pathologically normal patients. -
Kayhan, Arda;Gurdal, Sibel Ozkan;Ozaydin, Nilufer;Cabioglu, Neslihan;Ozturk, Enis;Ozcinar, Beyza;Aribal, Erkin;Ozmen, Vahit 1693
Background: The Bahcesehir Breast Cancer Screening Project is the first organized population based breast cancer mammographic screening project in Turkey. The objective of this prospective observational study was to demonstrate the feasibility of a screening program in a developing country and to determine the appropriate age (40 or 50 years old) to start with screening in Turkish women. Materials and Methods: Between January 2009 to December 2010, a total of 3,758 women aged 40-69 years were recruited in this prospective study. Screening was conducted biannually, and five rounds were planned. After clinical breast examination (CBE), two-view mammograms were obtained. True positivity, false positivity, positive predictive values (PPV) according to ACR, cancer detection rate, minimal cancer detection rate, axillary node positivity and recall rate were calculated. Breast ultrasound and biopsy were performed in suspicious cases. Results: Breast biopsy was performed in 55 patients, and 18 cancers were detected in the first round. The overall cancer detection rate was 4.8 per 1,000 women. Most of the screened women (54%) and detected cancers (56%) were in women aged 40-49. Ductal carcinoma in situ (DCIS) and stage I cancer and axillary node positivity rates were 22%, 61%, and 16.6%, respectively. The positive predictivity for biopsy was 32.7%, whereas the overall recall rate was 18.4 %. Conclusions: Preliminary results of the study suggest that population based organized screening are feasible and age of onset of mammographic screening should be 40 years in Turkey. -
Cui, Lin;Liu, Xing-Xiang;Jiang, Yong;Liu, Jian-Jun;Zhou, Xiang-Rong;He, Xue-Jun;Chen, Jue;Huang, Xin-En 1699
Objective: To evaluate clinical efficacy of a dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung (NSCLC). Methods: Patients with locally advanced NSCLC were treated with conventional fractionated radiotherapy or three dimensional conformal radiotherapy (3 DCRT), concurrently with a dose escalating schedule of paclitaxel. All patients were divided into three groups, A with paclitaxel$30mg/m^2$ , B with paclitaxel$60mg/m^2$ and C with paclitaxel$90mg/m^2$ . Paclitaxel was repeated every week for a total of 4 or 6 weeks. Results: Among 109 patients, response rates were 68.8%, 71.1% and 71.8% (p>0.05) for group A (n=32), B (n=38), and C (n=39) respectively. Accordingly, disease control rates were 81.3%, 81.6% and 82.1% (p>0.05). Progression-free survival time was$8.0{\pm}5.0$ months,$11.6{\pm}6.1$ months, and$14.8{\pm}7.9$ months (p<0.05), respectively. Overall survival time was$15.4{\pm}7.6$ months,$18.2{\pm}8.0$ months, and$22.0{\pm}7.6$ months (p<0.05), one-year survival rates were 62.5%, 73.1% and 90.0% (p>0.05) and two-year survival rates were 31.3%, 38.5% and 50.0% (p<0.05). Main side-effects were bone marrow suppression, radiation related esophagitis and gastrointestinal reaction. Conclusion: In treating patients with NSCLC, concurrent chemoradiotherapy with paclitaxel improves early response compared with conventional fractionated radiotherapy or 3 DCRT. The survival rate was improved with the addition of paclitaxel, but there was an increase in adverse reactions when the dose of paclitaxel was increased. -
Gan, Gin Gin;Subramaniam, Rajaletchumy;Bee, Ping Chong;Chin, Edmund Fui Min;Abdul-Halim, Habibah;Tai, Mei Chee 1703
Background: The current standard treatment for patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) is rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). A significant number of patients were not treated with recommended dose of rituximab due to limited financial resources in Malaysia. This study evaluates the efficacy of R-CHOP like chemotherapy in Malaysian patients with DLBCL. Materials and Methods: The study comprised a retrospective analysis of patients with DLBCL treated at a single centre. The outcome was compared with patients who were treated with R-CHOP like and CHOP like chemotherapy. Patients who were treated with lower dose of rituximab was subanalysed for outcome. Results: A total of 86 patients who had CHOP-like chemotherapy were included. Only 39 (45%) patients had rituximab and only 12 (29%) patients had the recommended dose. The overall response (OR) and complete response (CR) rates were 88% and 81% respectively. There was no significant difference in OR and CR in patients who had rituximab and those without rituxmab. Those with International Prognostic Index (IPI) score of${\leq}2$ had significant higher CR rate, progression free survival (PFS) and overall survival (p<0.001). Conclusions: The lack of significant improvement in CR and DFS in our patients may be due to an inadequate dose of rituximab. -
Sawazaki, Harutake;Sengiku, Atsushi;Imamura, Masaaki;Takahashi, Takeshi;Kobayashi, Hisato;Ogura, Keiji 1707
Background: The objective of this study was to evaluate baseline use and positive rates of staging images (bone scan, CT) in newly diagnosed patients with prostate cancer (PCa) and to improve staging image overuse. Materials and Methods: This retrospective study covered a consecutive series of patients with PCa who underwent stage imaging at our institution between 2006 and 2011. Various clinical and pathological variables (age, PSA, biopsy Gleason score, clinical T stage, positive biopsy core rate) were evaluated by multivariate logistic regression analysis for their ability to predict a positive staging image. All patients were stratified according to the NCCN risk stratification and positive rates were compared in each risk group. Results: 410 patients (100%) underwent a bone scan and 315 patients (76.8%) underwent a CT scan. Some 51 patients (12.4%) had a positive bone scan, clinical T3 and T4 being significant independent predictors. Positive bone scan rates for low-, intermediate-, high-, and very high-risk groups were 0%, 0%, 8.25%, and 56.6%. Some 59 (18.7%) patients had a positive CT scan, with elevated PSA and clinical T3, T4 as significant independent predictors. Low-, intermediate-, high- and very high-risk group rates were 0%, 0%, 13.8% and 80.0%. Conclusions: The incidences of positive staging image in low- and intermediate- risk group were reasonably low. Following feedback on these results, staging in low- and intermediate- risk groups could be omitted. -
Cai, Yong;Sheng, Zhao-Ying;Chen, Yun;Bai, Chong 1711
Objective: To explore the effect of Withaferin A on A549 cellular proliferation and apoptosis in non-small cell lung cancer (NSCLC). Materials and Methods: NSCLC cell line A549 was selected to explore the effect of Withaferin A on A549 cellular proliferation, apoptosis and the PI3K/Akt signal pathway capable of regulating tumor biological behavior by assessment of cellular proliferation, cellular apoptotic rates and cellular cycling as well as by immuno-blotting. Results: Withaferin A could inhibit A549 cellular proliferation and the control rate was dosage-dependent (P<0.05), which also increased time-dependently with the same dosage of Withaferin A (P<0.05). The apoptotic indexes in A549 cells treated with 0, 2.5, 5.0, 10.0 and 20.0${\mu}mol{\cdot}L^{-1}$ Withaferin A for 48 h were significantly different (P<0.05). In addition, the apoptotic rates of each group in both early and advanced stages were higher than those in 0${\mu}mol{\cdot}L^{-1}$ (P<0.05), which were evidently higher after 48 h than those after 24 h (P<0.05). A549 cells treated by Withaferin A for 48 h were markedly lower in Bcl-2 level and obviously higher in Bax and cleaved caspase-3 levels than those treated by 0${\mu}mol{\cdot}L^{-1}$ Withaferin A (P<0.05), and there were significant differences among 5, 10 and 20${\mu}mol{\cdot}L^{-1}$ Withaferin A (P<0.05). The ratios of A549 cells treated by Withaferin A for 48 h in G0/G1 stage were higher than those in 0${\mu}mol{\cdot}L^{-1}$ , while those in S and G2/M stages were obviously lower than those in G2/M stage, and there were significant differences in 5.0, 10.0 and 20.0${\mu}mol{\cdot}L^{-1}$ Withaferin A (P<0.05). Additionally, p-Akt/Akt values were in reverse association with dosage, and the differences were significant (P<0.05). Conclusion: Withaferin A can inhibit the proliferation and apoptosis of A549 cells by suppressing activation of the PI3K/Akt pathways. -
Jia, Hong-Ying;Liu, Jun-Li;Zhou, Cheng-Jun;Kong, Feng;Yuan, Ming-Zhen;Sun, Wen-Dong;Wang, Jue;Liu, Ling;Zhao, Jing-Jie;Luan, Yun 1715
The overall incidence and mortality of renal cell carcinoma (RCC), the most common kidney cancer, are steadily increasing for reasons that are not fully explained. Our aim was to explore the expression of membrane MHC class I chain-related gene A (mMICA) in human RCC cell lines and tissue specimens, and to determine expression of soluble MICA (sMICA) in serum of patients with renal cell carcinoma, we used flow cytometry (FCM) and immunohistochemistry as well as an enzyme linked immunosorbent assay (ELISA). The results showed that percentage of mMICA expression was significantly increased in human kidney cancer tissues and RCC cell lines (786-O and Ketr-3) than that in healthy adults and human embryonic kidney 293 (HEK293) cell line individuality (P<0.05). sMICA content in healthy adults was negative, but in renal cancer patients was significantly elevated (P<0.05). Our research showed that high expression of MICA in human kidney cancer, this results show that MICA might serve as potential tumor-associated antigen (TAA) in RCC. -
Dunna, Nageswara Rao;Naushad, Shaik Mohammad;Vuree, Sugunakar;Anuradha, Cingeetham;Sailaja, Kagita;Surekha, Damineni;Rao, Digumarti Raghunadha;Vishnupriya, Satti 1719
Background: The current study was aimed to elucidate the association of thymidylate synthase (TYMS) 5'-UTR 28bp tandem repeat and cytosolic serine hydroxymethyltransferase (cSHMT) C1420T polymorphisms with acute leukemia in South Indian subjects. A total of 812 subjects [523 healthy controls, 148 acute lymphoblastic leukemia (ALL) cases and 141 acute myeloid leukemia (AML) cases] were screened for TYMS 5'-UTR 28bp tandem repeat and cSHMT C1420T using PCR-AFLP and PCR-with confronting two-pair primers (CTPP) approaches. TYMS 5'-UTR 2R allele frequencies of controls, ALL and AML cases were 35.3%, 28.0% and 30.1% respectively. This polymorphism conferred protection against ALL (OR: 0.71, 95%CI: 0.53-0.96) while showing no statistically significant association with AML (OR: 0.79, 95%CI: 0.58, 1.07). The cSHMT variant allele (T-) frequencies of ALL and AML cases (6.42% and 5.68% respectively) were significantly lower compared to controls (58.3%). This polymorphism conferred protection against ALL (OR: 0.049, 95%CI: 0.029-0.081) and AML (OR: 0.043, 95%CI: 0.025-0.074). The TYMS 5'-UTR 2R2R genotype was associated with a lower total leukocyte count, smaller percentage of blasts, and more adequate platelet count compared to 2R3R and 3R3R genotypes in ALL cases. No such genotype-dependent differences were observed in AML cases. ALL cases carrying the cSHMT C1420T polymorphism showed higher disease free survival compared to those with the wild genotype. To conclude, the TYMS 5'-UTR 28bp tandem repeat reduces risk for ALL while cSHMT C1420T reduces risk for both ALL and AML. Both also influence disease progression in ALL. -
Wong, Yin-Ping;Shah, Shamsul Azhar;Shaari, Noorsajida;Mohamad Esa, Mohd Shafbari;Sagap, Ismail;Isa, Nurismah Md 1725
Management of patients with stage II colorectal carcinomas remains challenging as 20 - 30% of them will develop recurrence. It is postulated that these patients may harbour nodal micrometastases which are imperceptible by routine histopathological evaluation. The aims of our study were to evaluate (1) the feasibility of multilevel sectioning method utilizing haematoxylin and eosin stain and immunohistochemistry technique with cytokeratin AE1/AE3, in detecting micrometastases in histologically-negative lymph nodes, and (2) correlation between nodal micrometastases with clinicopathological parameters. Sixty two stage I and II cases with a total of 635 lymph nodes were reviewed. Five-level haematoxylin and eosin staining and one-level cytokeratin AE1/AE3 immunostaining were performed on all lymph nodes retrieved. The findings were correlated with clinicopathological parameters. Two (3.2%) lymph nodes in two patients (one in each) were found to harbour micrometastases detected by both methods. With cytokeratin AE1/AE3, we successfully identified four (6.5%) patients with isolated tumour cells, but none through the multilevel sectioning method. Nodal micrometastases detected by both multilevel sectioning and immunohistochemistry methods were not associated with larger tumour size, higher depth of invasion, poorer tumour grade, disease recurrence or distant metastasis. We conclude that there is no difference between the two methods in detecting nodal micrometastases. Therefore it is opined that multilevel sectioning is a feasible and yet inexpensive method that may be incorporated into routine practice to detect nodal micrometastases in centres with limited resources. -
Rafii, Forugh;Oskouie, Fatemeh;Shoghi, Mahnaz 1731
The life of a mother undergoes a dramatic change after a child is diagnosed with cancer. The present study aimed to determine effects on the everyday life process and health status of mothers with children suffering from leukemia. This qualitative study was based on a grounded theory approach with sixteen mothers. The results indicate that after onset of disease in their children, they marginalized their own health and tied their identities to taking care of the child and keeping the child healthy by ignoring themselves, becoming imprisoned in a taking-care-of-the-child position, and trying very hard for seek balance and stability Enduring physical pressures on the one hand, and constantly attempting to achieve balance and stability in family processes on the other hand, gradually cause exhaustion. It seems that health care providers and nurses should pay much more attention to the health status of this group of mothers. -
Ji, Ting;Zheng, Zhi-Guo;Wang, Feng-Mei;Xu, Li-Jian;Li, Lu-Feng;Cheng, Qi-Hui;Guo, Jiang-Feng;Ding, Xian-Feng 1739
MicroRNAs are a class of small noncoding RNA which play important regulatory roles in a variety of cancers. MiRNA-specific expression profiles have been reported for several pathological conditions. In this study, we combined large scale parallel Solexa sequencing to identify 11 up-regulated miRNAs and 19 down-regulated miRNAs with computational techniques in the sera of ovarian cancer patients while using healthy serum as the control. Among the above, four miRNAs (miR-22, miR-93, miR-106b, miR-451) were validated by quantitative RT-PCR and found to be significantly aberrantly expressed in the serum of ovarian cancer patients (P<0.05). There were no significant differences between samples from cancer stage I/II and III/IV. However, the levels of miR-106b (p=0.003) and miR-451 (p=0.007) were significantly different in those patients under and over 51 yearsof age. MiR-451 and miR-93 were also specific when analyzed with reference to different levels of CA125. This study shows that Solexa sequencing provides a promising method for cancer-related miRNA profiling, and selectively expressed miRNAs could be used as potential serum-based biomarkers for ovarian cancer diagnosis. -
Li, Ting;Xu, Wen-Shan;Wu, Guo-Sheng;Chen, Xiu-Ping;Wang, Yi-Tao;Lu, Jin-Jian 1745
Background: Platycodin D (PD), a triterpenoid saponin isolated from the Chinese medicinal herb Platycodonis radix, possesses anti-cancer effects in several cancer cell lines. The aim of this study was to evaluate its anticancer activities in hepatocellular carcinoma cells. Materials and Methods: MTT and colony formation assays were performed to evaluate cell proliferation, along with flow cytometry and Western blotting for apoptosis. Cell adhesion was tested by observing cellular morphology under a microscope, while the transwell assay was employed to investigate the cell migration and invasion. Results: PD concentration-dependently inhibited cell proliferation in both HepG2 and Hep3B cells, and significantly suppressed colony formation and induced apoptosis in HepG2 cells. The protein levels of cleaved poly ADP-ribose polymerase (PARP) and Bax were up-regulated while that of survivin was down-regulated after treatment with PD. Moreover, PD not only obviously suppressed the adhesion of HepG2 cells to Matrigel, but also remarkably depressed their migration and invasion induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). Conclusions: PD presents anti-cancer potential in hepatocellular carcinoma cells via inducing apoptosis, and inhibiting cell adhesion, migration and invasion, indicating promising features as a lead compound for anti-cancer agent development. -
Ocal, Irfan;Avci, Arzu;Cakalagaoglu, Fulya;Can, Huseyin 1751
Background: In this study prognostic correlations of histopathologic parameters and the Ki-67 proliferation index and as well as the diagnostic value of immunohistochemical markers in pheochromocytomas were evaluated. Materials and Methods: A total of 22 patients diagnosed with a pheochromocytoma between 2000-2010 in Izmir Katip Celebi University Ataturk Training and Research Hospital were included. Diagnostic value of the PASS scoring system, and prognostic correlations of histopathologic parameters and Ki-67 proliferation index were investigated. SPSS for Windows 17.0 software was used for statistical analysis. Results: There was no statistically significant correlation between recurrence and clinicopathologic parameters or the PASS score (PASS>4). In addition, there were no statistically significant correlations between PASS score and clinicopathologic parameters, such as diameter (5 cm), weight (>100g), gender (female/male ratio) and age (25-45/45-55/>55). Besides, there were no significant correlation between diameter and clinicopathological parameters and also recurrence. However, there was a statistically significant correlation between Ki-67 proliferation index and capsule invasion (p=0.047). Conclusions: Some but not most of the findings in our study were concordant with the literature. To clarify relationships, investigations with standard scoring systems which are not affected by subjective factors and feature appropriate histopathological criteria should be made on larger study groups. -
Rengarajan, Thamaraiselvan;Nandakumar, Natarajan;Rajendran, Peramaiyan;Haribabu, Lingaiah;Nishigaki, Ikuo;Balasubramanian, Maruthaiveeran Periyasamy 1757
Development of drugs from natural products has been undergoing a gradual evoluation. Many plant derived compounds have excellent therapeutic potential against various human ailments. They are important sources especially for anticancer agents. A number of promising new agents are in clinical development based on their selective molecular targets in the field of oncology. D-pinitol is a naturally occurring compound derived from soy which has significant pharmacological activitites. Therefore we selected D-pinitol in order to evaluate apoptotic potential in the MCF-7 cell line. Human breast cancer cells were treated with different concentrations of D-pinitol and cytotoxicity was measured by MTT and LDH assays. The mechanism of apoptosis was studied with reference to expression of p53, Bcl-2, Bax and NF-kB proteins. The results revealed that D-pinitol significantly inhibited the proliferation of MCF-7 cells in a concentration-dependent manner, while upregulating the expression of p53, Bax and down regulating Bcl-2 and NF-kB. Thus the results obtained in this study clearly vindicated that D-pinitol induces apotosis in MCF-7 cells through regulation of proteins of pro- and anti-apoptotic cascades. -
Unal, Dilek;Oguz, Arzu;Acmaz, Banu;Goksu, Sema Sezgin;Arslan, Alaettin;Eroglu, Celalettin 1763
Background: The influence of season of diagnosis on cancer survival has been an interesting issue for many years. Most studies have shown a possible association between seasonality and survival in some cancers. We aimed to investigate whether there is an association between season of diagnosis and survival in patients with gastric cancer. Materials and Methods: We reviewed retrospectively the files of 279 histologically proven gastric cancer patients. According to diagnosis date, the patients were grouped into 4 seasons of diagnosis groups, spring, summer, autumn, and winter. Results: There was no significant differences when the overall survival rates of the patients were compared according to the patients' season of diagnosis (p: 0.871). Median overall survival rates were 22.0 (14.5-29.5) months for the patients who were diagnosed in spring, 24.0 (12.4-35.6) for summer, 18.0 (9.96-26.0) for autumn and 21.0 (16.3-25.7) for winter. Median disease-free survival rates were 66.0 (44.1-68.1) months for the patients who were diagnosed in spring, 28.0 (17.0-39.0) for summer, 22.0 (0-46.4) for autumn and 23.0 (17.5-28.5) for winter. While the rate was best for the patients diagnosed in spring the differences were not statistically significant (p= 0.382). Conclusions: On the basis of the above results the season was not suggested as contributing to prognosis in gastric cancer cases in Kayseri, Turkey. -
Hou, Zhi-Bo;Lu, Kai-Jin;Wu, Xiao-Li;Chen, Cong;Huang, Xin-En;Yin, Hai-Tao 1767
Purpose: Lung cancer, one of the most frequently diagnosed cancers in the world, is characterized by relatively high morbidity and mortality. Berbamine (BER) has been initially reported to exert anti-proliferative effects against a series of cancers. Methods: In this study the in vitro cytotoxicity of BER was measured by MTT assay. In vivo anti-cancer efficacy of BER was assessed in A549 xenografts. Results: Cytotoxicity tests showed dose-dependent cell growth inhibition effects of BER against A549 cells. Moreover, BER significantly reduced the growth of lung cancer in a dose-dependent manner in nude mice with prolonged survival time. Conclusion: Therefore, BER might be in herbal medicine for cancer therapy and further efforts are needed to explore therapeutic strategies. -
Liu, Chun-Xia;Li, Xiao-Ying;Li, Cheng-Fang;Chen, Yun-Zhao;Cui, Xiao-Bin;Hu, Jian-Ming;Li, Feng 1771
The rhabdomyosarcoma (RMS) is the most common type of soft tissue tumor in children and adolescents; yet only a few screens for oncogenic mutations have been conducted for RMS. To identify novel mutations and potential therapeutic targets, we conducted a high-throughput Sequenom mass spectrometry-based analysis of 238 known mutations in 19 oncogenes in 17 primary formalin-fixed paraffin-embedded RMS tissue samples and two RMS cell lines. Mutations were detected in 31.6% (6 of 19) of the RMS specimens. Specifically, mutations in the NRAS gene were found in 27.3% (3 of 11) of embryonal RMS cases, while mutations in NRAS, HRAS, and PIK3CA genes were identified in 37.5% (3 of 8) of alveolar RMS (ARMS) cases; moreover, PIK3CA mutations were found in 25% (2 of 8) of ARMS specimens. The results demonstrate that tumor profiling in archival tissue samples is a useful tool for identifying diagnostic markers and potential therapeutic targets and suggests that these HRAS/ PIK3CA mutations play a critical role in the genesis of RMS. -
Dincbas, Fazilet Oner;Oksuz, Didem Colpan;Yetmen, Ozlem;Hiz, Murat;Dervisoglu, Sergulen;Turna, Hande;Kantarci, Fatih;Mandel, Nil Molinas;Koca, Sedat 1775
Background: To assess the long term clinical outcome of preoperative radiotherapy with or without chemotherapy followed by limb sparing surgery in patients with non-metastatic soft tissue sarcomas (STS) of the extremities. Materials and Methods: Sixty patients with locally advanced STS were retrospectively analyzed. The median tumor diameter was 12 cm. All patients were treated with preoperative radiotherapy delivered with two different fractionation schedules (35Gy/10fr or 46-50Gy/23-25fr). Neoadjuvant chemotherapy was added to 44 patients with large and/or high grade tumors. Surgery was performed 2-6 weeks after radiotherapy. Chemotherapy was completed up to 6 courses after surgery in patients who had good responses. Results: Median follow-up time was 67 months (8-268 months). All of the patients had limb sparing surgery. The 5-year local control (LC), disease free (DFS) and overall survival (OSS) rates for all of the patients were 81%, 48.1% and 68.3% respectively. 5-year LC, DFS and cause specific survival (CSS) were 81.7%, 47%, 69.8%, and 80%, 60%, 60% in the chemoradiotherapy and radiotherapy groups, respectively. On univariate analysis, patients who were treated with hypofractionation experienced significantly superior LC, DFS and CSS rates with similar rates of late toxicity when compared with patients who were treated with conventional fractionation and statistical significance was retained on multivariate analysis. Conclusions: Treatment results are consistent with the literature. As neoadjuvant chemoradiotherapy provides effective LC and CSS with acceptable morbidity, it should be preferred for patients with large and borderline resectable STS. -
Madjd, Zahra;Akbari, Mohammad Esmaeil;Zarnani, Amir Hassan;Khayamzadeh, Maryam;Kalantari, Elham;Mojtabavi, Nazanin 1783
Background: The EMSY gene encodes a BRCA2-binding partner protein that represses the DNA repair function of BRCA2 in non-hereditary breast cancer. Although amplification of EMSY gene has been proposed to have prognostic value in breast cancer, no data have been available concerning EMSY tissue expression patterns and its associations with clinicopathological features. Materials and Methods: In the current study, we examined the expression and localization pattern of EMSY protein by immunohistochemistry and assessed its prognostic value in a well-characterized series of 116 unselected breast carcinomas with a mean follow up of 47 months using tissue microarray technique. Results: Immunohistochemical expression of EMSY protein was detected in 76% of primary breast tumors, localized in nuclear (18%), cytoplasmic (35%) or both cytoplasmic and nuclear sites (23%). Univariate analysis revealed a significant positive association between EMSY expression and lymph node metastasis (p value=0.045) and larger tumor size (p value=0.027), as well as a non-significant relation with increased risk of recurrence (p value=0.088), whereas no association with patients' survival (log rank test, p value=0.482), tumor grade or type was observed. Conclusions: Herein, we demonstrated for the first time the immunostaining pattern of EMSY protein in breast tumors. Our data imply that EMSY protein may have impact on clinicipathological parameters and could be considered as a potential target for breast cancer treatment. -
Lee, Hee Yun;Tran, Marie;Jin, Seok Won;Bliss, Robin;Yeazel, Mark 1791
Background: Colorectal cancer (CRC) is a leading cause of cancer death among Vietnamese Americans, yet screening remains underutilized. We investigated the effectiveness of a culturally tailored DVD intervention in promoting CRC screening among unscreened Vietnamese Americans age 50 and over. Materials and Methods: Using a community-based participatory research approach, we conducted a trial comparing twenty-eight subjects who received a mailed DVD in Vietnamese, with twenty-eight subjects who received a mailed brochure in Vietnamese. Subjects completed telephone surveys at baseline, One-month, and one-year. The primary outcome was receipt of screening. Secondary measures were participants' knowledge, attitudes, and beliefs about CRC screening. Two focus groups explored the intervention's acceptability and effectiveness. Results: At one year, CRC screening rates of 57.1% and 42.9% were observed in experimental and control group respectively (p=0.42), Subjects in both groups showed increased knowledge about CRC after one month. Focus group findings revealed that the DVD was an effective method of communicating information and would help promote screening. Conclusions: The findings suggest that culturally tailored, linguistically appropriate content is more important than the type of media used. This relatively low intensity, low cost intervention utilizing a DVD can be another useful method for outreach to the often hard-to-reach unscreened population. -
Liu, Fen;Wei, Wen-Qiang;Cormier, Robert T.;Zhang, Shu-Tian;Qiao, You-Lin;Li, Xin-Qing;Zhu, Sheng-Tao;Zhai, Yan-Chun;Peng, Xiao-Xia;Yan, Yu-Xiang;Wu, Li-Juan;He, Dian;He, Yan 1797
Background: The prostaglandin-endoperoxide synthase 2 (PTGS2) and phospholipase A2 group IIA (PLA2G2A) genes encode enzymes that are involved in arachidonic acid and prostaglandin biosynthesis. Dysregulation of both genes is associated with inflammation and carcinogenesis, including esophageal squamous cell carcinoma (ESCC). We therefore hypothesized that there is an association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to ESCC. Methods: We performed a gene-wide tag SNP-based association study to examine the association of SNPs in PTGS2 and PLA2G2A with ESCC in 269 patients and 269 healthy controls from Taihangshan Mountain, Henan and Hebei Provinces, the rural area of China which has the highest incidence of esophageal cancer in the world. Thirteen tag SNPs in PLA2G2A and 4 functional SNPs in PTGS2 were selected and genotyped using a high-throughput Mass Array genotyping platform. Results: We found a modest increased risk of ESCC in subjects with the PTGS2 rs12042763 AA genotype (OR=1.23; 95% CI, 1.00-3.04) compared with genotype GG. For PLA2G2A, a decreased risk of ESCC was observed in subjects with the rs11677 CT (OR=0.51, 95%CI, 0.29-0.85) or TT genotype (OR=0.51, 95%CI, 0.17-0.96) or the T carriers (CT+TT) (OR=0.52, 95%CI, 0.31-0.85) when compared with the CC genotype. Also for PLA2G2A, rs2236771 C allele carriers were more frequent in the control group (P=0.02). Subjects with the GC (OR=0.55, 95%CI, 0.33-0.93) or CC genotype (OR=0.38, 95% CI, 0.16-0.94) or the C carriers (GC+CC) (OR=0.52, 95%CI, 0.32-0.85) showed a negative association with ESCC susceptibility. Conclusions: Our results suggest that PTGS2 and PLA2G2A gene polymorphisms may modify the risk of ESCC development. -
Wang, Jing;Ge, Jian;Zhang, Xiao-Hua;Liu, Ji-Yong;Yang, Chong-Mei;Zhao, Shu-Lei 1803
Endoscopic submucosal dissection (ESD) was originally developed for en bloc resection of large, flat gastrointestinal lesions. Compared with endoscopic mucosal resection (EMR), ESD is considered to be more time consuming and have more complications for treatment of early esophageal carcinoma, such as bleeding, stenosis and perforation. The objective of this study was to compare the efficacy and safety of ESD and EMR for such lesions. We searched databases, such as PubMed, EMBASE, Cochrane Library and Science Citation Index updated to 2013 for related trials. In the meta-analysis, the main outcome measurements were the en bloc resection rate, the histologically resection rate and the local recurrence rate. We also compared the operation time and the incidences of procedure-related complications. Five trials were identified, and a total of 710 patients and 795 lesions were included. The en bloc and histologically complete resection rates were higher in the ESD group compared with the EMR group (odds ratio (OR) 27.3; 95% CI, 11.5-64.8; OR 18.4; 95% CI, 8.82-38.59). The local recurrence rate was lower in the ESD group (OR 0.13, 95 % CI 0.04-0.43). The meta-analysis also showed ESD was more time consuming, but did not increase the complication rate (P=0.76). The results implied that compared with EMR, ESD showed better en bloc and histologically resection rates, and lower local recurrence, without increasing the incidence of procedure-related complications in the treatment of early esophageal carcinoma. -
Somchit, Mayura;Changtam, Chatchawan;Kimseng, Rungruedi;Utaipan, Tanyarath;Lertcanawanichakul, Monthon;Suksamrarn, Apichart;Chunglok, Warangkana 1807
Background: It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integral role during intestinal inflammation, an important factor for colon cancer development. Natural compounds from Curcuma longa L. (Zingiberaceae) have long been a potential source of bioactive materials with various beneficial biological functions. Among them, a major active curcuminoid, demethoxycurcumin (DMC) has been shown to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages or microglia cells. However, the role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinal mucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NO production of DMC in inflamed human intestinal Caco-2 cells. An in vitro model was generated and inhibitory effects on NO production of DMC at 65${\mu}M$ for 24-96 h were assessed by monitoring nitrite levels. Expression of iNOS mRNA and protein was also investigated. DMC significantly decreased NO secretion by 35-41% in our inflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS at mRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanism of action of DMC may be partly due to its potent inhibition of the iNOS pathway. Our findings suggest that DMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut. -
Inamoto, Teruo;Azuma, Haruhito;Nonomura, Norio;Nakatani, Tatsuya;Matsuda, Tadashi;Nozawa, Masahiro;Ueda, Takeshi;Kinoshita, Hidefumi;Nishimura, Kazuo;Kanayama, Hiro-Omi;Miki, Tsuneharu;Tomita, Yoshihiko;Yoshioka, Toshiaki;Tsujihata, Masao;Uemura, Hirotsugu 1811
Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients${\geq}$ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last followup. There were 86 (50%) patients${\geq}$ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC. -
Diao, Chun-Yu;Guo, Hong-Bing;Ouyang, Yu-Rong;Zhang, Han-Cong;Liu, Li-Hong;Bu, Jie;Wang, Zhi-Hua;Xiao, Tao 1817
Objective: The aim of this study was to screen for possible biomarkers of metastatic osteosarcoma (OS) using a DNA microarray. Methods: We downloaded the gene expression profile GSE49003 from Gene Expression Omnibus database, which included 6 gene chips from metastatic and 6 from non-metastatic OS patients. The R package was used to screen and identify differentially expressed genes (DEGs) between metastatic and non-metastatic OS patients. Then we compared the expression of DEGs in the two groups and sub-grouped into up-regulated and down-regulated, followed by functional enrichment analysis using the DAVID system. Subsequently, we constructed an miRNA-DEG regulatory network with the help of WebGestalt software. Results: A total of 323 DEGs, including 134 up-regulated and 189 down-regulated, were screened out. The up-regulated DEGs were enriched in 14 subcategories and most significantly in cytoskeleton organization, while the down-regulated DEGs were prevalent in 13 subcategories, especially wound healing. In addition, we identified two important miRNAs (miR-202 and miR-9) pivotal for OS metastasis, and their relevant genes, CALD1 and STX1A. Conclusions: MiR-202 and miR-9 are potential key factors affecting the metastasis of OS and CALD1 and STX1A may be possible targets beneficial for the treatment of metastatic OS. However, further experimental studies are needed to confirm our results. -
Song, Kui;Li, Min;Xu, Xiao-Jun;Xuan, Li;Huang, Gui-Nian;Song, Xiao-Ling;Liu, Qi-Fa 1823
Aims: Much evidence suggests that increased glucose metabolism in tumor cells might contribute to the development of acquired chemoresistance. However, the molecular mechanisms are not fully clear. Therefore, we investigated a possible correlation of mRNA expression of HIF-$1{\alpha}$ and GLUT1 with chemoresistance in acute myeloid leukemia (AML). Methods: Bone marrow samples were obtained from newly diagnosed and relapsed AML (M3 exclusion) cases. RNA interference with short hairpin RNA (shRNA) was used to stably silence GLUT1 or HIF-$1{\alpha}$ gene expression in an AML cell line and HIF-$1{\alpha}$ and GLUT1 mRNA expression was measured by real-time quantitative polymerase chain reaction assay (qPCR). Results: High levels of HIF-$1{\alpha}$ and GLUT1 were associated with poor responsiveness to chemotherapy in AML. Down-regulation of the expression of GLUT1 by RNA interference obviously sensitized drug-resistant HL-60/ADR cells to adriamycin (ADR) in vitro, comparable with RNA interference for the HIF-$1{\alpha}$ gene. Conclusions: Our data revealed that over-expression of HIF-$1{\alpha}$ and GLUT1 might play a role in the chemoresistance of AML. GLUT1 might be a potential target to reverse such drug resistance. -
Zhang, Yan;Tang, Jie;Liang, Hai-Dong;Lv, Fa-Qin;Song, Zhi-Gang 1831
Background: To investigate the relationship between extracellular matrix parameters and texture of prostatic lesions evaluated by transrectal real-time tissue elastography (TRTE). Methods: 120 patients suspicious for prostate cancer underwent TRTE. Targeted biopsies were carried out after 12-core systematic biopsy. Epithelia were stained with hematoxylin-eosin, and Victoria blue and Ponceau S were used to stain elastic-collagen fibers, and picric acid-sirius red for visualization of collagen type I (Col1) and III (Col3). Smooth muscles were visualized by immunohistochemistry. All image analyses were performed in a blind manner using Image Pro Plus 6.0, and the area ratios of epithelium, elastic fibers, collagen fibers and Col1/Col3 were determined. Results: 42 patients with typical elastograms were included in the final data analysis. Significant differences were detected between the benign and malignant groups in the area ratios of epithelium (P = 0.01), smooth muscles and Col1/Col3 (P = 0.04, P = 0.02, respectively). There were no significant differences in the area ratios of epithelium, smooth muscle and elastic fibers between the stiff and soft lesion groups. The area ratio of Col1 was ($0.05{\pm}0.03$ ) in the stiff group, and ($0.02{\pm}0.01$ ) in the soft group (P= 0.00). However, the area ratio of Col3 was ($0.03{\pm}0.02$ ) in the stiff group, and ($0.05{\pm}0.04$ ) in the soft group (P = 0.16). Col1/Col3 in the stiff group ($1.99{\pm}1.59$ ) was greater than in the soft group ($0.71{\pm}0.64$ ) (P = 0.01). Conclusions: Tissue hardness of prostatic tumors was mainly dependent on the Col1 content, Col1/Col3 being higher in malignant than in benign lesions, so the prostate tissue texture can be used as a target for distinguishing between the two with TRTE. -
Hanley, Sharon Janet Bruce;Yoshioka, Eiji;Ito, Yoshiya;Konno, Ryo;Sasaki, Yuri;Kishi, Reiko;Sakuragi, Noriaki 1837
Background: No studies on male attitudes towards HPV and HPV vaccination have been conducted in Japan, and little is known globally whether attitudes of single fathers differ to those living with a female partner. This exploratory study assessed whether Japanese fathers were likely to have their daughter vaccinated against HPV in a publically funded program and whether any differences existed regarding attitudes and knowledge about HPV according to marital status. Materials and Methods: Subjects were 27 fathers (16 single; 11 married) who took part in a study on HPV vaccine acceptability aimed at primary caregivers of girls aged 11-14 yrs in three Japanese cities between July and December 2010. Results: Knowledge about HPV was extremely poor (mean score out of 13 being$2.74{\pm}3.22$ ) with only one (3.7%) participant believing he had been infected with HPV and most (81.4%) believing they had no or low future risk. No difference existed regarding knowledge or awareness of HPV according to marital status. Concerning perceived risk for daughters, single fathers were significantly more likely to believe their daughter was at risk for both HPV (87.5% versus 36.4%; p=0.01) and cervical cancer (75.0% versus 27.3%; p=0.02). Acceptability of free HPV vaccination was high at 92% with no difference according to marital status, however single fathers were significantly more likely (p=0.01) to pay when vaccination came at a cost. Concerns specific to single fathers included explaining the sexual nature of HPV and taking a daughter to a gynecologist to be vaccinated. Conclusions: Knowledge about HPV among Japanese fathers is poor, but HPV vaccine acceptability is high and does not differ by marital status. Providing sexual health education in schools that addresses lack of knowledge about HPV as well as information preferences expressed by single fathers, may not only increase HPV vaccine acceptance, but also actively involve men in cervical cancer prevention strategies. However, further large-scale quantitative studies are needed. -
Bozkurt, Oktay;Karaca, Halit;Ciltas, Aydin;Kaplan, M. Ali;Benekli, Mustafa;Sevinc, Alper;Demirci, Umut;Eren, Tulay;Kodaz, Hilmi;Isikdogan, Abdurrahman;Ozkan, Metin;Buyukberber, Suleyman 1845
Background: There is no standard treatment for patients with colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment. Here we aimed to retrospectively evaluate the efficacy and tolerability of raltitrexed in combination with oral 5-fluoropyrimidine (uracil tegafur-UFT) or mitomycin C as salvage therapy in mCRC patients. Materials and Methods: A total of 62 patients who had received raltitrexed combined with UFT or mitomycin C were identified between December 2008 and June 2013. They were given raltitrexed 2.6$mg/m^2$ (max 5 mg) i.v. on day 1 in combination with either oral UFT 500 mg/day on days 1-14 every 3 weeks (group A) or mitomycin C 6$mg/m^2$ i.v. on day every 3 weeks (group B). Results: Forty-two patients (67.7%) were in group A and 20 (32.2%) in group B. In 15 patients (24%) grade 3/4 toxicity was observed, resulting in dose reduction, and in 13 patients (20.9%) dose delay was necessary. The median progression free survival (PFS) was 3 months (95%CI 2.65-3.34) and median overall survival (OS) was 6 months (95%CI 2.09-9.90) in the whole group. Median PFS was 3 months (95%CI 2.60-3.39) in group A vs 3 months (95%CI 1.64-4.35) in group B (p=0.90). Median OS was 6 months (95%CI 2.47-9.53) in group A vs 12 months (95%CI 2.83-21.1) in group B (p=0.46). Conclusions: The combination of raltitrexed with UFT or mitomycin C seem to be a salvage therapy option due to safety profile and moderate clinical activity in heavily-pretreated mCRC patients. -
Li, Cai-Hong;Wu, Dong-Fang;Ding, Hang;Zhao, Yang;Zhou, Ke-Yuan;Xu, De-Feng 1851
Objective: The main purpose of this work was to investigate the effect of berberine hydrochloride (BH) on the proliferation, apoptosis, migration, and invasion of CNE-1 nasopharyngeal carcinoma cells. Our results shed light on the functional components of traditional Chinese herbs for potential use in modern medicine. Methods: The CNE-1 cell line was treated with different concentrations of BH and effects on cell viability and proliferation were evaluated using the Cell Counting Kit-8 (CCK-8) assay. Anti-migratory and anti-invasive actions of BH were investigated using wound healing assays and the Millicell Hanging cell culture insert system, respectively. Expression of the epithelial-mesenchymal transition (EMT)-related gene twist (Twist) was analyzed by real-time PCR and Western blotting. Apoptosis was estimated with an annexin-V fluorescein (FITC) apoptosis detection kit, as well as with reference to levels of activated caspase-3 of CNE-1 cells before and after treatment with BH utilizing fluorescence spectroscopy. Results: BH was capable of reducing proliferation and viability of CNE-1 cells in a dose- and time-dependent manner, also demonstrating anti-migratory and anti-invasive capacities which correlated with reduction in expression of Twist. Finally, BH was able to induce significant amounts of apoptosis in CNE-1 cells, as demonstrated by an increase in the activity of caspase-3 and in annexin-V staining following treatment. Conclusion: BH extracted from rhizoma coptidis demonstrated an ability to block proliferation, induce apoptosis, and impair the migration and invasion of the CNE-1 cell line Considering these properties, our results suggest that BH could be an important compound for consideration in the treatment of nasopharyngeal carcinoma. -
Tang, Min;Hou, Yan-Li;Kang, Qiang-Qiang;Chen, Xing-Yue;Duan, Li-Qun;Shu, Jin;Li, Shao-Lin;Hu, Xiao-Li;Peng, Zhi-Ping 1859
Recently, the main therapy of medullary thyroid cancer (MTC) is surgical, but by which way there is a poor prognosis with a mean survival of only 5 years. In some cases, some researchers found that it is the medullary thyroid cancer stem cells (MTCSCs) that cause metastasis and recurrence. This study aimed to eradicate MTCSCs through administration of all-trans-retinoic acid (ATRA). Here we demonstrate that MTCSCs possess stemlike properties in serum-free medium. The ABCG2, OCT4 and sodium iodide symporter (NIS) were changed by ATRA. Additionally, we found that ATRA can increase the expression of NIS in vivo. All the data suggested that ATRA could increase the iodine uptake of MTCSCs through NIS. -
Mohamad Ashari, Zaidatul Shakila;Sulong, Sarina;Hassan, Rosline;Husin, Azlan;Sim, Goh Ai;Wahid, S. Fadilah Abdul 1863
The amplification of telomerase component (TERC) gene could play an important role in generation and treatment of haematological malignancies. This present study was aimed to investigate copy number amplification status of TERC gene in chronic myeloid leukaemia (CML) patients who were being treated with imatinib mesylate (IM). Genomic DNA was extracted from peripheral blood of CML-IM Resistant (n=63), CML-IM Respond (n=63) and healthy individuals (n=30). TERC gene copy number predicted (CNP) and copy number calculated (CNC) were determined based on$Taqman^{(R)}$ Copy Number Assay. Fluorescence in situ hybridization (FISH) analysis was performed to confirm the normal signal pattern in C4 (calibrator) for TERC gene. Nine of CML patients showed TERC gene amplification (CNP=3), others had 2 CNP. A total of 17 CML patients expressed CNC>2.31 and the rest had 2.31>CNC>1.5. TERC gene CNP value in healthy individuals was 2 and their CNC value showed in range 1.59-2.31. The average CNC TERC gene copy number was 2.07, 1.99 and 1.94 in CML-IM Resistant patients, CML-IM Respond and healthy groups, respectively. No significant difference of TERC gene amplification observed between CML-IM Resistant and CML-IM Respond patients. Low levels of TERC gene amplification might not have a huge impact in haematological disorders especially in terms of resistance towards IM treatment. -
Hematulin, Arunee;Ingkaninan, Kornkanok;Limpeanchob, Nanteetip;Sagan, Daniel 1871
Enhancing of radioresponsiveness of tumors by using radiosensitizers is a promising approach to increase the efficacy of radiation therapy. Recently, the ethanolic extract of the medicinal plant, Derris scandens Benth has been identified as a potent radiosensitizer of human colon cancer HT29 cells. However, cell death mechanisms underlying radiosensitization activity of D scandens extract have not been identified. Here, we show that treatment of HT-29 cells with D scandens extract in combination with gamma irradiation synergistically sensitizes HT-29 cells to cell lethality by apoptosis and mitotic catastrophe. Furthermore, the extract was found to decrease Erk1/2 activation. These findings suggest that D scandens extract mediates radiosensitization via at least two distinct modes of cell death and silences pro-survival signaling in HT-29 cells. -
Zhang, Qiang;Sun, Li-Jiang;Qi, Jun;Yang, Zhi-Gang;Huang, Tao 1879
Background: The relationship between obesity and prostate cancer aggressiveness is controversial in recent studies, partly because BMI is the only generally applied marker of obesity. Our study aimed at evaluating the correlation of periprostatic fat (PF) on magnatic resonance imaging (MRI) and adipocytokines with prostate cancer aggressiveness. Patients and method: A total of 184 patients who underwent radical retropubic prostatectomy (RRP) were analyzed retrospectively; different fat measurements on MRI slices and levels of adipocytokines were compared with the clinical and pathologic factors using SSPS ver.13.0. Result: The PF rates showed a statistically significant variation (p=0.019, 0.025) among groups, that is to say, more adipose tissue was distributed in periprostatic areas of high risk patients. Logistic regression analysis adjusted for age revealed a statistically association between the PF, the ratio and the risk of having high-risk disease (p=0.031, 0.024). The levels of IL-6, leptin and c-reactive protein (CRP) significantly increased with the aggressiveness of prostate cancer, and also with PF and its ratio. The strongest correlation was seen between IL-6 and PF (Pearson r coefficient=0.67, P<0.001). No association was observed between adipocytokines and BMI. Conclusion: Periprostatic adiposity not only affects prostate cancer aggressiveness, but also influences the secretion of adipocytokines. IL-6, PF and CRP have promoting effects on progression of prostate cancer. -
Varol, Umut;Yildiz, Ibrahim;Alacacioglu, Ahmet;Uslu, Ruchan 1885
Skin metastases of breast cancer are usually late events in the course of tumor progression and signify a poor prognosis. They may remain as a therapeutic challenge especially after failure of standard treatments. Topical interventions, together with or without radiotherapy, may only palliate the symptoms temporarily. However, there may be alternative treatment modalities for unresectable breast cancer skin metastases resistant to chemotherapy and radiotherapy. There are various genetic alterations in tumors and therapeutic potential of expression patterns for factors like epidermal growth factor receptor may have important clinical implications in case of disease refractory to the conventional treatments. Here, we clarified the therapeutic options and genetic alterations in skin metastatic breast cancer patients refractory to standard chemotherapeutics. -
Sezer, Ahmet;Sumbul, Ahmet Taner;Abali, Gulcan;Sumbul, Zehra;Muallaoglu, Sadik;Abali, Huseyin 1889