• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.1059-1063
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• 2012

Objective: Angiogenesis represents a key element in the pathogenesis of malignancy. There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic colorectal cancer treated with vascular endothelial growth factor (VEGF)-targeted therapy. The present study was conducted to establish a prognostic model for patients using an oxaliplatin-based or irinotecan-based chemotherapy plus bevacizumab in metastatic colorectal cancer. Methods: Baseline characteristics and outcomes on 170 patients treated with FOLFIRI or XELOX plus anti-VEGF therapy-naive metastatic colorectal cancer were collected from three Turkey cancer centers. Cox proportional hazards regression was used to identify independent prognostic factors for OS. Results: The median OS for the whole cohort was 19 months (95% CI, 14.3 to 23.6 months). Three of the seven adverse prognostic factors according to the Anatolian Society of Medical Oncology (ASMO) were independent predictors of short survival: serum lactate dehydrogenase (LDH) greater than the upper limit of normal (ULN; p<0.001); neutrophils greater than the ULN (p<0.0014); and progression free survival (PFS) less than 6 months (p =0.001). Conclusion: Serum LDH and neutrophil levels were the main prognostic factors in predicting survival, followed by PFS. This model validates incorporation of components of the ASMO model into patient care and clinical trials that use VEGF-targeting agents.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1841-1844
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• 2012

Background: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy has limited impact on overall survival (OS) so that eligible patients should be selected carefully. The aim of this study was to analyze prognostic factors for survival in Turkish advanced pancreatic cancer patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and receiving gemcitabine (Gem) alone or gemcitabine plus cisplatin (GemCis). Methods: This retrospective evaluation was performed for patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and who received gemcitabine between December 2005 and August 2011. Twenty-seven potential prognostic variables were chosen for univariate and multivariate analyses to identify prognostic factors associated with survival. Results: Among the 27 variables in univariate analysis, three were identified to have prognostic significance: sex (p = 0.04), peritoneal dissemination (p =0.02) and serum creatinine level (p=0.05). Multivariate analysis by Cox proportional hazard model showed only peritoneal dissemination to be an independent prognostic factor for survival. Conclusion: In conclusion, peritoneal metastasis was identified as an important prognostic factor in metastatic pancreatic cancer patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and receiving Gem or GemCis. The findings should facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.

• Molecules and Cells
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• v.45 no.5
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• pp.329-342
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• 2022

The liver is the predominant metastatic site for pancreatic cancer. However, the factors that determine the liver metastasis and the specific molecular mechanisms are still unclear. In this study, we used human pancreatic cancer cell line Hs766T to establish Hs766T-L3, a subline of Hs766T with stable liver metastatic ability. We performed RNA sequencing of Hs766T-L3 and its parental cell line Hs766T, and revealed huge differences in gene expression patterns and pathway activation between these two cell lines. We correlated the difference in pathway activation with the expression of the four core transcriptional factors including STAT1, NR2F2, GATA2, and SMAD4. Using the TCGA database, we examined the relative expression of these transcription factors (TFs) in pan-cancer and their relationship with the prognosis of the pancreatic cancer. Among these TFs, we considered GATA2 is closely involved in tumor metastasis and may serve as a potential metastatic driver. Further in vitro and in vivo experiments confirmed that GATA2-mediated transcriptional activation of Notch3 promotes the liver metastasis of Hs766T-L3, and knockdown of either GATA2 or Notch3 reduces the metastatic ability of Hs766T-L3. Therefore, we claim that GATA2 may serve as a metastatic driver of pancreatic cancer and a potential therapeutic target to treat liver metastasis of pancreatic cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4957-4961
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• 2014

Background: Head and neck cancer without distant metastases is amenable to various modalities of treatment. However, the stage at presentation is a very important determinant for treatment success. The present study was conducted to determine the stage-wise presentation of non-metastatic head and neck cancer patients from the hilly regions in Kumaon division of Uttarakhand, India. Materials and Methods: The hospital records for non-metastatic head and neck cancer patients from the only functional cancer centre of the region for the period of two-years (January 2012-December 2013) were included. Nasopharyngeal carcinoma was excluded due to its staging system being different. Non-squamous histopathologies were also excluded. Patients hailing from nearby regions of Uttar Pradesh and Nepal were excluded, as were patients from non-hilly regions of Kumaon. Results: Of the 271 patients of head and neck cancer, 27 with distant metastases at diagnosis were excluded from the analysis. Of the 244 eligible patient records, 90.1% (n=222) were male, and 9.9% (n=22) were female. The proportions of patients with carcinoma of the larynx, oropharynx, oral cavity, hypopharynx and maxillary antrum were 31.9% (n=78), 27.9% (n=68), 20.5% (n=50), 12.7% (n=31) and 1.2% (n=3). A further 5.7% (n=14) were diagnosed as having secondary involvement of neck nodes with unknown primaries. The proportion of patients presenting in stages I, II, III, IVA and IVB were 0.8% (n=2), 2.5% (n=6), 9.4% (n=23), 51.6% (n=126) and 35.7% (n=87) respectively. Conclusions: An abysmally low proportion (3.3%) of non-metastatic head and neck cancer patients presented in the early stages (I and II). A vast majority of the patients (88.1%) presented with stages IVA and IVB. Not only does this reflect a poor therapeutic outlook, but also exposes the dire need for programmes focusing on cancer awareness and early detection in the region.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.92-98
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• 2010

Breast cancer has been estimated as one of the most common causes of cancer death among women. The major cause of death from breast cancer is the metastatic spread of the disease from the primary tumor to distant sites in the body. Lycopene is one of the major carotenoids in fruits and vegetables including tomatoes. Epidemiological studies have shown that the dietary intake of lycopene is associated with decreased risk of cancer. Although mounting evidence shows the chemopreventive effect of lycopene, the role of lycopene in the prevention of metastatic potential of breast cancer has not been determined yet. In the present study, we investigated the inhibitory effect of lycopene on invasive and migratory phenotypes of two highly aggressive breast cancer cell lines, H-Ras-transformed MCF10A human breast epithelial cells (H-Ras MCF10A) and MDA-MB-231 human breast cancer cells. Here, we report that lycopene significantly inhibits invasion and migration as well as proliferation of H-Ras MCF10A and MDA-MB-231 cells. This study suggested an in vitro anti-cancer and anti-metastatic potential of lycopene. We also showed that activations of ERKs and Akt were inhibited by lycopene in H-Ras MCF10A cells, suggesting that the ERKs and Akt signaling pathways may be involved in lycopene-induced anti-proliferative and/or anti-invasive/migratory effects in these cells. Taken in conjunction with the fact that breast cancer metastasis is one of the most lethal malignancies in women, our findings may provide useful information for the application of lycopene in establishing strategy to prevent the metastatic breast cancer.

• The Korean Journal of Pain
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• v.24 no.2
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• pp.119-122
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• 2011

A rotator cuff tear causes shoulder pain and limits movement of the shoulder joint. A chronic degenerative change or impingement is the reason for a rotator cuff tear. Diagnosis is made based on medical history and, physical and radiological examinations. Other causes of shoulder pain include calcific tendinitis, degenerative arthropathy, joint dislocation, fracture, and primary or metastatic neoplasm. However, metastatic cancer in the shoulder joint is difficult to diagnosis. We experienced a case in which a 46-year-old female patient complained of left shoulder pain and limited joint mobility, and these symptoms were due to metastatic breast cancer in the shoulder.

• Journal of Gastric Cancer
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• v.11 no.2
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• pp.94-100
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• 2011

Purpose: The 7th AJCC tumor node metastasis (TNM) staging system modified the classification of the lymph node metastasis widely compared to the 6th edition. To evaluate the prognostic predictability of the new TNM staging system, we analyzed the survival rate of the gastric cancer patients assessed by the 7th staging system. Materials and Methods: Among 2,083 patients who underwent resection for gastric cancer at the department of surgery, Hanyang Medical Center from July 1992 to December 2009, This study retrospectively reviewed 5-year survival rate (5YSR) of 624 patients (TanyN3M0: 464 patients, TanyNanyM1: 160 patients) focusing on the number of metastatic lymph node and distant metastasis. We evaluated the applicability of the new staging system. Results: There were no significant differences in 5YSR between stage IIIC with more than 29 metastatic lymph nodes and stage IV (P=0.053). No significant differences were observed between stage IIIB with more than 28 metastatic lymph nodes and stage IV (P=0.093). Distinct survival differences were present between patients who were categorized as TanyN3M0 with 7 to 32 metastatic lymph nodes and stage IV. But patients with more than 33 metastatic lymph nodes did not show any significant differences compared to stage IV (P=0.055). Among patients with TanyN3M0, statistical significances were seen between patients with 7 to 30 metastatic lymph nodes and those with more than 31 metastatic lymph nodes. Conclusions: In the new staging system, modifications of N classification is mandatory to improve prognostic prediction. Further study involving a greater number of cases is required to demonstrate the most appropriate cutoffs for N classification.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3169-3173
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• 2014

Background: To investigate factors associated with overall survival in patients with newly diagnosed metastatic nasopharyngeal carcinoma. Materials and Methods: Two hundred and two consecutive patients with pathologically confirmed nasopharyngeal carcinoma with distant metastasis at diagnosis seen between December 2007 and May 2011 were reviewed. Patient, tumor and treatment factors were analyzed for their significance regarding overall survival. Results: The median follow-up time was 22 months. At the time of this report, 116 patients had died. For 112 patients, cause of death was nasopharyngeal carcinoma. The 1, 2, 3, and 4-year overall survival rates were 75.6%, 50.2%, 39.2%, and 28.2%, respectively. Cox regression multivariate analysis showed that T-stage (p=0.045), N-stage (p=0.014), metastasis number (p<0.001) and radiotherapy for nasopharynx and neck (p<0.001) were significant factors for overall survival. Conclusions: Early T-stage and N-stage, solitary metastasis in a single organ were good prognostic factors for patients with newly diagnosed metastatic nasopharyngeal carcinoma. Radiotherapy should be strongly recommended in systemic treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2729-2734
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• 2012

Despite clinical advances in anticancer therapy, there is still a need for novel anticancer metabolites, with higher efficacy and lesser side effects. Oroxylum indicum (L.) Vent. is a small tree of the Bignoniaceae family which is well known for its food and medicinal properties. In present study, the chemopreventive properties of O. indicum hot and cold non-polar extracts (petroleum ether and chloroform) were investigated with MDA-MB-231 (cancer cells) and WRL-68 (non-tumor cells) by XTT assay. All the extracts, and particularly the petroleum ether hot extract (PHO), exhibited significantly (P<0.05) higher cytotoxicity in MDA-MB-231 when compared to WRL-68 cells. PHO was then tested for apoptosis induction in estrogen receptor (ER)-negative (MDA-MB-231) and ER-positive (MCF-7) breast cancer cells by cellular DNA fragmentation ELISA, where it proved more efficient in the MDA-MB-231 cells. Further, when PHO was tested for anti-metastatic potential in a cell migration inhibition assay, it exhibited beneficial effects. Thus non-polar extracts of O. indicum (especially PHO) can effectively target ER-negative breast cancer cells to induce apoptosis, without harming normal cells by cancer-specific cytotoxicity. Hence, it could be considered as an extract with candidate precursors to possibly harness or alleviate ER-negative breast cancer progression even in advanced stages of malignancy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3015-3021
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• 2015

Background: Colorectal cancer (CRC) is a major cause of mortality in developed countries, and it is the third most frequent malignancy in Turkey. There are many biological, genetic, molecular, and tissue-derived prognostic factors for CRCs. In this study, we evaluated prognostic factors in patients who were metastatic at diagnosis or progressed to metastatic disease during follow-up. Patients and Methods: This study included 116 patients with malignancies either in the colon or rectum. Of these, 65 had metastatic disease at diagnosis, and 51 progressed to metastatic disease during the course of the disease. The parameters evaluated were age, gender, comorbidity, performance status and stage of the disease at the beginning, localization, history of surgery, chemotherapy regimen, response to first-line treatment, K-RAS status, site and number of metastases, expression of tumor predictors (CEA, CA19-9), and survival times. A multivariate analysis conducted with factors that considered statistically significant in the univariate analysis. Findings: Median age was 56 (32-82) years and the male/female ratio was 80/36. Eleven patients were at stage II, 40 at stage III, and 65 at stage IV at diagnosis. Twenty three patients had tumor in the right colon, 48 in the left colon, and 45 in the rectum. Ninety seven patients were operated, and 27 had surgical metastasectomy. Ninety three patients received targeted therapy. At the end of follow-up, 61 patients had died, and 55 survived. Metastatic period survival times were longer in the adjuvant group, but the difference did not reach the level of statistical significance (adjuvant group: median 29 months, metastatic group: median 22 months; p=0.285). In the adjuvant group before the metastatic first-line therapy, CEA and CA 19-9 levels were significiantly lower compared to the metastatic group (p<0.005). We also found that patients with elevated tumor predictor (CEA, CA 19-9) levels before the first-line therapy had significiantly poorer prognosis and shorter survival time. Survival was significiantly better with the patients who were younger than 65 years of age, had better initial performance status, a history of primary surgery and metastatectomy, and single site of metastasis. Those who benefitted from the first-line therapy were K-RAS wild type and whose tumor markers (CEA, CA 19-9) were not elevated before the first line therapy. Conclusions: Among the patients with metastatic CRC, those who benefited from first-line therapy, had history of metastasectomy, were K-RAS wild type and had low CA 19-9 levels before the first-line therapy, showed better prognosis independent of other factors.