• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5923-5931
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• 2015

Background: Registry data from four major public hospitals indicate trends over three decades from 1980 to 2010 in treatment and survival from colorectal cancer with distant metastases at diagnosis (TNM stage IV). Materials and Methods: Kaplan-Meier product-limit estimates and Cox proportional hazards models for investigating disease-specific survival and multiple logistic regression analyses for indicating first-round treatment trends. Results: Two-year survivals increased from 10% for 1980-84 to 35% for 2005-10 diagnoses. Corresponding increases in five-year survivals were from 3% to 16%. Time-to-event risk of colorectal cancer death approximately halved (hazards ratio: 0.48 (0.40, 0.59) after adjusting for demographic factors, tumour differentiation, and primary sub-site. Survivals were not found to differ by place of residence, suggesting reasonable equity in service provision. About 74% of cases were treated surgically and this proportion increased over time. Proportions having systemic therapy and/or radiotherapy increased from 12% in 1980-84 to 61% for 2005-10. Radiotherapy was more common for rectal than colonic cases (39% vs 7% in 2005-10). Of the cases diagnosed in 2005-10 when less than 70 years of age, the percentage having radiotherapy and/or systemic therapy was 79% for colorectal, 74% for colon and 86% for rectum (&RS)) cancers. Corresponding proportions having: systemic therapies were 75%, 71% and 81% respectively; radiotherapy were 24%, 10% and 46% respectively; and surgery were 75%, 78% and 71% respectively. Based on survey data on uptake of offered therapies, it is likely that of these younger cases, 85% would have been offered systemic treatment and among rectum (&RS) cases, about 63% would have been offered radiotherapy. Conclusions: Pronounced increases in survivals from metastatic colorectal cancer have occurred, in keeping with improved systemic therapies and surgical interventions. Use of radiotherapy and/or systemic therapy has increased markedly and patterns of change accord with clinical guideline recommendations.

• IMMUNE NETWORK
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• v.6 no.1
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• pp.43-51
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• 2006

Background: The DR-$70^{TM}$ immunoassay is a newly developed cancer diagnostic test which quantifies the serum fibrin degradation products (FDP), produced during fibrinolysis, by antibody reaction. The purpose of this study was to evaluate the potential of DR-$70^{TM}$ Immunoassay in screening malignant tumor. Methods: Sample subjects were 4,169 adults, both male and female, who visited the health promotion center of a general hospital from March 2004 to April 2005 and underwent the DR-$70^{TM}$ immunoassay test and other tests for cancer diagnosis. The patient group was defined as 42 adults out of the sample subjects who were newly diagnosed with cancer during the same time period when the DR-$70^{TM}$ immunoassay test was performed. Final confirmation of a malignant tumor was made by pathological analysis. Results: The mean DR-$70^{TM}$ level was $0.83{\pm}0.65{\mu}g/ml$ (range: 0.00 (0.0001)${\sim}7.42{\mu}g/ml)$ in the control group (n=4,127) as opposed to $2.70{\pm}2.33{\mu}g/ml$ (range: $0.12{\sim}9.30{\mu}g/ml)$ in the cancer group (n=42), and statistical significance was established (p<0.0001, Student t-test). When categorized by the type of malignant tumor, all cancer patients with the exception of the subgroups of colon and rectal cancer showed significantly higher mean DR-$70^{TM}$ levels compared with the control group (p<0.0001, Kruscal-Wallis test). The receiver operating characteristic (ROC) curve analysis revealed ${\geq}1.091{\mu}g/ml$ as the best cut-off value. Using this cut-off value, the DR-$70^{TM}$ immunoassay produced a sensitivity of 71.4%, a specificity of 70.1%, a positive predictability of 69.4%, and a negative predictability of 69.2% (1). Conclusion: A significant increase in the mean DR-$70^{TM}$ value was observed in the cancer group (thyroidal, gastric, breast, hepatic and ovarian) com pared with the control group. In particular, the specificity and sensitivity of the DR-$70^{TM}$ immunoassay was relatively high in the subgroups of breast, gastric, and thyroidal cancer patients. There is need for further studies on a large number of malignant tumor patients to see how the DR-$70^{TM}$ level might be changed according to the differentiation grade and postoperative prognosis of the malignant tumor.

• Journal of Hospice and Palliative Care
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• v.23 no.1
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• pp.5-10
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• 2020

Purpose: The aim of this study was to investigate celiac plexus neurolysis (CPN) for the treatment of cancerous upper abdominal pain in a tertiary university hospital in Korea. Methods: At the tertiary university hospital in Korea, electronic medical records of cancer patients who underwent CPN and died in the hospital from November 2009 to June 2018 were retrospectively analyzed. Results: The total number of subjects was 51. The 17 patients were from the Department of Gastroenterology (33.0%), followed by 11 patients from the Department of Hemato-oncology (21.6%), 11 patients from the Department of Anesthesia and Pain Medicine (21.6%), 9 patients from the Department of General Surgery (17.6%). The diagnosis was pancreatic cancer in 15 patients (29.4%), stomach cancer in 8 patients (15.7%), hepatobiliary cancer in 20 patients (39.2%), colon cancer in 1 patient (2.0%), esophageal cancer in 2 patient (3.9%) and intra-abdominal metastasis in 5 patients (9.8%). The mean survival time after the surgery was 66.4±55.0 days. The pain intensity before and 1 week after the procedure significantly decreased, but the amounts of opioids consumed before and 1 week after the procedure were not statistically significant. Side effects occurred after the procedure including temporary localized pain in 24 patients (47.0%), hypotension in 12 (23.5%), and diarrhea in 6 (11.8%). Conclusion: CPN is an effective and safe procedure for reducing upper abdominal pain caused by cancer, and it is necessary to perform CPN within the appropriate time by establishing a system of interdepartmental cooperation.

• Journal of Life Science
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• v.32 no.3
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• pp.210-221
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• 2022

This study investigated the mechanisms underlying the anti-cancer effects of non-steroidal anti-inflammatory drugs (NSAIDs) in human cancer cells in combination with either N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor, or MHY2245, a new synthetic sirtuin 1 inhibitor. The results showed both DAPT and MHY2245 as novel chemosensitizers of human colon cancer KM12 and human hepatocellular carcinoma SNU475 cells to NSAIDs involving celecoxib and 2, 5-dimethyl celecoxib. The NSAID-induced cytotoxicity of these cells was significantly increased by DAPT and MHY2245 in a cyclooxygenase-2 independent manner. In addition, DAPT and MHY2245 reduced levels of p62, Notch1 intracellular domain, and multiple cancer stemness (CS)-related markers including Notch1, CD44, CD133, octamer-binding transcription factor 4, mutated p53 and c-Myc. However, the level of activating transcription factor 4 (ATF4) was enhanced, probably indicating the down-regulation of multiple CS-related markers by DAPT or MHY2245-mediated autophagy induction. Moreover, the NSAID-mediated reduction of p62/nuclear factor erythroid-derived 2-like 2 and CS-related marker proteins and the up-regulation of C/EBP homologous protein (CHOP)/ATF4 were accelerated by DAPT and MHY2245. As such, the combination of NSAID and either DAPT or MHY2245 resulted in higher cytotoxicity than NSAID alone by accelerating the down-regulation of multiple CS-related markers and PARP activation, indicating that both inhibitors promote NSAID-mediated autophagic cell death, possibly through the CHOP/ATF4 pathway. In conclusion, either combination strategy may be useful for the effective treatment of human cancer cells expressing CS-related markers.

• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1206-1212
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• 2023

The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N⁶-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

• Journal of Nutrition and Health
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• v.53 no.2
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• pp.111-120
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• 2020

Purpose: Corosolic acid (CA), also known as 2α-hydroxyursolic acid, is present in numerous plants, and is reported to exhibit anti-cancer and anti-proliferative activities in various cancer cells such as osteosarcoma, hepatocellular carcinoma, lung adenocarcinoma, and colon cancer. However, the anti-cancer activity of CA on human breast cancer cells and the underlying mechanisms remain to be elucidated. The present study aimed to investigate the anticancer effects of CA in the human breast cancer cell line, MDA-MB-231. Methods: Cell viability, reactive oxygen species (ROS) production, apoptosis marker protein expression, migration, invasion rate, and vascular endothelial growth factor (VEGF) levels were assessed by treating MDA-MB-231 cells to increasing concentrations of CA. Results: The results showed that CA significantly inhibited the cell proliferation of MDA-MB-231 cells in a dose-dependent manner. To assess the effect of CA on apoptosis, nuclei of MDA-MB-231 cells were stained with DAPI solution. Chromatin condensation, which indicates apoptosis, was observed to increase dose-dependently. In addition, western-blot analysis revealed elevated levels of the apoptosis marker proteins (Bax and cleaved caspase 3) subsequent to MDA-MB-231 exposure to CA. ROS production was also increased in the CA-induced apoptosis in MDA-MB-231 treated cells. Interestingly, CA exposure resulted in significantly decreased migration and invasion rates in the MDA-MB-231 cells. Data further revealed that exposure to CA markedly decreased the VEGF concentration, thereby contributing to a reduction in angiogenesis. Conclusion: Our results determined that exposure to CA induces anti-proliferation, apoptosis, and ROS production, and suppresses cell migration and invasion rate in MDA-MB-231 cells. Taken together, these results indicate the potential of CA to be applied as an effective chemotherapeutic agent for treating breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4071-4075
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• 2016

Background: FDG PET/CT is at an equivocal stage to recommend for staging of colorectal cancer as compared to contrast-enhanced CT (ceCT). This study was intended to evaluate the value of FDG PET/ceCT in colorectal cancer staging as compared to ceCT alone. Materials and Methods: PET/ceCT was performed for 61 colorectal cancer patients who were prospectively enrolled in the study. Three patients were excluded due to loss to follow-up. PET/ceCT findings and ceCT results alone were read separately. The treatment planning was then determined by tumor board consensus. The criteria for T staging were determined by the findings of ceCT. Nodal positive by PET/ceCT imaging was determined by visual analysis of FDG uptake greater than regional background blood pool activity. The diagnostic accuracy of T and N staging was determined only in patients who received surgery without any neoadjuvant treatment. Results: Of 58 patients, there were 40 with colon cancers including sigmoid cancers and 18 with rectal cancers. PET/ceCT in pre-operative staging detected bone metastasis and metastatic inguinal lymph nodes (M1a) that were undepicted on CT in 2 patients (3%), clearly defined 19 equivocal lesions on ceCT in 18 patients (31%) and excluded 6 metastatic lesions diagnosed by ceCT in 6 patients (10%). These resulted in alteration of management plan in 15 out of the 58 cases (26%) i.e. changing from chemotherapy to surgery (4), changing extent of surgery (9) and avoidance of futile surgery (2). Forty four patients underwent surgery within 45 days after PET/CT. The diagnostic accuracy for N staging with PET/ceCT and ceCT alone was 66% and 48% with false positive rates of 24% (6/25) and 76% (19/25) and false negative rates of 47% (9/19) and 21% (4/19), respectively. All of the false negative lymph nodes from PET/ceCT were less than a centimeter in size and located in peri-lesional regions. The diagnostic accuracy for T staging was 82%. The sensitivity of the peri-lesional fat stranding sign in determining T3 stage was 94% and the specificity was 54%. Conclusions: Our study suggested promising roles of PET/ceCT in initial staging of colorectal cancer with better diagnostic accuracy facilitating management planning.

• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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• 2015.05a
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• pp.383-387
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• 2015

Bowel and rectal diseases are on the increase by irregular life and westernized eating habits of modern people, especially rectal cancer, which accounts for 50% of the entire colon cancer. For the initial rectal cancer, because there is no portion projecting on the surface, if not see inside the tissue with ultrasound, you make an errors that misdiagnosis as rectal abscess. However there is a need for more accurate diagnosis, because it is sometimes difficult to distinguish abscess from rectal cancer depending on staging, in spite of the ultrasonic diagnosis. Therefore, this study was performed quantitative analysis by using a computer algorithm for rectal cancer and abscess image. Each of 20 cases about normal, abscess and cancer by setting analysis region ($50{\times}50$ pixels) applies to GLCM algorithm and Autocorrelation, Max probability, Sum average, Sum variance in each image were analyzed by comparing the 4 single parameter. Consequently, The high lesion detection efficiency was presented 100% by the 3 parameter of Autocorrelation, Max probability, Sum variance and the parameter of Sum average presents 95% in cancer, more than 90% in abscess. Those parameters are valuable in distinction standard about normal, cancer and abscess in rectum. It is sufficient availability as a computer assisted diagnosis system depended on clinical using.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6025-6030
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• 2013

Background: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism (SNP) at -1306, which disrupts a Sp1-type promoter site (CCACC box), results in strikingly lower promoter activity with the T allele. In the present study, we investigated whether this MMP-2 genetic polymorphism might be associated with susceptibility to colorectal cancer (CRC) in the Saudi population. We also analyzed MMP-2 gene expression level sin CRC patients and 4 different cancer cell lines. Materials and Methods: TaqMan allele discrimination assays and DNA sequencing techniques were used to investigate the $C^{-1306}T$ SNP in the MMP-2 gene of Saudi colorectal cancer patients and controls. The MMP-2 gene expression level was also determined in 12 colon cancer tissue samples collected from unrelated patients and histologically normal tissues distant from tumor margins. Results and Conclusions: The MMP-2 $C^{-1306}T$ SNP in the promoter region was associated with CRC in our Saudi population and the MMP-2 gene expression level was found to be 10 times higher in CRC patients. The MMP-2 $C^{-1306}T$ SNP is significantly associated with CRC in the Saudi population and this finding suggested that MMP-2 variants might help predict CRC progression risk among Saudis. We propose that analysis of this gene polymorphism could assist in identification of patient subgroups at risk of a poor disease outcome.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3279-3283
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• 2015

Background: Colorectal cancer (CRC) is the most common gastrointestinal cancer and the incidence is increasing. CRC is more common with increasing age, but a proportion occurs in young adults, termed young CRC. This study assessed the incidence and the demographic of young CRC in Brunei Darussalam. Materials and Methods: All histologically proven CRC between 1986 and 2014 registered with the Department of Pathology cancer registry were reviewed and data extracted for analyses. Young CRC was defined as cancer in patients aged less than 45 years. The various population groups were categorized into locals (Malays, Chinese and Indigenous) and expatriates. Results: Over the study period, there were 1,126 histologically proven CRC (mean age $59.1{\pm}14.7$ years, Male 58.0%, Locals 91.8% and 8.2% expatriates). Young CRC accounted for 15.1% with the proportion declining over the years, from 29% (1986-1990) to 13.2% (2011-2014). The proportion of young CRC was highest among the indigenous (30.8%), followed by the expatriates (29.3%), Malays (14.3%) and lowest among the Chinese (10.8%). The mean age of young CRC was $35.9{\pm}6.2$; lowest among the indigenous ($33.5{\pm}6.7$), expatriate ($34.9{\pm}6.0$) groupd and the Malays ($35.6{\pm}6.5$) compared to the Chinese ($38.6{\pm}4.6$), a similar trend being observed in the non-young CRC groups. There were no difference between the genders and tumor locations (rectum or colon) between the young and the non-young CRC cases. Female young CRC was significantly younger than male (p<0.05) without any significant variation between the various population groups (p>0.05). Conclusions: Our study showed that the young CRC accounted for 15.1% of all CRC with declining trend observed over recent years. Young CRC was more common among indigenous, expatriates and Malays and least common among the Chinese. There were no differences in the gender and tumor locations.