• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5063-5067
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• 2015

Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy and is a significant cause of mortality. Its incidence is generally increasing in Asia. Reports from the West have indicated that the incidence of rectal cancer is increasing in the younger population. This study assessed the time trend of CRC in Brunei Darussalam specifically assessing the different age groups at which the incidences start to increase. Materials and Methods: The National Cancer registry was reviewed (1991 to 2014). The age standardized rate (ASR) and the age specific incidence rates (ASIRs) for three time periods (1991-1998), (1999-2006) and (2007-2014) were calculated. Results: The mean age of diagnosis was $59.3{\pm}14.6$ years old, incidences being slightly higher amongst men (57.6%) and Malays (67.1%). The most common tumor type was adenocarcinoma (96.4%). Rectal cancers accounted for 35.2% (n=372/1,056) of all cancers of the large bowel; more men were affected than women. The proportion of rectal cancer was also high among the indigenous group. In the three time periods, the ASR for CRC increased from 16 per 100,000 (1991-1998) to 19.6 per 100,000 (1999-2006) and 24.3 per 100,000 (2007-2014). The ASIRs for CRC increased markedly between the time periods 1998-2006 and 2007-2014, beginning in the 40-44 years age group. For rectal cancers, the ASIRs started to increase in the 25-29 age group onward whereas for colon cancers, the increase was observed at a later age, starting from the 45-49 age group. Conclusions: Our study showed an increase in the incidence of CRC including in the younger age groups. The increase was seen earlier in rectal cancer compared to colon cancer. These data mirror the trends reported from the West.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3209-3212
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• 2012

Introduction: Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy in the older population, but it is also quite frequent among young adults in developing countries. The aim of this study was to update the trends of clinicopathological features of CRC in young Nepalese. Methods: A retrospective comparative study on the data retrieved from the surgical records of all patients between 20 to 39 years of age with CRC was carried out for periods of 5 years each from 1999 to 2003 (early) and 2004 to 2008 (recent), treated at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Results: The number of young adults with CRC increased from 28 to 34. However, the proportion of young patients in both groups was 28% of all CRC patients. The mean ages were $34{\pm}4.7$ and $31.8{\pm}5.1$ years in early and recent 5 years, respectively, and the male female ratio changed from 2:3 to 4:3. Abdominal pain as the most common presenting symptom was replaced by bleeding per rectum in recent years. The mean duration from onset of symptoms to seeking medical advice decreased from 7.8 months to 5.6 months in recent years. More patients (85.3%) were subjected to endoscopic examination in recent years than early years (60.7%) and right colonic cancer increased from 10.7% to 26.5%. However, the rectum was the commonest site in both early (71.4%) and recent (50%) groups. CRC was detected significantly at an earlier stage (7.1% vs 32.4%) in recent years with large proportion of modified Dukes B stage. Poorly differentiated adenocarcinoma was the predominant histology in both groups (50% vs 60.7%). Curative resection had risen in recent years (39.3% vs 73.6%). Conclusion: CRC among Nepalese young adults accounts for a high incidence (28%) of all CRC cases. Although right sided colonic cancer has been increasing, rectum is the commonest site. There is also an increasing trend for diagnosis at earlier stages of the disease which can be treated with curative intent.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2823-2828
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• 2012

Objective: To explore a new model of in-situ xenograft lymphangiogenesis of human colonic adenocarcinomas in nude mice. Method: On the basis of establishing subcutaneous xenograft lymphangiogenesis model of human colonic adenocarcinoms, in-situ xenografts were established through the in situ growth of the HT-29 human colonic adenocarcinoma cell line in nude mice. The numbers of lymphangiogenic microvessels, the expression of lymphatic endothelial cell markers lymphatic vessel endothelial hyaloronic acid receptor-1 (LYVE-1), D2-40 and the lymphatic endothelial growth factors vascular endothelial growth factor-C (VEGF-C), -D (VEGF-D) and receptor-3 (VEGFR-3) were compared by immunohistochemical staining, Western bolt and quantitative RT-PCR in xenograft in-situ models. Results: Some microlymphatics with thin walls, large and irregular or collapsed cavities and increased LMVD, with strong positive of LYVE-1, D2-40 in immunohistochemistry, were observed, identical with the morphological characteristics of lymphatic vessels and capillaries. Expression of LYVE-1 and D2-40 proteins and mRNAs were significantly higher in xenograpfts in-situ than in the negative control group(both P<0.01). Moreover, the expression of VEGF-C, VEGF-D and VEGFR-3 proteins and mRNAs were significantly higher in xenografts in-situ (both P<0.01), in conformity with the signal regulation of the VEGF-C,-D/VEGFR-3 axis of tumor lymphangiogenesis. Conclusions: In-situ xenografts of a human colonic adenocarcinoma cell line demonstrate tumor lymphangiogenesis. This novel in-situ animal model should be useful for further studying mechanisms of lymph node metastasis, drug intervention and anti-metastasis therapy in colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2019-2022
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• 2013

Purpose: To investigate the safety and efficacy of pemetrexed combined with chemotherapy as second or third line in patients with stage IV colorectal cancer (CRC). Patients and Methods: This trial was conducted to evaluate the effectiveness and safety of pemetrexed given to patients with recurrent or metastatic colorectal carcinoma who previously received 5-FU-based chemotherapy. All patients were required to have a histological diagnosis of colorectal adenocarcinoma with measurable metastatic disease and prior chemotherapy. Patients received pemetrexed at a dose of 500 $mg/m^2$ by 10 minute infusion on day 1, repeated every 21 days. Doses were modified depending on nadir counts. Combined chemotherapy included Oxaliplatin, Irinotecan and cis-platinum. Results: Thirty patients were enrolled and twenty-nine were evaluable for response. One patient did not have repeat radiological testing to determine response because he went off study after only one cycle of treatment for economic reasons. For 29 evaluable patients, 1 partial response, 6 stable disease and 22 progressive disease were recorded. Response rate was 3.45% (1/29). All responses occurred in patients receiving a starting dose of pemetrexed 500 $mg/m^2$. Median time to progression for all eligible patients was 2.5 months. The most common toxicities experienced were mild to moderate fever, hepatic damage, myelosuppression, nausea, vomiting, constipation, abdominal pain, diarrhea, and skin rash. Conclusion: Pemetrexed at 500 $mg/m^2$ given every three weeks combined with chemotherapy is associated with moderate response and good tolerability in patients with stage IV CRC.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.21 no.1
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• pp.72-75
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• 2018

Colorectal carcinoma is a well-known malignancy in adults. However, it is rare in children. Besides, it also has different behaviour in paediatric age-group and usually presents with non-specific symptoms like abdominal pain, weight loss, and anaemia. This usually leads to delay in diagnosis. Adenocarcinoma in children has unfavourable tumour histology (mucinous subtype) and advanced disease stage at presentation which lead to poorer prognosis in children. Family history, genetic typing and sibling screening are essential components of management as this malignancy is frequently seen associated with hereditary syndromes. We describe a case of unusual presentation of rectal carcinoma in a 12-year-old girl.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1719-1722
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• 2012

The Wiskott-Aldrich Syndrome Protein family Verprolin - homologous proteins (WAVEs), encoded by a metastasis promoter gene, play considerable roles in adhesion of immune cells, cell proliferation, migration and destruction of foreign agents by reactive oxygen species. These diverse functions have lead to the hypothesis that WAVE proteins have multi-functional roles in regulating cancer invasiveness, metastasis, development of tumor vasculature and angiogenesis. Differentials in expression of WAVE proteins are associated with a number of neoplasms include colorectal cancer, hepatocellular cancer, lung squamous cell carcinoma, human breast adenocarcinoma and prostate cancer. In this review we attempt to unify our knowledge regarding WAVE proteins, focusing on their potentials as diagnostic markers and molecular targets for cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.603-608
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• 2016

Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features. Materials and Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these. Results: KRAS mutations were present in 33.6% cases (n=336). Of KRAS mutation positive cases, 85.1% were in codon 12 and 14.9% were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics. Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6997-7005
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• 2013

Aim: To present an epidemiological and histological perspective of diseases of the gastrointestinal tract (including liver and biliary tract) at the Section of Histopathology, Department of Pathology, AKUH, Karachi, Pakistan. Materials and Methods: All consecutive endoscopic biopsies and resections between October 1 and December 31, 2012 were included. Results: A total of 2,323 cases were included. Carcinoma was overwhelmingly the commonest diagnosis on esophageal biopsies (69.1%); chronic helicobacter gastritis (45.6%) followed by adenocarcinoma (23.5%) were the commonest diagnoses on gastric biopsies; adenocarcinoma (27.3%) followed by ulcerative colitis (13.1%) were the commonest diagnoses on colonic biopsies; acute appendicitis (59.1%) was the commonest diagnosis on appendicectomy specimens; chronic viral hepatitis (44.8%) followed by hepatocellular carcinoma (23.4%) were the commonest diagnoses on liver biopsies; chronic cholecystitis was the commonest diagnosis (over 89%) on cholecystectomy specimens. Conclusions: Squamous cell carcinoma comprised 88.8% of esophageal cancers. About 67% were in the lower third and 56.5% were moderately differentiated; mean ages 49.8 years for females and 55.8 years for males; 66% cases were from South West Pakistan. Over 67% patients with gastric adenocarcinoma were males; mean ages 59 and 44 years in males and females respectively, about 74% gastric carcinomas were poorly differentiated; and 62.2% were located in the antropyloric region. About 63% patients with colorectal adenocarcinoma were males; mean ages 46.1 and 50.5 years for males and females respectively; tumor grade was moderately differentiated in 54%; over 80% were located in the left colon. In 21.2% appendicectomies, no acute inflammation was found. Acute appendicitis was most common in young people. Hepatitis C (66.3%) was more common than hepatitis B (33.7%); about 78% cases of hepatocellular carcinoma occurred in males; females comprised 76.7% patients with chronic cholecystitis; and 77.8% patients with gall bladder carcinoma. All resection specimens showed advanced cancers. Most cancers occurred after the age of 50 years.

• Journal of Life Science
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• v.21 no.3
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• pp.417-423
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• 2011

Thymosin ${\beta}4$ (TB-4) has been reported to play a key role in tumor growth, metastasis and angiogenesis. In addition, TB-4 induced the expression of vascular endothelial growth factor (VEGF) and stabilized the hypoxia-inducible factor (HIF)-$1{\alpha}$ in melanoma cells. Although the importance of thymosin ${\beta}4$ in angiogenesis and metastasis has been proven, there are few studies that show the expression patterns of TB-4, VEGF and HIF-$1{\alpha}$. This study was conducted to analyze the relationship among these proteins in various tumors. Using tissue microarray analysis, we investigated the expression patterns of TB-4, VEGF and HIF-$1{\alpha}$ in various tumors to identify the expression patterns and relationships of these proteins in certain tumors. TB-4 was highly expressed in osteosarcoma, colon adenocarcinoma, esophageal squamous cell carcinoma, kidney and urinary bladder transitional carcinoma, lung cancer, and liver cancer. HIF-$1{\alpha}$ was highly expressed in nasal cavity inverted papilloma, lung cancer, and esophageal squamous cell carcinoma. The expression patterns of TB-4 and HIF-$1{\alpha}$ were almost similar and co-localized. VEGF expression was high in the blood vessels in tumors, but usually not high in the tumors themselves. VEGF was moderately expressed in stomach cancer, liver angiosarcoma, gall bladder adenocarcinoma, and uterus endometrial adenocarcinoma. The expression patterns of VEGF shows similarities in certain tumors including stomach cancer, osteosarcoma, liposarcoma, lung cancer, liver cancer, gall bladder adenocarcinoma, esophageal squamous cell carcinoma, stomach cancer, colorectal carcinoma and renal cell carcinoma. These results suggest that the expression patterns of TB-4, HIF-$1{\alpha}$ and VEGF were co-localized and related to tumorigenesis and angiogenesis of certain tumors.

• The Korea Journal of Herbology
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• v.21 no.2
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• pp.37-46
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• 2006

Objectives : The purpose of this study was to investigate the effect of Dangguibohyultang (DB) and its combination (DB-I; Astragali membraneus BUNGE : Angelica gigas NAKAI=5:1, DB-II; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:1, DB-III; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:5,) on apoptosis in human colorectal adenocarcinoma HCT116 cells. Methods : To study the cytotoxic effect of methanol extract of DB-I, DB-II and DB-III on HCT116 cells, the cell viability was determined by XTT reduction method and ttypan blue exclusion assay. To confirm the induction of apoptosis, the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of procaspase-3, -8 and -9 were examined by western blot analysis. Furthermore, DB-induced apoptosis was confirmed by DNA fragmentation. The release of cytochrome C from mitochondria to cytosol, the level of Bcl-2 and Bax, and the expressions of Raf/MEK/ERK were examined by western blot analysis. Results : DB-I and DB-II reduced proliferation of HCT116 cells in a dose-dependent manner. DB-I and DB-II decreased procaspase-3, -8, -9 levels in a dose-dependent manner and induced the clevage of PARP. DB-I and DB-II also triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome C from mitochondria to cytosol, decreasing of anti-apoptotic Bcl-2, and increasing of pro-apoptotic Bax. DB-I and DB-II decreased the activation of Ras/Raf/MEK/ERK cascade in a dose-dependent manner. Conclusion : These results suggest that DB-I and DB-II induce apoptosis via mitochondrial pathway in HCT116 cells. Furthermore, Raf/MEK/ERK cascade is involved in DB-induced apoptosis. These results suggest that DB is potentially useful as a chemotherapeutic agent in human liver cancer.