Background: Colorectal cancer is one of the major health problems worldwide. However, limited studies have been reported from ASEAN countries. This study was conducted to evaluate clinical characteristics and survival of colorectal cancer cases aged <65 years and ${\geq}65$ years in the central region of Thailand. Materials and Methods: Clinical information, histological features, endoscopic findings and treatment outcome were collected and reviewed from Thammasat University Hospital, Pathumthani, Thailand between November 2011 and October 2015. Results: A total of 121 colorectal cancer patients, comprising 69 men and 52 women with a mean age of 65.8 years, were included. There were 57 aged <65 years and 64 aged ${\geq}65$ years. Common presenting symptoms were abdominal pain (37%), weight loss (34%) and anemia (32%). Mean duration of symptoms prior to diagnosis was 173 days. However, longer diagnosis time was demonstrated in patients aged <65 years than age more than ${\geq}65$ years (119.4 vs 58.4 days, P-value=0.30). Colonic fungating mass was the most common endoscopic finding (64.4%) and the location was significantly more commonly left than right side of the colon, both in younger and elderly groups (87.7% vs 12.3%, P=0.02 and 70.3% vs 29.7%, P=0.02, respectively). Adenocarcinoma with moderated differentiated was the most common histology (67.3%). More than half of the patients presented with advanced stage (28.9% with TNM stage 3 and 38.8% TNM stage 4, respectively). Overall 1-year and 5-year survival rates were 76.9% and 5%. Conclusions: Most colorectal cancer patients in Thailand have adenocarcinomas and present at advanced stage with poor prognosis. Screening of high risk patients and early detection might be essential factors to improve the treatment outcome and overall survival rate of colon cancer patients in Thailand and other ASEAN countries.
TTYH2 is a calcium-activated, inwardly rectifying anion channel that has been shown to be related to renal cancer and colon cancer. Based on the topological prediction, TTYH2 protein has five transmembrane domains with the extracellular N-terminus and the cytoplasmic C-terminus. In the present study, we identified a vesicle transport protein, ${\beta}$-COP, as a novel specific binding partner of TTYH2 by yeast two-hybrid screening using a human brain cDNA library with the C-terminal region of TTYH2 (TTYH2-C) as a bait. Using in vitro and in vivo binding assays, we confirmed the protein-protein interactions between TTYH2 and ${\beta}$-COP. We also found that the surface expression and activity of TTYH2 were decreased by co-expression with ${\beta}$-COP in the heterologous expression system. In addition, ${\beta}$-COP associated with TTYH2 in a native condition at a human colon cancer cell line, LoVo cells. The over-expression of ${\beta}$-COP in the LoVo cells led to a dramatic decrease in the surface expression and activity of endogenous TTYH2. Collectively, these data suggested that ${\beta}$-COP plays a critical role in the trafficking of the TTYH2 channel to the plasma membrane.
This study was designed to determine the prevalence of gallstones in the last three years and evaluate the associated risk factors in the population who underwent health screening. Although there are many studies reporting the prevalence and risk factors of GB polyp, the results varied among each report. The aims of this study were to evaluate the prevalence rate and risk factors of GB polyp, colon polyp and fatty liver in the population who underwent health screening. The study population consisted of 4,877 visited the health promotion center in Dalseogu, Daegu in Korea from January 2011 to December 2013. Each participant in the study had their biliary system gallbladder examined using ultrasonography. The prevalence of GB polyp was evaluated along with age, gender, metabolic syndrom, body mass index (BMI), Fatty liver, Colon polyp. A showed of total 383 (7.9%) people were found to have GB polyps. The prevalence of sex among 256 (9.8%) patients men and 127 (5.6%) women which showed significantly higher in male than in female subjects(p=0.001). The mean size of the GB polyps 4.92 mm (1.6-17 mm). The sizes of most GB polyps (73.6%) were less than 10 mm in diameter. 122 subjects (31.28%) had multiple GB polyps which 2 or more polyps and 261 subjects (68.2%) had single polyp. Independent risk factors related with GB polyp were male gender (OR 0.551, p<0.001), overweight that BMI above $23kg/m^2$ (OR 0.713, p=0.002) triglyceride (OR 0.571, P<0.001), metabolic syndrome (OR 0.049, p=0.033) and colon polyp (OR 1.409, p=0.002). In spite of the conclusion, the prevalence GB polyp was higher than previous Korea and other country reports. The GB polyp in a healthy population was results as 7.9%. The risk factors of GB polyps were found to be male, being overweight, triglyceride, metabolic syndrome and colon polyp. Not only the subject of a health examination is needed but, a further study of the general public when possible.
Kunawudhi, Anchisa;Wong, Alexandra K;Alkasab, Tarik K;Mahmood, Umar
Asian Pacific Journal of Cancer Prevention
/
v.17
no.8
/
pp.4143-4147
/
2016
Purpose: We evaluated all PET/CTs acquired for patients without a primary diagnosis of colorectal cancer, and compared results for those who had subsequent colonoscopy within 6 months, to assess the accuracy of FDG PET/CT for detection of incidental pre-malignant polyps and malignant colon cancers. Materials and Methods: Medical records of 9,545 patients who underwent F-18 FDG PET/CT studies over 3.5 years were retrospectively reviewed. Due to pre-existing diagnosis of colorectal cancer, 818 patients were excluded. Of the remainder, 157 patients had colonoscopy within 6 months (79 males; mean age 61). We divided the colon into 4 regions and compared PET/CT results for each region with colonoscopy and histopathologic findings. True positive lesions included colorectal cancer, villous adenoma, tubulovillous adenoma, tubular adenoma and serrated hyperplastic polyp/hyperplastic polyposis. Results: Of 157 patients, 44 had incidental colonic uptake on PET/CT (28%). Of those, 25 had true positive (TP) uptake, yielding a 48% positive predictive value (PPV); 9% (4/44) were adenocarcinoma. There were 23 false positive (FP) lesions of which 4 were hyperplastic polyp, one was juvenile polyp and 7 were explained by diverticulitis. Fifty eight patients had false negative PET scans but colonoscopy revealed true pre-malignant and malignant pathology, yielding 23% sensitivity. The specificity, negiative predictive value (NPV) and accuracy were 96%, 90% and 87%, respectively. The average SUVmax values of TP, FP and FN lesions were 7.25, 6.11 and 2.76, respectively. There were no significant difference between SUVmax of TP lesions and FP lesions (p>0.95) but significantly higher than in FN lesions (p<0.001). The average size (by histopathology and colonoscopy) of TP lesions was 18.1 mm, statistically different from that of FN lesions which was 5.9 mm (p<0.001). Fifty-one percent of FN lesions were smaller than 5 mm (29/57) and 88% smaller than 10 mm (50/57). Conclusions: The high positive predictive value of incidental focal colonic FDG uptake of 48% for colonic neoplasia suggests that colonoscopy follow-up is warranted with this finding. We observed a low sensitivity of standardly acquired FDG-PET/CT for detecting small polyps, especially those less than 5 mm. Clinician and radiologists should be aware of the high PPV of focal colonic uptake reflecting pre-malignant and malignant lesions, and the need for appropriate follow up.
Habib, Abdul Musaweer;Islam, Md. Saiful;Sohel, Md.;Mazumder, Md. Habibul Hasan;Sikder, Mohd. Omar Faruk;Shahik, Shah Md.
Genomics & Informatics
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v.14
no.4
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pp.255-264
/
2016
The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1,499 proteins of F. nucleatum, which have no homolog's in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the three dimensional structure of these three proteins. Finally, determination of ligand binding sites of the 2 key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against F. nucleatum.
Background: The Asia Pacific consensus for colorectal cancer (CRC) recommends that screening programs should begin by the age of 50. However, there have been reports about increasing incidence of CRC at a younger age (i.e. early-onset CRC). Little is known about the features of early-onset CRC in the Vietnamese population. Aim: To describe the clinical, endoscopic and pathological characteristics of early-onset CRC in Vietnamese. Method: A prospective, cross-sectional study was conducted at the University Medical Center from March 2009 to March 2011. All patients with definite pathological diagnosis of CRC were recruited. The early-onset CRC group were analyzed in comparison with the late-onset (i.e. ${\geq}$ 50-year-old) CRC group. Results: The rate of early-onset CRC was 28% (112/400) with a male-to-female ratio of 1.3. Some 22.3% (25/112) of the patients only experienced abdominal pain and/or change in bowel habit without alarming symptoms, 42.9% (48/112) considering their symptoms intermittent. The rate of familial history of CRC in early-onset group was significantly higher that of the late-onset group (21.4% versus 7.6%, p<0.001). The distribution of CRC lesions in rectum, distal and proximal colon were 51.8% (58/112), 26.8% (30/112) and 21.4% (24/112), respectively; which was not different from that in the late-onset group (${\chi}2$, p = 0.29). The rates for poorly differentiated tumors were also not significantly different between the two groups: 12.4% (14/112) versus 8.3% (24/288) (${\chi}2$, p = 0.25). Conclusion: A high proportion of CRC in Viet Nam appear at an earlier age than that recommended for screening by the Asia Pacific consensus. Family history was a risk factor of early-onset CRC. Diagnosis of early-onset CRC needs more attention because of the lack of alarming symptoms and their intermittent patterns as described by the patients.
Yilmaz, Medine;Sanli, Deniz;Ucgun, Mujde;Kaya, Nur Sahin;Tokem, Yasemin
Asian Pacific Journal of Cancer Prevention
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v.14
no.5
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pp.3269-3274
/
2013
Background: The aim was to determine the lifestyle behaviors and the practices for early diagnosis of cancer of cancer patients. Materials and Methods: A descriptive cross-sectional design was used for this study. The sample consisted of 222 patients with a diagnosis of cancer (non-random sample method). Ethical permission was obtained of the Non-interventional Research Ethics Committee of our Institution. Values of p<0.05 were accepted as statistically significant. Results: It was observed that 54.4% of the patients had never performed breast self-examination, 60.8% had never had a mammography, and 71.2% had never had a Pap smear. Sixty-six point two percent of patients had never had screening for colon cancer within the past ten years. GIS cancers were higher in smokers and ex-smokers (p=0.005), in drinkers and in ex-drinkers (p=0.000). The breast cancer rate was higher in obese people (p=0.019). Conclusions: The results of this study provide information on the healthy lifestyle behavior of cancer patients before their diagnosis, and their use of early diagnosis practices. The important aspect of this study is to extend cancer patients' period of life after the diagnosis and treatment process, to make them conscious of risky lifestyle and nutritional behavior so that they can maintain a high quality of life, and to start initiatives in this direction that would ensure changes in behavior.
Redox factor-1 (Ref-1), known as a redox regulator, controls the DNA binding of AP-1 and is activated in HT29 colon cancer cells by hypoxia in vitro. REF-1 also increases tile DNA binding affinity of Hypoxia-inducible Factor-lalpha$ (HIF-lalpha$), HIF-like Factor (HLF) and early growth response-1 (Egr-1) which induce expression of the genes involved in angiogenesis, so that we speculate that REF-1 may play a role in hypoxia-induced angiogenesis. In this research we tried to detect novel proteins interacting with REF-1 using Yeast two-hybrid system using full-length REF-1 cDNA as bait. As result of such screening we detected 3 positive clones. DNA sequencing and GeneBank search revealed that one of the clones contained the same sequences as M.musculus cDNA for tioredoxin.
Vincristine and vinblastine isolated from Vinco spp. , and podophyllotoxine derivatives isolated from Podophyllum spp. are usefulas anticancerous components obtaned from higher plants. More thanten antineoplastic compounds are now following them as anticancerousagents from higher plants. In my laboratory, Sarcoma 180A has beenused as the first screening test. By this method, I have found outsome kinds of antineoplastic constituents from active plants extracts .For instance, bisaborane type compounds were isolated from Curcumaxanthorrhiza, one of Indonesian plants; a morphinane type compoundfromCocculus trilobus; cyclic hexapeptides from Rubia akane and R.cordiorta. Seven components having antineoplastic actirity wereisolated from Rubia spp. except. R. tinctoria. Their structures wereelucidated except RA-Vl by chemical reaction and variovs instrumentalanalysis as shown in Fig. Among of them, RA-Vll showed strong activityagainst P388 Lymphocytic leukemia, L2O, B16 melanoma, Lewis lungcarcinoma, colon 38 and Ehrlich carcinoma. RA-V revealed excellentactivity against MM2 mammary carcinoma. The· value of acute LD5O ofRA-ViI were 10. Omg/kg( iP) and 16.5mg/kg( po ) respectiveIy . Therapruticratio was 400, compared with 10 of mitomycin C. QSAR was also appliedto these compounds by elongation of ether and ester side chains atR'. Mechanism of action of RA-Vll was also investigated and wasassumed to be inhibition of protein biosynthesis .
The purpose of this study was to develop a cocktail approach for the measurement of the permeability of marker compounds, caffeine and propranolol (high permeability), ofloxacin (intermediate), atenolol (low), and quinidine (P-glycoprotein substrate), simultaneously. Then we compared the permeability in Caco-2 cells with that in rat intestinal segments. The difference between individual measurement and cocktail approach was less than 20 %, and the permeabilities of these compounds were similar to those previously reported, suggesting that the cocktail transport study and simultaneous drug analysis were successfully developed and validated in this study. Additionally, in the application of this cocktail method, the permeability of five drugs in rat jejunum was similar to that in ileum but different from that in colon, which was measured using the Ussing chamber system. Moreover, permeability in jejunum and ileum was similar to that in Caco-2 cells. In conclusion, the permeability in Caco-2 cells was equivalent to the permeability in rat jejunum and ileum determined with the Ussing system. Therefore, this newly developed cocktail assay and its application to the Ussing system can be a useful tool for robust and rapid screening for site-specific permeability in rat intestine, thus accelerating the prediction of absorption of new chemical entities.
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