Biomedical subjects

Hemant K Roy

Publications and source records attributed to Hemant K Roy.

23 records · Page 2Linked to original sources

PubMed2003

Increased cumulative incidence of prostate malignancies in colorectal cancer patients.

BACKGROUND: Identifying subjects at an increased risk of colorectal cancer (CRC) is of considerable importance in designing effective screening strategies. Malignancies that cosegregate with CRC provide important markers for higher-risk patients. CRC and prostate cancer share many similarities with regard to etiological factors. However, the previous reports on associations between these common malignancies are contradictory and confounded by a lack of rigorous controls. AIM OF THE STUDY: The aim of this study was to further elucidate the relationship between CRC and prostate cancer. METHODS: We performed a retrospective case-control study of subjects receiving medical care at the Omaha Veteran's Administration Medical Center between 1992 and 2002. Cases (patients with CRC) were obtained through the pathology records, whereas controls (patients with a negative colonoscopy during the same time period) were found through assessment of the endoscopy database. All subjects had the pathology database queried for other malignancies. The medical record also was assessed for confounding factors such as prostate cancer screening, radiation therapy status, and so on. RESULTS: We identified 149 male patients with CRC cases and 186 controls (age-matched male patients with a negative colonoscopy). The 10-yr cumulative incidence of prostate cancer was 10.7% of the cases but only 3.8% of the controls (p = 0.016). There were no significant differences between cases and controls among 11 other primary malignancies evaluated. The association between CRC and prostate cancer was unrelated to characteristics such as location in the colon and differentiation. Furthermore, confounding factors including frequency of prostate cancer screening and radiation therapy status did not explain the cosegregation between CRC and prostate. CONCLUSION: This preliminary report suggests that there is an association between CRC and prostate cancer. If replicated in other populations, this may have important implications for cancer screening strategies.

Adult↗

PubMed2002

AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis.

The inhibition of apoptosis is a critical event in the development of colorectal malignancies, although the mechanism(s) remain incompletely understood. The anti-apoptotic proto-oncogene, AKT, has been implicated in the molecular pathogenesis of a variety of human malignancies; however, no data exist on the role of AKT in colon carcinogenesis. We therefore evaluated the presence of AKT in human and experimental colon neoplasms by immunohistochemistry. Normal colonic mucosa and hyperplastic polyps exhibited no significant AKT expression, in marked contrast to the dramatic AKT immunoreactivity seen in colorectal cancers (57% positive) and in both human colorectal cancer cell lines examined. Importantly, AKT was also detected in 57% of the adenomas examined, implicating overexpression of this proto-oncogene as an early event during colon carcinogenesis. Moreover, in the rodent-carcinogen model, azoxymethane (AOM)-treatment induced AKT expression in premalignant rat colonocytes. Tumors that evolve via different genetic pathways displayed a lower incidence of AKT overexpression. Indeed, only 22% of mismatch repair defective tumors and 42% of AOM-induced rodent tumors upregulated AKT. Staining with an antibody specific for AKT 2 duplicated findings with the AKT 1&2 antibody, suggesting that AKT 2 was the predominant isoform involved in colon carcinogenesis. Furthermore, utilizing an antibody that specifically recognizes the serine-473 phosphorylated form of AKT, we observed that activated AKT was detectable in the neoplastic but not normal epithelium. In summary, our immunohistochemical analysis indicates AKT overexpression occurs frequently during human colon carcinogenesis, but is less common in colon cancers with microsatellite instability. The early inhibition of apoptosis during sporadic colon carcinogenesis may be related, at least partly, to the overexpression of AKT.

Animals↗

PubMed2002

Ethanol promotes intestinal tumorigenesis in the MIN mouse. Multiple intestinal neoplasia.

Epidemiological studies suggest that alcohol consumption increases the risk of developing colorectal cancer; however, these data are confounded by numerous cosegregating variables. Previous experimental reports with the rodent carcinogen model have also yielded discordant results. To clarify the alcohol-colon cancer relationship, we used the MIN (multiple intestinal neoplasia) mouse, a genetic model of intestinal tumorigenesis. Twenty-four MIN mice were randomized to ethanol supplementation in the drinking water (15% alternating with 20% on a daily basis) or control. Mice were sacrificed after 10 weeks, and the intestinal tumors were scored under magnification. Tissue sections were assessed for apoptosis and cell proliferation rates, along with the presence of the malondialdehyde-acetaldehyde (MAA) adduct, a mutagenic adduct associated with ethanol consumption. Ethanol supplementation resulted in a significant increase in tumor number (135 +/- 35%; P = 0.027 versus control). The induction of tumorigenesis by ethanol was most dramatic in the distal small bowel (167 +/- 56%; P = 0.01). In the uninvolved intestinal mucosa, there was no difference in proliferative or apoptotic indices. Cytoplasmic and nuclear MAA adducts were detected in both ethanol-treated and control mice. We demonstrated that ethanol ingestion increased intestinal tumorigenesis in the MIN mouse model. Furthermore, whereas mechanisms remain incompletely elucidated, our data implicate formation of MAA adducts. This report provides further support that ethanol consumption is a risk factor for colorectal cancer.

Abnormalities, Multiple↗

PubMedDate not supplied

Tobacco use and increased colorectal cancer risk in patients with hereditary nonpolyposis colorectal cancer (Lynch syndrome).

BACKGROUND: The marked variability in age at onset of colorectal cancer (CRC) in patients with hereditary nonpolyposis colorectal cancer (HNPCC) makes management decisions difficult. Environmental factors governing the phenotypic variability of cancer-associated syndromes such as HNPCC have not been elucidated. METHODS: We determined whether tobacco use would alter CRC risk in carriers of HNPCC-associated mutations, using a retrospective cohort study of germline mutation (hMLH1 or hMSH2) carriers from the Hereditary Cancer Institute at Creighton University, one of the oldest and largest registries of HNPCC patients. The main outcome measure was age at CRC onset, estimated by means of Cox proportional hazards modeling. RESULTS: Tobacco use, hMLH1 mutation carriage (as opposed to hMSH2), and male sex were significantly associated with increased risk of CRC (hazard ratios, 1.43, 2.07, and 1.58, respectively). Alcohol use did not alter CRC risk. CONCLUSIONS: Smoking cessation should be an integral part of HNPCC management. This study underscores the gene x environment interactions in cancer development.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening.

The phenomenon of enhanced backscattering (EBS) of light, also known as coherent backscattering (CBS) of light, has been the object of intensive investigation in nonbiological media over the last two decades. However, there have been only a few attempts to explore EBS for tissue characterization and diagnosis. We have recently made progress in the EBS measurements in tissue by taking advantage of low spatial coherence illumination, which has led us to the development of low-coherence enhanced backscattering (LEBS) spectroscopy. In this work, we review the current state of research on LEBS. After a brief discussion of the basic principle of EBS and LEBS, we present an overview of the unique features of LEBS for tissue characterization, and show that LEBS enables depth-selective spectroscopic assessment of mucosal tissue. Then, we demonstrate the potential of LEBS spectroscopy for predicting the risk of colon carcinogenesis and colonoscopy-free screening for colorectal cancer (CRC).

Animals↗