Background: Interleukin (IL) 10 is a potent anti-inflammatory cytokine. Disruption of the IL-I0 gene in C57/Black6 rnice results in enterocolitis in the presence of intestinal bacteria. This study investigated gut mucosal barrier function sequentially during the development of colitis in this modelo Methods: Animals were bred in specific pathogen-free conditions and transferred to convencional housing at 4weeks. Mice were evaluated at 6,8,10,12,14 and 15weeks ofage. Barrler function was assessed by measuring intestinal permeability and antibody response to systernic endotoxaernia (antibody to the core glycolipid region of lipopolysaccharide; EndoCAb). Colons were harvested and a histological injury score (IllS) was calculated. Results: The ms increased progressively until 12 weeks, with an associated increase in intestinal permeability, and irnmunoglobulin (Ig) M and IgG EndoCAb. The ms correlated positively with both intestinal permeability and IgM and IgG EndoCAb. Intestinal permeability showed a positive correlation with EndoCAb. Conclusion: n.-IO knockout rnice develop coli*1h an associated disturbance in gut mucosal barrier function, as measured by increased ~ermeability and endotoxaernia. The colitis found in the IL-I0 knockout mouse

PURPOSE Postoperative Adjuvant Radiation in Cervical Cancer (PARCER), a phase III randomized trial, compared late toxicity after image-guided intensity-modulated radiotherapy (IG-IMRT) with three-dimensional conformal radiation therapy (3D-CRT) in women with cervical cancer undergoing postoperative radiation. METHODS Patients were randomly assigned to receive either IG-IMRT or 3D-CRT after stratification for the type of hysterectomy and use of concurrent chemotherapy. The primary end point was 3-year grade ≥ 2 late GI toxicity assessed using Common Toxicity Criteria for Adverse Events v 3.0 and estimated using time-to-event, intention-to-treat analysis, with a study level type I error of 0.05 and a nominal α of .047 after accounting for one interim analysis. Secondary end points included acute toxicity, health-related quality of life, and pelvic relapse-free, disease-free, and overall survival. RESULTS Between 2011 and 2019, 300 patients were randomly assigned (IG-IMRT 151 and 3D-CRT 149). At a median follow-up of 46 (interquartile range 20-72) months, the 3-year cumulative incidence of grade ≥ 2 late GI toxicity in the IG-IMRT and 3D-CRT arms were 21.1% versus 42.4% (hazard ratio [HR] 0.46; 95% CI, 0.29 to 0.73; P < .001). The cumulative incidence of grade ≥ 2 any late toxicity was 28.1% versus 48.9% (HR 0.50; 95% CI, 0.33 to 0.76; P < .001), respectively. Patients reported reduced diarrhea ( P = .04), improved appetite ( P = .008), and lesser bowel symptoms ( P = .002) with IG-IMRT. However, no difference was observed in the time by treatment interaction. The 3-year pelvic relapse-free survival and disease-free survival in the IG-IMRT versus the 3D-CRT arm were 81.8% versus 84% (HR 1.17; 95% CI, 0.68 to 1.99; P = .55) and 76.9% versus 81.2% (HR 1.03; 95% CI, 0.62 to 1.71; P = .89), respectively. CONCLUSION IG-IMRT results in reduced toxicity with no difference in disease outcomes.

Persistent HPV infection plays a major role in cervical cancer. This study was undertaken to identify HPV types in a cohort of Indian women with locally advanced cervical cancer as well as to determine the physical state and/or site of viral integration in the host genome. Pretreatment biopsies (n = 270) from patients were screened for HPV infection by a high throughput HPV genotyping assay based on luminex xMAP technology as well as MY09/11 PCR and SPF1/2 PCR. Overall HPV positivity was observed to be 95%, with HPV16 being most common (63%) followed by infection with HPV18. Integration status of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT) assay in a subset of samples positive for HPV16 and/or HPV18 (n = 86) and with an adequate follow-up. The data was correlated with clinical outcome of the patients. Integration of the viral genome was observed in 79% of the cases and a preference for integration into the chromosomal loci 1p, 3q, 6q, 11q, 13q and 20q was seen. Clinical data revealed that the physical state of the virus (integrated or episomal) could be an important prognostic marker for cervical cancer.

The high burden of cervical cancer and inadequate/suboptimal cytology screening in developing countries led to the evaluation of visual screening tests, like visual inspection with acetic acid (VIA) and Lugol's iodine (VILI). We describe the performance of VIA, VILI and cytology, carried out in a multinational project called ''Screening Technologies to Advance Rapid Testing'' in 5,519 women aged 30-49 years, in detecting cervical intraepithelial neoplasia (CIN). VIA, VILI and cytology were positive in 16.9%, 15.6% and 6.1% women, respectively. We found 57 cases of CIN2, 55 of CIN3 and 12 of cervical cancer; 90% of CIN3 and 43% CIN2 cases were positive for p16 overexpression and high-risk HPV infection, indicating a high validity of histological diagnosis. The sensitivity of VIA, VILI and cytology to detect high-grade CIN were 64.5%, 64.5% and 67.7%, respectively; specificities were 84.2%, 85.5% and 95.4%. A high proportion of p16 positive CIN 3 (93.8%) and 2 (76.9%) were positive on cytology compared with visual tests (68.8% and 53.8%, respectively) indicating a higher sensitivity of cytology to detect p16 positive high-grade CIN. However, the immediate availability of the results from the visual tests permits diagnosis and/or treatment to be performed in the same sitting, which can potentially reduce loss to follow-up when women must be recalled following positive cytology. Organizing visual screening services in low-resource countries may facilitate the gradual building of an infrastructure committed to screening allowing the eventual introduction of more sensitive, highly objective, reproducible and affordable human papillomavirus screening tests in future.Early detection of high-grade cervical intraepithelial neoplasia (CIN 2-3 lesions) by screening and their effective treatment constitute the most common and widely used strategy to prevent cervical cancer throughout the world. Conventional cervical cytology is the most widely used screening test and the workhorse of large-scale cervical screening programs globally. Cytology is repeated frequently, at 1-5 year intervals, to ensure lesions missed in a given round of screening and incident lesions are detected in subsequent rounds. Collection of cervical cells, smear preparation, processing, reading and reporting requires several labor intensive steps as well as a laboratory infrastructure. Stringent quality assurance is vital to avoid any suboptimal performance of cytology in detecting cervical cancer precursors. The difficulties in ensuring optimal cytology screening with inadequate coverage for both testing and treatment of precursor lesions or lack of screening per se are responsible for the continuing high risk and burden of cervical cancer in developing countries.

Five-year DFS of 62% and 45% of Stage II and III patients treated under routine care represents comparable stage-matched results to the rest of the world, respectively.

No abstract

Histones through a complex repertoire of non-allelic variants and their post-translational modifications regulate gene expression. Though alterations in histone-modifying enzymes and post-translational modifications of histones have been studied in cancer, expression of histone variants has not been clearly associated with dedifferentiation and malignant transformation of hepatocyte in vivo. In the present work, the pattern of variants of histones was investigated during N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. Our studies show for the first time in vivo overexpression of a major histone H2A variant H2A.1 and a decrease in H2A.2 at protein and mRNA levels by sodium dodecyl sulfate-Acetic acid-Urea-Triton (SDS-AUT) two-dimensional gel electrophoresis followed by matrix-assisted-laser desorption/ionization time-of-flight (TOF)/TOF mass spectrometry and reverse transcriptase-polymerase chain reaction analysis during sequential development of hepatocellular carcinoma (HCC). H2A.1 and H2A.2 are highly homologous, replication-dependent, non-allelic variants of histone H2A differing at only three amino acid positions. Our results of increase in proliferating cell nuclear antigen expression indicate that with increase in replicating population of transformed cells in HCC, H2A.1 expression increases, suggesting association of H2A.1 overexpression with hyper-proliferation of hepatocytes during cellular dedifferentiation and progressive transformation of normal liver to preneoplastic and neoplastic stages of HCC.

The high incidence of gallstone-related gall bladder cancer in India is associated with metaplasia and a tendency to poorer differentiation in the tumour histology. These tumours are consequently less likely to express hormone receptors. Thus, there does not seem to be a role for anti-hormone therapy in patients with histogenesis similar to that seen in India.