2,971 publications from this institution
Abstract The B cell receptor (BCR) is essential for mature B cell lymphomas, serving as therapeutic target. Here, we show that high-grade B cell lymphomas with MYC and BCL2 rearrangements (HGBCL-DH- BCL2 ) predominantly exhibit immunoglobulin heavy (IGH) chain silencing, leading to BCR shutdown. HGBCL-DH- BCL2 with undetectable IGH (IGH UND ) differ from IGH-expressing counterparts for germinal center-zone gene programs, MYC expression and T cell infiltration. While IGH + HGBCL-DH- BCL2 prefer IGM/IG-Kappa expression, IGH UND counterparts have completed IGH class-switching, favoring IG-Lambda (IGL) light chains. IGH UND HGBCL-DH- BCL2 preserve IGHV gene integrity, overcoming antigen-driven selection. IGH silencing precedes onset and shapes evolution of HGBCL-DH- BCL2 from Follicular Lymphoma (FL) or FL/HGBCL-DH- BCL2 common precursor. In FL/HGBCL-DH- BCL2 pairs and HGBCL-DH- BCL2 models, BCR silencing promoted RAG1/2-dependent IG light chain editing, causing t(8;22)(q24;q11)/ IGL :: MYC . IGH silencing protected HGBCL-DH- BCL2 models from killing by CD79B-targeting Polatuzumab-Vedotin. Collectively, HGBCL-DH- BCL2 primarily originate from BCR-silenced isotype-switched t(14;18)/ IGH::BCL2 -positive (pre)FL cells acquiring I GL::MYC translocations during IG light chain revision, with clinical implications. Significance These findings link BCR silencing in isotype-switched t(14;18) + Follicular Lymphoma cells (or their precursors) to RAG1/2 re-expression, promoting IGL::MYC translocations responsible for transformation into high-grade B cell lymphomas (HGBCL). Predominant silencing of the BCR complex in HGBCL with MYC and BCL2 rearrangements protects tumor cells from CD79B-directed Polatuzumab-Vedotin killing.
Our study provided the first detailed analysis of risk factors for MF/SS and further investigation is needed to confirm these findings in prospective data and in other populations.
The relationship between spontaneous and induced abortions and breast cancer risk was analyzed using data from a case-control study conducted between June 1991 and February 1994 in 6 Italian centers on 2,569 histologically confirmed incident breast cancer cases and 2,588 controls admitted to hospital for a wide range of acute, non-neoplastic, non-hormone-related diseases. One or more abortions were reported by 31% of cases and 32% of controls, corresponding to a multivariate odds ratio (OR) of 1.0 (95% confidence interval [CI], 0.8-1.1). No trend in risk was observed with increasing number of total abortions or spontaneous and induced abortions separately. No significant relationship was found between the risk of breast cancer and history of spontaneous or induced or total abortions in separate strata of age at diagnosis, number of children, time of abortion in relation to first birth and family history of breast cancer. When abortion was the outcome of the first pregnancy, the OR was 1.2 for spontaneous and 1.3 for induced abortion, in relation to women with birth as outcome of the first pregnancy, and 1.0 and 1.1, respectively, when the reference category was nulligravidae. Thus, our results indicate a lack of association between induced and spontaneous abortions and breast cancer risk.
This study suggests that some micronutrients, including beta-carotene, may have a protective effect against endometrial carcinoma.
The relation between meal frequency and the risk of colorectal cancer was investigated in a case-control study conducted in North Italy on 889 cases of colon cancer, 581 cases of rectal cancer, and 2475 controls admitted to hospital for acute, nonneoplastic, or digestive disorders. As compared to individuals who reported 2 or fewer meals per day, the multivariate colon cancer odds ratios were 1.7 [95% confidence interval (95% CI), 1.5-2.1] for 3, and 1.9 (95% CI, 1.1-3.3) for 4 meals or more. Corresponding rectal cancer odds ratios were 1.4 (95% CI, 1.1-1.7) for 3, and 1.9 (95% CI, 1.1-3.5) for 4 meals or more. The direct trends in risk of colorectal cancer with frequency of eating were not substantially modified by allowance for various dietary and nondietary potential confounding factors, including an approximate measure of total energy intake, and did not show significant effect modification across strata of age, sex, education, and other major risk covariates. A role of meal frequency in the etiology of colorectal cancer is biologically plausible, since when a meal is eaten, the gallbladder contracts and releases bile acids. Thus, eating patterns can influence the enterohepatic circulation and, consequently, the exposure time of intestinal mucosa to bile acids.
ABSTRACT Background The contribution of children to viral spread in schools is still under debate. We conducted a systematic review and meta-analysis of studies to investigate SARS-CoV-2 transmission in the school setting. Methods Literature searches from April, 2021 and repeated on May, 15 th 2021 yielded a total of 1088 publications: screening, contact tracing and seroprevalence studies. MOOSE guidelines were followed and data analyzed using random-effects models. Results From screening studies involving more than 120,000 subjects, we estimated 0.31% (95% Confidence Interval [CI] 0.05-0.81%) SARS-CoV-2 point prevalence in schools. Contact tracing studies, involving a total of 112,622 contacts of children and adults, showed that onward viral transmission was limited (2.54%; 95%CI 0.76-5.31). Young index cases were found to be 74% significantly less likely than adults to favor viral spread (Odds Ratio [OR]=0.26; 95%CI 0.11-0.63) and were less susceptible to infection (OR=0.60; 95% CI 0.25-1.47). Finally, from seroprevalence studies, with a total of 17,879 subjects involved, we estimated that children are 43% significantly less likely than adults to test positive for antibodies (OR=0.57; 95%CI: 0.49-0.68). In conclusion, testing all subjects in schools, independently of symptoms, students less likely than adults favor viral spread and SARS-CoV-2 circulation in schools was found to be limited. KEY POINTS Question What is the infectivity and susceptibility of students and staff exposed to SARS-CoV-2 in the school setting? Findings This systematic review and meta-analysis of all available data shows that SARS-CoV-2 viral spread is limited and child-to-adult transmission in the school setting scarce. Summary estimates indicate that young index cases were 74% significantly less likely than adults to favor viral spread and children are 43% less susceptible than adults. Meaning Overall, SARS-CoV-2 circulation in schools was limited and could be reasonably controlled with appropriate mitigation measures.
We estimated the number of cancer cases and deaths attributable to alcohol drinking in 2002 by sex and WHO subregion, based on relative risks of cancers of the oral cavity, pharynx, esophagus, liver, colon, rectum, larynx and female breast obtained from recent meta- and pooled analyses and data on prevalence of drinkers obtained from the WHO Global Burden of Disease project. A total of 389,100 cases of cancer are attributable to alcohol drinking worldwide, representing 3.6% of all cancers (5.2% in men, 1.7% in women). The corresponding figure for mortality is 232,900 deaths (3.5% of all cancer deaths). This proportion is particularly high among men in Central and Eastern Europe. Among women, breast cancer comprises 60% of alcohol-attributable cancers. Although our estimates are based on simplified assumptions, the burden of alcohol-associated cancer appears to be substantial and needs to be considered when making public health recommendations on alcohol drinking.