Clinical Trial Service Unit

About: Clinical Trial Service Unit is a based out in . It is known for research contribution in the topics: Population & Stroke. The organization has 428 authors who have published 1387 publications receiving 181920 citations.

Frequency of CBFβ/MYH11 fusion transcripts in patients entered into the U.K. MRC AML trials

Abstract: It has been established that cytogenetic findings at diagnosis of acute myeloid leukaemia (AML) are a powerful prognostic indicator. Patients who have the inv(16)(p13q22), closely associated with the FAB subtype M4Eo. are deemed to have good-risk disease. This subtle translocation may be difficult to detect in poor-quality metaphase preparations and if missed could lead to the incorrect assignment of risk group and influence further treatment strategies. We studied 321 patients with AML at diagnosis for the presence of inv(16)(p13q22) and CBF beta/MYH11 fusion transcripts by cytogenetic and RT-PCR techniques respectively. Karyotypic analysis detected 21 cases of inv(16) (p13q22), all of which were PCR positive. A further 12 cases were detected at the molecular level only, in FAB types other than M4Eo. The observed frequencies of CBF beta/MYH11 fusion transcripts in our study have been adjusted for the reported incidence of each FAB subtype and we calculate that 10.1% of all new cases of AMLs have molecular evidence of inv(16)(p13q22). only half of which are of the M4Eo subtype. We conclude that molecular screening for the presence of CBF beta/MYH11 fusion transcripts should be mandatory in all case of AML at diagnosis.

Associations Between Hepatitis B Virus Infection and Risk of All Cancer Types.

Abstract: Importance Hepatitis B virus (HBV) has been identified as a major risk factor for hepatocellular carcinoma. However, the associations between HBV infection and other cancer types are not well understood. Objective To assess the associations between chronic HBV infection and risk of all cancer types. Design, Setting, and Participants This population-based study involved 3 cohorts in China. The China Kadoorie Biobank (CKB) prospective cohort study, conducted between June 2004 and July 2008, used a dipstick assay for detection of serum hepatitis B surface antigen (HBsAg) among 496 732 participants to determine the association between HBV infection and risk of all cancer types. Two cohort studies were used to validate the associations by applying more precise serum HBsAg detection assays: the Qidong cohort (37 336 participants enrolled from November 2007 to April 2011) and the Changzhou nested case-control study (17 723 participants enrolled from June 2004 to September 2005). A total of 97 samples of stomach cancer tissues, 10 samples of pancreatic cancer tissues, and 9 samples of lung cancer tissues were included to assess the presence of HBV replication and expression. Statistical analysis was performed from December 2016 to October 2018. Exposures Serum HBsAg status in the population-based stage and HBV DNA status, the expression of hepatitis B X protein, and hepatitis B core antibody (anti-HBc) in the tissue-based stage. Main Outcomes and Measures Incidence of all cancer types during follow-up. Results In the CKB cohort, the mean (SD) age of the 496 732 participants was 51.5 (10.7) years; 59.0% of the participants were women. After 4.4 million person-years of follow-up, participants who were HBsAg seropositive (n = 15 355) had a higher risk of hepatocellular carcinoma (hazard ratio [HR], 15.77; 95% CI, 14.15-17.57), stomach cancer (HR, 1.41; 95% CI, 1.11-1.80), colorectal cancer (HR, 1.42; 95% CI, 1.12-1.81), oral cancer (HR, 1.58; 95% CI, 1.01-2.49), pancreatic cancer (HR, 1.65; 95% CI, 1.03-2.65), and lymphoma (HR, 2.10; 95% CI, 1.34-3.31) when compared with participants who were HBsAg seronegative (n = 481 377). Because of the limitation of sample size, only associations of HBV infection with hepatocellular carcinoma and stomach cancer were validated in the Qidong cohort (hepatocellular carcinoma: HR, 17.51; 95% CI, 13.86-22.11; stomach cancer: HR, 2.02; 95% CI, 1.24-3.29); the Changzhou nested case-control study validated only an association between HBV infection and stomach cancer (odds ratio, 1.76; 95% CI, 1.04-2.98). Moreover, among 22 participants with stomach cancer from the Qidong cohort who were anti-HBc seropositive, 12 samples (54.5%) of cancer tissues were HBV DNA positive, while among 25 participants with stomach cancer who were anti-HBc seronegative, no HBV DNA was detected. The same negative and positive rate was observed in the validation set from Zhejiang Tumor Hospital (19 of 35 samples [54.3%] were HBV DNA positive). Moreover, among the 8 patients with stomach cancer from the Qidong cohort who were anti-HBc seropositive, anti-HBc and hepatitis B X protein were expressed in all of their stomach cancer tissue samples. The same phenomenon was observed in the patients with pancreatic cancer but not in the patients with lung cancer, which was consistent with the population-based results of the CKB cohort. Conclusions and Relevance This study found that HBV infection was also associated with the risk of nonliver cancer, especially digestive system cancers among adults in China.

Cholesterol fractions and apolipoproteins as risk factors for heart disease mortality in older men.

Abstract: out CVD and a slight nonsignificant inverse association in men with CVD were observed (HR, 1.47 vs 0.84). The patterns were similar for low-density lipoprotein cholesterol levels (HR, 1.50 vs 0.98) and for apolipoprotein B levels (HR, 1.68 vs 0.93). Ischemic heart disease risks were inversely associated with high-density lipoprotein cholesterol levels and with apolipoprotein A1 levels in men with and without CVD. Ischemic heart disease risks were strongly associated with total–high-density lipoprotein cholesterol levels (HR, 1.57) and apolipoprotein B–apolipoprotien A1 levels (HR, 1.54), and remained strongly related at all ages. Conclusions: Blood lipid levels other than total cholesterol levels were associated with IHD in older men. Differences in lipid levels that are achievable by statin use were associated with about a one-third lower risk of IHD, irrespective of age.

Cancer and the immortal strand hypothesis.

Abstract: THE main causes of mortality in the Western world are largely a matter of somatic genetics. As we age, our cells accumulate more and more mutations. Eventually one of them acquires a set of changes in phenotype that allows it to generate an expanding clone of descendants, causing an atheromatous plaque in an artery or an invasive cancer. These changes are the result of a cumulative process extending throughout our life, as is demonstrated in the relation between smoking and lung cancer and between pregnancy and breast cancer. Someone who started smoking at the age of 15 will, when 65, have a higher risk of lung cancer than someone who started at 20, showing that lungs can store for half a century the damage acquired in your teenage years (Doll and Peto 1981). Conversely, because pregnancy protects somewhat against the subsequent risk of breast cancer, a woman who first became pregnant when 13 will, when 70, have a lower risk of breast cancer than a woman whose first pregnancy was in her 20s, showing that the latter was accumulating risk as a teenager (MacMahon et al. 1973). Long-lived animals protect themselves from the physical and chemical dangers of their environment by continuous replacement of the cells on their external surfaces and it is in these sites of continuous cell division that most human cancers arise. An adult human contains ∼1012 rapidly multiplying cells. During a life span of ∼30,000 days, each of us makes and discards from skin, gut, and certain internal organs such as lymph glands and bone marrow about one-third of these cells each day (Potten and Morris 1988). If all these 1012 cells divide every third day, the cells remaining after 80 years would each have had ∼10,000 successive divisions in their ancestry. So by the age of 80, given a mutation rate of ∼10−6/gene/replication (Drake 1999), 1 in 100 of the copies of each gene would be mutant. In a collection of 1012 cells, 1010 would have a mutant copy of any particular gene, 108 would have mutations in any pair of genes, and a million would have mutations in any trio of genes. Nevertheless, despite there being many combinations of mutant genes that can trigger cancer (Hahn and Weinberg 2002), most people never develop cancer. So there must be some feature of multicellular systems that slows the rate of accumulation of replication errors.