International journal of cancer. Journal international du cancer
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Multicenter Study
Human papillomavirus prevalence and type distribution in invasive cervical cancer in sub-Saharan Africa.
In sub-Saharan Africa, invasive cervical cancer (ICC) incidence and mortality are among the highest in the world. This cross-sectional epidemiological study assessed human papillomavirus (HPV) prevalence and type distribution in women with ICC in Ghana, Nigeria, and South Africa. Cervical biopsy specimens were obtained from women aged ≥ 21 years with lesions clinically suggestive of ICC. ⋯ In ICC cases with single HPV infection (447/515 [86.8%]), the most commonly detected HPV types were HPV16 (51.2%), HPV18 (17.2%), HPV35 (8.7%), HPV45 (7.4%), HPV33 (4.0%) and HPV52 (2.2%). The prevalence of single and multiple HPV infections seemed higher among HIV-positive women and HPV type distribution appeared to differ according to tumor type and HIV status. In conclusion, HPV16, 18, 45 and 35 were the most common HPV types in sub-Saharan African women with ICC and HPV infections were more common in HIV-positive women.
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Pancreatic ductal adenocarcinoma (PDAC) is known for its aggressive growth, and is characterized by early tissue invasion and metastasis with poor prognosis. Identifying prognostic markers and delineating the underlying mechanisms that promote progression of PDAC are important for the treatment of pancreatic cancer. TIP30, a newly identified tumor suppressor, appears to be involved in multiple processes during tumor development and metastasis. ⋯ Suppression of TIP30 resulted in upregulation of Snail and subsequent downregulation of E-cadherin in SW1990 cells containing high-level of endogenous TIP30. However, in the PANC-1 cells containing low level of endogenous TIP30, suppressing TIP30 caused upregulation of Slug instead of Snail, followed by upregulation of MMP9 rather than E-cadherin. Taken together, our work reveals that decreased TIP30 expression is able to enhance invasion and metastasis of pancreatic cancer cells through upregulation of the Snail family members and may serve as an independent predictor for poor outcomes in PDAC patients.
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Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. ⋯ In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.
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Crizotinib is an oral tyrosine kinase inhibitor approved for treating patients with non-small cell lung cancer (NSCLC) containing an anaplastic lymphoma kinase (ALK) rearrangement. We used knockout mice to study the roles of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) in plasma pharmacokinetics and brain accumulation of oral crizotinib, and the feasibility of improving crizotinib kinetics using coadministration of the dual ABCB1/ABCG2 inhibitor elacridar. In vitro, crizotinib was a good transport substrate of human ABCB1, but not of human ABCG2 or murine Abcg2. ⋯ Importantly, oral elacridar coadministration increased the plasma and brain concentrations and brain-to-plasma ratios of crizotinib in wild-type mice, equaling the levels in Abcb1a/1b;Abcg2(-/-) mice. Our results indicate that crizotinib oral availability and brain accumulation were primarily restricted by Abcb1 at a non-saturating dose, and that coadministration of elacridar with crizotinib could substantially increase crizotinib oral availability and delivery to the brain. This principle might be used to enhance therapeutic efficacy of crizotinib against brain metastases in NSCLC patients.
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To estimate the risk of late morbidity leading to hospitalization among young adult cancer 5-year survivors compared to the general population and to examine the long-term effects of demographic and disease-related factors on late morbidity, a retrospective cohort of 902 five-year survivors of young adult cancer diagnosed between 1981 and 1999 was identified from British Columbia (BC) Cancer Registry. A matched comparison group (N = 9020) was randomly selected from the provincial health insurance plan. All hospitalizations until the end of 2006 were determined from the BC health insurance plan hospitalization records. ⋯ The highest risks were found for hospitalization due to blood disease (RR = 4.2; 95% CI = 1.98-8.78) and neoplasm (RR = 4.3; 95% CI = 3.41-5.33). Survivors with three treatment modalities had three-fold higher risk of having any type of late morbidity (RR = 3.22; 95% CI = 2.09-4.94) than the comparators. These findings emphasize that young adult cancer survivors still have high risks of a wide range of late morbidities.