Egypt has possibly the highest Hepatitis C Virus (HCV) prevalence worldwide. A high proportion of HCV infections become chronic and lead to liver cirrhosis and hepatocellular carcinoma (HCC). The cellular and molecular mechanisms behind the complication of HCV infection are not completely understood although apoptosis has been implicated in this process. We examined whether T cells; isolated from patients with HCV and HCV-associated HCC (HCV-HCC); are predestined in vivo to undergo spontaneous apoptosis using flow cytometry. Also, the role of p53; a key in apoptotic process; in the development of HCC was examined. Our data showed that T cells were severely depleted in HCV-HCC patients and its spontaneous apoptosis was higher in patient groups as compared to normal controls as did the expression of p53, which correlated well with the HCC grade. In conclusion, HCV infection induces peripheral T cell apoptosis, depletion and subsequently immune-suppression in HCV patients and this may lead to persistence of infection. Also, p53 is implicated in the poor prognosis of HCV-HCC and could be used as a biomarker to assess the prognosis of HCC patients.
response to therapy. This study aimed to assess Top II, KI67 and P53 expression on clinical outcome and response to therapy of non-muscle invasive urothelial carcinoma. Methods: Fifty cases of non-muscle invasive urothelial carcinoma were collected; Top II, KI67, and P53 expression were evaluated. Patients received treatment then recurrence was correlated with the expression of previous markers. Results: There was a significant association between high Top II score, P53 and Ki67 and high grade (P ¼ 0.0001, 0.001, 0.0001), submucosal infiltration (P ¼ 0.0001, 0.01) and recurrence (P ¼ 0.01, 0.001, 0.001). Conclusions: Top II, P53, and Ki-67 may predict response to therapy and the clinical outcome in non-muscle invasive urothelial carcinoma.Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.13P Expression of HER2-neu, SKP2 and HIF-1 and their role in predicting the response of muscle invasive urothelial carcinoma to bladderpreservation chemotherapy
Background: Cancers arising in BRCA1 mutation carriers are highly sensitive to cisplatin due to somatic inactivation of the wild-type BRCA1 allele. Accordingly, BRCA1-driven OCs usually respond well to NACT and therefore almost always undergo complete cytoreduction. However, despite this seemingly effective treatment and continuation of platinum therapy in the adjuvant setting, almost all BRCA1associated OCs inevitably relapse. Methods: We compared BRCA1 LOH status in paired OC samples before and after NACT. Results: BRCA1 LOH was detected in 19/28 chemonaive OCs. Surprisingly, heterozygous status was restored in 13/19 (68%) samples after median of 3 cycles of NACT. The analysis of linked SNPs demonstrated that the restoration of BRCA1 proficiency is not due to the second mutation in the BRCA1 gene, but due to selection of pre-existing BRCA1-proficient cells. Furthermore, the persistence of isolated BRCA1-heterozygous cells in the chemonaïve OCs was confirmed by FISH analysis. Absence of BRCA1 LOH in post-NACT samples could not be explained by errors in tumor microdissection, as residual cancer tissues still retained TP53 mutation. Relapsed OC tissues were analyzed in 4 patients, who experienced the restoration of BRCA1 heterozygosity during NACT; the return to the BRCA1-deficient state during platinum-free interval was observed in 3 of these cases. Conclusions: 1) Loss of the remaining BRCA1 allele is not the first molecular event in the pathogenesis of BRCA1-associated cancers: it is likely to occur only after TP53 gene inactivation. 2) BRCA1-driven chemonaive cancers still contain a fraction of BRCA1proficient cells even if they demonstrate LOH in a gross tumor mass. Therefore, drugs targeting BRCA1 deficiency are unlikely to be curative if applied alone. 3) The ratio between BRCA1-deficient and -proficient cells undergoes rapid changes during platinum therapy and platinum-free intervals. 4) Continuation of platinum therapy in the adjuvant setting for the tumors with restored BRCA1 status does not have a biologic rationale. 5) Intratumoral interactions between BRCA1-deficient and -proficient cells deserve further investigation.
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