The development of primary liver cancer frequently is associated with persistent HBV infection, and tumours may arise in individuals who are anti-HBe positive. However, it is unclear whether viruses with an HBeAg-negative phenotype are associated with tumour development or are selected, during seroconversion, after chromosomal integration of wild-type viral DNA. In order to investigate the temporal evolution of the HBV genome in such individuals, the polymerase chain reaction was used to amplify HBV DNA from tumour tissue and serum of 14 patients from Guangxi, China with hepatocellular carcinoma. Comparison of nucleotide and amino acid sequences of the precore and proximal core region of HBV from the two sites in each patient produced evidence of divergence following integration in the tumour, but in most cases, HBeAg-negativity could not be explained by precore mutations. Sequences from the core promoter region were therefore examined and mutations were found in the majority, which are believed to upregulate transcription of the core (and pregenomic) RNA but to downregulate precore mRNA. To determine whether this finding merely reflected sequence variation among geographical isolates of HBV, the same region of HBV DNA from asymptomatic controls was sequenced and these mutations were found to be rare. We hypothesise that HBV with the core promoter mutations replicates at higher levels than the wild type, with the consequence that more integrations occur into the hepatocyte chromosomes during the early stages of infection. These hepatocytes may expand clonally and be targets for further mutagenic events leading to tumour development.
BackgroundAlthough triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS.MethodsIn this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48.ResultsA total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points.ConclusionsThe vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.
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