De novo transcriptome analysis of Perna viridis highlights tissue-specific patterns for environmental studies

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Apigenin impedes cell cycle progression at G2 phase in prostate cancer cells

As a natural flavone, apigenin is abundantly present in vegetables, fruits, oregano, tea, chamomile, wheat sprout and is regarded as a major component of the Mediterranean diet. Apigenin is known to inhibit proliferation in different cancer cell lines by inducing G2/M arrest, but it is unclear whether this action is predominantly imposed on G2 or M phases. In this study, we demonstrate that apigenin arrests prostate cancer cells at G2 phase by flow cytometric analysis of prostate cancer cells co-stained for phospho-Histone H3 and DNA. Concurrently, apigenin also reduces the mRNA and protein levels of the key regulators that govern G2-M transition. Further analysis using chromatin immunoprecipitation (ChIP) confirmed the diminished transcriptional activities of the genes coding for these regulators. Unravelling the inhibitory effect of apigenin on G2-M transition in cancer cells provides the mechanistic understanding of its action and supports the potential for apigenin as an anti-cancer agent. Graphical Abstract: [Figure not available: see fulltext.

Hypoxic gene expression in chronic hepatitis B virus infected patients is not observed in state-of-the-art in vitro and mouse infection models

Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. The prolyl hydroxylase domain (PHD)-hypoxia inducible factor (HIF) pathway is a key mammalian oxygen sensing pathway and is frequently perturbed by pathological states including infection and inflammation. We discovered a significant upregulation of hypoxia regulated gene transcripts in patients with chronic hepatitis B (CHB) in the absence of liver cirrhosis. We used state-of-the-art in vitro and in vivo HBV infection models to evaluate a role for HBV infection and the viral regulatory protein HBx to drive HIF-signalling. HBx had no significant impact on HIF expression or associated transcriptional activity under normoxic or hypoxic conditions. Furthermore, we found no evidence of hypoxia gene expression in HBV de novo infection, HBV infected human liver chimeric mice or transgenic mice with integrated HBV genome. Collectively, our data show clear evidence of hypoxia gene induction in CHB that is not recapitulated in existing models for acute HBV infection, suggesting a role for inflammatory mediators in promoting hypoxia gene expression

The prognostic significance of positive peritoneal cytology in endometrial cancer

A retrospective analysis of clinical data extracted from hospital records of 145 patients who had had primary surgical treatment for endometrial cancer in Queen Mary Hospital, Hong Kong, from 1987 to 1993 was performed to study the prognostic significance of positive peritoneal cytology. Positive peritoneal cytology was found to be associated with poor prognostic factors such as deep myometrial invasion, high grade tumor, extrauterine spread and lymphovascular permeation. By univariate analysis, all the poor prognostic factors were found to be significant in affecting survival. These included age above 65, nonadenocarcinoma histology, deep myometrial invasion, positive cytology, extrauterine involvement and lymphovascular involvement. By multivariate analysis, only histology and extrauterine involvement remained significant. In patients with positive cytology, 61.1% had extrauterine involvement at initial presentation. Patients who had positive cytology and extrauterine disease had the shortest survival. The survival was independent of cytology result when the tumor was confined to the uterus.link_to_subscribed_fulltex

Prognostic significance of tumour markers in endometrial cancer

Serum cancer antigen (CA) 125, CA15.3, CA19.9, carcinoembryonic antigen and tissue polypeptide antigen were analyzed in 100 normal subjects, 47 patients with benign gynaecological diseases and 97 patients with endometrial cancer. The incidence of individual elevated turnout markers (>2SD) was 21.5- 30.9% in cancer patients. Elevations of CA125 and CA15.3 were significantly associated with poor prognostic clinical factors. Univariate anaylses showed that elevated CA125, CA15.3 and CA19.9 were significantly associated with shorter survival. In multivariate analyses, CA15.3 was highly significant and had a larger hazard ratio. In conclusion, CA15.3 is a useful marker for the prognosis of patients with endometrial cancer.link_to_subscribed_fulltex

Role of serial tumor markers in the surveillance for recurrence in endometrial cancer

The aim of this study is to evaluate the usefulness of tumor markers in the follow-up of patients with endometrial cancer. The sera of 23 patients with elevated pretreatment CA125, CA15.3, and CA19.9 were collected at each follow-up visit and analyzed. Eleven patients had normal posttreatment levels and none of them developed recurrence. Twelve patients had one or more increased tumor markers, 7 (58.3%) of them developed recurrence. Among these seven patients, six had CA 125 elevated by at least 10-fold and one had elevated CA 19.9. The median lead time between elevation of tumor markers and clinical evidence of recurrence was 6 months. Hence posttreatment elevation of CA 125 is a useful predictor for recurrence in patients with elevated pretreatment levels.link_to_subscribed_fulltex

De novo transcriptome analysis of the mussel Perna viridis with an emphasis on tissue-specific patterns for ecotoxicological and environmental studies

Oral presentatio

Transcriptional regulation of G<inf>2</inf>/M regulatory proteins and perturbation of G<inf>2</inf>/M Cell cycle transition by a traditional Chinese medicine recipe

Ethnopharmacological relevance: Hedyotis diffusa Willd. (H) and Scutellaria barbata D.Don (S) are ancient anti-cancer Chinese herb medicines. When combined, known as HS, it is one of the most commonly prescribed Chinese Medicines for cancer patients today in China. Aim of the study: The prevention of disease progression is a dominant concern for the growing number of men with prostate cancer. The purpose of this work is to evaluate the action and mode of action of Chinese Medicine recipe HS in inhibiting prostate cancer progression in preclinical models. Methods: Effects of HS were analyzed in prostate cancer cell lines by evaluating proliferation, cell cycle profile, DNA damage and key regulators responsible for G2 to M phase transition. The transcriptional activities of these regulators were determined by RT-PCR and ChIP. The efficacy of HS in vitro was validated in an animal model. Results: HS treatment was observed to reduce DNA content and accumulated prostate cancer cells at the G2/M phase. Immunolabeling for phospho-Histone H3 in association with nocodazole to capture mitotic cells confirmed that HS impeded G2 to M transition. After excluding DNA damage-induced G2 arrest, it was revealed that HS reduced expression of Cyclin B1, CDK1, PLK1 and Aurora A at both protein and mRNA levels, with concomitant reduction of H3K4 tri-methylation at their promoter-regions. Animals that received oral administration of HS with a dosage relevant to clinical application showed reduced tumor volume and weight with a reduction of Cyclin B1, CDK1, PLK1 and Aurora A protein levels. Conclusions: HS acts by impeding the G2 to M transition of prostate cancer cells. It is likely that the mode of action is transcriptionally suppressing proteins governing mitotic entry, without eliciting significant DNA damage