Occult hepatitis B infection (OBI) is a public health problem in Burkina Faso. OBI represents a risk factor for the development of cirrhosis and hepatocellular carcinoma (HCC). OBI could be due to ...mutant viruses undetectable by HBsAg assays or a strong suppression of viral replication and gene expression under the pression of the host immune system. To investigate the role of killer cell immunoglobulin‑like receptor (KIR) gene polymorphisms in patients with OBI in Burkina Faso compared to healthy and chronic hepatitis B subjects. A total of 286 participants was recruited, including 42 cases of OBI, 110 cases of chronic hepatitis B and 134 HBV negative subjects. SSP‑PCR was performed to search for the presence of KIR genes. The HBV viral load was determined by qPCR. The frequencies of the activator gene KIR2DS5 (P=0.045) and the pseudogene KIR2DP1 (P0.001) in patients with OBI were higher than those in patients with chronic hepatitis B. These genes are associated with susceptibility of occult hepatitis B infection. The frequencies of the inhibitory KIR gene KIR2DL3 (P=0.01) of patients with occult hepatitis B were lower than those in chronic hepatitis B patients. This gene KIR2DL3 is associated with protection against occult hepatitis B infection. Also, the frequencies of the inhibitory KIR genes KIR2DL2 (P0.001), KIR2DL3 (P0.001) and activators KIR2DS2 (P0.001) in chronic hepatitis B patients were higher compared to the frequencies of the KIR genes in healthy subjects. These genes KIR2DL3, KIR2DL5 (A, B), KIR3DL3, KIR3DS1, KIR2DL2 and KIR2DS2 are thought to be genes associated with the susceptibility to OBI. The KIR2DS5 and KIR2DP1 genes could be associated with susceptibility to OBI. As for the KIR gene KIR2DL3 could be associated with protection against occult hepatitis B infection.
Background and aims
Biliary tract cancers (BTCs) are uncommon, but highly lethal, gastrointestinal malignancies. Gemcitabine/cisplatin is a standard‐of‐care systemic therapy, but has a modest impact ...on survival and harbors toxicities, including myelosuppression, nephropathy, neuropathy, and ototoxicity. Whereas BTCs are characterized by aberrations activating the cyclinD1/cyclin‐dependent kinase (CDK)4/6/CDK inhibitor 2a/retinoblastoma pathway, clinical use of CDK4/6 inhibitors as monotherapy is limited by lack of validated biomarkers, diffident preclinical efficacy, and development of acquired drug resistance. Emerging studies have explored therapeutic strategies to enhance the antitumor efficacy of CDK4/6 inhibitors by the combination with chemotherapy regimens, but their mechanism of action remains elusive.
Approach and results
Here, we report in vitro and in vivo synergy in BTC models, showing enhanced efficacy, reduced toxicity, and better survival with a combination comprising gemcitabine/cisplatin and CDK4/6 inhibitors. Furthermore, we demonstrated that abemaciclib monotherapy had only modest efficacy attributable to autophagy‐induced resistance. Notably, triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Correspondingly, abemaciclib potentiated ribonucleotide reductase catalytic subunit M1 reduction, resulting in sensitization to gemcitabine.
Conclusions
As such, these data provide robust preclinical mechanistic evidence of synergy between gemcitabine/cisplatin and CDK4/6 inhibitors and delineate a path forward for translation of these findings to preliminary clinical studies in advanced BTC patients.
<正>Objective:To evaluate the prevalence of toxoplasmosis and rubella among pregnant women at Ouagadougou in Burkina Faso.Methods:All patient sera were tested for rubella and toxoplasmosis ...anti-IgG using commercial ELISA kits(PlateliaTMRubella IgG and Platelia? Toxo IgG).The presence of anti-rubella and anti-toxoplasmosis tgM in serum samples was tested using commercial ELISA kits Platelia Rubella TgM and Platelia Toxo IgM.Results:Among all the pregnant women tested for toxoplasmosis and rubella,their prevalence were 20.3% and 77.0%,respectively.Pregnant women in the age group of 18-25 years showed the highest frequency of anti-toxoplasmosis（34.5%） and anti-rubella IgG（84.6%）.The prevalence of anti-toxoplasma and anti-rubella IgG decreased between 2006 and 2008 from 32.7%to 12.1%and 84.6% to 65.0%,respectively.There was no significant association between age and the mean titer of anti-toxoplasmosis IgG among pregnant women.Conclusions:The diagnosis of toxoplasmosis and rubella is necessary in pregnant women in Burkina Faso because of the low immunization coverage rate of rubella and the high level of exposure to these two infections which can be harmful to the newborn if contracted by women before the third trimester of pregnancy.
Recombinant vesicular stomatitis virus (VSV)-fusion and hemagglutinin (FH) was developed by substituting the promiscuous VSV-G glycoprotein (G) gene in the backbone of VSV with genes encoding for the ...measles virus envelope proteins F and H. Hybrid VSV-FH exhibited a multifaceted mechanism of cancer-cell killing and improved neurotolerability over parental VSV in preclinical studies. In this study, we evaluated VSV-FH in vitro and in vivo in models of hepatobiliary and pancreatic cancers. Our results indicate that high intrahepatic doses of VSV-FH did not result in any significant toxicity and were well tolerated by transgenic mice expressing the measles virus receptor CD46. Furthermore, a single intratumoral treatment with VSV-FH yielded improved survival and complete tumor regressions in a proportion of mice in the Hep3B hepatocellular carcinoma model but not in mice xenografted with BxPC-3 pancreatic cancer cells. Our preliminary findings indicate that VSV-FH can induce potent oncolysis in hepatocellular and pancreatic cancer cell lines with concordant results in vivo in hepatocellular cancer and discordant in pancreatic cancer without the VSV-mediated toxic effects previously observed in laboratory animals. Further study of VSV-FH as an oncolytic virotherapy is warranted in hepatocellular carcinoma and pancreatic cancer to understand broader applicability and mechanisms of sensitivity and resistance.
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Oncolytic vesicular stomatitis virus (VSV)-FH is a hybrid virus with shared attributes of VSV and measles virus (MV). Herein, we present novel experiments, including safety pharmacology assessment of VSV-FH in receptor-positive animals and efficacy in hepatobiliary and pancreatic cancer (HBPC) models which, to our knowledge, have not been previously described.
<正>Objective:To evaluate efficiency of HAART in the prevention of mother to child HIV transmission.Methods:A longitudinal study was conducted on 1 300 women attending the antenatal service at ...Saint Camille Medical Centre from September 2010 to July 2011.The HIV status of mothers was determined by rapid tests and EUSA.Discordant results were confirmed by real-time PCR.PCR was used to determine HIV status of children born from HIV-positive mothers.Results:Among 1 300 pregnant women tested for HIV,378 were seropositive.Mothers were predominantly housewives(69.7%),and their mean age was(28.32±0.15) years.The overall prevalence of HIV transmission from mother to child was 4.8%(18/378).This prevalence differed significantly from 0.0%(0/114) to 6.8%(18/264) in children born from mothers under HAART and those with mothers under New Prophylactic Protocol(ACT + 3TC + NVP),respectively(P< 0.01).Children’s mortality rate during the medical follow up was 1.3%(5/378).Among 16 women with HIV dubious status by ELISA,the Real Time PCR confirmed 2/16(12.5%) as HIV positive. Conclusions:The protocol of prevention of mother to children HIV transmission(PMTCT) is effective.The rate of HIV vertical transmission is significantly reduced.Early diagnosis determined by PCR of children born from HIV- positive mother is necessary and recommended in the context of PMTCT in Burkina Faso.We also found that PCR is an effective tool to confirm HIV status in pregnant women.
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