Meta-analysis of the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer.

BACKGROUND: Neither improvements in surgical techniques and methods nor advances in radiotherapy equipment and techniques have significantly improved cervical cancer survival rates for quite some time. AIM: By comparing the effectiveness of neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer, this study aimed to explore effective treatment methods for locally advanced cervical cancer, and provide a theoretical basis to guide clinical practice. METHODS: A search of PubMed, Embase, Scopus, Web of Science and Cochrane databases was undertaken to identify randomized controlled trials on the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer, where the intervention in the experimental group was neoadjuvant chemotherapy. Based on the inclusion and exclusion criteria, the studies were evaluated for quality according to the Cochrane Quality Rating Scale. Baseline information, intervention information and outcome indicators of the included studies were extracted. Meta-analysis was performed using RevMan 5.4. RESULTS: Significant differences in overall survival [relative risk (RR) 1.63, 95 % confidence interval (CI) 0.69-2.57; p = 0.0007] and complete remission rate (RR 0.37, 95 % CI -0.49 to 1.23; p = 0.041) were found between the two groups. Heterogeneity of the objective response rate showed p < 0.0001 and I2 = 99 % (I2 = 99 > 50 % and p > 0.1 for the Q-test suggested strong heterogeneity). The fixed effects model was chosen for the integration statistic [standardized mean difference (SMD) 0.81, 95 % CI -0.21 to 1.83; p = 0.12]; the difference was not significant (p > 0.05). Heterogeneity of the adverse effects of neoadjuvant chemotherapy showed p < 0.0001 and I2 = 98 % (I2 = 98 %>50 % and p > 0.1 for the Q-test suggested strong heterogeneity). The fixed effects model was chosen for the integration statistic (SMD -0.023, 95 % CI -0.95 to 0.49; p = 0.53); the difference was not significant (p > 0.05). CONCLUSIONS: The use of neoadjuvant chemotherapy for the treatment of locally advanced cervical cancer improved the objective response rate and the complete remission rate of patients, but failed to improve overall survival and adverse effects.

Superior vena cava syndrome early after pacemaker implantation in a patient with lung carcinoma: A case report.

Superior vena cava (SVC) syndrome is typically dramatic. Although the diagnosis is usually easy, elucidation of the etiology is difficult. We present a patient who developed SVC syndrome early after transvenous pacemaker implantation and who was subsequently diagnosed with lung carcinoma. The pathogenesis seems to be explained by a combination of two etiologies: lung carcinoma plus transvenous pacemaker implantation. We emphasize that common etiologies such as malignancy should be considered first when faced with SVC syndrome.

Dalbergia odorifera extract promotes angiogenesis through upregulation of VEGFRs and PI3K/MAPK signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The heart wood of Dalbergia odorifera is a Chinese herbal medicine commonly used for the treatment of various ischemic diseases in Chinese medicine practice. AIM OF THE STUDY: In this study, therapeutic angiogenesis effects of the Dalbergia odorifera extract (DOE) were investigated on transgenic zebrafish in vivo and human umbilical vein endothelial cells (HUVECs) in vitro. MATERIALS AND METHODS: The pro-angiogenic effects of DOE on zebrafish were examined by subintestinal vessels (SIVs) sprouting assay and intersegmental vessels (ISVs) injury assay. And the pro-angiogenic effects of DOE on HUVECs were examined by MTT, scratch assay, protein chip and western blot. RESULTS: In the in vivo studies, we found that DOE was able to dose-dependently promote angiogenesis in zebrafish SIVs area. In addition, DOE could also restore the injury in zebrafish ISVs area and upregulate the reduced mRNA expression of VEGFRs including kdr, kdrl and flt-1 induced by VEGF receptor kinase inhibitor II (VRI). In the in vitro studies, we observed that DOE promoted the proliferation, migration of HUVECs and also restored the injury induced by VRI. Moreover, protein chip and western blot experiments showed the PI3K/MAPK cell proliferation/migration pathway were activated by DOE. CONCLUSIONS: DOE has a therapeutic effects on angiogenesis, and its mechanism may be related to adjusting the VEGFRs mRNA and activation of PI3K/MAPK signaling pathway. These results suggest a strong potential for Dalbergia odorifera to be developed as an angiogenesis-promoting therapeutic.

HEDD: the human epigenetic drug database.

Epigenetic drugs are chemical compounds that target disordered post-translational modification of histone proteins and DNA through enzymes, and the recognition of these changes by adaptor proteins. Epigenetic drug-related experimental data such as gene expression probed by high-throughput sequencing, co-crystal structure probed by X-RAY diffraction and binding constants probed by bio-assay have become widely available. The mining and integration of multiple kinds of data can be beneficial to drug discovery and drug repurposing. HEMD and other epigenetic databases store comprehensively epigenetic data where users can acquire segmental information of epigenetic drugs. However, some data types such as high-throughput datasets are not provide by these databases and they do not support flexible queries for epigenetic drug-related experimental data. Therefore, in reference to HEMD and other epigenetic databases, we developed a relatively comprehensive database for human epigenetic drugs. The human epigenetic drug database (HEDD) focuses on the storage and integration of epigenetic drug datasets obtained from laboratory experiments and manually curated information. The latest release of HEDD incorporates five kinds of datasets: (i) drug, (ii) target, (iii) disease, (vi) high-throughput and (v) complex. In order to facilitate data extraction, flexible search options were built in HEDD, which allowed an unlimited condition query for specific kinds of datasets using drug names, diseases and experiment types.Database URL: http://hedds.org/.

Urocortin-2 suppression of p38-MAPK signaling as an additional mechanism for ischemic cardioprotection.

Urocortin-2 (UCN2) is cardioprotective in ischemia/reperfusion injury (I/R) through short-lived activation of ERK1/2. Key factors involved in I/R, e.g. apoptosis, mitochondrial damage, p38 kinase, and Bcl-2 family, have not been well-investigated in UCN2-induced cardioprotection. We assessed the role of p38-MAPK in anti-apoptotic Bcl-2 signaling and mitochondrial stabilization as a putative mechanisms in UCN2-induced cardioprotection. Isolated hearts from adult Sprague-Dawley rats and cultured H9c2 cells were subjected to I/R protocols with or without 10 nM UCN2 treatment. The effect of a specific p38 inhibitor SB202190 was tested in H9c2 cells. Cardiac function, LDH release, and mitochondrial membrane potential (MMP) were used to assess the degree of myocardial injury in hearts and H9c2 cells. Post-perfusion, hearts were collected for Western blot analyses or mitochondria/cytosol isolation to analyze p38 activation and Bcl-2 family members. UCN2 treatment improved rate-pressure product (58 ± 5 vs. 31 ± 4 % of Baseline; P < 0.05) and decreased LDH release (20 ± 9 vs. 90 ± 40 mU/ml LDH, P < 0.01) at the end of 60 min reperfusion. UCN2 reduced phospho-p38 levels and Bax activation. UCN2 increased the expression of Bcl-2 and inhibited the accumulation of p-Bim. With additional experiments, it was confirmed that UCN2 increases the phosphorylation of ERK1/2 in the early phase of UCN2 treatment and increases the overshot recovery of ERK1/2 phosphorylation during reperfusion. UCN2 and SB202190 partially prevented the loss of MMP induced by I/R. However, combined treatment with UCN2 and SB202190 did not provide additive benefit. UCN2 is cardioprotective in I/R in association with reduced phosphorylation of p38 together with the increased ERK1/2 activation and increased Bcl-2 family member pro-survival signaling. These changes may stabilize cardiac mitochondria, similar to p38 inhibitors, as part of a pro-survival mechanism during I/R.

mTORC2 phosphorylation of Akt1: a possible mechanism for hydrogen sulfide-induced cardioprotection.

Hydrogen sulfide (H2S) is known to have cardiac protective effects through Akt activation. Akt acts as a 'central sensor' for myocyte survival or death; its activity is regulated by multiple kinases including PI3K, mTORC2, PDK1 and phosphatases including PTEN, PP2A and PHLPPL. Based on the previous finding that PI3K inhibitor LY294002 abolishes H2S-induced Akt phosphorylation and cardioprotection, it is accepted that PI3K is the mediator of H2S-induced Akt phosphorylation. However, LY294002 inhibits both PI3K and mTOR, and PI3K only recruits Akt to the membrane where Akt is phosphorylated by Akt kinases. We undertook a series of experiments to further evaluate the role of mTORC2, PDK1, PTEN, PP2A and PHLPPL in H2S-induced Akt phosphorylation and cardioprotection, which, we believe, has not been investigated before. Hearts from adult Sprague-Dawley rats were isolated and subjected to (i) normoxia, (ii) global ischemia and (iii) ischemia/reperfusion in the presence or absence of 50 µM of H2S donor NaHS. Cardiac mechanical function and lactate dehydrogenase (LDH) release were assessed. All hearts also were Western analyzed at the end of perfusion for Akt and a panel of appropriate Akt regulators and targets. Hearts pretreated with 50 µM NaHS had improved function at the end of reperfusion (Rate pressure product; 19±4×10(3) vs. 10±3×10(3) mmHg/min, p<0.05) and reduced cell injury (LDH release 19±10 vs. 170±87 mU/ml p<0.05) compared to untreated hearts. NaHS significantly increased phospho-Akt, phospho-mTOR, phospho-Bim and Bcl-2 in reperfused hearts (P<0.05). Furthermore using H9c2 cells we demonstrate that NaHS pretreatment reduces apoptosis following hypoxia/re-oxygenation. Importantly, PP242, a specific mTOR inhibitor, abolished both cardioprotection and protein phosphorylation in isolated heart and reduced apoptotic effects in H9c2 cells. Treating hearts with NaHS only during reperfusion produced less cardioprotection through a similar mechanism. These data suggest mTORC2 phosphorylation of Akt is a key mediator of H2S-induced cardioprotection in I/R.

[Immunosuppressive action of dendritic cells sensitized by oligodeoxynucleotides and CA125 on human OVCAR3 ovarian carcinoma xenografts in nude mice].

OBJECTIVE: To explore the immunosuppressive action of dendritic cells (DC) sensitized by oligodeoxynucleotides containing "un-methylated cytosine phosphodiester bond-guanylic acid" motif (CpG ODN) and CA125 on human ovarian carcinoma xenografts in nude mice. METHODS: Human peripheral blood-derived dendritic cells were isolated and identified by flow cytometry. The DC sensitized by CpG ODN and CA125 were then co-cultured with T cells and finally cytotoxic T lymphocytes (CTL) were induced. Nude mice bearing OVCAR3 transplanted tumor were immunized with induced CTL by subcutaneous injection and tumor growth and cell apoptosis observed. RESULTS: Premature DC had a low expression of CD83 and CD86. In vivo, delayed growth of OVCAR3 xenografts was observed after immunotherapy with CTL induced by DC pulsed by CpG ODN and CA125. The inhibition rate of tumor was 50.71% and it was better than CpG ODN-pulsed and CA125-pulsed groups (P < 0.05). Cell apoptotic rate was (29.6 ± 3.0)% in CpG ODN+CA125-pulsed group versus (21.8 ± 2.7)% in CpG ODN-pulsed group. And both were more than those of unpulsed and CA125-pulsed groups (P < 0.05). CONCLUSION: CTL induced by DC sensitized by CpG ODN and CA125 can inhibit the growth of ovarian carcinoma xenografts and promote tumor cell apoptosis.

[Turbid-phlegm is an important pathogenesis of restenosis after percutaneous transluminal coronary intervention].

The occurrence rate of restenosis after percutaneous transluminal coronary intervention (PCI) was quite high. Traditional Chinese medicine (TCM) has been proved to have the effect in preventing and curing restenosis. In this article, turbid-phlegm was proved to be directly related with restenosis after PCI in aspects of coronary arteriography, blood lipid, blood viscosity, fibrolysis system, free radicals, plasma homocysteine, insulin resistance, etc. So it is one of the important pathogenetic factors of restenosis after PCI in TCM.