Angiogenesis Inhibitor Bevacizumab Increases the Risk of Ischemic Heart Disease Associated With Chemotherapy: A Meta-Analysis.

Angiogenesis Inhibitor Bevacizumab Increases the Risk of Ischemic Heart Disease Associated with Chemotherapy: A Meta-Analysis.

PLoS One. 2013; 8(6): e66721
Chen XL, Lei YH, Liu CF, Yang QF, Zuo PY, Liu CY, Chen CZ, Liu YW

Concerns have arisen regarding the risk of ischemic heart disease with the novel antiangiogenic agent bevacizumab, a recombinant humanised monoclonal antibody to the vascular endothelial growth factor that is widely used in cancer treatment. Currently, the role of bevacizumab in ischemic heart disease is controversial. This meta-analysis was therefore performed to assess the overall risk of ischemic heart disease associated with the use of bevacizumab. The databases of PubMed, EMBASE and Web of Science were searched for English language studies of randomised controlled trials comparing bevacizumab with control therapy published through October 25, 2012. Summary incidence rates, relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies. A total of 4,617 patients from 7 randomised controlled trials were identified and included for analysis. Among those patients receiving bevacizumab, the summary incidence of ischemic heart disease was 1.0% (95% CI, 0.6%-1.4%). Patients treated with bevacizumab had a significantly increased risk of ischemic heart disease with an RR of 2.49 (95% CI, 1.37-4.52) compared with controls. In addition, both high doses and low doses of bevacizumab increased the risk of cardiac ischemia (low dose at 2.5 mg/kg per week: RR, 2.14 [95% CI, 1.09-4.19]; high dose at 5 mg/kg per week: RR, 4.81 [95% CI, 1.03-22.42]). Bevacizumab was also found to significantly increase the risk of cardiac ischemia in patients with colorectal cancer (RR, 2.13; 95% CI, 1.11-4.06) compared with controls. This meta-analysis shows the use of bevacizumab was associated with an increased risk of developing ischemic heart disease in colorectal cancer patients receiving this drug. Our conclusions are limited by the available data. Further evaluations of high-quality RCTs are needed. HubMed – drug


Neuropathy in Parkinson’s Disease Patients with Intestinal Levodopa Infusion versus Oral Drugs.

PLoS One. 2013; 8(6): e66639
Jugel C, Ehlen F, Taskin B, Marzinzik F, Müller T, Klostermann F

Severe polyneuropathy has been observed in a number of patients treated for Parkinson’s disease with Levodopa/Carbidopa intestinal gel infusion. This may reflect a rare individual complication or a systematic side effect.To investigate whether peripheral nerve function differed between patients with oral treatment versus Levodopa/Carbidopa intestinal gel infusion.In an observational design, data from median, tibial, and peroneal neurography were prospectively assessed and compared between patients with conventional drug treatment (n?=?15) and with Levodopa/Carbidopa intestinal gel infusion (n?=?15). The groups were matched for age and disease duration. In view of the medical risk profile for polyneuropathy, comorbidity and basic serological parameters were assessed.Axonal neuropathy was common in both patient groups. However, although group differences in risk factors for polyneuropathy were not evident, neurographic abnormalities were more severe in the patients treated with Levodopa/Carbidopa intestinal gel infusion than in the orally treated patients. In the group with Levodopa/Carbidopa intestinal gel infusion, the degree of neuropathic change correlated with weight lost since therapy initiation and with the drug dose. In contrast to the axonal abnormalities, conduction velocity was found normal in both groups.The results are compatible with the promotion of axonal neuropathy by Levodopa/Carbidopa intestinal gel infusion. This could be due to the intrinsically high levodopa doses associated with the therapy and/or malnutritional effects from intestinal drug application. The results should be corroborated by a larger longitudinal and controlled trial. HubMed – drug


Potentiating the Efficacy of Molecular Targeted Therapy for Hepatocellular Carcinoma by Inhibiting the Insulin-Like Growth Factor Pathway.

PLoS One. 2013; 8(6): e66589
Ou DL, Lee BS, Chang YC, Lin LI, Liou JY, Hsu C, Cheng AL

Insulin-like growth factor (IGF) signaling pathway is an important regulatory mechanism of tumorigenesis and drug resistance in many cancers. The present study explored the potential synergistic effects between IGF receptor (IGFR) inhibition and other molecular targeted agents (MTA) in HCC cells. HCC cell lines (Hep3B, PLC5, and SK-Hep1) and HUVECs were tested. The MTA tested included sorafenib, sunitinib, and the IGFR kinase inhibitor NVP-AEW541. The potential synergistic antitumor effects were tested by median dose effect analysis and apoptosis assay in vitro and by xenograft models in vivo. The activity and functional significance of pertinent signaling pathways and expression of apoptosis-related proteins were measured by RNA interference and Western blotting. We found that IGF can activate IGFR and downstream AKT signaling activities in all the HCC cells tested, but the growth-stimulating effect of IGF was most prominent in Hep3B cells. NVP-AEW541 can abrogate IGF-induced activation of IGFR and AKT signaling in HCC cells. IGF can increase the resistance of HCC cells to sunitinib. The apoptosis-inducing effects of sunitinib, but not sorafenib, were enhanced when IGFR signaling activity was inhibited by NVP-AEW541 or IGFR knockdown. Chk2 kinase activation was found contributory to the synergistic anti-tumor effects between sunitinib and IGFR inhibition. Our data indicate that the apoptosis-potentiating effects of IGFR inhibition for HCC may be drug-specific. Combination therapy of IGFR inhibitors with other MTA may improve the therapeutic efficacy in HCC. HubMed – drug


Informal Trade of Psychoactive Herbal Products in the City of Diadema, SP, Brazil: Quality and Potential Risks.

Evid Based Complement Alternat Med. 2013; 2013: 894834
Soares Neto JA, Kato EM, Bugno A, Galduróz JC, Marques LC, Macrini T, Rodrigues E

The present study aimed to assess the quality and risks involved in the consumption of psychoactive herbal products (PHs) that are available through informal commerce in the city of Diadema, SP, Brazil. Methods of ethnography were used to conduct the fieldwork during which four dealers were selected to record the collection, handling, packaging, types of PHs marketed, and their therapeutic purposes. In addition, lots of the PHs selected were purchased from the dealers and analyzed using microbiology and pharmacognosy techniques. 217 PHs were recorded and categorized into two main groups: stimulants (67%) and depressants (27%) of the central nervous system; sixteen of them were selected, and their 52 lots were acquired. The deficiencies observed in handling and packaging these lots by dealers were confirmed by microbiological analysis; 80.8% of them presented risk according to the indicators defined by the Brazilian Pharmacopoeia. The pharmacognostic analysis confirmed the authenticity of only 9 to 16 PHs analyzed. In addition, descriptions of contraindications, adverse reactions, and drug interactions were found in the literature for the PHs. The results of this study allow the observation of the priorities for the sanitary adequacy of the popular trade of herbs. HubMed – drug