METHODS: The study follows a systematic review approach that has been implemented to analyze the qualitative published data from previous studies. Studies related with the trials of angiogenesis and bevacizumab were selected in the review.
RESULTS: In general, the management of gynecological cancers include chemotherapy, surgery and radiation therapy. Results suggest bevacizumab as an effective treatment modality for cervical and several other cancers. Overall, bevacizumab showed promising results in improving the overall survival rate of gynecological cancer patients through the combination of bevacizumab with other chemotherapeutic agents.
CONCLUSION: Bevacizumab possess less documented adverse effects when compared to other chemotherapeutic agents. The manifestation and severity of adverse effects reported varied according to the chemotherapeutic agent(s) that were used with bevacizumab in combination therapy. Overall, bevacizumab effectively improved the survival rate in patients with several gynaecological cancers.
Purpose: In this study, we have investigated the cytotoxic effects of the B. javanica hexane, ethanolic extracts against colon cancer cells. HT29 colon cells were selected as an in vitro cancer model to evaluate the anticancer activity of B. javanica ethanolic extract (BJEE) and the possible mechanisms of action that induced apoptosis.
Methods: 3-(4,5-dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT), lactate dehydrogenase, acridine orange/propidium iodide, and annexin-V-fluorescein isothiocyanate assays were performed to determine the antiproliferative and apoptosis validation of BJEE on cancer cells. Measurement of reactive oxygen species (ROS) production, caspase activities, nucleus factor-κB activity, and gene expression experiments was done to investigate the potential mechanisms of action in the apoptotic process.
Results: The results obtained from this study illustrated the significant antiproliferative effect of BJEE on colorectal cancer cells, with a concentration value that inhibits 50% of the cell growth of 25±3.1 µg/mL after 72 h of treatment. MTT assay demonstrated that the BJEE is selectively toxic to cancer cells, and BJEE induced cell apoptosis via activation of caspase-8 along with modulation of apoptosis-related proteins such as Fas, CD40, tumor necrosis factor-related apoptosis-inducing ligands, and tumor necrosis factor receptors, which confirmed the contribution of extrinsic pathway. Meanwhile, increased ROS production in treated cells subsequently activated caspase-9 production, which triggered the intrinsic pathways. In addition, overexpression of cytochrome-c, Bax, and Bad proteins along with suppression of Bcl-2 illustrated that mitochondrial-dependent pathway also contributed to BJEE-induced cell death. Consistent with the findings from this study, BJEE-induced cancer cell death proceeds via extrinsic and intrinsic mitochondrial-dependent and -independent events.
Conclusion: From the evidence obtained from this study, it is concluded that the BJEE is a promising natural extract to combat colorectal cancer cells (HT29 cells) via induction of apoptosis through activation of extrinsic and intrinsic pathways.
OBJECTIVES: This study was performed to identify mechanisms of afatinib resistance and to explore potential afatinib-based combination treatments with other targeted inhibitors in oral squamous cell carcinoma.
METHODS: We determined the anti-proliferative effects of afatinib on a panel of oral squamous cell carcinoma cell lines using a crystal violet-growth inhibition assay, click-iT 5-ethynyl-2'-deoxyuridine staining, and cell-cycle analysis. Biochemical assays were performed to study the underlying mechanism of drug treatment as a single agent or in combination with the MEK inhibitor trametinib. We further evaluated and compared the anti-tumor effects of single agent and combined treatment by using oral squamous cell carcinoma xenograft models.
RESULTS: In this study, we showed that afatinib inhibited oral squamous cell carcinoma cell proliferation via cell-cycle arrest at the G0/G1 phase, and inhibited tumor growth in xenograft mouse models. Interestingly, we demonstrated reactivation of the mitogen-activated protein kinase (ERK1/2) pathway in vitro, which possibly reduced the effects of ErbB inhibition. Concomitant treatment of oral squamous cell carcinoma cells with afatinib and trametinib synergized the anti-tumor effects in oral squamous cell carcinoma-bearing mouse models.
CONCLUSIONS: Our findings provide insight into the molecular mechanism of resistance to afatinib and support further clinical evaluation into the combination of afatinib and MEK inhibition in the treatment of oral squamous cell carcinoma.
AIM OF THE STUDY: The molecular mechanisms of the anti-inflammatory properties of M. accedens are not yet understood. Therefore, we examined those mechanisms using a methanol extract of M. accedens (Ma-ME) and determined the target molecule in macrophages.
MATERIALS AND METHODS: We evaluated the anti-inflammatory effects of Ma-ME in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in an HCl/EtOH-triggered gastritis model in mice. To investigate the anti-inflammatory activity, we performed a nitric oxide (NO) production assay and ELISA assay for prostaglandin E2 (PGE2). RT-PCR, luciferase gene reporter assays, western blotting analyses, and a cellular thermal shift assay (CETSA) were conducted to identify the mechanism and target molecule of Ma-ME. The phytochemical composition of Ma-ME was analyzed by HPLC and LC-MS/MS.
RESULTS: Ma-ME suppressed the production of NO and PGE2 and the mRNA expression of proinflammatory genes (iNOS, IL-1β, and COX-2) in LPS-stimulated RAW264.7 cells without cytotoxicity. Ma-ME inhibited NF-κB activation by suppressing signaling molecules such as IκBα, Akt, Src, and Syk. Moreover, the CETSA assay revealed that Ma-ME binds to Syk, the most upstream molecule in the NF-κB signal pathway. Oral administration of Ma-ME not only alleviated inflammatory lesions, but also reduced the gene expression of IL-1β and p-Syk in mice with HCl/EtOH-induced gastritis. HPLC and LC-MS/MS analyses confirmed that Ma-ME contains various anti-inflammatory flavonoids, including quercetin, daidzein, and nevadensin.
CONCLUSIONS: Ma-ME exhibited anti-inflammatory activities in vitro and in vivo by targeting Syk in the NF-κB signaling pathway. Therefore, we propose that Ma-ME could be used to treat inflammatory diseases such as gastritis.