Sorafinib

Gasdermin-E (GSDME), the executioner of pyroptosis when cleaved by caspase 3, plays a crucial role in tumor defense and the response to chemotherapy drugs in cells. So far, there are poorly known mechanisms for the expression regulation of GSDME during cell death. Here, we identify the transcription factor Sp1 (Specificity protein 1) as a positive regulator of GSDME-mediated pyroptosis. Sp1 directly interacts with the GSDME promoter at -36 ~ -28 site and promotes GSDME gene transcription. Further, Sp1 knockdown or inhibition suppresses GSDME expression, thus reducing chemotherapy drugs (topotecan, etoposide, doxorubicin, sorafinib and cisplatin) induced cell pyroptosis...

Long non-coding RNA (lncRNA) is a kind of important molecules involved in the formation of immune landscape in tumor microenvironment. However, there are few studies on the relationship between lncRNA and immunomodulatory regulation of hepatocellular carcinoma (HCC). In this study, we combined with single cell transcriptome sequencing and TCGA data to analyze the relationship between lncRNA MIAT and immune cells in HCC. TIMER database analysis indicated that the expression of MIAT in HCC was negatively correlated with tumor purity, positively correlated with the number of immune cells such as B cells, T lymphocytes and macrophages, and positively correlated with the expression of immune checkpoint molecules such as PD-1, PD-L1 and CTLA4...

INTRODUCTION: Leishmaniasis remains one of the neglected tropical diseases. Repurposing existing drugs has proven to be successful for treating neglected tropical diseases while combination therapy is a strategic alternative for the treatment of infectious diseases. Auranofin, lopinavir/ritonavir, and sorafenib are FDA approved drugs used in the treatment of diverse diseases by acting on different essential biological enzymes. OBJECTIVE: To evaluate the effects of monotherapy and combined therapies with the three drugs against Leishmania infantum...

Natural Killer (NK) cells are effector lymphocytes involved in tumor immunosurveillance, however, the specific mechanism in hepatocellular carcinoma (HCC) has not been well understood. In the present study, we estimated the relative abundances of NK cells in HCC using gene expression data, and found that NK cell abundance was lower in HCC tissues than in the adjacent normal tissues. With the common HCC subclasses, we also found that three HCC subclasses had distinct abundances of NK cells. Moreover, we also found strong association between NK cell abundances and genes encoding immune checkpoint proteins, such as KLRD1, CD96, TIGIT, CD86, HAVCR2, PDCD1 (PD-1), HLA-E, CD274 (PD-L1), and CTLA4, among which, KLRD1 vs...

Cholangiocarcinoma is an aggressive malignancy with rapid invasion, metastasis and poor prognosis, however, the mechanism mediating its cholangiocarcinoma development needs further investigation. Here, we demonstrate that decreased miR-138 in tumor tissues is related to the poor prognosis in patients, and that miR-138 mediates sorafenib-induced cell survival in cholangiocarcinoma cells. Moreover, miR-138 negatively regulates SOX4 expression by specifically targeting its 3' untranslated region (3' UTR). As per our results, overexpression of SOX4 reversed sorafenib-induced changes in cell viability and apoptosis...

Sorafenib provides survival benefits in patients with advanced renal cell carcinoma (RCC), but its use is hampered by acquired drug resistance. It is important to fully clarify the molecular mechanisms of sorafenib resistance, which can help to avoid, delay or reverse drug resistance. Extracellular vesicles (EVs) can mediate intercellular communication by delivering effector molecules between cells. Here, we studied whether EVs are involved in sorafenib resistance of RCC and its possible molecular mechanisms...

Osimertinib, a new-generation inhibitor of the epidermal growth factor, has been used for the clinical treatment of advanced T790M mutation-positive tumors. In this research, an original analysis method was established for the quantification of osimertinib by ultra-performance liquid chromatography with time of flight mass spectrometry (UPLC-TOF-MS) in rat plasma. After protein precipitation with acetonitrile and sorafinib (internal standard, IS), they were chromatographed through a Waters XTerra MS C18 column...

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Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) or lymphatic/extrahepatic metastasis is classified as advanced stage (Stage C of Bacelona Clinic Liver Cancer Staging). There is few effective therapy for the advanced stage HCC, leading to an extremly poor prognosis. For these patients, Sorafinib is recommended as the only therapy by European and American guidelines, which has limited clinic effect. In China, besides Sorafinib, various therapies have also been suggested, including surgery, trans-arterial chemoembolization (TACE), radiotherapy, as well as traditional Chinese medicine...

In our effort to develop potent and effective agents with anti-proliferative activity towards HepG2 hepatocellular carcinoma cells with potential inhibitory activity against VEGFR-2, a novel series of 1-(4-((2-oxoindolin-3-ylidene)amino)phenyl)-3-arylureas was designed and synthesized. All the newly prepared ureas 9a-x were evaluated in vitro for their anti-proliferative activity against HepG2 hepatocellular carcinoma cell line. Compounds 9a-c, 9e, 9f, 9j, 9m-o, 9t-v and 9x exhibited good activity against HepG2 cancer cells (IC50 = 1...

BACKGROUND: Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Insulin-like growth factor-1 (IGF-1) levels reflect hepatic function and are inversely correlated with the severity of background chronic liver disease. OBJECTIVE: This study evaluated whether basal serum IGF-1 levels can predict prognosis of HCC patients according to different risks of disease progression. MATERIALS AND METHODS: A total of 89 patients with hepatocellular carcinoma (HCC) were recruited in 3 groups: Group I, 30 HCC patients receiving sorafinib; Group II, 30 HCC patients with best supportive care; and Group III include 29 patients undergoing transcatheter arterial chemoembolization (TACE)...

Hepatocellular carcinoma (HCC) is the fifth common malignancy worldwide and the third leading cause of cancer-related death. Targeted therapies for HCC are being extensively developed with the limited success of sorafinib. In the present study, we investigated the potential antitumor activity of zardaverine, a dual-selective phosphodiesterase (PDE) 3/4 inhibitor in HCC cells both in vitro and in vivo. Although all zardaverine, PDE3 inhibitor trequinsin and PDE4 inhibitor rolipram increased intracellular cAMP levels through inhibiting PDE activity, only zardaverine significantly and selectively inhibited the proliferation of certain HCC cells, indicating that the antitumor activity of zardaverine is independent of PDE3/4 inhibition and intracellular cAMP levels...

PURPOSE: We undertook a meta-analysis of randomized trials to evaluate the efficacy of multitargeted antiangiogenic tyrosine kinase inhibitors (MATKIs) in addition to chemotherapy in metastatic breast cancer. METHODS: PubMed, Web of Knowledge databases and the ASCO meeting abstracts were searched for eligible literature published up to August 30, 2013. The endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and toxicities...

BACKGROUND: Hand-foot syndrome (HFS) is the most frequently reported side effect of oral capecitabine therapy. In addition to treatment interruption and dose reduction, supportive treatments can help alleviate symptoms. Although its efficacy has not been proven in clinical studies, certain authors report on the use of prophylactic or therapeutic pyridoxine supplementation for the prevention of minimization to be useful in preventing worsening of HFS but are no substitute for dose modifications...

BACKGROUND: Aggressive fibromatosis (AF) or desmoid tumor of the head and neck region is a rare, usually unresectable, benign soft tissue tumor with locally aggressive behavior. METHODS AND RESULTS: A 31-year-old woman presented with a progressive trismus, a swelling in the retromandibular area, as well as loss of sensibility of the maxillary and mandibular branch of the trigeminal nerve. MRI of the head and neck revealed an infiltrative mass involving the masticator, parapharyngeal, and prevertebral and paravertebral space on the left with intracranial extension through the orbital fissure...

PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wildtype lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6, paclitaxel showed a dose response in vitro, but cells remained resistant to PA-U2/LF even in the presence of paclitaxel...

BACKGROUND: The tyrosine kinase inhibitors (TKIs) sunitinib, the first targeted agent for the first line treatment of metastatic renal cell carcinoma (RCC), targets the vascular endothelial growth factor (VEGF) pathway. The objective of this study was to investigate the efficacy and safety of sunitinib in treating metastatic clear-cell RCC and to confirm if hypertension is an effective predictive factor. METHODS: A total of 36 patients with metastatic RCC were enrolled between June 2008 and December 2010...

Hepatocellular carcinoma (HCC) with atypical cytomorphological features and presenting with bone and soft tissue metastasis is very rare. We report a 65-year-old male patient of HCC who presented with bone and soft tissue metastases and was clinically and radiologically suspected to have a soft tissue sarcoma. The patient presented with severe cervical pain with palpable masses in right scapular, nape of neck, and occiput area of scalp. Radiologically, these were large, bulky soft tissue masses expansile, destructive, and lytic in nature...

Ixabepilone demonstrates marked synergistic activity in combination with capecitabine, which served as the rationale for the evaluation of this combination in the clinic. Ixabepilone plus capecitabine is currently approved for patients with locally advanced or metastatic breast cancer (MBC) progressing after treatment with an anthracycline and a taxane; approval was based on the results of two phase III trials comparing the combination with capecitabine monotherapy. An array of preclinical studies in multiple solid tumor types show that ixabepilone demonstrates therapeutic synergy with targeted therapies including trastuzumab, bevacizumab, brivanib, and cetuximab; with immune-modulating agents such as anti-CTLA-4 antibody; and with other chemotherapy drugs such as irinotecan and epirubicin...