scholarly journals Bivalent aptamer-dual siRNA chimera is emerging as a new combination therapy

RNA & DISEASE ◽  
2017 ◽  
Keyword(s):  
Combination Therapy ◽  
New Combination

scholarly journals Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1878 ◽  
Author(s):  
Sami Znati ◽  
Rebecca Carter ◽  
Marcos Vasquez ◽  
Adam Westhorpe ◽  
Hassan Shahbakhti ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Cell Lines ◽  
Radiation Treatment ◽  
Combined Treatment ◽  
New Combination ◽  
Migration And Invasion ◽  
Syngeneic Mouse Model

Hepatocellular Carcinoma (HCC) is increasing in incidence worldwide and requires new approaches to therapy. The combination of anti-angiogenic drug therapy and radiotherapy is one promising new approach. The anti-angiogenic drug vandetanib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and RET proto-oncogene with radio-enhancement potential. To explore the benefit of combined vandetanib and radiotherapy treatment for HCC, we studied outcomes following combined treatment in pre-clinical models. Methods: Vandetanib and radiation treatment were combined in HCC cell lines grown in vitro and in vivo. In addition to 2D migration and clonogenic assays, the combination was studied in 3D spheroids and a syngeneic mouse model of HCC. Results: Vandetanib IC 50 s were measured in 20 cell lines and the drug was found to significantly enhance radiation cell kill and to inhibit both cell migration and invasion in vitro. In vivo, combination therapy significantly reduced cancer growth and improved overall survival, an effect that persisted for the duration of vandetanib treatment. Conclusion: In 2D and 3D studies in vitro and in a syngeneic model in vivo, the combination of vandetanib plus radiotherapy was more efficacious than either treatment alone. This new combination therapy for HCC merits evaluation in clinical trials.

scholarly journals Severe Drug-Induced Liver Injury from Combination Encorafenib/Binimetinib

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Nicholas Gravbrot ◽  
Srinath Sundararajan
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Combination Therapy ◽  
Hepatic Injury ◽  
Mek Inhibitor ◽  
New Combination ◽  
Normal Range ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
First Case

Encorafenib/binimetinib is a new combination BRAF/MEK inhibitor used in the treatment of advanced or metastatic BRAFV600-mutant melanoma. Though generally tolerated well, mild to moderate aminotransferase elevations are common. However, significant liver injury has not been demonstrated in the literature. Here, we report the first case of severe hepatic injury associated with encorafenib/binimetinib in a 58-year-old gentleman requiring admission and extensive workup. He was successfully treated by withdrawing the combination therapy, and liver function returned to normal range.

A pilot study to evaluate a new combination therapy for gastric ulcer:Helicobacter pylorieradication therapy followed by gastroprotective treatment with rebamipide

2006 ◽  
Vol 21 (1) ◽  
pp. 103-109 ◽  
Author(s):  
AKIRA TERANO ◽  
TETSUO ARAKAWA ◽  
TOSHIRO SUGIYAMA ◽  
TOSHIKAZU YOSHIKAWA ◽  
KEN HARUMA ◽  
...  
Keyword(s):  
Pilot Study ◽  
Combination Therapy ◽  
New Combination

Nelfinavir potentiation of imatinib cytotoxicity in meningioma cells via survivin inhibition

2007 ◽  
Vol 23 (4) ◽  
pp. E9 ◽  
Author(s):  
Vinay Gupta ◽  
Christian G. Samuleson ◽  
Susan Su ◽  
Thomas C. Chen
Keyword(s):  
Combination Therapy ◽  
Colony Formation ◽  
New Combination ◽  
Protein Ratio ◽  
In Vivo Models ◽  
Protein Levels ◽  
Survivin Protein ◽  
Dose Combination ◽  
Future Therapy

✓ Although most meningiomas are treated surgically, it may not be possible to completely remove atypical, malignant, and surgically inaccessible meningiomas; in the majority of these cases there is tumor recurrence. The authors have already reported initial preclinical results on the efficacy of imatinib in the treatment of meningiomas; however, a recent Phase II trial of imatinib in patients with recurrent meningiomas did not demonstrate significant antitumor activity. To enhance the activity of imatinib, the authors investigated the use of a combination therapy with nelfinavir on primary meningioma cells and meningioma cell lines IOMM-Lee and CH157. Cytotoxicity was measured using methylthiotetrazole and colony formation assays. In low-dose combination therapy with imatinib, nelfinavir potentiated the antiproliferative and anti–colony formation effects of imatinib. Primary meningioma cells responded better to combination therapy than to imatinib alone. Treatment induced a dose-dependent antiproliferative effect, decreased cell survival, and inhibited colony formation. Western blotting demonstrated decreased levels of survivin protein on combination therapy. Because meningiomas have very high levels of survivin protein, survivin inhibition by nelfinavir may represent a potential mechanism for the additive effect observed with imatinib. Moreover, an increase in the proapoptotic Bax/Bcl-2 protein ratio was demonstrated with the combination of imatinib and nelfinavir. The authors propose that nelfinavir not only potentiates imatinib efficacy, it also abrogates resistance to imatinib by decreasing survivin protein levels in meningiomas. In an in vivo assay, this combination therapy was found to be more effective than imatinib alone. More preclinical work with in vivo models is needed to determine if this new combination therapy will translate into a viable future therapy for meningiomas.

scholarly journals PARP Inhibitor Upregulates PD-L1 Expression and Provides a New Combination Therapy in Pancreatic Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Yali Wang ◽  
Kun Zheng ◽  
Hua Xiong ◽  
Yongbiao Huang ◽  
Xiuqiong Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Combination Therapy ◽  
Checkpoint Inhibitors ◽  
Parp Inhibitors ◽  
New Combination ◽  
Treatment Modalities ◽  
Pancreatic Cancer Cells ◽  
Programmed Death

Despite recent improvements in treatment modalities, pancreatic cancer remains a highly lethal tumor with mortality rate increasing every year. Poly (ADP-ribose) polymerase (PARP) inhibitors are now used in pancreatic cancer as a breakthrough in targeted therapy. This study focused on whether PARP inhibitors (PARPis) can affect programmed death ligand-1 (PD-L1) expression in pancreatic cancer and whether immune checkpoint inhibitors of PD-L1/programmed death 1 (PD-1) can enhance the anti-tumor effects of PARPis. Here we found that PARPi, pamiparib, up-regulated PD-L1 expression on the surface of pancreatic cancer cells in vitro and in vivo. Mechanistically, pamiparib induced PD-L1 expression via JAK2/STAT3 pathway, at least partially, in pancreatic cancer. Importantly, pamiparib attenuated tumor growth; while co-administration of pamiparib with PD-L1 blockers significantly improved the therapeutic efficacy in vivo compared with monotherapy. Combination therapy resulted in an altered tumor immune microenvironment with a significant increase in windiness of CD8+ T cells, suggesting a potential role of CD8+ T cells in the combination therapy. Together, this study provides evidence for the clinical application of PARPis with anti-PD-L1/PD-1 drugs in the treatment of pancreatic cancer.

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