Prognostic Significance of VEGF and HIF-1 α in Hepatocellular Carcinoma Patients Receiving Sorafenib Versus Metformin Sorafenib Combination

Shorbagy, Shereen El; Abu-Taleb, Fouad; Labib, Hany A.; Ebian, Huda F; Harb, Ola A.; Mohammed, M.; Rashied, Hanaa; Elbana, Khaled A.; Haggag, Rasha

doi:10.1007/s12029-020-00389-w

Cited by 22 publications

(14 citation statements)

References 37 publications

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“…Tumor cells directly or indirectly participate in the formation of tumor blood vessels. In hypoxic environment, hypoxia-inducible factor (HIF) directly upregulates the gene expression of VEGF and other angiogenic factors [ 49 ]. Marjon et al found that VEGF mRNA expression level was increased by 10–50 times when the oxygen concentration of tumor cells was reduced from 21 to 0.3% [ 50 ].…”

Section: Vascular Microenvironmentmentioning

confidence: 99%

Tumor microenvironment and immunotherapy of oral cancer

et al. 2022

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Oral cancer is one of the most common malignant tumors of the head and neck, not only affects the appearance, but also affects eating and even endangers life. The clinical treatments of oral cancer mainly include surgery, radiotherapy, and chemotherapy. However, unsatisfactory therapeutic effect and toxic side effects are still the main problems in clinical treatment. Tumor microenvironment (TME) is not only closely related to the occurrence, growth, and metastasis of tumor but also works in the diagnosis, prevention, and treatment of tumor and prognosis. Future studies should continue to investigate the relationship of TME and oral cancer therapy. This purpose of this review was to analyze the characteristics of oral cancer microenvironment, summarize the traditional oral cancer therapy and immunotherapy strategies, and finally prospect the development prospects of oral cancer immunotherapy. Immunotherapy targeting tumor microenvironment is expected to provide a new strategy for clinical treatment of oral cancer.

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Section: Vascular Microenvironmentmentioning

confidence: 99%

Tumor microenvironment and immunotherapy of oral cancer

et al. 2022

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“…HCC has significantly higher serum levels of HIF-1α than benign liver diseases. 9 Hypoxia is also a common element in the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma, a highly deadly cancer. 10 HIF-1α can promote invasion and metastasis of pancreatic cancer cells and their resistance to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…HIF-1α activates VEGF to promote angiogenesis in cancer. 9 VEGF can promote tumor dedifferentiation and epithelial mesenchymal transition (EMT) transition through the phosphorylation of AKT , ERK1/2, and other signaling pathways. It also enhances tumor migration and survival ability and plays a significant role in the function and self-renewal of tumor stem cells, increasing the degree of malignancy of tumors.…”

Section: Introductionmentioning

confidence: 99%

ɑ-Solanine Affects the Apoptosis and Angiogenesis of M2-Like TAMs Cells by Regulating the PI3K/AKT/mTOR Signaling Pathway Under Hypoxia

Huang

Wang

Pan

et al. 2023

Natural Product Communications

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Objectives Blood vessels provide convenient conditions for tumor cell proliferation and distant metastasis. Antiangiogenesis and proapoptosis of tumor cells have become critical means of clinically treating tumors. This study aimed to investigate the antiangiogenic and pro-apoptotic abilities of α-solanine. Methods This study used the CCK8 method to select appropriate drug concentrations. Next, the antitumor mechanism of α-solanine under hypoxia was investigated using wound healing, transwell, cellular immune, and Western blot assays. Finally, a reverse validation was performed by adding MHY1485, an mammalian targets of rapamycin ( mTOR) activator. Results α-Solanine significantly decreased B-cell lymphoma2-related protein , n-Ca, vascular endothelial growth factor , MMP2, and MMP9 expression in cells. In addition , Bax, p53, TIMP1, and E-Ca expressions were upregulated. However, this study found that adding MHY1485 significantly attenuated the effects of α-solanine. These results suggest that α-solanine may achieve these functions by regulating the PI3K/Akt/mTOR signaling pathway. Conclusion α-Solanine is highly resistant to angiogenesis and promotes apoptosis of M2 tumor-associated macrophages. These effects may depend on the PI3K/Akt/mTOR signaling pathway. The present study demonstrated that α-solanine has a strong anticancer effect under hypoxic conditions.

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“…Metformin, a biguanide derivative that is commonly used as a hypoglycemic agent, inhibits cell proliferation in several human malignancies, including pancreatic, thyroid, gastric, endometrial, and ovarian cancers [ 8 , 9 ]. It demonstrated significant synergy with chemotherapeutic drugs in both in vitro and in vivo models, including cisplatin, gefitinib [ 10 ], sorafenib [ 11 ], everolimus, or trastuzumab. Metformin induces apoptosis and inhibits angiogenesis and the metastatic spread of ovarian cancer [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Metformin Affects Olaparib Sensitivity through Induction of Apoptosis in Epithelial Ovarian Cancer Cell Lines

Gralewska

Gajek

Marczak

et al. 2021

IJMS

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This study examined the effect of combination treatment with the poly (ADP-ribose) polymerase inhibitor olaparib and metformin on homologous recombination (HR)-proficient epithelial ovarian cancer (EOC). Ovarian cancer cell lines (OV-90 and SKOV-3) were treated with olaparib, metformin, or a combination of both. Cell viability was assessed by MTT and colony formation assays. The production of reactive oxygen species (ROS) and changes in mitochondrial membrane potential were examined using the specific fluorescence probes, DCFH2-DA (2′,7′-dichloro-dihydrofluorescein diacetate) and JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine). Apoptotic and necrotic changes were measured by double staining with Hoechst 33258 and propidium iodide, orange acridine and ethidium bromide staining, phosphatidylserine externalization, TUNEL assay, caspase 3/7 activity, and cytochrome c and p53 expression. Compared with single-drug treatment, the combination of olaparib and metformin significantly inhibited cell proliferation and colony formation in HR-proficient ovarian cancer cells. ROS production preceded a decrease in mitochondrial membrane potential. The changes in ROS levels suggested their involvement in inducing apoptosis in response to combination treatment. The present results indicate a shift towards synergism in cells with mutant or null p53, treated with olaparib combined with metformin, providing a new approach to the treatment of gynecologic cancers. Taken together, the results support the use of metformin to sensitize EOC to olaparib therapy.

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Prognostic Significance of VEGF and HIF-1 α in Hepatocellular Carcinoma Patients Receiving Sorafenib Versus Metformin Sorafenib Combination

Cited by 22 publications

References 37 publications

Tumor microenvironment and immunotherapy of oral cancer

Tumor microenvironment and immunotherapy of oral cancer

ɑ-Solanine Affects the Apoptosis and Angiogenesis of M2-Like TAMs Cells by Regulating the PI3K/AKT/mTOR Signaling Pathway Under Hypoxia

Metformin Affects Olaparib Sensitivity through Induction of Apoptosis in Epithelial Ovarian Cancer Cell Lines

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