VEGFA Status as a Predictive Marker of Therapy Outcome in Metastatic Gastric Cancer Patients Following Ramucirumab-Based Treatment.

Metastatic gastric cancer (mGC) often has a poor prognosis and may benefit from a few targeted therapies. Ramucirumab-based anti-angiogenic therapy targeting the VEGFR2 represents a milestone in the second-line treatment of mGC. Several studies on different cancers are focusing on the major VEGFR2 ligand status, meaning VEGFA gene copy number and protein overexpression, as a prognostic marker and predictor of response to anti-angiogenic therapy.

Corrigendum: Variations in circulating levels of angiopoietin-2 over time are predictive of ramucirumab-paclitaxel therapy outcome in advanced gastric cancer: results of prospective study.

[This corrects the article DOI: 10.3389/fonc.2022.

The multiple combination of Paclitaxel, Ramucirumab and Elacridar reverses the paclitaxel-mediated resistance in gastric cancer cell lines.

Introduction: Paclitaxel (PTX) interferes with microtubule architecture by binding to β-tubulin, thereby blocking progression at the G2/M phase and inducing apoptosis. This study aimed to investigate molecular processes underlying PTX-mediated resistance in gastric cancer (GC) cells.

Methods: PTX-mediated resistance involves many processes, and in this work some of the factors involved in the resistance mechanism were identified by comparing two GC lines with PTX induced resistance to their sensitive counterparts.

Variations in Circulating Levels of Angiopoietin-2 Over Time Are Predictive of Ramucirumab-Paclitaxel Therapy Outcome in Advanced Gastric Cancer: Results of Prospective Study.

The combination of paclitaxel and ramucirumab is the second-line therapy of choice in the treatment of advanced gastric cancer. To date, no biomarkers are available in gastric cancer to predict the outcome of antiangiogenic therapy. The present prospective study included 35 patients undergoing second-line therapy with ramucirumab and paclitaxel.

Nonalcoholic Fatty Liver Disease: Focus on New Biomarkers and Lifestyle Interventions.

Nonalcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome, characterized from pathological changes in lipid and carbohydrate metabolism. Its main characteristics are excessive lipid accumulation and oxidative stress, which create a lipotoxic environment in hepatocytes leading to liver injury. Recently, many studies have focused on the identification of the genetic and epigenetic modifications that also contribute to NAFLD pathogenesis and their prognostic implications.

Molecular mechanisms of synergistic action of Ramucirumab and Paclitaxel in Gastric Cancers cell lines.

Ramucirumab is approved both as monotherapy and in combination with Paclitaxel for advanced gastric cancer in patients with disease progression after chemotherapy. In tumor cells, the VEGFA-VEGFR2 binding activates autocrine survival and migration signaling in angiogenesis independent manner. The present in vitro study investigated the effects of single and combined treatments with Ramucirumab and Paclitaxel on cell growth and migration highlighting the mechanisms underlying the interaction between the two drugs in gastric cancer cells.

Integrated immune gene expression signature and molecular classification in gastric cancer: New insights.

Gastric cancer (GC) is characterized by extreme heterogeneity due to histopathological differences, molecular characteristics, and immune gene expression signature. Until recently, several targeted therapies failed due to this complexity. The recent immunotherapy resulted in more effective and safe approaches in several malignancies.

Inflammatory Mechanisms of HCC Development.

HCC (hepatocellular carcinoma) is the second leading cause of cancer deaths worldwide, with several etiologic causes, mostly inflammation-associated. Different inflammatory responses in the liver can be triggered by different etiological agents. The inflammatory process can be resolved or be persistent, depending on the etiology and multiple other factors.

FZD10 Carried by Exosomes Sustains Cancer Cell Proliferation.

Extracellular vesicles (EVs) are involved in intercellular communication during carcinogenesis, and cancer cells are able to secrete EVs, in particular exosomes containing molecules, that can be transferred to recipient cells to induce pathological processes and significant modifications, as metastasis, increase of proliferation, and carcinogenesis evolution. FZD proteins, a family of receptors comprised in the Wnt signaling pathway, play an important role in carcinogenesis of the gastroenteric tract. Here, a still unknown role of Frizzled 10 (FZD10) protein was identified.

Ramucirumab and GSK1838705A Enhance the Inhibitory Effects of Low Concentration Sorafenib and Regorafenib Combination on HCC Cell Growth and Motility.

Several new multikinase inhibitors have recently been introduced into clinical practice for hepatocellular carcinoma (HCC) therapy. Small increases in survival were reported as well as considerable toxicity. There is thus a need for effective therapies with lower toxicities.

Cannabinoid Receptor-1 Up-regulation in Azoxymethane (AOM)-treated Mice After Dietary Treatment with Quercetin.

Background/aim: The expression of cannabinoid receptor-1 (CB1-R) seems to be modulated by bioactive natural components such as the flavonoid quercetin. The aim of this study was to determine in an animal model of induced-colon cancer, whether quercetin inhibits colon carcinogenesis through changes in the expression of CB1-R.

Materials And Methods: C57BL/6J male mice were randomly assigned to standard diet or experimental diet supplemented with 0.

Chlorogenic Acid Improves the Regorafenib Effects in Human Hepatocellular Carcinoma Cells.

Chlorogenic acid (CGA) is a polyphenol present in many human dietary foods. Several studies indicated a beneficial role of CGA in the prevention of cancer and an enhancement of chemotherapy when combined with CGA in the treatment of human hepatocarcinoma (HCC). Drug toxicity, resistance and subsequent disease progression represent a problem in HCC management, although treatment with the multikinase inhibitor Regorafenib improved overall survival.

Strong enhancement by IGF1-R antagonists of hepatocellular carcinoma cell migration inhibition by Sorafenib and/or vitamin K1.

Purpose: Emerging evidence indicates that combining Sorafenib with vitamin K1 (VK1) may result in a synergistic inhibition of hepatocellular carcinoma (HCC) cell migration and proliferation. Despite this synergy, its benefits may be limited due to drug resistance resulting from cross-talk with the tumor microenvironment. Insulin-like growth factor-1 (IGF1) signaling acts as an important modulator of HCC cell growth, motility and drug resistance.

IGF-1R tyrosine kinase inhibitors and Vitamin K1 enhance the antitumor effects of Regorafenib in HCC cell lines.

The recent RESORCE trial showed that treatment with Regorafenib after Sorafenib failure provided a significant improvement in overall survival in HCC patients. Preclinical and clinical trial data showed that Regorafenib is a more potent drug than Sorafenib. In this study we aimed at improving Regorafenib actions and at reducing its toxicity, by targeting parallel pathways or by combination with Vitamins K (VKs).

Modulation of sensitivity and resistance to multikinase inhibitors by microenvironmental platelet factors in HCC.

Introduction: Response of a tumor to chemotherapy or multikinase inhibitor therapy has been traditionally thought to be a reflection of the sum of the characteristics of both the drug and of the tumor cell resistance mechanisms. More recently, there has been a growing awareness of the role of non-tumor factors-both cellular and humoral-in the tumor microenvironment that can increase or decrease the tumor cellular responses to the therapy. This article focuses on platelet factors in clinical HCC and experimental evidence that they provide growth stimulants that can antagonize the growth inhibitory effects of therapy.

Resistance to multikinase inhibitor actions mediated by insulin like growth factor-1.

Background: Blood platelet numbers are correlated with growth and aggressiveness of several tumor types, including hepatocellular carcinoma (HCC). We previously found that platelet lysates (hPLs) both stimulated HCC cell growth and migration, and antagonized the growth-inhibitory and apoptotic effects of Regorafenib, multikinase growth inhibitor, on HCC cell lines. We evaluated the effects of human insulin-like growth factor-1 (IGF1), a mitogen contained in platelets, on the Regorafenib-mediated growth inhibition.

Modulation of Regorafenib effects on HCC cell lines by epidermal growth factor.

Purpose: Blood platelet numbers are correlated to growth and aggressiveness of several tumor types, including hepatocellular carcinoma (HCC). We previously found that platelet lysates (hPLs) also stimulated growth and migration, and antagonized the growth-inhibitory and apoptotic effects of both Sorafenib and Regorafenib, two multikinase inhibitors, on three HCC cell lines. In this study, in vitro function of human epidermal growth factor (EGF) with and without Sorafenib or Regorafenib was investigated.

Anti Proliferative and Pro Apoptotic Effects of Flavonoid Quercetin Are Mediated by CB1 Receptor in Human Colon Cancer Cell Lines.

Quercetin, the major constituent of flavonoid and widely present in fruits and vegetables, is an attractive compound for cancer prevention due to its beneficial anti proliferative effects, showing a crucial role in the regulation of apoptosis and cell cycle signaling. In vitro studies have demonstrated that quercetin specifically influences colon cancer cell proliferation. Our experiments, using human colon adenocarcinoma cells, confirmed the anti proliferative effect of quercetin and gave intriguing new insight in to the knowledge of the mechanisms involved.

Modulation of Doxorubicin mediated growth inhibition of hepatocellular carcinoma cells by platelet lysates.

Purpose: Platelet extracts can stimulate cell growth and contribute to tumor biology. It was recently shown that they stimulate the growth of hepatocellular carcinoma (HCC) cells and decrease apoptosis. Doxorubicin is a commonly used HCC chemotherapy that increases apoptosis.

Antagonism of sorafenib and regorafenib actions by platelet factors in hepatocellular carcinoma cell lines.

Background: Platelets are frequently altered in hepatocellular carcinoma (HCC) patients. Platelet lysates (hPL) can enhance HCC cell growth and decrease apoptosis. The aims were to evaluate whether hPL can modulate the actions of sorafenib or regorafenib, two clinical HCC multikinase antagonists.

Platelet extracts induce growth, migration and invasion in human hepatocellular carcinoma in vitro.

Background: Thrombocytopenia has been reported to be associated with small size HCCs, and thrombocytosis to be associated with large size HCCs. The aim was to examine the effects of platelets in relation to HCC cell growth.

Methods: The effects of time-expired pooled normal human platelets were examined on human HCC cell line growth and invasion.

Reversibility of regorafenib effects in hepatocellular carcinoma cells.

Purpose: Multikinase growth inhibitors inhibit their target kinases with varying potency. Patients often require lower doses or therapy breaks due to drug toxicities. To evaluate the effects of drug withdrawal on hepatocellular carcinoma cells after incubation with growth-inhibitory concentrations of regorafenib, cell growth, migration and invasion, and signaling were examined.

Antiproliferative, antioxidant and anti-inflammatory effects of hydroxytyrosol on human hepatoma HepG2 and Hep3B cell lines.

Background: Olive oil intake has been shown to induce beneficial effect on health. This study aimed to investigate the effects of olive oil polyphenol hydroxytyrosol (HT) on cell proliferation and its antioxidant and anti-inflammatory capacity in human hepatoma Hep3B and HepG2 cell lines.

Materials And Methods: Cell growth after HT treatment was measured by 3-(4,5 di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test.

Effects of low concentrations of regorafenib and sorafenib on human HCC cell AFP, migration, invasion, and growth in vitro.

Sorafenib was shown in clinical trial to enhance survival in hepatocellular carcinoma (HCC) patients, but with minimal tumor shrinkage. To correlate several indices of HCC growth at various drug concentrations, HCC cells were grown in various low concentrations of two multikinase inhibitors, regorafenib (Stivarga) and sorafenib (Nexavar) and their effects were examined on alpha-fetoprotein (AFP), cell growth, migration, and invasion. In two AFP positive human HCC cell lines, AFP was inhibited at 0.

Fluoro-Sorafenib (Regorafenib) effects on hepatoma cells: growth inhibition, quiescence, and recovery.

To evaluate the growth-inhibitory properties of the potent multi-kinase antagonist Regorafenib (Fluoro-Sorafenib), which was synthesized as a more potent Sorafenib, a Raf inhibitor and to determine whether similar mechanisms were involved, human hepatoma cell lines were grown in the presence or absence of Regorafanib and examined for growth inhibition. Western blots were performed for Raf targets, apoptosis, and autophagy. Regorafenib inhibited growth of human Hep3B, PLC/PRF/5, and HepG2 cells in a concentration- and time-dependent manner.