FEN1 knockdown improves trastuzumab sensitivity in human epidermal growth factor 2-positive breast cancer cells.

Trastuzumab has been widely applied as a treatment for human epidermal growth factor 2 (HER2)-overexpressing breast cancer. However, the therapeutic efficacy of trastuzumab is limited. Flap endonuclease 1 (FEN1) is a multifunctional endonuclease that has a crucial role in DNA recombination and repair.

Efficacy of Thalidomide in Preventing Delayed Nausea and Vomiting Induced by Highly Emetogenic Chemotherapy: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase III Trial (CLOG1302 study).

Purpose We examined the efficacy and safety of thalidomide (THD) for the prevention of delayed nausea and vomiting in patients who received highly emetogenic chemotherapy (HEC). Patients and Methods In a randomized, double-blind, active-controlled, phase III trial, chemotherapy-naive patients with cancer who were scheduled to receive HEC that contained cisplatin or cyclophosphamide-doxorubicin/epirubincin ≥ 50 mg/m regimens were randomly assigned to a THD group (100 mg twice daily on days 1 to 5) or placebo group, both with palonosetron (0.25 mg on day 1) and dexamethasone (12 mg on day 1; 8 mg on days 2 to 4).

4-Phenybutyric acid promotes gastric cancer cell migration via histone deacetylase inhibition-mediated HER3/HER4 up-regulation.

Dysregulation of histone acetylation plays an important role in tumor development. Histone acetylation regulates gene transcription and expression, which is reversibly regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC). As an HDAC inhibitor, 4-phenylbutyric acid (4-PBA) can increase histone acetylation levels by inhibiting HDAC activity.

A General Chemoenzymatic Strategy for the Synthesis of Glycosphingolipids.

A concise, prototypical, and stereoselective strategy for the synthesis of therapeutically and immunologically significant glycosphingolipids has been developed. This strategy provides a universal platform for glycosphingolipid synthesis by block coupling of enzymatically prepared free oligosaccharideglycans to lipids using glycosyl -phenyltrifluoroacetimidates as efficient activated intermediates. As demonstrated here, two different types of glycosphingolipids were obtained in excellent yields using the method.

Dual inhibition of MET and SRC kinase activity as a combined targeting strategy for colon cancer.

Hepatocyte growth factor (HGF)/MET signaling is implicated in the development of colorectal cancer (CRC) and possesses therapeutic value for various types of cancer. However, inhibition of MET alone has been demonstrated to have limited efficacy. The present study examined the combined inhibition of MET and SRC kinase activity in colon cancer cells.

CXCL12/SDF-1α induces migration via SRC-mediated CXCR4-EGFR cross-talk in gastric cancer cells.

Metastasis is the primary cause of mortality in patients with advanced gastric carcinoma, and multiple signaling pathways promote the development of this condition. Stromal cell-derived factor-1 (SDF-1α/CXCL12), the main ligand for CXC chemokine receptor-4 (CXCR4), serves an important role in gastric cancer cell migration. Previous studies have demonstrated that CXCL12 could also stimulate the secretion of epidermal growth factor receptor (EGFR) ligands, including amphiregulin and heparin-binding epidermal growth factor-like growth factor, from gastric cancer cells, resulting in an increase in the ability of migration.

Tamoxifen reverses epithelial-mesenchymal transition by demethylating miR-200c in triple-negative breast cancer cells.

Background: Although the efficacy of tamoxifen (TAM) for breast cancer has been attributed to inducing cell cycle arrest and apoptosis by inhibiting estrogen receptor (ER) signaling, recent evidence indicates that TAM also possesses ER-independent antitumor activity through an unclear mechanism. The present study investigated the anti-tumor mechanism of TAM on mesenchymal triple-negative breast cancer (TNBC).

Methods: The inhibitory effect of TAM on tumor migration and metastasis was analyzed by transwell chamber in vitro and by murine xenograft model in vivo.

Gastric cancer-derived exosomes promote peritoneal metastasis by destroying the mesothelial barrier.

An intact mesothelium serves as a protective barrier to inhibit peritoneal carcinomatosis. Cancer-derived exosomes can mediate directional tumor metastasis; however, little is known about whether gastric cancer-derived exosomes will destroy the mesothelial barrier and promote peritoneal dissemination. Here, we demonstrate that gastric cancer-derived exosomes facilitate peritoneal metastasis by causing mesothelial barrier disruption and peritoneal fibrosis.

A Four-Factor Immunoscore System That Predicts Clinical Outcome for Stage II/III Gastric Cancer.

The American Joint Committee on Cancer (AJCC) staging system is insufficiently prognostic for operable gastric cancer patients; therefore, complementary factors are under intense investigation. Although the focus is on immune markers, the prognostic impact of a single immune factor is minimal, due to complex antitumor immune responses. A more comprehensive evaluation may engender more accurate predictions.

Role of patient-, tumor- and systemic inflammatory response-related factors in predicting survival of patients with node-negative gastric cancer.

It is currently unclear as to which patients with node-negative gastric cancer can benefit from adjuvant chemotherapy. This study aimed to develop a prognostic model based on patient-, tumor-, and host-related factors to stratify high-risk patients eligible for adjuvant therapy. Correlations of clinicopathological and hematological features with overall survival were analyzed using a Cox model.

PHF6 regulates phenotypic plasticity through chromatin organization within lineage-specific genes.

Developmental and lineage plasticity have been observed in numerous malignancies and have been correlated with tumor progression and drug resistance. However, little is known about the molecular mechanisms that enable such plasticity to occur. Here, we describe the function of the plant homeodomain finger protein 6 (PHF6) in leukemia and define its role in regulating chromatin accessibility to lineage-specific transcription factors.

A novel function of hepatocyte growth factor in the activation of checkpoint kinase 1 phosphorylation in colon cancer cells.

The ATR/checkpoint kinase 1 (Chk1) pathway plays an essential role in modulating the DNA damage response and homologous recombination. Particularly, Chk1 phosphorylation is related to cancer prognosis and therapeutic resistance. Some receptor tyrosine kinases participate in the regulation of Chk1 phosphorylation; however, the effect of hepatocyte growth factor (HGF) on Chk1 phosphorylation is unknown.

Whole-transcriptome screening reveals the regulatory targets and functions of long non-coding RNA H19 in epileptic rats.

Understanding the molecular mechanisms mediating epileptogenesis may lead to the development of preventative therapies against epilepsy. Our previous study demonstrated that the long non-coding RNA H19 contributes to epileptogenesis by aggravating status epilepticus-induced neuronal loss, glial cell activation, mossy fiber sprouting, and cognitive impairments in epileptic rats. However, the systematic functions and downstream targets of H19 associated with epileptogenesis are still unknown.

Formation of the IGF1R/CAV1/SRC tri-complex antagonizes TRAIL-induced apoptosis in gastric cancer cells.

Lipid rafts provide a biological platform for apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We previously reported that insulin-like growth factor 1 receptor (IGF1R) translocation into lipid rafts helped to explain TRAIL resistance. However, it was not clear whether TRAIL resistance was caused by the interaction of IGF1R with caveolin-1 (CAV1) and the non-receptor tyrosine kinase SRC in lipid rafts of gastric cancer cells.

E3 Ubiquitin Ligase Cbl-b Prevents Tumor Metastasis by Maintaining the Epithelial Phenotype in Multiple Drug-Resistant Gastric and Breast Cancer Cells.

Multiple drug resistance (MDR) and metastasis are two major factors that contribute to the failure of cancer treatment. However, the relationship between MDR and metastasis has not been characterized. Additionally, the role of the E3 ubiquitin ligase Cbl-b in metastasis of MDR gastric and breast cancer is not well known.

Beneficial Rhizobacterium Bacillus amyloliquefaciens SQR9 Induces Plant Salt Tolerance through Spermidine Production.

The inoculation of plants with plant-growth-promoting rhizobacterium has been an effective strategy for enhancing plant salt tolerance to diminish the loss of agricultural productivity caused by salt stress; however, the signal transmitted from bacteria to the plant under salt stress is poorly understood. In this study, the salt tolerance of Arabidopsis thaliana and Zea mays was enhanced by inoculation with Bacillus amyloliquefaciens SQR9. Using dialysis bags with different molecular weight cutoffs, we sorted through the molecules secreted by SQR9 and found that spermidine is responsible for enhancing plant salt tolerance.

A general strategy for the synthesis of homogeneous hyaluronan conjugates and their biological applications.

Here, we developed a general strategy for synthesizing homogeneous HA conjugates, and generated homogeneous HA-pNP, HA-biotin, and HA-oroxylin conjugates to investigate the relationships between HA chain length and its diverse biological functions.

A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress.

Cisplatin and its platinum analogs, carboplatin and oxaliplatin, are some of the most widely used cancer chemotherapeutics. Although cisplatin and carboplatin are used primarily in germ cell, breast and lung malignancies, oxaliplatin is instead used almost exclusively to treat colorectal and other gastrointestinal cancers. Here we utilize a unique, multi-platform genetic approach to study the mechanism of action of these clinically established platinum anti-cancer agents, as well as more recently developed cisplatin analogs.

Pretreatment platelet-to-lymphocyte ratio is associated with the response to first-line chemotherapy and survival in patients with metastatic gastric cancer.

Background: Several studies have shown that platelet-to-lymphocyte ratio (PLR) is a prognostic factor for various cancers. However, there is no study about the role of PLR in predicting response to first-line chemotherapy of metastatic gastric cancer. Therefore, this study aimed to establish whether PLR is associated with the response to first-line chemotherapy and survival in patients with metastatic gastric cancer.

Historical factors shaped species diversity and composition of Salix in eastern Asia.

Ambient energy, niche conservatism, historical climate stability and habitat heterogeneity hypothesis have been proposed to explain the broad-scale species diversity patterns and species compositions, while their relative importance have been controversial. Here, we assessed the relative contributions of contemporary climate, historical climate changes and habitat heterogeneity in shaping Salix species diversity and species composition in whole eastern Asia as well as mountains and lowlands using linear regressions and distance-based redundancy analyses, respectively. Salix diversity was negatively related with mean annual temperature.

IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights.

The insulin-like growth factor-I (IGF-I) signaling induces epithelial to mesenchymal transition (EMT) program and contributes to metastasis and drug resistance in several subtypes of tumors. In preclinical studies, targeting of the insulin-like growth factor-I receptor (IGF-IR) showed promising anti-tumor effects. Unfortunately, high expectations for anti-IGF-IR therapy encountered challenge and disappointment in numerous clinical trials.

MiR-338-3p inhibits the growth and invasion of non-small cell lung cancer cells by targeting IRS2.

MicroRNA-338-3p (miR-338-3p) has recently been reported to have anti-cancer efficacy in several types of cancers. However, its biological function and underlying mechanism involved in modulation of human non-small cell lung cancer (NSCLC) remain largely unknown. The present study was designed to investigate the function and underlying mechanism of miR-338-3p in human NSCLC tissues and cell lines.

RANKL/RANK pathway abrogates cetuximab sensitivity in gastric cancer cells via activation of EGFR and c-Src.

Overexpression of EGFR is commonly seen in gastric cancer (GC). However, patients with GC show resistance to anti-EGFR treatments. mutations are rare in GC and cannot explain de novo resistance to EGFR treatments.