Tumor-derived interleukin 35 mediates the dissemination of gemcitabine resistance in pancreatic adenocarcinoma.

Rapid development of drug resistance after chemotherapy is a major cause of treatment failure in individuals with pancreatic ductal adenocarcinoma (PDAC). In this study, we illustrate that tumor-derived interleukin 35 (IL-35) mediates the accelerated resistance of PDAC to gemcitabine (GEM). We observe that GEM resistance can spread from GEM-resistant PDAC cells to GEM-sensitive cells, and that IL-35 is responsible for the propagation of chemoresistance, which is supported by sequencing and experimental data.

BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis.

VEGF inhibitors are one of the most successful antiangiogenic drugs in the treatment of many solid tumors. Nevertheless, pancreatic adenocarcinoma (PAAD) cells can reinstate tumor angiogenesis via activation of VEGF-independent pathways, thereby conferring resistance to VEGF inhibitors. Bioinformatic analysis showed that BICC1 was one of the top genes involved in the specific angiogenesis process of PAAD.

Serum IL-35 levels is a new candidate biomarker of cancer-related cachexia in stage IV non-small cell lung cancer.

Background: Cancer-related cachexia is a major cause of treatment resistance and poor prognosis, which is characterized by anorexia and skeletal muscle depletion. To date, there have been no reports on the relationship between IL-35 and cancer-related cachexia in patients with stage IV non-small cell lung cancer.

Methods: Serum IL-35 levels in 86 patients with stage IV NSCLC were measured and statistically analyzed based on patients' clinicopathological parameters.

BZW1 Facilitates Glycolysis and Promotes Tumor Growth in Pancreatic Ductal Adenocarcinoma Through Potentiating eIF2α Phosphorylation.

Background & Aims: Pancreatic ductal adenocarcinoma (PDAC) is characterized by severe metabolic stress due to fibrosis and poor vascularization. BZW1 is an eIF5-mimic protein involved in tumorigenesis and progression. The aim of this study was to investigate the role of BZW1 in metabolic stress resistance in PDAC.

[Research Progress of Cancer-associated Fibroblasts in Lung Cancer].

Tumor stroma plays key roles in promoting tumor recurrence and treatment resistance. Cancer-associated fibroblasts (CAFs) are one of the most abundant and key components in the stroma of lung cancer. CAFs secrete a variety of inflammatory cytokines and extracellular matrix to form a desmoplastic tumor niche, which play important roles in the occurrence and development of lung cancer.

Fascin Controls Metastatic Colonization and Mitochondrial Oxidative Phosphorylation by Remodeling Mitochondrial Actin Filaments.

The deregulation of the actin cytoskeleton has been extensively studied in metastatic dissemination. However, the post-dissemination role of the actin cytoskeleton dysregulation is poorly understood. Here, we report that fascin, an actin-bundling protein, promotes lung cancer metastatic colonization by augmenting metabolic stress resistance and mitochondrial oxidative phosphorylation (OXPHOS).

RETRACTED: HIF-1α mediates tumor-nerve interactions through the up-regulation of GM-CSF in pancreatic ductal adenocarcinoma.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).

STAT1-mediated inhibition of FOXM1 enhances gemcitabine sensitivity in pancreatic cancer.

Forkhead box protein M1 (FOXM1) was identified as an oncogenic transcription factor and master regulator of tumor progression and metastasis. FOXM1 expression often correlates with poor prognosis and chemotherapy resistance. In the present study, we investigated the association of FOXM1 expression and chemoresistance in pancreatic cancer.

LIMS1 Promotes Pancreatic Cancer Cell Survival under Oxygen-Glucose Deprivation Conditions by Enhancing HIF1A Protein Translation.

Purpose: Oxygen and glucose deprivation is a common feature of the solid tumor. Regulatory network underlying the adaptation of cancer cells to the harsh microenvironment remains unclear. We determined the mechanistic role of LIM and senescent cell antigen-like-containing domain protein 1 (LIMS1) in cancer cell survival under oxygen-glucose deprivation conditions.

Interleukin 35 Expression Correlates With Microvessel Density in Pancreatic Ductal Adenocarcinoma, Recruits Monocytes, and Promotes Growth and Angiogenesis of Xenograft Tumors in Mice.

Background & Aims: Cells of the monocyte lineage contribute to tumor angiogenesis. Interleukin 35 (IL35) is a member of the IL12 family produced by regulatory, but not effector, T cells. IL35 is a dimer comprising the IL12 alpha and IL27 beta chains, encoded by IL12A and EBI3, respectively.

HIF-2-dependent expression of stem cell factor promotes metastasis in hepatocellular carcinoma.

Stem cell factor (SCF) is a multifunctional cytokine responsible for tumorigenesis and progression. In this study, we report that increased expression of SCF in hepatocellular carcinoma (HCC) patients is highly associated with metastasis and poor prognosis. SCF inhibition with RNAi inhibited HCC cell migration, invasion in vitro, and reduced intrahepatic metastases burden and significantly prolonged survival in a HCC xeograft mouse model.

Tumour-derived Interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression.

Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood.

Hypoxia Inducible Factor 1 (HIF-1) Recruits Macrophage to Activate Pancreatic Stellate Cells in Pancreatic Ductal Adenocarcinoma.

Hypoxia inducible factor 1 (HIF-1) is a transcription factor composed of two subunits, namely, HIF-1α and HIF-1β, in which HIF-1β is constitutively expressed. HIF-1 upregulates several hypoxia-responsive proteins, including angiogenesis factors, glycolysis solution enzymes, and cell survival proteins. HIF-1 is also associated with the degree of inflammation in the tumor region, but the exact mechanism remains unclear.

MiR-497 Suppresses YAP1 and Inhibits Tumor Growth in Non-Small Cell Lung Cancer.

Background/aims: To investigate the expression, clinical significance and the cellular effects of miR-497 in non-small cell lung cancer (NSCLC).

Methods: NSCLC cells were transiently transfected with miR-497 mimics or siRNA to up-regulate or down-regulate expression. Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA level of miR-497.

Wnt2 promotes non-small cell lung cancer progression by activating WNT/β-catenin pathway.

Background: Wnt2 is overexpressed and able to promote tumorigenesis in many types of cancer. However, its expression and role in lung cancer has not been well clarified yet. In this study, we aims to investigate the expression pattern, clinical significance and the underlying molecular mechanism of Wnt2 in non-small lung cancer (NSCLC).

Usefulness of the neutrophil-to-lymphocyte ratio in predicting lymph node metastasis in patients with non-small cell lung cancer.

Preoperative neutrophil-to-lymphocyte ratio (NLR) is a new hotspot for its prognostic significance in many types of cancers. In this study, a novel diagnosing model-the combination of enhanced contrast computed tomography (ECCT) and NLR (COCT-NLR) was constructed to detect the lymph nodal involvement in patients with non-small cell lung cancer (NSCLC). The clinicopathological parameters and thoracic ECCT images of 353 NSCLC patients were retrospectively reviewed.