Identification of anaplastic lymphoma kinase fusions in clear cell renal cell carcinoma.

As one of the most common types of renal cancer, clear cell renal cell carcinoma (ccRCC) in advanced stages constitutes a continued major challenge for uro‑oncologists, as the identification of novel driver mutations and the development of novel targeted therapies against them remain an unmet need. Aberrations in anaplastic lymphoma kinase (ALK), a rational therapeutic target, as verified in lung cancer with ALK rearrangement, have been implicated in the pathogenesis of multiple human cancers. In the present study, we screened ALK expression in 87 pathologically defined ccRCCs via immunohistochemistry (IHC) using a newly developed rabbit anti‑human ALK monoclonal antibody (clone D5F3).

New peptide MY1340 revert the inhibition effect of VEGF on dendritic cells differentiation and maturation via blocking VEGF-NRP-1 axis and inhibit tumor growth in vivo.

The development and clinical application of immunostimulatory therapy provides us a new and exciting strategy in cancer treatment of which the agents act on crucial receptors. Given the fact that Neuropilin-1(NRP-1) is essential for vascular endothelial growth factor (VEGF) to inhibit LPS-dependent maturation of dendritic cells (DCs), it may present a potentially meaningful target in cancer immunotherapy. To explore this hypothesis, we synthesized a novel polypeptide called MY1340 consist of 32 amino acids with the aim of targeting VEGF-NRP-1 axis.

Leukemia-related protein 16 (LRP16) promotes tumor growth and metastasis in pancreatic cancer.

Background: Leukemia related protein 16 (LRP16), one of the genes belonging to the macro domain family, has been found up-regulated in various tumors including testicles, ovaries and mucosa of colon and is associated with poor clinical outcomes.

Purpose: The objective of this study was to investigate expression pattern and biological roles of LRP16 in pancreatic cancer.

Patients And Methods: Western blot and immunohistochemistry were used to investigate the expression of LRP16 in pancreatic cancer cell lines and tissues.

MMP-9-cleaved osteopontin isoform mediates tumor immune escape by inducing expansion of myeloid-derived suppressor cells.

As an extracellular matrix protein, osteopontin (OPN) has been shown to play an important role in regulation of the immune response to tumors. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid progenitors, are major components of the immune suppressive tumor microenvironment and contribute to tumor evasion of the immune response. However, the specific regulating mechanisms underlying MDSCs expansion remain unclear.

TIP30 regulates lipid metabolism in hepatocellular carcinoma by regulating SREBP1 through the Akt/mTOR signaling pathway.

Lipid reprogramming has been considered as a crucial characteristic in hepatocellular carcinoma (HCC) initiation and progression. However, detailed molecular mechanisms have yet to be clearly defined. Here, we examined the effects of tumor suppressor TIP30 on the regulation of HCC lipid metabolism.

Osteopontin facilitates tumor metastasis by regulating epithelial-mesenchymal plasticity.

Tumor metastasis leads to high mortality; therefore, understanding the mechanisms that underlie tumor metastasis is crucial. Generally seen as a secretory protein, osteopontin (OPN) is involved in multifarious pathophysiological events. Here, we present a novel pro-metastatic role of OPN during metastatic colonization.

Methyl jasmonate induces the apoptosis of human colorectal cancer cells via downregulation of EZH2 expression by microRNA‑101.

Methyl jasmonate is found universally in the plant kingdom and functions to regulate plant growth and development, as well as in stress responses through signal transduction pathways. The present study aimed to investigate the anticancer effect of methyl jasmonate on SW620 human colorectal cancer cells and its potential underlying mechanism. SW620 cells were treated with 0, 0.

Conditional knockout of TFPI-1 in VSMCs of mice accelerates atherosclerosis by enhancing AMOT/YAP pathway.

Background: Tissue factor pathway inhibitor-1 (TFPI-1) has multiple functions and its precise role and molecular mechanism during the development of atherosclerosis are not clear.

Objectives: To determine the effect and molecular mechanism of TFPI-1 deficiency in vascular smooth muscle cells (VSMCs) in atherosclerosis in the apolipoprotein E knockout (ApoE) mouse.

Methods And Results: A mouse model with a conditional knockout of TFPI-1 in VSMCs in an atherosclerosis-prone background (ApoE) was generated.

Osteopontin induces autophagy to promote chemo-resistance in human hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a major health burden worldwide for its high incidence and mortality. Osteopontin (OPN) is a chemokine-like, matricellular phosphoglycoprotein whose expression is elevated in various types of cancer including HCC. OPN has been shown to be involved in tumorigenesis, chemo-resistance, metastasis and sustaining stem-like properties of cancer cells.

ASPP2 suppresses stem cell-like characteristics and chemoresistance by inhibiting the Src/FAK/Snail axis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of death in cancer patients worldwide. Understanding the molecular pathogenesis of HCC recurrence and chemoresistance is key to improving patients' prognosis. In this study, we report that downregulation of ASPP2, a member of the ankyrin-repeat-containing, SH3-domain-containing, and proline-rich-region-containing protein (ASPP) family, bestowed HCC cells with stem-like properties and resistance to chemotherapy, including the expansion of side population fractions, formation of hepatospheroids, expression of stem cell-associated genes, loss of chemosensitivity, and increased tumorigenicity in immunodeficient mice.

Quantitative analysis of histone H3 and H4 post-translational modifications in doxorubicin-resistant leukemia cells.

The epigenetic remodeling of chromatin through histone modifications has been widely implicated in drug resistance of cancer cells. However, whether epigenetic mechanisms contribute specifically to doxorubicin resistance in leukemia has not been carefully examined. Using a stable and sensitive workflow based on LC-MS, we quantitatively compared the extents of methylation and acetylation of histone H3 and H4 in acute leukemia cell line HL60 and its doxorubicin-resistant derivative, HL60/ADR, as well as the chronic leukemia cell line K562 and its doxorubicin-resistant derivative, K562/ADR.

Osteopontin Promotes Hepatic Progenitor Cell Expansion and Tumorigenicity via Activation of β-Catenin in Mice.

Upregulation of osteopontin (OPN) has been found in hepatic progenitor cells (HPCs) in several liver diseases with portal biliary proliferation. Here, we investigated the role of HPC-derived autocrine OPN in regulating HPC expansion, migration, and hepatocarcinogenesis in mice. Five-week-old, weighing between 18 and 20 g of either wild type (WT) or OPN gene knockout (OPN-KO) male mice were treated with modified choline-deficient, ethionine-supplemented diet (modified choline-deficient [MCDE]) for 2 weeks to induce HPC production, or 6-12 months to induce tumorigenesis.

Osteopontin promotes a cancer stem cell-like phenotype in hepatocellular carcinoma cells via an integrin-NF-κB-HIF-1α pathway.

There is increasing evidence to suggest that hepatocellular carcinomas (HCCs) are sustained by a distinct subpopulation of self-renewing cells known as cancer stem cells. However, the precise signals required for maintenance of stemness-like properties of these cells are yet to be elucidated. Here, we demonstrated that the level of oncoprotein osteopontin (OPN) in tumor cells of the edge of bulk tumors was significantly correlated with the clinical prognosis of patients with HCC.

Intracellular Osteopontin inhibits toll-like receptor signaling and impedes liver carcinogenesis.

Osteopontin (OPN) has been implicated widely in tumor growth and metastasis, but the range of its contributions is not yet fully understood. In this study, we show that genetic ablation of Opn in mice sensitizes them to diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Opn-deficient mice (Opn(-/-) mice) exhibited enhanced production of proinflammatory cytokines and compensatory proliferation.

Four-in-one antibodies have superior cancer inhibitory activity against EGFR, HER2, HER3, and VEGF through disruption of HER/MET crosstalk.

The anti-HER receptor antibodies cetuximab, trastuzumab, and pertuzumab are used widely in clinic to treat metastatic cancer. However, activation of the extensive crosstalk among the HER receptors as well as other RTKs, particularly HER-MET crosstalk, has emerged as a likely source of drug resistance. In this study, we developed two new types of tetra-specific antibodies that recognize EGFR, HER2, HER3, and VEGF.

ASPP2 controls epithelial plasticity and inhibits metastasis through β-catenin-dependent regulation of ZEB1.

Epithelial to mesenchymal transition (EMT), and the reverse mesenchymal to epithelial transition (MET), are known examples of epithelial plasticity that are important in kidney development and cancer metastasis. Here we identify ASPP2, a haploinsufficient tumour suppressor, p53 activator and PAR3 binding partner, as a molecular switch of MET and EMT. ASPP2 contributes to MET in mouse kidney in vivo.

Contribution of TIP30 to chemoresistance in laryngeal carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is one of the most common carcinomas of the head and neck. Despite advances in diagnosis and treatment, the survival of patients with LSCC has not improved in the past two decades. TIP30, a newly identified tumour suppressor, appears to be involved in multiple processes during tumour development.

Anti-osteopontin monoclonal antibody prevents ovariectomy-induced osteoporosis in mice by promotion of osteoclast apoptosis.

Osteopontin (OPN) is abundant in mineralized tissues and has long been implicated in bone remodeling. However, the therapeutic effect of targeting OPN in bone loss diseases and the underlying molecular mechanism remain largely unknown. Here, we reported that anti-OPN mAb (23C3) could protect against ovariectomy-induced osteoporosis in mice, demonstrated by microcomputed tomography analysis and histopathology evaluation.

Insights into HER2 signaling from step-by-step optimization of anti-HER2 antibodies.

HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer; however, resistance to trastuzumab is common. The development of monoclonal antibodies that have complementary mechanisms of action results in a more comprehensive blockade of ErbB2 signaling, especially HER2/HER3 signaling.

Decreased TIP30 promotes Snail-mediated epithelial-mesenchymal transition and tumor-initiating properties in hepatocellular carcinoma.

The poor prognosis of hepatocellular carcinoma (HCC) is mainly due to tumor recurrence and metastases. Recently, epithelial-mesenchymal transition (EMT) has been implicated in tumor invasion and metastasis. However, the underlying molecular mechanisms are yet to be elucidated.

Enhanced myeloid differentiation factor 88 promotes tumor metastasis via induction of epithelial-mesenchymal transition in human hepatocellular carcinoma.

Metastasis is the leading cause of death in patients with hepatocellular carcinoma (HCC) after curative resection. Therefore, it is critical to understand the mechanisms underlying tumor metastasis in HCC. We have previously shown that elevated expression of myeloid differentiation factor 88 (MyD88) may promote tumor growth and metastasis in HCC.

The ErbB2-targeting antibody trastuzumab and the small-molecule SRC inhibitor saracatinib synergistically inhibit ErbB2-overexpressing gastric cancer.

The anti-ErbB2 antibody trastuzumab has shown significant clinical benefits in ErbB2-overexpressing breast and gastric cancer, but resistance to the drug is common. Here, we investigated the antitumor activity of the combination of trastuzumab and the SRC inhibitor saracatinib in ErbB2-overexpressing trastuzumab-resistant gastric cancer. The ErbB2-overexpressing human gastric cancer cell line NCI-N87 was treated with trastuzumab to obtain the trastuzumab-resistant cell line NCI-N87R.

Akt-p53-miR-365-cyclin D1/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency.

Although PTEN/Akt signaling is frequently deregulated in human gastric cancers, the in vivo causal link between its dysregulation and gastric tumorigenesis has not been established. Here we show that inactivation of PTEN in mouse gastric epithelium initiates spontaneous carcinogenesis with complete penetrance by 2 months of age. Mechanistically, activation of Akt suppresses the abundance of p53, leading to decreased transcription of miR-365, thus causing upregulation of cyclin D1 and cdc25A, which promotes gastric cell proliferation.