Rab11 suppresses neuronal stress signaling by localizing dual leucine zipper kinase to axon terminals for protein turnover.

Dual leucine zipper kinase (DLK) mediates multiple neuronal stress responses, and its expression levels are constantly suppressed to prevent excessive stress signaling. We found that Wallenda (Wnd), the ortholog of DLK, is highly enriched in the axon terminals of sensory neurons in vivo and that this subcellular localization is necessary for Highwire-mediated Wnd protein turnover under normal conditions. Our structure-function analysis found that Wnd palmitoylation is essential for its axon terminal localization.

Targeting isoforms of RON kinase (MST1R) drives antitumor efficacy.

Recepteur d'origine nantais (RON, MST1R) is a single-span transmembrane receptor tyrosine kinase (RTK) aberrantly expressed in numerous cancers, including various solid tumors. How naturally occurring splicing isoforms of RON, especially those which are constitutively activated, affect tumorigenesis and therapeutic response, is largely unknown. Here, we identified that presence of activated RON could be a possible factor for the development of resistance against anti-EGFR (cetuximab) therapy in colorectal cancer patient tissues.

Mutant PIK3CA as a negative predictive biomarker for treatment with a highly selective PIM1 inhibitor in human colon cancer.

Significant improvement in targeted therapy for colorectal cancer (CRC) has occurred over the past few decades since the approval of the EGFR inhibitor cetuximab. However, cetuximab is used only for patients possessing the wild-type oncogene KRAS, NRAS, and BRAF, and even most of these eventually acquire therapeutic resistance, via activation of parallel oncogenic pathways such as RAS-MAPK or PI3K/Akt/mTOR. The two aforementioned pathways also contribute to the development of therapeutic resistance in CRC patients, due to compensatory and feedback mechanisms.

CJ14939, a Novel JAK Inhibitor, Increases Oxaliplatin-induced Cell Death Through JAK/STAT Pathway in Colorectal Cancer.

Background/aim: Colorectal cancer is reported to have the highest mortality rate among human malignancies. Although many research results for the treatment of colorectal cancer have been reported, there is no suitable treatment when resistance has developed. Therefore, it is necessary to develop new therapeutic agents.

miR-3188 Enhances Sensitivity of Breast Cancer Cells to Ionizing Radiation by Down-regulating Rictor.

Background/aim: Rictor is an adaptor protein essential for mTORC2, which regulates cell growth and survival. The aim of this study was to identify microRNAs (miR) that down-regulate Rictor and investigate their function on breast cancer cell survival.

Materials And Methods: Trypan blue assay, MTT assay, polymerase chain reaction analysis, luciferase reporter assay and western blot analysis were carried out in breast cancer cell lines HCC1954, MDA-MB-231, SK-BR-3, and BT474.

Erlotinib Activates Different Cell Death Pathways in EGFR-mutant Lung Cancer Cells Grown in 3D 2D Culture Systems.

Background/aim: Non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation have been shown to have a good response to erlotinib, a receptor tyrosine kinase inhibitor of EGFR. In this study, we found that the cell death pathways activated by erlotinib in 2D and 3D culture systems are different.

Materials And Methods: The cell death pathways induced by erlotinib were evaluated by flow cytometry and immunoblotting in both 2D and 3D culture systems of EGFR mutant lung cancer cells.

Inhibition of JAK1/2 can overcome EGFR-TKI resistance in human NSCLC.

Non-small lung cancer (NSCLC) is the most common cancer in the world. The epidermal growth factor receptor (EGFR) gene is mutated in approximately 10% of lung cancer cases in the US and 50% of lung cancer in Asia. The representative target therapeutic agent, erlotinib (EGFR tyrosine kinase inhibitor; EGFR TKI), is effective in inactivating EGFR in lung cancer patients.

Targeting β-catenin overcomes MEK inhibition resistance in colon cancer with KRAS and PIK3CA mutations.

Background: Mitogen-activated protein kinases (MEK 1/2) are central components of the RAS signalling pathway and are attractive targets for cancer therapy. These agents continue to be investigated in KRAS mutant colon cancer but are met with significant resistance. Clinical investigations have demonstrated that these strategies are not well tolerated by patients.

EBV-encoded EBNA1 regulates cell viability by modulating miR34a-NOX2-ROS signaling in gastric cancer cells.

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is a viral protein expressed in all EBV-infected cells that induces malignant transformation. EBNA1 is reported to contribute to tumor progression through an increase in reactive oxygen species via nicotinamide adenine dinucleotide phosphate oxidase. However, the underlying molecular mechanism of EBNA1-induced ROS accumulation in gastric cancer is poorly understood.

Human breast cancer cells display different sensitivities to ABT-263 based on the level of survivin.

ABT-263 (navitoclax), a Bcl-2 family protein inhibitor, was clinically tested as an anti-cancer agent. However, the clinical trials were limited given the occurrence of resistance to monotherapy in breast cancer cells. Our study investigates the mechanisms for overcoming navitoclax resistance by combining it with an mTOR inhibitor to indirectly target survivin.

Epstein-Barr virus-encoded latent membrane protein 1 induces epithelial to mesenchymal transition by inducing V-set Ig domain containing 4 (VSIG4) expression via NF-kB in renal tubular epithelial HK-2 cells.

The epithelial to mesenchymal transition (EMT), a hallmark of chronic kidney disease, is a key event in the conversion from tubular epithelial cells to myofibroblasts in renal fibrosis. Epstein-Barr virus (EBV) is a γ-herpes oncovirus associated with chronic kidney disease. However, the relationship between EBV and the EMT process in renal tubular epithelial cells is not well understood.

RPS27a enhances EBV-encoded LMP1-mediated proliferation and invasion by stabilizing of LMP1.

Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is an oncoviral protein that plays a pivotal role in EBV-induced oncogenic transformation. The function of LMP1 in EBV-induced oncogenesis has been well studied. However, the molecular mechanisms underlying LMP1 protein stability remain poorly understood.

SH003 selectively induces p73‑dependent apoptosis in triple‑negative breast cancer cells.

Triple-negative breast cancer (TNBC) is a breast cancer subtype that has an aggressive phenotype, is highly metastatic, has limited treatment options and is associated with a poor prognosis. In addition, metastatic TNBC has no preferred standard chemotherapy due to resistance to anthracyclines and taxanes. The present study demonstrated that a herbal extract, SH003, reduced cell viability and induced apoptosis in TNBC without cell cytotoxicity.

L-Ascorbic acid can abrogate SVCT-2-dependent cetuximab resistance mediated by mutant KRAS in human colon cancer cells.

Colon cancer patients with mutant KRAS are resistant to cetuximab, an antibody directed against the epidermal growth factor receptor, which is an effective clinical therapy for patients with wild-type KRAS. Numerous combinatorial therapies have been tested to overcome the resistance to cetuximab. However, no combinations have been found that can be used as effective therapeutic strategies.

SAHA, an HDAC inhibitor, overcomes erlotinib resistance in human pancreatic cancer cells by modulating E-cadherin.

Pancreatic cancer is one of the most lethal cancers and remains a major unsolved health problem. Less than 20 % of patients are surgical candidates, and the median survival for non-resected patients is approximately 3 to 4 months. Despite the existence of many conventional cancer therapies, few targeted therapies have been developed for pancreatic cancer.

Targeting FGFR Pathway in Human Hepatocellular Carcinoma: Expressing pFGFR and pMET for Antitumor Activity.

The MET receptor tyrosine kinase, the receptor for hepatocyte growth factor (HGF), has been implicated in cancer growth, invasion, migration, angiogenesis, and metastasis in a broad variety of human cancers, including human hepatocellular carcinoma (HCC). Recently, MET was suggested to be a potential target for the personalized treatment of HCC with an active HGF-MET signaling pathway. However, the mechanisms of resistance to MET inhibitors need to be elucidated to provide effective treatment.

Fibroblast growth factor receptor isotype expression and its association with overall survival in patients with hepatocellular carcinoma.

Background/aims: Fibroblast growth factor signaling is involved in hepatocarcinogenesis. The aim of this study was to determine the fibroblast growth factor receptor (FGFR) isotype expression in hepatocellular carcinoma (HCC) and neighboring nonneoplastic liver tissue, and elucidate its prognostic implications.

Methods: Immunohistochemical staining of FGFR1, -2, -3, and -4 was performed in the HCCs and paired neighboring nonneoplastic liver tissue of 870 HCC patients who underwent hepatic resection.

Cellular inhibitor of apoptosis protein 1 (cIAP1) stability contributes to YM155 resistance in human gastric cancer cells.

YM155, which blocks the expression of survivin, a member of the inhibitor of apoptosis (IAP) family, induces cell death in a variety of cancer types, including prostate, bladder, breast, leukemia, and non-small lung cancer. However, the mechanism underlying gastric cancer susceptibility and resistance to YM155 is yet to be specified. Here, we demonstrate that cIAP1 stability dictates resistance to YM155 in human gastric cancer cells.

TFAP2E methylation status and prognosis of patients with radically resected colorectal cancer.

Objectives: This study investigates the clinical significance of the gene encoding AP-2ε (TFAP2E) in colorectal cancer (CRC) patients undergoing curative resection.

Methods: A single-institution cohort of 248 patients who underwent curative resection of stage I/II/III CRCs between March and December 2004 was enrolled, and 193 patients whose tumors were available for the determination of the TFAP2E methylation status were included in the analysis.

Results: TFAP2E hypermethylation was detected in 112 patients (58%) and was significantly associated with distally located CRCs, low pathologic T stage (T1/T2), and stage I tumors.

NPS-1034, a novel MET inhibitor, inhibits the activated MET receptor and its constitutively active mutants.

The MET proto-oncogene product, which is the receptor for hepatocyte growth factor (HGF), has been implicated in tumorigenesis and metastatic progression. Point mutations in MET lead to the aberrant activation of the receptor in many types of human malignancies, and the deregulated activity of MET has been correlated with tumor growth, invasion, and metastasis. MET has therefore attracted considerable attention as a potential target in anticancer therapy.

The effect of resin cements and primer on retentive force of zirconia copings bonded to zirconia abutments with insufficient retention.

Purpose: The purpose of this study was to investigate the effect of resin cements and primer on the retentive force of zirconia copings bonded to zirconia abutments with insufficient retention.

Materials And Methods: Zirconia blocks (Lava, 3M ESPE, St. Paul, MN, USA) were obtained and forty sets of zirconia abutments and copings were fabricated using CAD/CAM technology.

YM155 induces EGFR suppression in pancreatic cancer cells.

YM155, which inhibits the anti-apoptotic protein survivin, is known to exert anti-tumor effects in various cancers, including prostate and lung cancer. However, there are few reports describing the inhibitory effect of YM155 on human pancreatic cancers that highly express survivin. Here, we tested the effects of YM155 on a variety of cancer cell lines, including pancreatic cancer cells.

Physicochemical Characteristics and Antioxidant Capacity of Rice Cake (Sulgitteok) Supplemented with Lyophilized Sedum sarmentosum (Dolnamul) Powder.

This study was performed to increase the availability of Sedum sarmentosum (Dolnamul) and to improve the nutraceutical value of rice cakes (sulgitteok). The contents of crude protein, mineral, dietary fiber, water holding capacity, and hardness significantly and directly increased with lyophilized sedum powder (SP). Pore ratio and expansion rate decreased in samples containing more than 10% SP compared to the control.

Ring finger protein 149 is an E3 ubiquitin ligase active on wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF).

Members of the RAF family (ARAF, BRAF, and CRAF/RAF-1) are involved in a variety of cellular activities, including growth, survival, differentiation, and transformation. An oncogene encodes BRAF, the function of which is linked to MEK activation. BRAF is the most effective RAF kinase in terms of induction of MEK/ERK activity.