Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling.

It has been shown that the high expression of human epididymis protein 4 (HE4) in most lung cancers is related to the poor prognosis of patients, but the mechanism of pathological transformation of HE4 in lung cancer is still unclear. The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma (LUAD). Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies, and through analysis of The Cancer Genome Atlas (TCGA) dataset.

Activity and resistance to KRAS inhibitors in non-small cell lung cancer and colorectal cancer.

Non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) are associated with a high mortality rate. Mutations in the V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) proto-oncogene GTPase (KRAS) are frequently observed in these cancers. Owing to its structural attributes, KRAS has traditionally been regarded as an "undruggable" target.

KIT ATP-Binding Pocket/Activation Loop Mutations in GI Stromal Tumor: Emerging Mechanisms of Kinase Inhibitor Escape.

Purpose: Imatinib resistance in GI stromal tumors (GISTs) is primarily caused by secondary mutations, and clonal heterogeneity of these secondary mutations represents a major treatment obstacle. KIT inhibitors used after imatinib have clinical activity, albeit with limited benefit. Ripretinib is a potent inhibitor of secondary KIT mutations in the activation loop (AL).

SETDB1 tumour suppressor roles in near-haploid mesothelioma involve TP53.

Background: Mutational inactivation of the SETDB1 histone methyltransferase is found in a subset of mesothelioma, particularly in cases with near-haploidy and TP53 mutations. However, the tumourigenic consequences of SETDB1 inactivation are poorly understood.

Methods: In this study, we investigated SETDB1 tumour suppressor functions in mesothelioma and explored biologic relationships between SETDB1 and TP53.

Co-targeting of ACK1 and KIT triggers additive anti-proliferative and -migration effects in imatinib-resistant gastrointestinal stromal tumors.

Most gastrointestinal stromal tumors (GIST) harbor mutated receptor tyrosine kinase (RTK) KIT/PDGFRA, which provides an attractive therapeutic target. However, a majority of GISTs ultimately develop resistance to KIT/PDGFRA inhibitor imatinib, multiple therapeutic targets will be identified as a reasonable strategy in imatinib-resistant GISTs. Biological mechanisms of non-RTK activated CDC42 associated kinase 1 (ACK1) are still unclear, which has been found to be activated in GISTs.

Effects of cancer-associated point mutations on the structure, function, and stability of isocitrate dehydrogenase 2.

Mutations in isocitrate dehydrogenase (IDH) are frequently found in low-grade gliomas, secondary glioblastoma, chondrosarcoma, acute myeloid leukemias, and intrahepatic cholangiocarcinoma. However, the molecular mechanisms of how IDH2 mutations induce carcinogenesis remain unclear. Using overlapping PCR, transfection, immunoblotting, immunoprecipitation, measurements of enzyme activity, glucose, lactic acid, ATP, and reactive oxygen species (ROS), cell viability, protein degradation assays post-inhibition of the 26S proteasome (bortezomib) or HSP90 (17-AAG), and a homology model, we demonstrated that the properties of ten cancer-associated IDH2 variants (R140G/Q/W and R172S/K/M/W/G/C/P) arising from point mutations are closely related to their structure and stability.

Concurrent inhibition of CDK2 adds to the anti-tumour activity of CDK4/6 inhibition in GIST.

Background: Advanced gastrointestinal stromal tumour (GIST) is characterised by genomic perturbations of key cell cycle regulators. Oncogenic activation of CDK4/6 results in RB1 inactivation and cell cycle progression. Given that single-agent CDK4/6 inhibitor therapy failed to show clinical activity in advanced GIST, we evaluated strategies for maximising response to therapeutic CDK4/6 inhibition.

SALL4 Oncogenic Function in Cancers: Mechanisms and Therapeutic Relevance.

SALL4, a member of the SALL family, is an embryonic stem cell regulator involved in self-renewal and pluripotency. Recently, SALL4 overexpression was found in malignant cancers, including lung cancer, hepatocellular carcinoma, breast cancer, gastric cancer, colorectal cancer, osteosarcoma, acute myeloid leukemia, ovarian cancer, and glioma. This review updates recent advances of our knowledge of the biology of SALL4 with a focus on its mechanisms and regulatory functions in tumors and human hematopoiesis.

Biosynthesis of silver nanoparticles with antimicrobial and anticancer properties using two novel yeasts.

AgNPs are nanomaterials with many potential biomedical applications. In this study, the two novel yeast strains HX-YS and LPP-12Y capable of producing biological silver nanoparticles were isolated. Sequencing of ribosomal DNA-ITS fragments, as well as partial D1/D2 regions of 26S rDNA indicated that the strains are related to species from the genus Metschnikowia.

Insights Into Dendritic Cells in Cancer Immunotherapy: From Bench to Clinical Applications.

Dendritic cells (DCs) are efficient antigen-presenting cells (APCs) and potent activators of naïve T cells. Therefore, they act as a connective ring between innate and adaptive immunity. DC subsets are heterogeneous in their ontogeny and functions.

Proteasome Inhibition Suppresses KIT-Independent Gastrointestinal Stromal Tumors Via Targeting Hippo/YAP/Cyclin D1 Signaling.

Gastrointestinal stromal tumors (GISTs) are the most common malignant tumor of mesenchymal origin of the digestive tract. A yet more challenging resistance mechanism involves transition from oncogenic KIT to a new imatinib-insensitive oncogenic driver, heralded by loss of KIT expression. Our recent studies have shown that inhibition of cyclin D1 and Hippo signaling, which are overexpressed in KIT-independent GIST, is accompanied by anti-proliferative and apoptosis-promoting effects.

YWHAE-NUTM2 oncoprotein regulates proliferation and cyclin D1 via RAF/MAPK and Hippo pathways.

Endometrial stromal sarcoma (ESS) is the second most common subtype of uterine mesenchymal cancer, after leiomyosarcoma, and oncogenic fusion proteins are found in many ESS. Our previous studies demonstrated transforming properties and diagnostic relevance of the fusion oncoprotein YWHAE-NUTM2 in high-grade endometrial stromal sarcoma (HG-ESS) and showed that cyclin D1 is a diagnostic biomarker in these HG-ESS. However, YWHAE-NUTM2 mechanisms of oncogenesis and roles in cyclin D1 expression have not been characterized.

AXL Inactivation Inhibits Mesothelioma Growth and Migration via Regulation of p53 Expression.

Malignant mesothelioma is a locally aggressive and highly lethal neoplasm. Dysregulation and activation of Gas6/AXL tyrosine kinase signaling are associated with mesothelioma progression, but the mechanisms of these AXL tumorigenic roles are poorly understood. p53 mutants in lung carcinoma upregulate AXL expression by binding and acetylating the promoter.

Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC), a main subtype of lung cancer, is one of the most common causes of cancer death in men and women worldwide. Circulating tumor DNA (ctDNA), tyrosine kinase inhibitors (TKIs) and immunotherapy have revolutionized both our understanding of NSCLC, from its diagnosis to targeted NSCLC therapies, and its treatment. ctDNA quantification confers convenience and precision to clinical decision making.

Coordinated targeting of CK2 and KIT in gastrointestinal stromal tumours.

Background: Most gastrointestinal stromal tumours (GIST) are driven by activating oncogenic mutations of KIT/PDGFRA, which provide a compelling therapeutic target. Our previous studies showed that CDC37, regulated by casein kinase 2 (CK2), is a crucial HSP90 cofactor for KIT oncogenic function and a promising and more selective therapeutic target in GIST.

Methods: Biologic mechanisms of CK2-mediated CDC37 regulation were assessed in GISTs by immunoblotting, immunoprecipitations, knockdown and inactivation assays.

Co-targeting CK2α and YBX1 suppresses tumor progression by coordinated inhibition of the PI3K/AKT signaling pathway.

Protein kinase CK2 alpha (CK2α) is involved in the development of multiple malignancies. Overexpression of Y-box binding protein 1 (YBX1) is related to tumor proliferation, drug resistance, and poor prognosis. Studies have demonstrated that both CK2 and YBX1 could regulate the PI3K/AKT pathway.

Cyclin D1 is a mediator of gastrointestinal stromal tumor KIT-independence.

Oncogenic KIT or PDGFRA tyrosine kinase mutations are compelling therapeutic targets in most gastrointestinal stromal tumors (GISTs), and the KIT inhibitor, imatinib, is therefore standard of care for patients with metastatic GIST. However, some GISTs lose expression of KIT oncoproteins, and therefore become KIT-independent and are consequently resistant to KIT-inhibitor drugs. We identified distinctive biologic features in KIT-independent, imatinib-resistant GISTs as a step towards identifying drug targets in these poorly understood tumors.

WITHDRAWN: Effects of cancer-associated point mutations on the structure, function, and stability of succinate dehydrogenase A.

This article has been withdrawn by the authors. Some of the SDHA enzyme activity data were flawed and were not performed and analyzed correctly. The withdrawing authors are in the process of correcting the data and re-evaluating them for resubmission.

Anaplastic lymphoma kinase fusions: Roles in cancer and therapeutic perspectives.

Receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (ALK) serves a crucial role in brain development. is located on the short arm of chromosome 2 (2p23) and exchange of chromosomal segments with other genes, including nucleophosmin (), echinoderm microtubule-associated protein-like 4 () and -fused gene (), readily occurs. Such chromosomal translocation results in the formation of chimeric fusion oncoproteins, which possess potential oncogenic functions due to constitutive activation of ALK kinase.

Activated tyrosine kinases in gastrointestinal stromal tumor with loss of KIT oncoprotein expression.

Oncogenic KIT or PDGFRA receptor tyrosine kinase (TK) mutations are compelling therapeutic targets in gastrointestinal stromal tumors (GISTs), and the KIT/PDGFRA kinase inhibitor, imatinib, is the standard of care for patients with metastatic GIST. However, approximately 10% of KIT-positive GIST metastases lose KIT expression at the time of clinical progression during imatinib therapy. In the present report, we performed TK-activation screens, using phosphotyrosine-TK double immunoaffinity purification and mass spectrometry, in GIST in vitro models lacking KIT expression.

The hippo pathway provides novel insights into lung cancer and mesothelioma treatment.

Purpose: Lung cancer and mesothelioma are two types of respiratory disease that have fatal courses and poor prognoses. Although a substantial number of targeted small molecules and antibody drugs have been developed, the 5-year survival rates of these patients remain relatively low. Moreover, most patients inevitably develop clinical resistance to treatment.

Leukemia inhibitory factor regulates marmoset induced pluripotent stem cell proliferation via a PI3K/‌Akt‑dependent Tbx‑3 activation pathway.

Leukemia inhibitory factor (LIF) is the most pleiotropic cytokine of the interleukin‑6 family, and is widely used to establish and maintain pluripotent stem cells, particularly mouse pluripotent stem cells. However, no reports have fully elucidated the application of LIF in marmoset induced pluripotent stem cell (iPSC) culture, particularly the underlying mechanisms. To demonstrate the feasibility of the application of LIF to marmoset iPSCs, the present study assessed these cells in the presence of LIF.

Comparative study on the composition of free amino acids and derivatives in the two botanical origins of an edible Chinese herb "Xiebai", i.e., Allium chinense G. Don and Allium macrostemon Bunge species.

Xiebai is an edible Chinese herb with various health and therapeutic benefits. To evaluate its nutritional and health values, the free amino acids and derivatives of its two botanical origins (i.e.

Human-induced pluripotent stem cell-derived macrophages and their immunological function in response to tuberculosis infection.

Background: Induced pluripotent stem cells (iPS) represent an innovative source for the standardized in vitro generation of macrophages (Mφ). Mφ show great promise in disease pathogenesis, particularly tuberculosis. However, there is no information about human iPS-derived (hiPS) macrophages (hiPS-Mφ) in response to tuberculosis infection.