Aldehyde Dehydrogenase-1A1 (ALDH1A1): The Novel Regulator of Chemoresistance in Pancreatic Cancer Cells.

Aldehyde dehydrogenase-1A1 (ALDH1A1), a member of a superfamily of 19 isozymes, exhibits various biological functions and is involved in several important physiological and pathological processes, including those associated with various diseases including cancers such as pancreatic cancer. Chemotherapy is one of the most important strategies for the treatment of pancreatic cancer; however, the chemoresistance exhibited by pancreatic cancer cells is a leading cause of chemotherapy failure. It has been reported that overexpression of ALDH1A1 significantly correlates with poor prognosis and tumor aggressiveness, and is clinically associated with chemoresistance.

Antibacterial, Antihemolytic, Cytotoxic, Anticancer, and Antileishmanial Effects of Transgenic Plants.

Herbal and traditional medicines can play a pivotal role in combating cancer and neglected tropical diseases. , family Lamiaceae, is an important medicinal plant. The genetic transformation of with genes of further enhances its metabolic content.

[Corrigendum] Emerging roles of non‑coding RNAs in the response of rectal cancer to radiotherapy (Review).

Following the publication of the above review article, the authors have realized that they overlooked including the funding information in the Declarations section. Therefore, the following text should also have been included with the review: Funding: The present review was supported by the National Research Foundation of Korea grant funded by the Korean government (grant no. 2020R1F1A1061122) and Gachon University Research fund of 2018 (GCU-2018-0670) to SH.

Clinical evaluation of RB1 genetic testing reveals novel mutations in Vietnamese patients with retinoblastoma.

Clinical evaluation of the genetic testing strategy is essential for ensuring the correct determination of mutation carriers. The current study retrospectively analyzed genetic and clinicopathological data from 62 Vietnamese patients with retinoblastoma (RB) referred to the Vinmec Hi-Tech Center for RB transcriptional corepressor 1 () genetic testing between 2017 and 2019. The present study aimed to evaluate the sensitivity of the Next Generation Sequencing (NGS) method to identify novel mutations, and to consider using age at diagnosis as a risk factor.

Emerging roles of non‑coding RNAs in the response of rectal cancer to radiotherapy (Review).

Radiotherapy (RT) followed by radical surgery is an effective standard treatment strategy for various types of cancer, including rectal cancer. The response to RT varies among patients, and the radiosensitivity of cancer cells determines the clinical outcome of patients. However, the application of RT to patients with radioresistant tumors may result in radiation‑induced toxicity without clinical benefits.

The X-linked trichothiodystrophy-causing gene RNF113A links the spliceosome to cell survival upon DNA damage.

Prolonged cell survival occurs through the expression of specific protein isoforms generated by alternate splicing of mRNA precursors in cancer cells. How alternate splicing regulates tumor development and resistance to targeted therapies in cancer remain poorly understood. Here we show that RNF113A, whose loss-of-function causes the X-linked trichothiodystrophy, is overexpressed in lung cancer and protects from Cisplatin-dependent cell death.

Anticancer activity and mechanism of bis-pyrimidine based dimetallic Ru(II)(η-p-cymene) complex in human non-small cell lung cancer via p53-dependent pathway.

Non-small cell lung cancer (NSCLC) is the most common cancer worldwide, which is related with poor prognosis and resistance to chemotherapy. Notably, ruthenium-based complexes have emerged as good alternative to the currently used platinum-based drugs for cancer therapy. In the present study, we synthesized a novel bis-pyrimidine based ligand 1,3-bis(2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)benzene (L) and used it in the synthesis of a dimetallic Ru(II) cymene complex [(Ru(η-p-cymene)Cl)(1,3-bis(2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)benzene)] (L-Ru).

ONS-donor ligand based Pt(II) complexes display extremely high anticancer potency through autophagic cell death pathway.

The current study unveils ONS-donor ligand based Pt(II) complexes with unusual anticancer potency showing higher anticancer effect as compared to cisplatin. This series of Pt(II)(R-salicylaldimine)Cl (C1a-C4a) (R = 5-H, 5-CH, F, 3-CHO) complexes were prepared in single step in good isolated yields from commercially available materials. The chloride ancillary ligand of "a" series (C1a-C4a) was replaced with 4-picoline and "b" series of four complexes Pt(II)(R-salicylaldimine)(4-picoline)BF (C1b-C4b) (R = 5-H, 5-CH, F, 3-CHO) was obtained.

Dimetallic Ru(II) arene complexes appended on bis-salicylaldimine induce cancer cell death and suppress invasion via p53-dependent signaling.

A series of bis-salicylaldimine ligands bearing two ON-donor functions were reacted with dichloro(p-cymene)ruthenium(II) dimer in the presence of base (NaOAc) and a series of four dimetallic Ru(II) arene complexes (Ru(p-cymene))(bis-salicylaldimine)Cl (C1C4) were prepared. These complexes were obtained in excellent isolated yields and characterized in detail by using different spectroscopic techniques. The structure of C1 was also determined in solid state by single crystal X-ray analysis.

The Endosomal Protein CEMIP Links WNT Signaling to MEK1-ERK1/2 Activation in Selumetinib-Resistant Intestinal Organoids.

MAPK signaling pathways are constitutively active in colon cancer and also promote acquired resistance to MEK1 inhibition. Here, we demonstrate that -mutated colorectal cancers acquire resistance to MEK1 inhibition by inducing expression of the scaffold protein CEMIP through a β-catenin- and FRA-1-dependent pathway. CEMIP was found in endosomes and bound MEK1 to sustain ERK1/2 activation in MEK1 inhibitor-resistant BRAF-mutated colorectal cancers.

Homo- and heteroleptic Pt(II) complexes of ONN donor hydrazone and 4-picoline: A synthetic, structural and detailed mechanistic anticancer investigation.

Two series of homoleptic Pt(II)(hydrazone)Cl (C1a-C5a) and heteroleptic Pt(II)(hydrazone)(4-picoline). BF (C1b-C5b) complexes were prepared and characterized by H, C, F NMR and HR ESI-MS. Structure of C2b was confirmed by single crystal X-ray analysis.

Silencing of NRF2 Reduces the Expression of ALDH1A1 and ALDH3A1 and Sensitizes to 5-FU in Pancreatic Cancer Cells.

Pancreatic cancer remains an intractable cancer with a poor five-year survival rate, which requires new therapeutic modalities based on the biology of pancreatic oncogenesis. Nuclear factor E2 related factor-2 (NRF2), a key cytoprotective nuclear transcription factor, regulates antioxidant production, reduction, detoxification and drug efflux proteins. It also plays an essential role in cell homeostasis, cell proliferation and resistance to chemotherapy.

Morpholine or methylpiperazine and salicylaldimine based heteroleptic square planner platinum (II) complexes: In vitro anticancer study and growth retardation effect on E. coli.

Morpholine and methylpiperazine are among the most important structural parts of different drugs including organic chemotherapeutic agents. In the current study we incorporated these entities as co-ligand and a series of structurally related mono- and di-metallic square planner Pt(II) complexes (Pt(II)(salicylaldimine)(morpholine)Cl C1a-C3a, Pt(II)(salicylaldimine) (methylpiperazine)Cl C1b-C3b, di-metallic Pt(II)(bis-salicylaldimine)(morpholine)ClC4a and Pt(II)(bis-salicylaldimine)(methylpiperazine)ClC4b were prepared. These complexes were characterized by H, C, F, 2D NOESY NMR, HR ESI-MS and elemental analyses, while structures of C2a, C3a and C4b were determined by single crystal X-ray analysis.

Evolutionary phylodynamics of foot-and-mouth disease virus serotypes O and A circulating in Vietnam.

Background: Foot-and-mouth disease virus (FMDV) is one of the highest risk factors that affects the animal industry of the country. The virus causes production loss and high ratio mortality in young cloven-hoofed animals in Vietnam. The VP1 coding gene of 80 FMDV samples (66 samples of the serotype O and 14 samples of the serotype A) collected from endemic outbreaks during 2006-2014 were analyzed to investigate their phylogeny and genetic relationship with other available FMDVs globally.

Novel phenylenediamine bridged mixed ligands dimetallic square planner Pt(II) complex inhibits MMPs expression via p53 and caspase-dependent signaling and suppress cancer metastasis and invasion.

Novel phenylenediamine bridged mixed ligands dimetallic square planner Pt(II) complex (L-Pt-Py) was synthesized from simple commercially available precursors in good yield and characterized by H, C, 2D NOESY NMR and high resolution mass spectrometry (HR-ESI-MS). The stability of L-Pt-Py was checked by H NMR in mixed DMSO-d/DO solvents. L-Pt-Py showed considerable in vitro cytotoxicity in lung (A549), breast (MCF-7) and liver (HepG2) cancer cell lines and strong in vivo growth inhibition in Escherichia coli (E.

The Prosurvival IKK-Related Kinase IKKε Integrates LPS and IL17A Signaling Cascades to Promote Wnt-Dependent Tumor Development in the Intestine.

Constitutive Wnt signaling promotes intestinal cell proliferation, but signals from the tumor microenvironment are also required to support cancer development. The role that signaling proteins play to establish a tumor microenvironment has not been extensively studied. Therefore, we assessed the role of the proinflammatory Ikk-related kinase Ikkε in Wnt-driven tumor development.

Tumor-suppressive p53 Signaling Empowers Metastatic Inhibitor KLF17-dependent Transcription to Overcome Tumorigenesis in Non-small Cell Lung Cancer.

Metastasis, which is controlled by concerted action of multiple genes, is a complex process and is an important cause of cancer death. Krüppel-like factor 17 (KLF17) is a negative regulator of metastasis and epithelial-mesenchymal transition (EMT) during cancer progression. However, the underlying molecular mechanism and biological relevance of KLF17 in cancer cells are poorly understood.

A role for APPL1 in TLR3/4-dependent TBK1 and IKKε activation in macrophages.

Endosomes have important roles in intracellular signal transduction as a sorting platform. Signaling cascades from TLR engagement to IRF3-dependent gene transcription rely on endosomes, yet the proteins that specifically recruit IRF3-activating molecules to them are poorly defined. We show that adaptor protein containing a pleckstrin-homology domain, a phosphotyrosine-binding domain, and a leucine zipper motif (APPL)1, an early endosomal protein, is required for both TRIF- and retinoic acid-inducible gene 1-dependent signaling cascades to induce IRF3 activation.

Combination of dasatinib and gemcitabine reduces the ALDH1A1 expression and the proliferation of gemcitabine-resistant pancreatic cancer MIA PaCa-2 cells.

Gemcitabine-based chemotherapy is the standard for treatment of pancreatic cancer; however, intrinsic and acquired resistance to gemcitabine commonly occurs. Aldehyde dehydrogenase 1A1 (ALDH1A1), one of the characteristic features of tumor-initiating and/or cancer stem cell (CSC) properties, is important in both intrinsic and acquired resistance to gemcitabine. In this study, we investigated the effectiveness of dasatinib, an SRC inhibitor, and gemcitabine combination to inhibit the survivals of parental (MIA PaCa-2/P) and gemcitabine-resistant (MIA PaCa-2/GR) cell lines.

Cholesterol induces autophagic and apoptotic death in gastric carcinoma cells.

Despite conflicting results, there is evidence to suggest an inverse link between total body cholesterol levels and the risk of certain malignancies. Based on previous reports, this phenomenon appears to vary with cancer site, and, in particular, more consistent data on inverse relations was reported in the risk of gastric cancer. In the current study, the effect of cholesterol on gastric cancer cell viability was examined using an in vitro cell culture system.