Pancreatic ductal adenocarcinoma (PDAC) still has a poor response to therapies, partly due to their cancer-associated fibroblasts (CAFs). Here, we investigate the synergistic impact of a combinatory approach between a known chemotherapy agent, such as gemcitabine (GEM), and gene-modified human mesenchymal stromal/stem cells (MSCs) secreting the pro-apoptotic soluble (s)TRAIL (sTRAIL MSCs) on both PDAC cells and CAFs. The combo significantly impacts on PDAC survival in 2D and 3D models.
View Article and Find Full Text PDFObjective: The immunoregulatory properties of mesenchymal stromal/stem cells (MSCs) bring a promise for the treatment of inflammatory diseases. However, their ability to suppress the immune system is unstable. To enhance their effectiveness against immune responses, it may be necessary to manipulate MSCs.
View Article and Find Full Text PDFCrit Rev Oncol Hematol
September 2023
Preclinical models are extensively employed in cancer research because they can be manipulated in terms of their environment, genome, molecular biology, organ systems, and physical activity to mimic human behavior and conditions. The progress made in in vivo cancer research has resulted in significant advancements, enabling the creation of spontaneous, metastatic, and humanized mouse models. Most recently, the remarkable and extensive developments in genetic engineering, particularly the utilization of CRISPR/Cas9, transposable elements, epigenome modifications, and liquid biopsies, have further facilitated the design and development of numerous mouse models for studying cancer.
View Article and Find Full Text PDFOne third of the world population has a history of exposure to the hepatitis B virus (HBV), and two billion people are infected with latent tuberculosis (TB). Occult hepatitis B infection (OBI) is defined as the presence of replicative-competent HBV DNA in the liver with detectable or undetectable HBV DNA in the serum of individuals testing negative for the HBV surface antigen (HBsAg). Screening with HBV DNA could identify OBI and significantly reduce carriers and complications of chronic hepatitis B (CHB).
View Article and Find Full Text PDFObjectives: The B18R protein encoded by the Vaccinia virus decoys Type 1 interferons and inhibits the activity of several type I IFN members. In vitro transcription protocols benefit from this molecule's involvement in enhancing cell viability by inhibiting interferon signal transduction. As a result of their immunomodulatory properties and potential to regenerate, mesenchymal stromal cells (MSCs) are increasingly considered an alternative treatment for a wide range of immune disorders.
View Article and Find Full Text PDFBackground: Mesenchymal stromal/stem cells (MSCs) are known for their involvement in modulating the immune system of mammals. This potency could be enhanced by different strategies, including regulation of key proteins, in order to meet desirable therapeutic properties. Nanos2, encoding an RNA-binding protein involved in regulation of key spermatogonial signaling pathways, has been demonstrated to downregulate a range of immune related genes in mouse embryonic fibroblasts (MEFs).
View Article and Find Full Text PDFBackground: Epithelial cancers acquire the epithelial to mesenchymal transition (EMT), which leads tumor cells to invade and metastasize to adjacent and distant tissues. The mechanisms involved in EMT phenotype are controlled by numerous markers as well as signalling pathways. Recently, long non-coding RNAs (lncRNAs) were introduced that play the regulatory role in EMT via crosstalk with EMT-related transcription factors and signalling pathways.
View Article and Find Full Text PDFObjective: Gastric cancer (GC) is one of the most common lethal malignancies worldwide. The molecular mechanisms underlying GC early detection are poorly understood. Identifying potential coding and non-coding markers and related pathways in the GC progression is essential.
View Article and Find Full Text PDFGene delivery to esophageal tissue could provide novel treatments for diseases, such as cancer. The Sleeping Beauty (SB) transposon system, as a natural and non-viral tool, is efficient at transferring transgene into the human genome for human cell genetic engineering. The plasmid-based SB transposon can insert into chromosomes through an accurate recombinase-mediated mechanism, providing long-term expression of transgene integrated into the target cells.
View Article and Find Full Text PDFC-X-C chemokine receptor type 4 (CXCR4), initially recognized as a co-receptor for HIV, contributes to several disorders, including the WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome. CXCR4 binds to its ligand SDF-1 to make an axis involved in the homing property of stem cells. This study aimed to employ WHIM syndrome pathogenesis as an inspirational approach to reinforce cell therapies.
View Article and Find Full Text PDFEsophageal cancer is the most common cause of cancer-related death worldwide with a diverse geographical distribution, poor prognosis, and diagnosis in advanced stages of the disease. Identification of the mechanisms involved in esophageal cancer development is evaluative to improve outcomes for patients. Genetically engineered mouse models (GEMMs) of cancer provide the physiologic, molecular, and histologic features of the human tumors to determine the pathogenesis and treatments for cancer, hence exhibiting a source of tremendous potential for oncology research.
View Article and Find Full Text PDFObjectives: Cell-based therapeutic approaches have witnessed significant developments during the last decade especially after approval of MSCs based treatment of graft versus host disease. Several cell-based approaches have shown immunomodulatory behavior during regeneration following the unknown cascade of events but the exact mechanisms are yet to be defined. Clinical applications of cell-based drugs are hampered all over the world because of incomplete understanding of molecular mechanisms requiring the application of mechanistic approaches to solving the mystery.
View Article and Find Full Text PDFBackground: Ovarian cancer has the highest ratio of mortality among gynecologic malignancies. Chemotherapy is one of the most common treatment options for ovarian cancer. However, tumor relapse in patients with advanced tumor stage is still a therapeutic challenge for its clinical management.
View Article and Find Full Text PDFPurpose: Esophageal squamous cancer cell (ESCC), with late diagnosis and poor rate of survival, is a significant cause of mortality in the developing countries. The hypothesis of rare high penetrance with mutations in new genes may explain the underlying predisposition in some of these familial cases.
Methods: Exome sequencing was performed in the patients with ESCC with strong disease aggregation, two sisters with ESCC cancer, and one with breast cancer.
Avicenna J Med Biotechnol
January 2018
Background: Cancer/Testis Antigens (CTAs) are a sub-group of tumor-associated antigens which are expressed normally in germ line cells and trophoblast, and aberrantly in a variety of malignancies. One of the most important CTAs is Developmental Pluripotency Associated-2(DPPA2) with unknown biological function. Considering the importance of in developmental events and cancer, preparing a suitable platform to analyze roles in the cells seems to be necessary.
View Article and Find Full Text PDFThe self-renewal capacity of germline derived stem cells (GSCs) makes them an ideal source for research and use in clinics. Despite the presence of active gene network similarities between embryonic stem cells (ESCs) and GSCs, there are unanswered questions regarding the roles of evolutionary conserved genes in GSCs. To determine the reprogramming potential of germ cell- specific genes, we designed a polycistronic gene cassette expressing Stella, Oct4 and Nanos2 in a lentiviral-based vector.
View Article and Find Full Text PDFBiochem Biophys Res Commun
November 2016
Germline stem cells (GSCs) are attractive biological models because of their strict control on pluripotency gene expression, and their potential for huge epigenetic changes in a short period of time. Few data exists on the cooperative impact of GSC-specific genes on differentiated cells. In this study, we over-expressed 3 GSC-specific markers, STELLA, OCT4 and NANOS2, collectively designated as (SON), using the novel polycistronic lentiviral gene construct FUM-FD, in HEK293T cells and evaluated promoter activity of the Stra8 GSC marker gene We could show that HEK293T cells expressed pluripotency and GSC markers following ectopic expression of the SON genes.
View Article and Find Full Text PDFUnlabelled: Overexpression of MAGEA4 oncogene has been demonstrated in different malignancies; however, little is known about its exact mechanism for overexpression. TWIST1, as a bHLH transcription factor, activates a cell migration-invasion program involved in both embryonic and tumor development. Since MAGEA4 overexpression was statistically correlated to TWIST1, we aimed to elucidate the probable regulatory role of TWIST1 on MAGEA4 expression in KYSE30 cells.
View Article and Find Full Text PDFEpithelial-mesenchymal transition (EMT) is crucial for specific morphogenetic movements during embryonic development as well as pathological processes of tumor cell invasion and metastasis. TWIST and SNAIL play vital roles in both developmental and pathological EMT. Our aim in this study was to investigate the functional correlation between TWIST1 and SNAIL in human ESCC cell line (KYSE-30).
View Article and Find Full Text PDFJ Gastrointest Cancer
September 2016
Purpose: Homeobox (HOX) transcription factors are critical regulators of cell fate, stem cell functions, and gastrointestinal development. They require three-amino acid loop extension (TALE) homeodomain proteins such as Meis1 to enhance their transcriptional efficiencies. There are complicated associations between different signaling pathways such as the Wnt and NOTCH and tumor progression.
View Article and Find Full Text PDFObjectives: The limited homing potential of bone-marrow-derived mesenchymal stem cells (BM-MSC) is the key obstacle in MSC-based therapy. It is believed that chemokines and chemokine receptor interactions play key roles in cellular processes associated with migration. Meanwhile, MSCs express a low level of distinct chemokine receptors and they even lose these receptors on their surface after a few passages which influence their therapeutic applications negatively.
View Article and Find Full Text PDFThe three amino acid loop extension (TALE) class myeloid ecotropic viral integration site 1 (MEIS1) homeobox gene is known to play a crucial role in normal and tumor development. In contrast with its well-described cancer stemness properties in hematopoietic cancers, little is known about its role in solid tumors like esophageal squamous cell carcinoma (ESCC). Here, we analyzed MEIS1 expression and its clinical relevance in ESCC patients and also investigated its correlation with the SOX2 self-renewal master transcription factor in the ESCC samples and in the KYSE-30 ESCC cell line.
View Article and Find Full Text PDFAlthough chicken spermatogonial stem cells (SSCs) have received considerable attention in recent years, only a few studies so far have focused on their derivation and characterization in vitro. Identification of specific molecular biomarkers and differentiation capacity of chicken SSCs would not only help us to understand cell and molecular biology of these cells, but also can contribute to their applications in biotechnology. In this regard, we found that colony-forming cells (SSCs) in newborn chicken testicular cell cultures were positive for alkaline phosphatase activity and also expressed specific markers including DAZL, STRA-8, CVH, PLZF, SPRY-1, GFRα1, GDNF, POU5F1, NANOG, GPR125, THY-1, c-KIT, and BCL6B, at mRNA level.
View Article and Find Full Text PDFIran J Basic Med Sci
November 2014
Objectives: Epigenetic regulation of gene expression can be carried out through chromatin remodeling enzymes such as SWI/SNF. Brg1 also known as SMARCA4 is a catalytic subunit of SWI/SNF, which is necessary for MMPs expression. Matrix metalloproteinases (MMPs) are known as important player enzymes during tumor progression and metastasis.
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