Search results for "Genesis"

Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis

2020

Although innovative therapeutic concepts have led to better treatment of advanced renal cell carcinoma (RCC), efficacy is still limited due to the tumor developing resistance to applied drugs. Artesunate (ART) has demonstrated anti-tumor effects in different tumor entities. This study was designed to investigate the impact of ART (1&ndash

NOTCH3 expression is linked to breast cancer seeding and distant metastasis

2018

Background Development of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination of cancer cells from the primary tumor to secondary organs. NOTCH developmental signaling plays a critical role in promoting epithelial-to-mesenchymal transition, tumor stemness, and metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive. Methods We have established metastatic xenografts expressing high endogenous levels of NOTCH3 using estrogen receptor alpha-positive (ERα+) MCF…

Interleukin-6 increases expression of serine protease inhibitor Kazal type 1 through STAT3 in colorectal adenocarcinoma

2015

Inflammation promotes colorectal cancer (CRC) tumorigenesis, but the underlying molecular mechanisms are still being uncovered. Proinflammatory cytokine interleukin-6 (IL-6) stimulates survival signaling in CRC; inflammatory signals also regulate production and activity of proteases and their inhibitors. Over-expression of serine protease inhibitor Kazal type 1 (SPINK1) predicts an unfavorable outcome in colon cancer. The SPINK1 gene contains an IL-6 responsive element, suggesting it could act as an acute phase reactant. We assessed the connection between IL-6 and SPINK1, and the function and mechanism of this signaling. Our results show that Colo205 and HT-29 cells express and secrete SPIN…

2019

Colorectal cancer (CRC) and cachexia are associated with the gut microbiota and microbial surface molecules. We characterized the CRC-associated microbiota and investigated whether cachexia affects the microbiota composition. Further, we examined the possible relationship between the microbial surface molecule flagellin and CRC. CRC cells (C26) were inoculated into mice. Activin receptor (ACVR) ligands were blocked, either before tumor formation or before and after, to increase muscle mass and prevent muscle loss. The effects of flagellin on C26-cells were studied in vitro. The occurrence of similar phenomena were studied in murine and human tumors. Cancer modulated the gut microbiota witho…

Potential Molecular Players of the Tumor Microenvironment in Extracranial Pediatric Solid Tumors

2020

Pediatric cancers are rare malignancies worldwide and represent around 1% of all new cancer diagnoses [...]

Abstract LB-130: Combinatorial treatment with intratumoral cytokine mRNAs results in high frequency of tumor rejection and development of anti-tumor …

2018

Abstract Cancer immunotherapy localized to the tumor microenvironment holds great potential to promote innate and adaptive immune responses against tumors, while avoiding toxicities related to systemic administration of immuno-modulatory therapeutics. Current strategies for tumor-targeted, gene-based delivery of immune therapies face limitations in the clinic due to suboptimal target expression, anti-vector immunity, potential for unwanted genomic rearrangements and other off target effects. We developed a highly potent synthetic mRNA-based platform for in vivo transfection and sustained intratumoral expression of immuno-modulatory molecules that is capable of inducing immunity to tumor spe…

Aberrant splicing of the tumor suppressor CYLD promotes the development of chronic lymphocytic leukemia via sustained NF-κB signaling

2017

The pathogenesis of chronic lymphocytic leukemia (CLL) has been linked to constitutive NF-κB activation but the underlying mechanisms are poorly understood. Here we show that alternative splicing of the negative regulator of NF-κB and tumor suppressor gene CYLD regulates the pool of CD5+ B cells through sustained canonical NF-κB signaling. Reinforced canonical NF-κB activity leads to the development of B1 cell-associated tumor formation in aging mice by promoting survival and proliferation of CD5+ B cells, highly reminiscent of human B-CLL. We show that a substantial number of CLL patient samples express sCYLD, strongly implicating a role for it in human B-CLL. We propose that our new CLL-l…

Relevance of the natural HDAC inhibitor sulforaphane as a chemopreventive agent in urologic tumors.

2018

Due to an increased understanding of molecular biology and the genomics of cancer, new and potent agents have been approved by the Food and Drug Administration (FDA) to fight this disease. However, all of these drugs cause severe side effects and resistance inevitably develops, re-activating tumor growth and dissemination. For this reason, patients turn to natural compounds as alternative or complementary treatment options, since it has been found that natural plant products may block, inhibit, or reverse cancer development. The present review focusses on the role of the natural compound sulforaphane (SFN) as an anti-tumor agent in urologic cancer. SFN is a natural compound found in crucife…

Hypoxia-Inducible Factor-1α Activity as a Switch for Glioblastoma Responsiveness to Temozolomide

2018

Rationale: The activity of the transcription factor, hypoxia-inducible factor (HIF)-1?, is a common driver of a number of the pathways involved in the aggressiveness of glioblastomas (GBMs), and it has been suggested that the reduction in this activity observed, soon after the administration of temozolomide (TMZ), can be a biomarker of an early response in GBM models. As HIF-1? is a tightly regulated protein, studying the processes involved in its downregulation could shed new light on the mechanisms underlying GBM sensitivity or resistance to TMZ. Methods: The effect of HIF-1? silencing on cell responsiveness to TMZ was assessed in four genetically different human GBM cell lines by evaluat…

Targeting Immune Modulators in Glioma While Avoiding Autoimmune Conditions

2021

Simple Summary Glioblastoma multiforme is a futile disease usually leading to the patient’s death within one year post-diagnosis; therefore, novel treatment options are desperately needed. In this regard, activation of the inert immune system has moved into focus in recent years. Malignant brain tumors, as well as autoimmune diseases, elicit aberrant immune responses. In this way, glioma escapes the host’s immune system and, thus, activation of the immune response in order to reduce tumor tolerance can serve as an alternative treatment option. Immune checkpoint modulators in combination with traditional therapies have gained attention in both glioma and autoimmune diseases. In this review, …