Search results for "cept"

Abstract 2810: Pterostilbene, a natural phytoalexin, weakens the antioxidant defenses of aggressive cancer cells in vivo: a pituitary gland- and Nrf2…

2016

Abstract Polyphenolic phytochemicals have anticancer properties. However, in mechanistic studies lack of correlation to the bioavailable concentrations is a critical issue. We studied the underlying mechanisms using different human melanomas (A2058, MeWo and MelJuso) and pancreatic cancers (AsPC-1 and BxPC-3) (with genetic backgrounds correlating with most tumors in patients), growing in nude mice as xenografts, and pterostilbene (Pter, 3’,5’-dimethoxy-4-stilbenol; abundant in e.g. blueberries and a natural dimethoxylated analog of resveratrol). RESULTS: Intravenous administration of Pter decreased human melanoma and pancreatic cancer growth (an effect associated with lower rates of tumor c…

A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers

2018

Single nucleotide polymorphisms (SNPs) in DNA glycosylase genes involved in the base excision repair (BER) pathway can modify breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We previously found that SNP rs34259 in the uracil-DNA glycosylase gene (UNG) might decrease ovarian cancer risk in BRCA2 mutation carriers. In the present study, we validated this finding in a larger series of familial breast and ovarian cancer patients to gain insights into how this UNG variant exerts its protective effect. We found that rs34259 is associated with significant UNG downregulation and with lower levels of DNA damage at telomeres. In addition, we found that this SNP is associated with…

A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer

2019

No luminal; Subtipus intrínsec; Càncer de mama No luminal; Subtipo intrínseco; Cáncer de mama Non-luminal; Intrinsic subtype, Breast cancer Background: In hormone receptor-positive (HR+)/HER2-negative breast cancer, the HER2-enriched and Basal-like intrinsic subtypes are associated with poor outcome, low response to anti-estrogen therapy and high response to chemotherapy. To date, no validated biomarker exists to identify both molecular entities other than gene expression. Methods: PAM50 subtyping and immunohistochemical data were obtained from 8 independent studies of 1,416 HR+/HER2-negative early breast tumors. A non-luminal disease score (NOLUS) from 0 to 100, based on percentage of estr…

2017

AbstractInterleukin-4 plays a critical role in the regulation of immune responses and has been detected at high levels in the tumour microenvironment of cancer patients, where concentrations correlate with the grade of malignancy. In prostate cancer, interleukin-4 has been associated with activation of the androgen receptor, increased proliferation and activation of survival pathways such as Akt and NF-κB. However, its role in therapy resistance has not yet been determined. Here we investigate the influence of interleukin-4 on primary epithelial cells from prostate cancer patients. Our data demonstrate an increase in the clonogenic potential of these cells when cultured in the presence of i…

The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment

2021

Simple Summary Immunotherapy improved the therapeutic landscape for patients with advanced cancer diseases. However, many patients do not benefit from immunotherapy. The bidirectional crosstalk between myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) contributes to immune evasion, limiting the success of immunotherapy by checkpoint inhibitors. This review aims to outline the current knowledge of the role and the immunosuppressive properties of MDSC and Treg within the tumor microenvironment (TME). Furthermore, we will discuss the importance of the functional crosstalk between MDSC and Treg for immunosuppression, issuing particularly the role of cell adhesion molecules. …

Platelet-Derived GARP Induces Peripheral Regulatory T Cells—Potential Impact on T Cell Suppression in Patients with Melanoma-Associated Thrombocytosis

2020

Platelets have been recently described as an important component of the innate and adaptive immunity through their interaction with immune cells. However, information on the platelet&ndash

Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases

2021

Simple Summary Metastatic disease remains one of the biggest challenges for tumor therapy. The aim of our study was the preclinical evaluation of adapter chimeric antigen receptor (AdCAR)-engineered NK-92 cell efficacy as a possible treatment strategy for various types of bone metastatic cancers. We confirmed that AdCAR NK-92 cells successfully induces tumor cell lysis in bone metastasis cell lines derived from mammary, renal cell and colorectal carcinoma as well as melanoma in a specific and controllable manner, thus, establishing a potent cellular product with universal applicability and quick clinical translation potential for the treatment of solid tumors, including metastases. Abstract…

Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum

2018

The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A(2A) receptor (A(2A)R) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A(2A)R and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A(2A)R-CB1R heteromeric complexes. However, th…

2021

Brain homeostasis is the dynamic equilibrium whereby physiological parameters are kept actively within a specific range. The homeostatic range is not fixed and may change throughout the individual's lifespan, or may be transiently modified in the presence of severe perturbations. The endocannabinoid system has emerged as a safeguard of homeostasis, e.g., it modulates neurotransmission and protects neurons from prolonged or excessively strong activation. We used genetically engineered mouse lines that lack the cannabinoid type-1 receptor (CB1) either in dorsal telencephalic glutamatergic or in forebrain GABAergic neurons to create new allostatic states, resulting from alterations in the exci…

2018

Defining functional domains and amino acid residues in G protein coupled receptors (GPCRs) represent an important way to improve rational drug design for this major class of drug targets. The cannabinoid type 1 (CB1) receptor is one of the most abundant GPCRs in the central nervous system and is involved in many physiological and pathophysiological processes. Interestingly, cannabinoid type 1 receptor with a phenylalanine 238 to leucine mutation (CB1F238L) has been already linked to a number of both in vitro and in vivo alterations. While CB1F238L causes significantly reduced presynaptic neurotransmitter release at the cellular level, behaviorally this mutation induces increased risk taking…