Search results for "Carcinogen"

Weight loss programmes using low carbohydrate diets to control the cardiovascular risk in adolescents (Review).

2020

Cardiovascular risk (CVR) is a broad term that includes traditional factors like hypertension, hyper lipidemia, abdominal obesity, hyperinsulinemia or overt type 2 diabetes mellitus (T2DM), and emerging ones such as hypothyroidism or inflammatory diseases. In epidemiologic studies, all of these factors are associated with atherogenesis and have complex interactions between them. They have in common an increased prevalence in the general population beginning in childhood, and are correlated with endothelial damage as demonstrated by echocardiographic modifications of the left ventricle or carotid intima-media thickness. Adolescence is a transition period where behavioural eating patterns dev…

LC3-Associated Phagocytosis (LAP): A Potentially Influential Mediator of Efferocytosis-Related Tumor Progression and Aggressiveness

2020

One aim of cancer therapies is to induce apoptosis of tumor cells. Efficient removal of the apoptotic cells requires coordinated efforts between the processes of efferocytosis and LC3-associated phagocytosis (LAP). However, this activity has also been shown to produce anti-inflammatory and immunosuppressive signals that can be utilized by live tumor cells to evade immune defense mechanisms, resulting in tumor progression and aggressiveness. In the absence of LAP, mice exhibit suppressed tumor growth during efferocytosis, while LAP-sufficient mice show enhanced tumor progression. Little is known about how LAP or its regulators directly affect efferocytosis, tumor growth and treatment respons…

Repurposing of plant alkaloids for cancer therapy: Pharmacology and toxicology.

2019

Drug repurposing (or repositioning) is an emerging concept to use old drugs for new treatment indications. Phytochemicals isolated from medicinal plants have been largely neglected in this context, although their pharmacological activities have been well investigated in the past, and they may have considerable potentials for repositioning. A grand number of plant alkaloids inhibit syngeneic or xenograft tumor growth in vivo. Molecular modes of action in cancer cells include induction of cell cycle arrest, intrinsic and extrinsic apoptosis, autophagy, inhibition of angiogenesis and glycolysis, stress and anti-inflammatory responses, regulation of immune functions, cellular differentiation, a…

Preclinical models for precision oncology

2018

Precision medicine approaches have revolutionized oncology. Personalized treatments require not only identification of the driving molecular alterations, but also development of targeted therapies and diagnostic tests to identify the appropriate patient populations for clinical trials and subsequent therapeutic implementation. Preclinical in vitro and in vivo models are widely used to predict efficacy of newly developed treatments. Here we discuss whether, and to what extent, preclinical models including cell lines, organoids and tumorgrafts recapitulate key features of human tumors. The potential of preclinical models to anticipate treatment efficacy and clinical benefit is also presented,…

2021

Background Malignant melanoma is an immunogenic skin cancer with an increasing global incidence. Advanced stages of melanoma have poor prognoses. Currently, there are no reliable parameters to predict a patient's response to immune checkpoint inhibitor (ICI) therapy. Methods This study highlights the relevance of a distinct immune signature in the blood for response to ICI therapy and overall survival (OS). Therefore, the immune cell composition in the peripheral blood of 45 melanoma patients prior to ICI therapy was analyzed by flow cytometry and complete blood count. Results Responders to ICI therapy displayed an abundance of proliferating CD4+ T cells, an increased lymphocyte-to-monocyte…

Frequency and prognostic impact of ALK amplifications and mutations in the European Neuroblastoma Study Group (SIOPEN) high-risk neuroblastoma trial …

2021

Purpose: In neuroblastoma (NB), the ALK receptor tyrosine kinase can be constitutively activated through activating point mutations or genomic amplification. We studied ALK genetic alterations in high-risk (HR) patients on the HR-NBL1/SIOPEN trial to determine their frequency, correlation with clinical parameters, and prognostic impact. Materials and methods: Diagnostic tumor samples were available from 1,092 HR-NBL1/SIOPEN patients to determine ALK amplification status (n = 330), ALK mutational profile (n = 191), or both (n = 571). Results: Genomic ALK amplification (ALKa) was detected in 4.5% of cases (41 out of 901), all except one with MYCN amplification (MNA). ALKa was associated with …

The secreted protein acidic and rich in cysteine is a critical mediator of cell death program induced by WIN/TRAIL combined treatment in osteosarcoma…

2015

Abstract Secreted protein acidic and rich in cysteine (SPARC) is a multi-functional protein which modulates cell-cell and cell-matrix interactions. In cancer cells, SPARC behaves as a tumor promoter in a number of tumors, but it can also act as a tumor suppressor factor. Our previous results showed that the synthetic cannabinoid WIN55,212-2 (WIN), a potent cannabinoid receptor agonist, is able to sensitize osteosarcoma MG63 cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis which is accompanied with endoplasmic reticulum (ER)-stress induction and the increase in autophagic markers. In the present investigation, we studied the role of SPARC in WIN/TRAIL-induced apoptosi…

2021

The prognosis for advanced prostate carcinoma (PCa) remains poor due to development of therapy resistance, and new treatment options are needed. Shikonin (SHI) from Traditional Chinese Medicine has induced antitumor effects in diverse tumor entities, but data related to PCa are scarce. Therefore, the parental (=sensitive) and docetaxel (DX)-resistant PCa cell lines, PC3, DU145, LNCaP, and 22Rv1 were exposed to SHI [0.1–1.5 μM], and tumor cell growth, proliferation, cell cycling, cell death (apoptosis, necrosis, and necroptosis), and metabolic activity were evaluated. Correspondingly, the expression of regulating proteins was assessed. Exposure to SHI time- and dose-dependently inhibited tum…

Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells

2019

To fight resistances to radiotherapy, the understanding of escape mechanisms of tumor cells is crucial. The aim of this study was to identify phosphoproteins that are regulated upon irradiation. The comparative analysis of the phosphoproteome before and after irradiation brought nucleophosmin (NPM1) into focus as a versatile phosphoprotein that has already been associated with tumorigenesis. We could show that knockdown of NPM1 significantly reduces tumor cell survival after irradiation. NPM1 is dephosphorylated stepwise within 1 hour after irradiation at two of its major phosphorylation sites: threonine-199 and threonine-234/237. This dephosphorylation is not the result of a fast cell cycl…

Molecular Engineering Strategies Tailoring the Apoptotic Response to a MET Therapeutic Antibody

2020

The MET oncogene encodes a tyrosine kinase receptor involved in the control of a complex network of biological responses that include protection from apoptosis and stimulation of cell growth during embryogenesis, tissue regeneration, and cancer progression. We previously developed an antagonist antibody (DN30) inducing the physical removal of the receptor from the cell surface and resulting in suppression of the biological responses to MET. In its bivalent form, the antibody displayed a residual agonist activity, due to dimerization of the lingering receptors, and partial activation of the downstream signaling cascade. The balance between the two opposing activities is variable in different…