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Incubation of both cell lines with M22 (0.006-50 ng/mL) resulted in a dose-dependent increase in cAMP levels with linear ranges for the MC4 and WT cells of 0.8-12.5 and 0.2-3.125 ng/mL, respectively. Comparison of cAMP and luciferase levels in M22-treated MC4 and WT cells also showed a positive correlation (r = 0.88, p less then 0.001 and 0.75, p = 0.002). A positive correlation was also noted when using patient samples (r = 0.96, p less then 0.001) that were all TSH-R-Ab binding assay positive. Conclusion The novel, rapid, simple-to-perform cAMP assay provides TSAb-mediated stimulatory results comparable to a luciferase-based bioassay. Copyright © 2019 by S. Karger AG, Basel.Introduction Injection of 3-iodothyronamine into experimental animals profoundly affects their metabolism and body temperature. As 3-iodothyronamine is rapidly acetylated in vivo after injection, it was hypothesized that the metabolites N- or O-acetyl-3-iodothyronamines could constitute the active hormones. Methods Adult male mice were injected once daily with one of the metabolites (5 mg/kg body weight intraperitoneally dissolved in 60% DMSO in PBS) or solvent. Metabolism was monitored by indirect calorimetry, body temperature by infrared thermography, and body composition by nuclear magnetic resonance analysis. Signaling activities in brown fat or liver were assessed by studying target gene transcription by qPCR including uncoupling protein 1 or deiodinase type 1 or 2, and Western blot. Results The markers of metabolism, body composition, or temperature tested were similar in the mice injected with solvent and those injected with one of the acetylated 3-iodothyronamines. Birabresib inhibitor Conclusions In our experimental setup, N- and O-acetyl-3-iodothyronamine do not constitute compounds contributing to the metabolic or temperature effects described for 3-iodothyronamine. The acetylation of 3-iodothyronamine observed in vivo may thus rather serve degradation and elimination purposes. Copyright © 2019 by S. Karger AG, Basel.Background Platinum-based agents, including cisplatin, carboplatin, and oxaliplatin, are indispensable for the treatment of lung cancer. The development of toxicity frequently necessitates dose reduction or discontinuation of therapy, despite the clinical response. Pharmacogenomics studies were reviewed to identify the possible genetic variants that underlie individual susceptibility to platinum-related toxicities. Method We conducted a systematic search in PubMed and Embase for pharmacogenomics reports that focused on commonly reported platinum-induced toxicities, such as gastrointestinal (GI), hematological, neurological, and other toxicities, in patients diagnosed with lung cancer. Meta-analyses were conducted to determine the association between genetic polymorphisms and platinum-induced toxicity by checking the odds ratio (OR) and 95% confidence interval (CI) using random or fixed-effects models as appropriate. Results Twenty eligible studies that met the inclusion criteria with sufficient data were extracted and presented comprehensively. A total of 16 polymorphisms from 11 genes were included in the meta-analysis. MTHFR rs1801131 and MDM2 rs1690924 were significantly correlated with platinum-induced GI toxicity (P = 0.04 and P = 0.02, respectively). Patients with the MTHFR rs1801131AA and MDM2 rs1690924TC/CC genotype tended to have a higher risk of GI toxicity than patients with other genotypes did (OR = 1.73, 95% CI = 0.86-2.18; and OR = 0.51, 95% CI = 0.29-0.88, respectively). Compared to carriers of the MTHFR rs1801133CC genotype, carriers of the CT/TT genotype had a significantly increased risk of hematological toxicity (P = 0.01, OR = 1.68, 95% CI = 1.12-2.52). Conclusion In the future, physicians should pay careful attention to MTHFR and MDM2 for personalized chemotherapy treatment among patients with lung cancer. Copyright © 2020 Liu, Wang, Luo, Yuan and Luo.Accumulating evidence suggests that platelets play a key role in cancer metastatic dissemination through their multilevel interaction with tumor cells. Most crucial is the contribution of platelets to the formation and expansion of the early metastatic niche, a protective microenvironment that nurtures the first metastatic cells and is necessary for the establishment of overt metastatic disease. A multitude of mechanisms have been proposed toward this effect. The current review examines the implication of platelets in the three most well-studied mechanisms (a) the initial preparation of the metastatic microenvironment by the formation of the extracellular matrix (ECM) and the recruitment of granulocytes, (b) the creation of the neovasculature (important for providing the developing tumor with oxygen and nutrients and clearing away the metabolic waste), and (c) the evasion of the immune response by the creation of an immune-suppressive environment around the developing metastases. Finally, the review provides current perspectives on the potential clinical relevance of platelets in cancer progression and their consequent role in cancer therapeutics. Copyright © 2020 Gkolfinopoulos, Jones and Constantinidou.Lung cancer is one of the deadliest diseases in the world and is the leading cause of cancer-related deaths. Among the histological types, adenocarcinoma is the most common, and it is characterized by a high degree of heterogeneity at many levels including clinical, behavioral, cellular and molecular. While most lung cancers are known for their aggressive behavior, up to 18.5% of lung cancers detected by CT screening are indolent and put patients at risk for overdiagnosis and overtreatment. The cellular and molecular underpinnings of tumor behavior remain largely unknown. In the recent years, the study of intratumor heterogeneity has become an attractive strategy to understand tumor progression. This review will summarize some of the current known determinants of lung adenocarcinoma behavior and discuss recent efforts to dissect its intratumor heterogeneity. Copyright © 2020 Senosain and Massion.Radiation therapy (RT) of thoracic cancers may cause severe radiation dermatitis (RD), which impacts on the quality of a patient's life. Aim of this study was to analyze the incidence of acute RD and develop normal tissue complication probability (NTCP) models for severe RD in thoracic cancer patients treated with Intensity-Modulated RT (IMRT) or Passive Scattering Proton Therapy (PSPT). We analyzed 166 Non-Small-Cell Lung Cancer (NSCLC) patients prospectively treated at a single institution with IMRT (103 patients) or PSPT (63 patients). All patients were treated to a prescribed dose of 60 to 74 Gy in conventional daily fractionation with concurrent chemotherapy. RD was scored according to CTCAE v3 scoring system. For each patient, the epidermis structure (skin) was automatically defined by an in house developed segmentation algorithm. The absolute dose-surface histogram (DSH) of the skin were extracted and normalized using the Body Surface Area (BSA) index as scaling factor. Patient and treatment-related characteristics were analyzed.