Transforming growth factor-β and oxidative stress in cancer: A crosstalk in driving tumor transformation.

SIMPLE SUMMARY: Metabolic changes in tumor microenvironment play a critical role in cancer, related to the accumulated alterations in signaling pathways that control cellular metabolism. Cancer metabolic deregulation is related to specific events such as the control of oxidative stress, and in particular the redox imbalance with aberrant oxidant production and/or a deregulation of the efficacy of the antioxidant systems. In cancer cells, different cytokines are involved in the development and/or progression of cancer; among these cytokines, the transforming growth factor β (TGF-β) is central to tumorigenesis and cancer progression. In tumor cells, it has been demonstrated that there is a close correlation between oxidative stress and TGF-β; this crosstalk strongly contributes to tumorigenesis, both in tumor development and in mediating its invasiveness. This review is addressed to better understanding this crosstalk between TGF-β and oxidative stress in cancer cell metabolism, in an attempt to improve the pharmacological and therapeutic approach against cancer. ABSTRACT: Cancer metabolism involves different changes at a cellular level, and altered metabolic pathways have been demonstrated to be heavily involved in tumorigenesis and invasiveness. A crucial role for oxidative stress in cancer initiation and progression has been demonstrated; redox imbalance, due to aberrant reactive oxygen species (ROS) production or deregulated efficacy of antioxidant systems (superoxide dismutase, catalase, GSH), contributes to tumor initiation and progression of several types of cancer. ROS may modulate cancer cell metabolism by acting as secondary messengers in the signaling pathways (NF-kB, HIF-1α) involved in cellular proliferation and metastasis. It is known that ROS mediate many of the effects of transforming growth factor β (TGF-β), a key cytokine central in tumorigenesis and cancer progression, which in turn can modulate ROS production and the related antioxidant system activity. Thus, ROS synergize with TGF-β in cancer cell metabolism by increasing the redox imbalance in cancer cells and by inducing the epithelial mesenchymal transition (EMT), a crucial event associated with tumor invasiveness and metastases. Taken as a whole, this review is addressed to better understanding this crosstalk between TGF-β and oxidative stress in cancer cell metabolism, in the attempt to improve the pharmacological and therapeutic approach against cancer

A decrease of calcitonin serum concentrations less than 50 percent 30 minutes after thyroid surgery suggests incomplete C-cell tumor tissue removal

The prognosis of medullary thyroid carcinoma (MTC) depends on the completeness of the first surgical treatment. To date, it is not possible to predict whether the tumor has been completely removed after surgery. The aim of this study was to evaluate the reliability of an intraoperative calcitonin monitoring as a predictor of the final outcome after surgery in patients with MTC

Thyroid nodules treated with percutaneous radiofrequency thermal ablation: a comparative study

Percutaneous radiofrequency thermal ablation (RTA) was reported as an effective tool for the management of thyroid nodules (TNs). The aim of this study was to investigate the effects of RTA and to establish whether they were treatment-related by comparison with a matched, untreated control group

Sorafenib in advanced iodine-refractory differentiated thyroid cancer: efficacy, safety and exploratory analysis of role of serum thyroglobulin and FDG-PET.

Context Radioactive iodine is a crucial tool for treatment of differentiated thyroid cancer (DTC). In 5% of cases, DTCs lose I-131 avidity and assume an aggressive behaviour. Treatment options for iodine-refractory DTC are limited. We report the experience of off-label use of the tyrosine kinase inhibitor sorafenib for treatment of advanced iodine-refractory DTC. Design Patients with progressive DTC refractory to radioactive iodine were treated with sorafenib used off-label independently from their performance status. Primary study end-points were radiological response, progression-free survival (PFS) and safety. Secondary end-points were site-specific radiological response and overall survival (OS). An exploratory analysis of the role of serum thyroglobulin (Tg) and fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed. Results A total of 17 patients were included in the study. Median follow-up was 15·5 months. Clinical benefit was obtained in 71% of subjects (30% partial response and 41% stable disease). Sorafenib was mostly well tolerated, but a high incidence of fatal events was reported (three patients died from severe bleeding events and two from cardiac arrest). Median PFS was 9 months. Median OS was 10 months. The best responses were observed in lymph nodes and lung. Baseline Tg levels and the Tg response to treatment were correlated to both radiological response and PFS. Baseline FDG-PET assessment and early FDG-PET response were correlated to radiological response. Conclusions Sorafenib allows morphological disease control in the majority of patients with iodine-refractory DTC. Progression-free survival and overall survival were lower than in previous studies as a consequence of the worse clinical condition of our patients. Sorafenib is mostly well tolerated but could have been responsible for the reported fatal events. Baseline Tg and the Tg response to treatment could be useful for predicting morphological response and clinical outcome. Early FDG-PET response could be helpful for the timely identification of nonresponding patients

Combined biological therapy with lanreotide autogel and cabergoline in the treatment of MEN-1-related insulinomas.

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome associated with the development of many endocrine tumors, involving mainly pituitary, parathyroids, pancreas, although a proliferative state interests all neuroendocrine system. MEN1 pancreatic neuroendocrine tumors (pNETs) are multiples and can secrete different hormones. The therapeutic approach is based on surgery which usually is followed by tumor relapse or persistence unless to be highly aggressive. Biotherapy with somatostatin analogs and dopamine agonists could be of great benefit to manage these patients without altering their life quality. We report a case of a 36-year-old MEN1 man affected with multicentric pNETs associated with insulinoma syndrome. Therapy with symptomatic agents (diazoxide), as well as biotherapy (lanreotide, cabergoline) was started. At 6-month follow-up, symptomatic agents were stopped and disease control was only based on lanreotide plus cabergoline. This combined biotherapy was able to control endocrine syndromes and tumor growth. Subsequently, a safer and selective surgical intervention on pNETs was performed. An excellent response to therapy with lanreotide autogel and cabergoline has been observed in a MEN1 patient with pNETs associated with insulinoma syndrome. The potential synergistic effects of lanreotide autogel and cabergoline on insulin-secreting neuroendocrine tumors are discussed

Prediction of response to vemurafenib in BRAF V600E mutant cancers based on a network approach

Lung adenocarcinoma is the tumor with the highest number of switch genes (298) compared to its normal tissue, followed by thyroid (227) and colorectal (183) cancers. Switch genes codifying for kinases were 14,7 and 3 respectively.We looked for three homology sequences identified across vemurafenib targets and we found that thyroid cancer and lung adenocarcinoma have a similar number of putative targetable switch genes kinase (5-6); on the contrary, colorectal cancer has just one,with minor homology sequence

Reclassification of Subspecies of \u3ci\u3eAcidovorax avenae\u3c/i\u3e as \u3ci\u3eA. Avenae\u3c/i\u3e (Manns 1905) emend., \u3ci\u3eA. cattleyae \u3c/i\u3e (Pavarino, 1911)comb.nov., \u3ci\u3eA. citrulli\u3c/i\u3e Schaad et al.,1978)comb.nov., and proposal of \u3ci\u3eA. oryzae \u3c/i\u3esp. nov.

The bacterium Acidovorax avenae causes disease in a wide range of economically important monocotyledonous and dicotyledonous plants, including corn, rice, watermelon, anthurium, and orchids.Genotypic and phenotypic relatedness among strains of phytopathogenic A. avenae sub sp. avenae, A. avenae sub sp. citrulli, A. avenae subsp. cattleyae and A. konjaci, as well as all other Acidovorax species, including A. facilis, the type strain of Acidovorax, was determined.The16s rDNA sequencing confirmed previous studies showing the environmental species to be very distant from the phytopathogenic species. DNA/DNA reassociation assays on the different strains of A. avenae revealed four(A, B, C, and D) distinct genotypes. Taxon A included six A. avenae subsp. avenaestrains from corn that had a mean reciprocal similarity of 81%; taxon B included six A. avenae sub sp. avenae strains from rice that had a mean reciprocal similarity of 97%; taxon C contained 11 A. avenae sub sp. citrulli strains from cucurbits (cantaloupe, watermelon, and pumpkin) that had a mean reciprocal similarity of 88%, and taxon D contained four A. avenae sub sp. cattleyae strains from orchids that had a mean similarity of 98%

Computing, Design, Art: Reflections on an Innovative Moment in History

The paper is concerned with the role of art and design in the history and philosophy of computing. It offers insights arising from research into a period in the 1960s and 70s, particularly in the UK, when computing became more available to artists and designers, focusing on John Lansdown (1929-1999) and Bruce Archer (1922-2005) in London. Models of computing interacted with conceptualisations of art, design and related creative activities in important ways

Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness