Lindhardtsloth6368

Large granular lymphocyte leukemia (LGLL) is a chronic proliferation of clonal cytotoxic lymphocytes, usually presenting with cytopenias and yet lacking a specific therapy. The disease is heterogeneous, including different subsets of patients distinguished by LGL immunophenotype (CD8+ Tαβ, CD4+ Tαβ, Tγδ, NK) and the clinical course of the disease (indolent/symptomatic/aggressive). Even if the etiology of LGLL remains elusive, evidence is accumulating on the genetic landscape driving and/or sustaining chronic LGL proliferations. The most common gain-of-function mutations identified in LGLL patients are on STAT3 and STAT5b genes, which have been recently recognized as clonal markers and were included in the 2017 WHO classification of the disease. A significant correlation between STAT3 mutations and symptomatic disease has been highlighted. At variance, STAT5b mutations could have a different clinical impact based on the immunophenotype of the mutated clone. In fact, they are regarded as the signature of an aggressive clinical course with a poor prognosis in CD8+ T-LGLL and aggressive NK cell leukemia, while they are devoid of negative prognostic significance in CD4+ T-LGLL and Tγδ LGLL. Knowing the specific distribution of STAT mutations helps identify the discrete mechanisms sustaining LGL proliferations in the corresponding disease subsets. Some patients equipped with wild type STAT genes are characterized by less frequent mutations in different genes, suggesting that other pathogenetic mechanisms are likely to be involved. In this review, we discuss how the LGLL mutational pattern allows a more precise and detailed tumor stratification, suggesting new parameters for better management of the disease and hopefully paving the way for a targeted clinical approach. Copyright © 2020 Teramo, Barilà, Calabretto, Vicenzetto, Gasparini, Semenzato and Zambello.Objective Recently, performing locoregional surgical treatment still remains debatable in patients with metastatic breast cancer (MBC). Current study aimed to develop prognostic nomograms for predicting the long-term survival in MBC patients with or without surgical intervention, thereby assisting clinicians in making individualized choice. Methods The training set included 5173 patients who were diagnosed with MBC in 2010-2013 from the Surveillance, Epidemiology, and End Results Program, while the validation set comprised 2924 patients diagnosed in 2014-2015. Multivariant Cox hazard model was applied to determine the independent risk factors for overall survival (OS) and breast cancer specific survival (BCSS). Then, individualized pre- and postoperative nomograms for predicting 1- or 3-year survival probabilities were constructed accordingly. Internal and external validations were conducted to determine the accuracy of these nomograms by calculating concordance index (C-index) and plotting calibration curvesZheng, Zhong, Yu, Lei and Yang.Combinational use of drugs has been a common strategy in cancer treatment because of synergistic advantages in reducing dose and toxicity, minimizing or delaying drug resistance. To improve the efficacy of chemotherapy, various potential combinations have been investigated. Ruthenium complex is considered a potential alternative of the platinum-based drugs due to its significant efficacy and safety. Previously, we reported that ruthenium(II) complex (Δ-Ru1) has great anticancer potential and minor toxicity toward normal tissues. However, the therapeutic efficacy and mechanism of action of ruthenium(II) complex combined with other anticancer drugs is still unknown. Here, we investigated the combinational effect of Δ-Ru1 and doxorubicin in different cancer cells. The data assessed by Chou-Talalay method showed significant synergism in MCF-7 cells. Furthermore, the results in antiproliferation efficacy indicated that the combination showed strong cytotoxicity and increasing apoptosis of MCF-7 cells in 2D and 3D multicellular tumor spheroids (MCTSs). Significant inhibition of MCF-7 cells accompanied with increased ROS generation was observed. Furthermore, the expression of PI3K/AKT was significantly down-regulated, while the expression of PTEN was strongly up-regulated in cells treated with combination of Δ-Ru1 and doxorubicin. The expression of NF-κB and XIAP decreased while the expression of P53 increased and associated with apoptosis. These findings suggest that the combination of ruthenium complex and doxorubicin has a significant synergistic effect by down-regulating the PI3K/AKT signaling pathway in MCF-7 cells. This study may trigger more research in ruthenium complex and combination therapy that will be able to provide opportunities for developing better therapeutics for cancer treatment. Copyright © 2020 Lin, Rong, Chen, Zhao, Bo, Qiao, Hao and Wang.Lung cancer mortality represents the leading cause of cancer related deaths in the United States and worldwide. Almost half of these deaths occur in female patients, making lung cancer the most common cause of cancer mortality in women with a higher annual mortality rate than breast, uterine, and ovarian cancers combined. The distinct epidemiological, histological and biological presentation of non-small cell lung cancer (NSCLC) in women combined with extensive preclinical data have demonstrated that the female sex hormone β-estradiol (E2) plays an important role in NSCLC tumorigenesis, prognosis, and treatment response. Estrogen receptors are widely expressed on stromal and immune cells, and estrogen-linked signaling pathways are known to be involved in regulating the response of both the innate and adaptive immune system. selleck kinase inhibitor Immune evasion has been recognized as a "hallmark" of cancer and immunotherapy has re-defined standard of care treatment for NSCLC. Despite these advancements, the low response rates obsererapy agents. Copyright © 2020 Smida, Bruno and Stabile.Introduction Lacrymal cystic adenoid carcinoma is a rare disease for which optimal treatment is still debated. In fact, despite aggressive treatment such as eye sparing surgery or orbital exenteration, following by adjuvant radiotherapy, local recurrence and distant metastatic disease are common. This study aims to describe outcomes of eye surgery associated with high dose exclusive adjuvant proton beam irradiation. Materials and Methods This is a monocentric institutional retrospective study. We retrospectively reviewed records of patients treated in our institution since 2008 with high dose adjuvant proton irradiation for a lacrymal cystic adenoid carcinoma up to a maximum of 75.6Gy(RBE). Other histologies or patients treated with a mix of photon-proton were excluded. A total of 15 patients were finally included. Results Fifteen patients (80% women, 100% Performance status 0-1) with locally advanced disease (33% T3-T4, 47% R1-R2) were included. After a median follow-up of 67.4 months [13.4-122] the 3 years Overall Survival, local Progression free survival, and progression free survival rates were 78, 70, and 58%, respectively.