How Do Cytotoxic Lymphocytes Kill Cancer Cells?

In the past few years, cancer immunotherapy has emerged as a safe and effective alternative for treatment of cancers that do not respond to classical treatments, including those types with high aggressiveness. New immune modulators, such as cytokines, blockers of CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and PD-1(programmed cell death protein 1)/PD-L1 (programmed death-ligand 1), and interaction or adoptive cell therapy, have been developed and approved to treat solid and hematologic carcinomas. In these scenarios, cytotoxic lymphocytes (CL), mainly cytotoxic T cells (Tc) and natural killer (NK) cells, are ultimately responsible for killing the cancer cells and eradicating the tumor. Extensive studies have been conducted to assess how Tc and NK cells get activated and recognize the cancer cell. In contrast, few studies have focused on the effector molecules used by CLs to kill cancer cells during cancer immunosurveillance and immunotherapy. In this article, the two main pathways involved in CL-mediated tumor cell death, granule exocytosis (perforin and granzymes) and death ligands, are briefly introduced, followed by a critical discussion of the molecules involved in cell death during cancer immunosurveillance and immunotherapy. This discussion also covers unexpected consequences of proinflammatory and survival effects of granzymes and death ligands and recent experimental evidence indicating that perforin and granzymes of CLs can activate nonapoptotic pathways of cell death, overcoming apoptosis defects and chemoresistance. The consequences of apoptosis versus other modalities of cell death for an effective treatment of cancer by modulating the patient immune system are also briefly discussed. Clin Cancer Res; 21(22); 5047–56. ©2015 AACR

GZMA (granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3))

Review on GZMA (granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)), with data on DNA, on the protein encoded, and where the gene is implicated

Benefits of Adding an Aquatic Resistance Interval Training to a Nutritional Education on Body Composition, Body Image Perception and Adherence to the Mediterranean Diet in Older Women

The human population is increasing due to lengthening life expectancy, but the quality of life and health of people is moving in the opposite direction. The purpose of this study is to evaluate how aquatic resistance interval training can influence body composition, body image perception and adherence to the Mediterranean diet (MD) in older women participants in a nutrition education program and to study the relation between these variables. Thirty-four participants aged 69 ± 4 years were randomly assigned into two groups: experimental (aquatic resistance interval training plus nutritional intervention) and control (nutritional intervention). The intervention consisted of resistance training in an aquatic environment carried out for 14 weeks (three sessions per week; 60 min each). Body composition, body image perception and adherence to MD diet were evaluated at baseline and 14 weeks. No significant differences were found between groups regarding body image perception and adherence to the MD. There was a significant increase in muscle mass (kg) (p < 0.001) and a significant decrease in fat mass (kg) (p < 0.001) in the intervention group when compared to the control group. The addition of aquatic resistance interval training to a nutritional intervention was not sufficient to change body image perception and adherence to MD but produced improvement in body composition (through an increase in muscle mass and decrease on fat mass) in older women

Wear Behavior of a Ni/Co Bilayer Coating by Physical Vapor Deposition on AISI 1045 Steel

Coatings by physical vapor deposition (PVD) have become highly relevant due to their wide range of applications and the rapid rate of coating formation. In this work, AISI steel 1045 was coated with two layers, Ni and Co using the PVD technique. Each coating was deposited with a thickness of 1 μm. After applying the coatings, a post-treatment was applied in an AC plasma reactor using a boron nitride blank in an Ar atmosphere at a pressure of 3 Torr, 0.3 A, and 460 V at 4, 8, and 12h. The post-treatment was characterized by optical emission spectroscopy (OES) in a range of 200-1100 nm. The main species observed by OES were Ar+, N2, N2+, and B+. The coatings on 1045 steel and posttreatment were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Also, were subjected to tribological tests to analyze wear resistance, using the Pin-on-Disk technique. The coatings on steel 1045 present remarkably better wear properties than the uncoated 1045 steel, being the sample post-treated at 4h that showed a lower wear rate

Role of the extended lymphadenectomy in gastric cancer surgery: experience

Although curative resection is the treatment of choice for gastric cancer, controversy exists about the adequate extent of lymph node dissection when resection is performed. METHODS: We retrospectively assessed 85 patients who underwent a limited lymphadenectomy (D1) and 71 who had an extended lymph node dissection (D2) in a single institution between 1990 and 1998 (median follow-up, 37.3 months). Prognostic factors were assessed by Cox proportional hazard models adjusted for potential confounders. RESULTS: We found no significant difference in the length of hospital stay (median, 12.1 and 13.1 days), overall morbidity (48.2% and 53.5%), or operative mortality (2.3% and 0%) between D1 and D2, respectively. Five-year survival in the D2 group was longer (50.6%) than in the D1 group (41.4%) for tumor stages (tumor-node-metastasis) >I. In multivariate analysis, tumor-node-metastasis stage (hazard ratio for stages >I vs. 0-I, 11.6), the ratio between invaded and removed lymph nodes, the presence of distant metastases, Lauren classification, and the extent of lymphadenectomy (hazard ratio for D1 vs. D2, 2.3; 95% confidence interval, 1.25-4.30) were the only significant prognostic factors. CONCLUSIONS: Our experience shows that extended (D2) lymph node dissection improves survival in patients with resected gastric cancer

Measurement of urea and creatinine in saliva of dogs : a pilot study

Urea and creatinine in saliva have been reported to be possible markers of chronic kidney disease (CKD) in humans. The aim of this study was to assess if urea and creatinine could be measured in canine saliva, and to evaluate their possible changes in situations of CKD

The Multifaceted Function of Granzymes in Sepsis: Some Facts and a Lot to Discover

Sepsis is a serious global health problem. In addition to a high incidence, this syndrome has a high mortality and is responsible for huge health expenditure. The pathophysiology of sepsis is very complex and it is not well-understood yet. However, it is widely accepted that the initial phase of sepsis is characterized by a hyperinflammatory response while the late phase is characterized by immunosuppression and immune anergy, increasing the risk of secondary infections. Granzymes (Gzms) are a family of serine proteases classified according to their cleavage specificity. Traditionally, it was assumed that all Gzms acted as cytotoxic proteases. However, recent evidence suggests that GzmB is the one with the greatest cytotoxic capacity, while the cytotoxicity of others such as GzmA and GzmK is not clear. Recent studies have found that GzmA, GzmB, GzmK, and GzmM act as pro-inflammatory mediators. Specially, solid evidences show that GzmA and GzmK function as extracellular proteases that regulate the inflammatory response irrespectively of its ability to induce cell death. Indeed, studies in animal models indicate that GzmA is involved in the cytokine release syndrome characteristic of sepsis. Moreover, the GZM family also could regulate other biological processes involved in sepsis pathophysiology like the coagulation cascade, platelet function, endothelial barrier permeability, and, in addition, could be involved in the immunosuppressive stage of sepsis. In this review, we provide a comprehensive overview on the contribution of these novel functions of Gzms to sepsis and the new therapeutic opportunities emerging from targeting these proteases for the treatment of this serious health problem

Impact of the COVID-19 pandemic on the care of cancer patients in Spain

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Càncer; EspanyaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cáncer; EspañaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cancer; SpainBackground Studies evaluating the effects of the COVID-19 pandemic on public healthcare systems are limited, particularly in cancer management. As no such studies have been carried out in Spain, our objective is to describe and quantify the impact of the COVID-19 pandemic on cancer patients in Spanish hospitals during the first wave of the pandemic. Materials and methods This retrospective, multicenter, nationwide study collected information from hospital departments treating oncology patients. An electronic questionnaire comparing outcomes and management of oncohematological patients for the March-June 2019 and March-June 2020 periods was used. Results Information from 78 departments (36 tertiary hospitals) was analyzed. Forty-four departments implemented adapted protocols during March 2020. Most of these (n = 38/44; 86.4%) carried out COVID-19 triage, while 26 of 44 (59.1%) carried out onsite polymerase chain reaction tests for clinically suspected cases. A shift from in-person to telephone visits was observed in 43 of 44 (97.7%) departments. Comparing the March-June 2019 and March-June 2020 periods, the number of new patients decreased by 20.8% (from 160.2 to 126.4). Decreases were also seen in the mean number of total (2858.2 versus 1686.1) and cancer (465.5 versus 367.2) biopsies, as well as the mean number of bone marrow biopsies (30.5 versus 18.6). Concerning the number of patients visiting specific cancer care departments, a decrease from 2019 to 2020 was seen for mean number of chemotherapy treatments (712.7 versus 643.8) and radiation therapy (2169.9 versus 2139.9). Finally, a reduction from 2019 to 2020 of 12.9% (from 8.6 to 7.4) in the mean number of patients included in clinical trials was noted. Conclusions This study provides the first comprehensive data concerning the impact of COVID-19 on cancer care in Spain. The pandemic caused a 20.8% decrease in newly diagnosed patients, which may impact future outcomes. Measures must be taken to ensure cancer management receives priority in times of healthcare emergencies.This work was supported by funding from the AECC, a non-profit organization, whose medical department funded the study and the medical writing (no grant number)

Toward the biochemical assessment of myocardial fibrosis in hypertensive patients

The serum concentrations of amino-terminal procollagen type III and carboxy-terminal procollagen type I-derived peptides, which have been proposed as useful markers of the tissue synthesis of collagen types III and type I, respectively, were abnormally increased in patients with essential hypertension and became normal after angiotensin-converting enzyme (ACE) inhibition. An association was found between baseline serum concentrations of these peptides and left ventricular hypertrophy, diastolic dysfunction, and ventricular arrhythmias in hypertensive patients. On the other hand, increased serum concentration of the carboxy-terminal procollagen type I-derived peptide was found in spontaneously hypertensive rats compared with normotensive Wistar-Kyoto control rats. An association was found between the serum concentration of this peptide and the extent of myocardial fibrosis and the hydroxyproline concentration in the left ventricle of spontaneously hypertensive rats. It is proposed that procollagen-derived peptides in serum may be markers of exaggerated collagen tissue synthesis involved in hypertensive myocardial fibrosis

Effect of aquatic resistance interval training and dietary education program on physical and psychological health in older women: Randomized controlled trial

Due to demographic changes, the world’s population is progressively aging. The physiological deterioration of the older adult may lead to reduced balance capacity and increased risk of falls, among others, due to the prevalence of degenerative diseases. Physical exercise can be effective in reducing the risk of disease and slowing functional decline in older people. The aim of the research is to test the effects of aquatic resistance training and dietary education on health indicators, strength, balance, functional autonomy, perception of satisfaction with life. Thirty-four participants aged 69 ± 4 years were randomly assigned into two groups: experimental (aquatic resistance interval training) and control group (no intervention). The intervention consisted of resistance training in an aquatic environment carried out for 14 weeks (three sessions per week: 60 min each). All variables were analyzed twice; pre - post intervention. Aquatic resistance training has positive effects on strength (p < 0.001), functional self-sufficiency (p < 0.001) and aerobic capacity (p < 0.001), however, no significant differences were observed in the perception of satisfaction with life and balance. Research results suggest that older women who engage in regular, scheduled aquatic resistance training have greater autonomy in performing activities of daily living, agility, gait control, and body composition variables (lower fat compartment and greater muscle mass)