Cancer-associated mesenchymal stem/stromal cells: role in progression and potential targets for therapeutic approaches

Malignancies contain a relatively small number of Mesenchymal stem/stromal cells (MSCs), constituting a crucial tumor microenvironment (TME) component. These cells comprise approximately 0.01–5% of the total TME cell population. MSC differentiation potential and their interaction with the tumor environment enable these cells to affect tumor cells’ growth, immune evasion, metastasis, drug resistance, and angiogenesis. This type of MSC, known as cancer-associated mesenchymal stem/stromal cells (CA-MSCs (interacts with tumor/non-tumor cells in the TME and affects their function by producing cytokines, chemokines, and various growth factors to facilitate tumor cell migration, survival, proliferation, and tumor progression. Considering that the effect of different cells on each other in the TME is a multi-faceted relationship, it is essential to discover the role of these relationships for targeting in tumor therapy. Due to the immunomodulatory role and the tissue repair characteristic of MSCs, these cells can help tumor growth from different aspects. CA-MSCs indirectly suppress antitumor immune response through several mechanisms, including decreasing dendritic cells (DCs) antigen presentation potential, disrupting natural killer (NK) cell differentiation, inducing immunoinhibitory subsets like tumor-associated macrophages (TAMs) and Treg cells, and immune checkpoint expression to reduce effector T cell antitumor responses. Therefore, if these cells can be targeted for treatment so that their population decreases, we can hope for the treatment and improvement of the tumor conditions. Also, various studies show that CA-MSCs in the TME can affect other vital aspects of a tumor, including cell proliferation, drug resistance, angiogenesis, and tumor cell invasion and metastasis. In this review article, we will discuss in detail some of the mechanisms by which CA-MSCs suppress the innate and adaptive immune systems and other mechanisms related to tumor progression

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Examining the Role of Predictor Variables of Mental Health and Personality Subscales in Internet Addiction of Students in Medical and non-Medical Universities of Sanandaj in 2014

Background and objective: According to the high and increasing prevalence of internet addiction, and the fact that little research has been done on the predictors of internet addiction in Iran, the purpose of this study was to examine the role of predictor variables of mental health and personality subscales in internet addiction of students in medical and non-medical universities of Sanandaj in 2014. Methods: The Method of this research was correlation and the statistical population were all of medical and non-medical students of Sanandaj Universities in 2014. In this study, 250 students (125 female and 125 male), were randomly selected, and completed the checklist of mental health symptoms, NEO personality questionnaire, and internet addiction questionnaire. Data were analyzed using Pearson Correlation, stepwise regression, and T test by SPSS software version 20. Results: The results indicated that obsession-compulsion, openness, consciousness, aggression and somatization subscales had predictor roles in internet addiction, and totally 51 percent of variances predicted the internet addiction (F=29.97; P=0.001). Conclusion: The internet addiction of university students is dependent upon their mental health and personality, and one can predict the internet addiction of students via subscales of mental health and personality

A cross-sectional multicenter linkage study of hospital admissions and mortality due to methanol poisoning in Iranian adults during the COVID-19 pandemic

Abstract A methanol poisoning outbreak occurred in Iran during the initial months of coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate the epidemiology of the outbreak in terms of hospitalizations and deaths. A cross-sectional linkage study was conducted based on the hospitalization data collected from thirteen referral toxicology centers throughout Iran as well as mortality data obtained from the Iranian Legal Medicine Organization (LMO). Patient data were extracted for all cases aged > 19 years with toxic alcohol poisoning during the study period from February until June 2020. A total of 795 patients were hospitalized due to methanol poisoning, of whom 84 died. Median [interquartile ratio; IQR] age was 32 [26, 40] years (range 19–91 years). Patients had generally ingested alcohol for recreational motives (653, 82.1%) while 3.1% (n = 25) had consumed alcohol-based hand sanitizers to prevent or cure COVID-19 infection. Age was significantly lower in survivors than in non-survivors (P < 0.001) and in patients without sequelae vs. with sequelae (P = 0.026). Twenty non-survivors presented with a Glasgow Coma Scale (GCS) score > 8, six of whom were completely alert on presentation to the emergency departments. The time from alcohol ingestion to hospital admission was not significantly different between provinces. In East Azerbaijan province, where hemodialysis was started within on average 60 min of admission, the rate of sequelae was 11.4% (compared to 19.6% average of other provinces)—equivalent to a reduction of the odds of sequelae by 2.1 times [95% CI 1.2, 3.7; p = 0.009]. Older patients were more prone to fatal outcome and sequelae, including visual disturbances. Early arrival at the hospital can facilitate timely diagnosis and treatment and may reduce long-term morbidity from methanol poisoning. Our data thus suggest the importance of raising public awareness of the risks and early symptoms of methanol intoxication

The burden of metabolic risk factors in North Africa and the Middle East, 1990–2019: findings from the Global Burden of Disease StudyResearch in context

Summary: Background: The objective of this study is to investigate the trends of exposure and burden attributable to the four main metabolic risk factors, including high systolic blood pressure (SBP), high fasting plasma glucose (FPG), high body-mass index (BMI), and high low-density lipoproteins cholesterol (LDL) in North Africa and the Middle East from 1990 to 2019. Methods: The data were retrieved from Global Burden of Disease Study 2019. Summary exposure value (SEV) was used for risk factor exposure. Burden attributable to each risk factor was incorporated in the population attributable fraction to estimate the total attributable deaths and disability-adjusted life-years (DALYs). Findings: While age-standardized death rate (ASDR) attributable to high-LDL and high-SBP decreased by 26.5% (18.6–35.2) and 23.4% (15.9–31.5) over 1990–2019, respectively, high-BMI with 5.1% (−9.0–25.9) and high-FPG with 21.4% (7.0–37.4) change, grew in ASDR. Moreover, age-standardized DALY rate attributed to high-LDL and high-SBP declined by 30.2% (20.9–39.0) and 25.2% (16.8–33.9), respectively. The attributable age-standardized DALY rate of high-BMI with 8.3% (−6.5–28.8) and high-FPG with 27.0% (14.3–40.8) increase, had a growing trend. Age-standardized SEVs of high-FPG, high-BMI, high-SBP, and high-LDL increased by 92.4% (82.8–103.3), 76.0% (58.9–99.3), 10.4% (3.8–18.0), and 5.5% (4.3–7.1), respectively. Interpretation: The burden attributed to high-SBP and high-LDL decreased during the 1990–2019 period in the region, while the attributable burden of high-FPG and high-BMI increased. Alarmingly, exposure to all four risk factors increased in the past three decades. There has been significant heterogeneity among the countries in the region regarding the trends of exposure and attributable burden. Urgent action is required at the individual, community, and national levels in terms of introducing effective strategies for prevention and treatment that account for local and socioeconomic factors. Funding: Bill & Melinda Gates Foundation