CTLA-4 Blockade of Natural Killer Cells Increases Cytotoxicity against Acute Lymphoid Leukaemia Cells Neda.

OBJECTIVE: There is interest in using cytotoxic T lymphocyte antigen-4 (CTLA-4) immunotherapy to treat blood cancers. Unfortunately, patients with acute lymphoblastic leukaemia (ALL) frequently exhibit resistance to treatment and natural killer (NK) cell exhaustion. This study aims to increase the cytotoxic potency of natural killer cells by using CTLA-4 to block the Nalm-6 leukaemia cell line. MATERIALS AND METHODS: In this experimental study, NK cells were purified from the peripheral blood mononuclear cells (PBMCs) of 10 healthy people and assessed by flow cytometry for purity and viability. The purified cells were activated overnight at 37°C and 5% CO2 with interleukin-15 (IL-15, 10 ng/ml) followed by evaluation of expressions of CTLA-4, activating and inhibitory receptors, and the release of interferon gamma (IFN-γ) and granzyme B (GZM B). CTLA-4 expression on NK cells from recurrent ALL patients was also evaluated. Finally, the cytotoxic activity of NK cells was assessed after the CTLA-4 blockade. RESULTS: The purity of the isolated cells was 96.58 ± 2.57%. Isolated NK cells activated with IL-15 resulted in significantly higher CTLA-4 expression (8.75%, P<0.05). Similarly, CTLA-4 expression on the surface of NK cells from patients with ALL was higher (7.46%) compared to healthy individuals (1.46%, P<0.05). IL-15 reduced NKG2A expression (P<0.01), and increased expressions of NKP30 (P<0.05) and NKP46 (P<0.01). The activated NK cells released more IFN-γ (P<0.5) and GZM B (P<0.01) compared to unactivated NK cells. Blockade of CTLA-4 enhanced the NK cell killing potential against Nalm-6 cells (56.3%, P<0.05); however, IFN-γ and GZM B levels were not statistically different between the blocked and non-blocked groups. CONCLUSION: Our findings suggest that CTLA-4 blockage of Nalm-6 cells causes an increase in antitumour activity of NK cells against these cells. Our study also provides evidence for the potential of cancer immunotherapy treatment using blocking anti-CTLA-4 mAbs.

New classifications for quantum bioinformatics: Q-bioinformatics, QCt-bioinformatics, QCg-bioinformatics, and QCr-bioinformatics.

Bioinformatics has revolutionized biology and medicine by using computational methods to analyze and interpret biological data. Quantum mechanics has recently emerged as a promising tool for the analysis of biological systems, leading to the development of quantum bioinformatics. This new field employs the principles of quantum mechanics, quantum algorithms, and quantum computing to solve complex problems in molecular biology, drug design, and protein folding. However, the intersection of bioinformatics, biology, and quantum mechanics presents unique challenges. One significant challenge is the possibility of confusion among scientists between quantum bioinformatics and quantum biology, which have similar goals and concepts. Additionally, the diverse calculations in each field make it difficult to establish boundaries and identify purely quantum effects from other factors that may affect biological processes. This review provides an overview of the concepts of quantum biology and quantum mechanics and their intersection in quantum bioinformatics. We examine the challenges and unique features of this field and propose a classification of quantum bioinformatics to promote interdisciplinary collaboration and accelerate progress. By unlocking the full potential of quantum bioinformatics, this review aims to contribute to our understanding of quantum mechanics in biological systems.

Comparative assessment of direct and indirect cold atmospheric plasma effects, based on helium and argon, on human glioblastoma: an in vitro and in vivo study.

Recent research has highlighted the promising potential of cold atmospheric plasma (CAP) in cancer therapy. However, variations in study outcomes are attributed to differences in CAP devices and plasma parameters, which lead to diverse compositions of plasma products, including electrons, charged particles, reactive species, UV light, and heat. This study aimed to evaluate and compare the optimal exposure time, duration, and direction-dependent cellular effects of two CAPs, based on argon and helium gases, on glioblastoma U-87 MG cancer cells and an animal model of GBM. Two plasma jets were used as low-temperature plasma sources in which helium or argon gas was ionized by high voltage (4.5 kV) and frequency (20 kHz). In vitro assessments on human GBM and normal astrocyte cell lines, using MTT assays, flow cytometry analysis, wound healing assays, and immunocytochemistry for Caspase3 and P53 proteins, demonstrated that all studied plasma jets, especially indirect argon CAP, selectively induced apoptosis, hindered tumor cell growth, and inhibited migration. These effects occurred concurrently with increased intracellular levels of reactive oxygen species and decreased total antioxidant capacity in the cells. In vivo results further supported these findings, indicating that single indirect argon and direct helium CAP therapy, equal to high dose Temozolomide treatment, induced tumor cell death in a rat model of GBM. This was concurrent with a reduction in tumor size observed through PET-CT scan imaging and a significant increase in the survival rate. Additionally, there was a decrease in GFAP protein levels, a significant GBM tumor marker, and an increase in P53 protein expression based on immunohistochemical analyses. Furthermore, Ledge beam test analysis revealed general motor function improvement after indirect argon CAP therapy, similar to Temozolomide treatment. Taken together, these results suggest that CAP therapy, using indirect argon and direct helium jets, holds great promise for clinical applications in GBM treatment.

Ambient air pollutants and breast cancer stage in Tehran, Iran.

This study aimed to examine the impacts of single and multiple air pollutants (AP) on the severity of breast cancer (BC). Data of 1148 diagnosed BC cases (2008-2016) were obtained from the Cancer Research Center and private oncologist offices in Tehran, Iran. Ambient PM10, SO2, NO, NO2, NOX, benzene, toluene, ethylbenzene, m-xylene, p-xylene, o-xylene, and BTEX data were obtained from previously developed land use regression models. Associations between pollutants and stage of BC were assessed by multinomial logistic regression models. An increase of 10 µg/m3 in ethylbenzene, o-xylene, m-xylene, and 10 ppb of NO corresponded to 10.41 (95% CI 1.32-82.41), 4.07 (1.46-11.33), 2.89 (1.08-7.73) and 1.08 (1.00-1.15) increase in the odds of stage I versus non-invasive BC, respectively. Benzene (OR, odds ratio = 1.16, 95% CI 1.01-1.33) and o-xylene (OR = 1.18, 1.02-1.38) were associated with increased odds of incidence of BC stages III & IV versus non-invasive stages. BC stage I and stage III&IV in women living in low SES areas was associated with significantly higher levels of benzene, ethylbenzene, o-xylene, and m-xylene. The highest multiple-air-pollutants quartile was associated with a higher odds of stage I BC (OR = 3.16) in patients under 50 years old. This study provides evidence that exposure to AP is associated with increased BC stage at diagnosis, especially under premenopause age.

[68Ga]Ga-FAP-2286, a novel promising theragnostic approach for PET/CT imaging in patients with various type of metastatic cancers.

BACKGROUND: Fibroblast activation protein (FAP) has emerged as a promising target for diagnosis and therapeutic intervention due to high expression and accumulation in the stromal compartments of a variety of malignant tumors. FAP-2286 utilizes cyclic peptides with FAP-binding characteristics to enhance the retention of the imaging agent within tumors, in contrast to the small-molecule FAP inhibitors (FAPI) like FAPI-04/46. The aim of this study was to quantify the tumor uptake of [68Ga] Gallium-FAP-2286 within primary solid tumors, adjacent excised tissues, and metastatic lesions. METHODS: In this prospective study, 21 patients (average age 51.9) with various diagnoses of remaining and metastatic cancers participated. Among them, six had metastatic sarcoma, and 14 had adenocarcinoma, including eight breast, two rectum, two lung, two pancreas, and one thyroid cases. The patients underwent a [68Ga]Ga-FAP-2286 PET/CT scan. An hour post-administration of [68Ga]Ga-FAP-2286, a visual assessment of whole body scans and semi-quantification of the PET/CT results were carried out. The standardized uptake values (SUV)max of [68Ga]Ga-FAP-2286 in tumor lesions and the tumor-to-background ratio (TBR) were then calculated. RESULTS: The vital signs of the patients, such as heart rate, blood pressure, and temperature, were observed before, during, and after the diagnostic procedure during the 4-h follow-up. All individuals underwent the [68Ga]Ga-FAP-2286 PET/CT scans without any signs of drug-associated pharmacological effects. The PET/CT scans displayed substantial absorption of [68Ga]Ga-FAP-2286 in tumor lesions in all patients (100% (21/21)). Irrespective of the tumors' origins (epithelial or mesothelium) and whether they exhibited local recurrence, distant recurrence, or metastatic lesions, the PET/CT scans revealed the uptake of [68Ga]Ga-FAP-2286 in these lesions. CONCLUSION: Overall, these data suggest that [68Ga]Ga-FAP-2286 is a promising FAP derivative for efficient metastatic cancer diagnosis and being considered as a potential compound for therapeutic application in patients with advanced metastatic cancers.

Sexual function index adaptation for breast cancer patients (FSFI-BC)- translation and psychometric properties of Persian version.

BACKGROUND: Effective interventions to improve sexual dysfunction in breast cancer survivors need screening of these dysfunctions with a suitable instrument. The aim of present study was translation and identifying psychometric properties of Female Sexual Function Index - Adapted for Breast Cancer (FSFI-BC) which has been specifically developed for breast cancer survivors. METHOD: This methodological study was performed between February 2017 and October 2018. 200 breast cancer survivors in stage 1 or 2 who were selected through convenience sampling method, completed the questionnaire. Reliability was assessed by Cronbach's alfa and test re-test analysis and construct validity was performed through confirmatory (CFA) and exploratory factor analysis( EFA). RESULTS: Six factors were extracted in exploratory factor analysis (EFA). These factors explained 74.6% of the total variance in in NSA group and 0.821 in SA group. Reliability evaluation indicated high internal consistency and good test re-test reliability. Cronbach's alpha coefficient in all areas of the tool was above 0.7 (the lowest and the highest measures were 0.885 and 0.945, respectively), which is a good indicator for reliability of an instrument. Confirmatory factor analysis showed an acceptable fitness for seven factors of FSFI-BC questionnaire (Normed Fit Index or NFI = 0.9 for both groups, Comparative of Fit Index or CFI = 0.93 and 0.92, χ 2/df = 1.68 and 1.71 for SA(Sexually Active) and NSA(No Sexually Active) individuals, respectively) . CONCLUSION: Study findings suggest that Persian version of FSFI-BC is a suitable instrument for sexual dysfunction screening in breast cancer survivors.

Locoregional therapy containing surgery in metastatic breast cancer: Systematic review and meta-analysis.

INTRODUCTION: The role of locoregional therapy (LRT) containing surgery and systematic therapy in metastatic breast cancer patients remains controversial. This study investigated the effect of LRT in patients who were initially diagnosed with metastatic breast cancer (MBC) on overall survival (OS), locoregional progression-free survival (PFS), and distant systemic PFS. METHODS: The related keywords were searched in MEDLINE/PubMed, SCOPUS, and Web of Science databases up to August 15th, 2022. Hazard ratios (HR) with 95% confidence intervals (CIs) were pooled by the random-effects model. RESULTS: Seven articles with 1626 participants compared LRT with only systemic therapy (ST) for patients with de novo MBC. LRT did not improve (p = 0.28) OS compared to ST (HR: 0.83, 95% CI: 0.60, 1.16). LRT significantly improved locoregional PFS outcomes compared to ST (HR: 0.31, 95% CI: 0.15, 0.60, p = 0.001). LRT significantly (p = 0.001) improved OS in patients with solitary bone metastases (HR: 0.48; 95% CI: 0.35-0.67). CONCLUSION: LRT improves locoregional PFS. Furthermore, LRT improves OS in patients with solitary bone metastases.

Risk factors of developing contralateral breast cancer after first primary breast cancer treatment.

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. Increased survival of primary BC (PBC) has increased contralateral breast cancer (CBC) and become a health problem. AIMS: This study aimed to determine the effect of disease-free interval (DFI), risk factors and PBC characteristics on the progression of CBC within primary BC survivors. METHODS AND RESULTS: This retrospective study identified 5003 women diagnosed with breast cancer between 2000 and 2020 in the cancer research center. The study included 145 CBC and 4858 PBC survivors, with CBC diagnosed at least 6 months after the detection of primary BC. ER+, PR+, and HER2+ were reported in 72.13%, 66.67%, and 30% of CBC patients. Invasive ductal carcinoma (IDC) BC was reported in 69.57% of patients, and 81.90% and 83.64% of the patients were treated with adjuvant chemotherapy and external radiotherapy. The Kaplan-Meier method indicated that the median time interval between PBC and CBC was 3.92 years, and the 5-year DFI was 97%. The Cox proportional hazard regression model indicated that although more than half of the participants had no family history of BC (69.57%), women 60 years and older were negatively associated with CBC. CONCLUSION: This study provides the first investigation of CBC and DFI risk factors among PBC survivors in Iran. Age was found to be negatively associated with CBC development particularly after the age of 60, indicating the necessity of tracking CBC survivors carefully in this age group.

Cancer incidence in Iran in 2016: A study based on the Iranian National Cancer Registry.

BACKGROUND: Cancer poses an escalating public health challenge, necessitating a comprehensive understanding of cancer incidence to formulate effective control strategies. AIMS: This study aims to present a comprehensive overview of cancer incidence in Iran, utilizing data from the Iranian National Population-based Cancer Registry (INPCR) for the year 2016. METHODS: The study employed INPCR data to compute crude and age-standardized incidence rates (ASR) per 100 000 for the most common cancers among men and women across Iran's 31 provinces. Data analysis utilized Excel (2019) and STATA 14. RESULTS: In 2016, 124 833 new cancer cases were registered, with 65 495 (52.90%) occurring in men and 58 312 (47.10%) in women. ASRs for all cancers in the total population were 177.48, with specific rates for men and women at 192.96 and 162.33, respectively. The five most common cancers in men were prostate (23.25), stomach (21.56), colon (19.30), bladder (16.20), and lung (13.15). Among women, the leading cancers were breast (40.60), colon (14.64), thyroid (10.84), stomach (10.25), and lung (5.63). West Azarbaijan had the highest incidence among men, while Yazd topped the list for women. Age-specific incidence rates revealed peaks in the 67-74 age group for men and the 40-50 age group for women. CONCLUSION: This study affirms that while Iran exhibits a lower cancer incidence compared to global averages, there has been a temporal increase. Disparities in ASR exist across sexes and provinces, with shifts in the ranking of common cancers by sex compared to previous reports.

BMC3PM: bioinformatics multidrug combination protocol for personalized precision medicine and its application in cancer treatment.

BACKGROUND: In recent years, drug screening has been one of the most significant challenges in the field of personalized medicine, particularly in cancer treatment. However, several new platforms have been introduced to address this issue, providing reliable solutions for personalized drug validation and safety testing. In this study, we developed a personalized drug combination protocol as the primary input to such platforms. METHODS: To achieve this, we utilized data from whole-genome expression profiles of 6173 breast cancer patients, 312 healthy individuals, and 691 drugs. Our approach involved developing an individual pattern of perturbed gene expression (IPPGE) for each patient, which was used as the basis for drug selection. An algorithm was designed to extract personalized drug combinations by comparing the IPPGE and drug signatures. Additionally, we employed the concept of drug repurposing, searching for new benefits of existing drugs that may regulate the desired genes. RESULTS: Our study revealed that drug combinations obtained from both specialized and non-specialized cancer medicines were more effective than those extracted from only specialized medicines. Furthermore, we observed that the individual pattern of perturbed gene expression (IPPGE) was unique to each patient, akin to a fingerprint. CONCLUSIONS: The personalized drug combination protocol developed in this study offers a methodological interface between drug repurposing and combination drug therapy in cancer treatment. This protocol enables personalized drug combinations to be extracted from hundreds of drugs and thousands of drug combinations, potentially offering more effective treatment options for cancer patients.

Beneficial effects of the combination of BCc1 and Hep-S nanochelating-based medicines on IL-6 in hospitalized moderate COVID-19 adult patients: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: In the severe forms of COVID-19 and many other infectious diseases, the patients develop a cytokine storm syndrome (CSS) where pro-inflammatory cytokines such as IL-6 and TNF-α play a key role in the development of this serious process. Selenium and iron are two important trace minerals, and their metabolism is tightly connected to immune system function. Numerous studies highlight the role of selenium and iron metabolism changes in the procedure of COVID-19 inflammation. The immunomodulator effect of nanomedicines that are synthesized based on nanochelating technology has been proved in previous studies. In the present study, the effects of the combination of BCc1(with iron-chelating property) and Hep-S (containing selenium) nanomedicines on mentioned cytokines levels in hospitalized moderate COVID-19 patients were evaluated. METHODS: Laboratory-confirmed moderate COVID-19 patients were enrolled to participate in a randomized, double-blind, placebo-controlled study in two separate groups: combination of BCc1 and Hep-S (N = 62) (treatment) or placebo (N = 60) (placebo). The blood samples were taken before medications on day zero, at discharge, and 28 days after consumption to measure hematological and biochemical parameters and cytokine levels. The clinical symptoms of all the patients were recorded according to an assessment questionnaire before the start of the treatment and on days 3 and discharge day. RESULTS: The results revealed that consumption of the nanomedicines led to a significant decrease in the mean level of IL-6 cytokine, and at the end of the study, there was a 77% downward trend in IL-6 in the nanomedicine group, while an 18% increase in the placebo group (p < 0.05). In addition, the patients in the nanomedicines group had lower TNF-α levels; accordingly, there was a 21% decrease in TNF-α level in the treatment group, while a 31% increase in this cytokine level in the placebo was observed (p > 0.05). On the other hand, in nanomedicines treated groups, clinical scores of coughing, fatigue, and need for oxygen therapy improved. CONCLUSIONS: In conclusion, the combination of BCc1 and Hep-S inhibits IL-6 as a highly important and well-known cytokine in COVID-19 pathophysiology and presents a promising view for immunomodulation that can manage CSS. TRIAL REGISTRATION: Iranian Registry of Clinical Trials RCT20170731035423N2 . Registered on June 12, 2020.

A human pilot study on positive electrostatic charge effects in solid tumors of the late-stage metastatic patients.

Background: Correlative interactions between electrical charges and cancer cells involve important unknown factors in cancer diagnosis and treatment. We previously reported the intrinsic suppressive effects of pure positive electrostatic charges (PEC) on the proliferation and metabolism of invasive cancer cells without any effect on normal cells in cell lines and animal models. The proposed mechanism was the suppression of pro-caspases 3 and 9 with an increase in Bax/Bcl2 ratio in exposed malignant cells and perturbation induced in the KRAS pathway of malignant cells by electrostatic charges due to the phosphate molecule electrostatic charge as the trigger of the pathway. This study aimed to examine PECs as a complementary treatment for patients with different types of solid metastatic tumors, who showed resistance to chemotherapy and radiotherapy. Methods: In this study, solid metastatic tumors of the end-stage patients (n = 41) with various types of cancers were locally exposed to PEC for at least one course of 12 days. The patient's signs and symptoms, the changes in their tumor size, and serum markers were followed up from 30 days before positive electrostatic charge treating (PECT) until 6 months after the study. Results: Entirely, 36 patients completed the related follow-ups. Significant reduction in tumor sizes and cancer-associated enzymes as well as improvement in cancer-related signs and symptoms and patients' lifestyles, without any side effects on other tissues or metabolisms of the body, were observed in more than 80% of the candidates. Conclusion: PECT induced significant cancer remission in combination with other therapies. Therefore, this non-ionizing radiation would be a beneficial complementary therapy, with no observable side effects of ionizing radiotherapy, such as post-radiation inflammation.

Descriptive Epidemiology and Survival Rate of Osteosarcoma: The First National Population-Based Study in the Middle East (2008-2014).

Objectives: The epidemiology of osteosarcoma (OS), the most common primary bone sarcoma, was not evaluated in the Middle East. Therefore, this study aimed to examine the incidence, demographic characteristics, epidemiology, and survival rate of patients with different subtypes of OS, based on data derived from the Iran National Cancer Registry (INCR) to evaluate the influence of ethnicity and race. Methods: All OS patients registered in the INCR between March 20, 2008, and March 20, 2014, were enrolled in this study, and information such as age, gender, cancer location, OS subtype, and survival time were evaluated statistically. Results: The Age-Standardized Incidence Rate (ASIR) for OS was 3.02 per million person-years, with a mean age of 25.6 years and a male-female ratio of 1.54:1. Not Otherwise Specified (NOS) OS, chondroblastic OS, and central OS had the highest frequencies among the subtypes of OS. The overall one-, three-, and five-year survival rates were 87%, 61%, and 49%, respectively, with a mean duration of 6.16 years. Conclusion: The ASIR of OS in our country was similar to that in the US and higher than that in China. The peak frequency was between 15-19 years old. The male-female ratio in our patients was higher than the OS gender ratio in most series. Although it was not statistically significant, older age at the time of diagnosis, axial location, and male gender were the poorest prognosis factors.

Tumor characteristics and survival rate of HER2-low breast cancer patients: a retrospective cohort study.

HER2 is an important prognostic marker in breast cancer (BC) patients, which also plays a crucial role in their therapeutic plan. Consequently, a great desire is to thoroughly assess the patients based on their HER2 status. In the current study, we aimed to evaluate HER2-low breast cancer as a new subtype in the standard classification of BC patients and review its characteristics and survival rate in a tertiary center in Iran. We retrospectively evaluated disease-free survival (DFS), overall survival (OS), and clinicopathological characteristics of BC patients referred to the Cancer Research Center in Tehran, Iran from 1991 to 2022. Patients' clinical characteristics, including HER2 status, which is classified as HER2-low, HER2-positive, or HER2-negative, were obtained from prospectively maintained registries. Among the total 3582 recruited patients, 60.2%, 13.6%, and 26.2% were HER2-negative, HER2-low, and HER2-positive, respectively. HER2-positive patients showed a significantly higher Hazard Ratio (HR) for DFS (HR 1.44, 95% CI 1.01-2.05) and OS (HR 2.05, 95% CI 1.31-3.20), compared to HER2-low. Moreover, HER2-low and HER2-negative were found to show the same proportion of high-grade tumors (28 and 28.4%), while 40% of the HER2-positive tumors were high-grade. Accordingly, HER2-low patients had a lower metastasis risk than the others (P-value = 0.01). The Ki67 percentage was significantly lower in the HER2-low group compared to the HER2-positive (P-value < 0.001). HER2-low, a new subtype of HER2-status classification with distinct biological and clinicopathological traits, represented the highest survival rate and less invasive characteristics. This difference was statistically significant when compared to HER2-positive, but not when compared to HER2-negative.Research registration unique identifying number: NCT05754047.

A registration trend in eyelid skin cancers and associated risk factors in Iran, 2005-2016.

BACKGROUND: Eyelid skin cancers are the most prevalent ophthalmic malignancies. This study aimed to evaluate the association of the Human Development Index (HDI) and lifestyle risk factors with eyelid skin cancers in Iran. METHODS: This ecological study analyzed the data collected from the Iranian National Population-based Cancer Registry (2005-2016). The data on provincial-level eyelid skin cancer risk factors were obtained from national sources. The association between provincial HDI and lifestyle risk factors with the prevalence of eyelid skin cancers was assessed. RESULTS: The mean 12-year age-standardized incidence rate (ASIR) of eyelid skin cancers was 16.22 per 100,000 (9,104 cases). The overall ASIR showed an upward trend with an estimated annual average increase of 0.006 per year. There were positive correlations between the prevalence of overall eyelid skin cancers and provincial HDI, smoking, and obesity (r = 0.32, 0.42, and 0.37, respectively). In multivariate analysis, obesity/overweight remained a positive predictor for high prevalence of total eyelid skin cancers (OR = 1.97, 95%CI = 1.08-3.58, P = 0.026), carcinoma (2.10, 1.15-3.83, P = 0.015), and basal cell carcinoma (1.48, 0.99-2.20, P = 0.054). CONCLUSIONS: An increasing trend in ASIR of eyelid skin cancers was observed in more than a decade in Iran which was positively associated with provincial HDI and prevalence of obesity. The findings of the study highlight the importance of promotional programs for preventing obesity/overweight and appropriate allocation of screening facilities based on the HDI level.

The effect of anamorelin (ONO-7643) on cachexia in cancer patients: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cachexia is associated with increased morbidity and mortality rates in patients with cancer. This meta-analysis aims to explore the effect of anamorelin on cancer cachexia markers. METHODS: We searched MEDLINE/PubMed, SCOPUS, and WOS from their inception until 5 June 2022. A systematic search was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We included trials investigating the effect of anamorelin on body weight, lean body mass, fat mass, insulin-like growth factor 1 (IGF-1), handgrip, quality of life insulin-like growth factor-binding protein 3 (IGFBP-3), and in patients with cancer. A random-effects model was run to pooled results. RESULTS: Five articles providing 1331 participants were analyzed in this study. Pooled analysis revealed a significant increase in body weight (weighted mean difference (WMD): 1.56 kg, 95% confidence interval (CI): 1.20, 1.92; I2= 0%), lean body mass (WMD: 1.36 kg, 95% CI: 0.85, 1.86; I2= 53.1%), fat mass (WMD: 1.02 kg, 95% CI: 0.51, 1.53; I2= 60.7%), IGF-1 (WMD: 51.16 ng/mL, 95% CI: 41.42, 60.90, I2= 0%), and IGFBP-3 (WMD: 0.43 µg/mL, 95% CI: 0.17, 0.68, I2= 98.6%). Results showed no significant increase in appetite when analysis run on all studies without considering different doses 0.29 (95% CI: -0.30, 0.89, I2= 73.8%), however, there was a significant increase in appetite without heterogeneity and inconsistency 0.59 (95% CI: 0.32, 0.86; I2= 0%) in the 100 mg/day group compared to anamorelin non-user. CONCLUSIONS: Patients with cancer who receive anamorelin as a treatment for cachexia showed a significant increase in body weight, lean body mass, fat mass, IGF-1, and IGFBP-3.

Ovarian Cancer in Iran: National Based Study.

Background: Ovarian cancer (OC) is the 7th most common cancer, with 239,000 new cases per year. In Iran, it is the 8th most common cancer, with an ASIR of 3.9/100,000 women. The 5-year overall survival in Iran based on previous studies is about 61% which in comparison with eastern countries has better survival. Methods: The study included patients from the Iran National Cancer Registry from 2009-2014. Several steps were taken to control data quality. This study used a Kaplan-Meier survival curve to compare OC survival rates across geographical, pathological, and other variables. All analyses were done in R (4.02) and SPSS (26), with a 0.05 P-value considered statistically significant. Results: The study enrolled 7977 cases of OC. OC's ASIR was 4.10/100,000. In epithelial and non-specific OC, ASIR was >0.5. Five-year survival was 55% and 10-year survival was 45%. Conclusion: OC is the 8th most common cancer in Iran, with lower age-specific incidence and better overall survival than East Asia and North America. In Iran, as in Eastern Europe, OC incidence correlated with reduced total fertility rate and population aging. Five and 10-year overall survival rates were 55% and 44%, respectively, higher than the West. This may be because late stage OC patients are excluded from pathology and classified as "undiagnosed" in death certificates or hospitalization files.

Time-related survival prediction in molecular subtypes of breast cancer using time-to-event deep-learning-based models.

Background: Breast cancer (BC) survival prediction can be a helpful tool for identifying important factors selecting the effective treatment reducing mortality rates. This study aims to predict the time-related survival probability of BC patients in different molecular subtypes over 30 years of follow-up. Materials and methods: This study retrospectively analyzed 3580 patients diagnosed with invasive breast cancer (BC) from 1991 to 2021 in the Cancer Research Center of Shahid Beheshti University of Medical Science. The dataset contained 18 predictor variables and two dependent variables, which referred to the survival status of patients and the time patients survived from diagnosis. Feature importance was performed using the random forest algorithm to identify significant prognostic factors. Time-to-event deep-learning-based models, including Nnet-survival, DeepHit, DeepSurve, NMLTR and Cox-time, were developed using a grid search approach with all variables initially and then with only the most important variables selected from feature importance. The performance metrics used to determine the best-performing model were C-index and IBS. Additionally, the dataset was clustered based on molecular receptor status (i.e., luminal A, luminal B, HER2-enriched, and triple-negative), and the best-performing prediction model was used to estimate survival probability for each molecular subtype. Results: The random forest method identified tumor state, age at diagnosis, and lymph node status as the best subset of variables for predicting breast cancer (BC) survival probabilities. All models yielded very close performance, with Nnet-survival (C-index=0.77, IBS=0.13) slightly higher using all 18 variables or the three most important variables. The results showed that the Luminal A had the highest predicted BC survival probabilities, while triple-negative and HER2-enriched had the lowest predicted survival probabilities over time. Additionally, the luminal B subtype followed a similar trend as luminal A for the first five years, after which the predicted survival probability decreased steadily in 10- and 15-year intervals. Conclusion: This study provides valuable insight into the survival probability of patients based on their molecular receptor status, particularly for HER2-positive patients. This information can be used by healthcare providers to make informed decisions regarding the appropriateness of medical interventions for high-risk patients. Future clinical trials should further explore the response of different molecular subtypes to treatment in order to optimize the efficacy of breast cancer treatments.

Spatiotemporal variations in childhood lymphoma cancer incidence and its survival rate in Iran, 2005-2015: a cross-sectional study.

BACKGROUND: Childhood lymphoma is the second leading cause of cancer in children under 15 years of age in Iran. The aim of this study was to investigate the spatial and time variations in lymphoma incidence as well as the children's survival time in Iran. METHOD: This cross-sectional study was conducted using lymphoma cases (children under 14 years of age) from 2005 to 2015, and the data were obtained from the National Cancer Registry Center. The frequency, age-standardised incidence rate (ASIR), spatial clustering in national level and the survival rate (1 year and 5 years) using Kaplan-Meier method were evaluated. We used Spatial and Temporal Scan statistics software in order to detect statistically significant clusters in spatial analysis. RESULTS: A total number of 746 girls and 1610 boys were diagnosed with lymphoma during a 10-year period. ASIRs (per 100 000 people) for girls ranged from 0 in Ilam to 3.47 in Yasuj, and it ranged from 0.19 in Ilam to 5.91 in Yazd for boys from 2005 to 2015. Spatial analysis result showed a large statistically significant cluster (the most likely cluster) for both boys (relative risk (RR)=2.37) and girls (RR=2.49) located in the northwest of Iran. Fortunately, survival rate for both boys and girls was over 95.5%. CONCLUSION: Lymphoma incidence rates had heterogeneous geographical distribution, and some significant clusters were identified which strengthens the role of possible aetiological factors, and further studies are needed to clarify this ambiguity. Fortunately, the survival rate of this cancer in Iran was good and it was similar to the high-income countries.