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Background High rate of cardiovascular disease (CVD) have been reported among patients with novel coronavirus disease (COVID-19). Meanwhile there were controversies among different studies about CVD burden in COVID-19 patients. Hence, we aimed to study CVD burden among COVID-19 patients, using a systematic review and meta-analysis. Methods We have systematically searched databases including PubMed, Embase, Cochrane Library, Scopus, Web of Science as well as medRxiv pre-print database. Hand searched was also conducted in journal websites and Google Scholar. Meta-analyses were carried out for Odds Ratio (OR) of mortality and Intensive Care Unit (ICU) admission for different CVDs. We have also performed a descriptive meta-analysis on different CVDs. Results Fifty-six studies entered into meta-analysis for ICU admission and mortality outcome and 198 papers for descriptive outcomes, including 159,698 COVID-19 patients. Results of meta-analysis indicated that acute cardiac injury, (OR: 13.29, 95% CI 7.35-24.03), hypertension (OR: 2.60, 95% CI 2.11-3.19), heart Failure (OR: 6.72, 95% CI 3.34-13.52), arrhythmia (OR: 2.75, 95% CI 1.43-5.25), coronary artery disease (OR: 3.78, 95% CI 2.42-5.90), and cardiovascular disease (OR: 2.61, 95% CI 1.89-3.62) were significantly associated with mortality. Arrhythmia (OR: 7.03, 95% CI 2.79-17.69), acute cardiac injury (OR: 15.58, 95% CI 5.15-47.12), coronary heart disease (OR: 2.61, 95% CI 1.09-6.26), cardiovascular disease (OR: 3.11, 95% CI 1.59-6.09), and hypertension (OR: 1.95, 95% CI 1.41-2.68) were also significantly associated with ICU admission in COVID-19 patients. Conclusion Findings of this study revealed a high burden of CVDs among COVID-19 patients, which was significantly associated with mortality and ICU admission. Proper management of CVD patients with COVID-19 and monitoring COVID-19 patients for acute cardiac conditions is highly recommended to prevent mortality and critical situations., Graphical abstract Unlabelled Image

The pandemic of coronavirus disease (COVID)-2019 has been affected many people all around the world. Patients with mental disorders are not as safe as others; also, they might be more vulnerable in such situations. These patients take various medications, which can lead to numerous drug-drug interactions with experimental drugs uses against COVID-19. According to the potential critical interactions, we reviewed the reputable databases to find the interactions between main categories of psychiatric medications (e.g., antidepressants, anti-psychotics, sedative/hypnotics, and mood stabilizers) when used in concomitant with COVID-19 experimental agents (e.g., hydroxychloroquine, lopinavir/ritonavir, atazanavir, and chloroquine). We hope the list provided in this review helps the clinical care staff in treating patients with mental illness infected with severe acute respiratory syndrome coronavirus 2 during the COVID-19 pandemic.

Integrins are interesting targets in oncology. RGD sequence has high affinity for αVβ3 integrin receptors. Diagnostic/therapeutic agents can be selectively delivered into cancer cells overexpressing αVβ3 integrin by using RGD as a carrier. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown anticancer properties in in vitro and in vivo studies. The anti-cancer properties of NSAIDs occur though COX-2 inhibition. Regarding the anti-cancer properties of NSAIDs and overexpression of COX-2 enzyme in cancer cells, targeted delivery of NSAIDs into cancer cells to maximize their efficiency and minimize their side effects may gain increased clinical interest. In this study, RGD was conjugated to ketoprofen/Naproxen to selectively transfer these non-selective COX inhibitors into cancer cells. Keto/Nap-RGD-N4 peptides were synthesized based on solid phase fmoc peptide synthesis. Radiolabeling with [99mTc] via N4 (GGAG) ligand was done for biological evaluation. Affinity and specificity of Keto/Nap-RGD-N4 to integrin was determined using A2780, OVCAR-3, SKOV-3 and HT-1080 cell lines. Percentage of Intenalization was measured in A2780 cells. Biodistriburion was studied in normal and tumor model mice. Radiolabeled compounds showed high affinity to cells expressing αVβ3 integrin in comparison to cells not expressing αVβ3. The affinity to A2780 was significantly higher than OVCAR-3 cells. The %internalization into A2780 cells was quite low. Compounds showed more than 50% inhibition on A2780 and OVCAR-3 cells, less than 10% on MCF-7 and HT-1080 cells and no cytotoxicity on fibroblast cells after 48 h incubation. Although uptake of radiolabeled compounds in tumor was high at 1 h post-injection, the tumor/blood ratio was less than 1.5 which made SPECT imaging impossible. Provided that NSAID drugs are conjugated to RGD, there will be a selective delivery to target tissues as well as synergetic anti-tumor effects which reduce systemic doses and toxicity.

Glioma is the oneof the most prevalent primarybrain tumors. There is a variety of oxidative stresses, inflammatory pathways, apoptosis signaling, and Na+ /H + exchangers (NHEs) involved in the pathophysiology of glioma. Previous studies have indicated a relationship between NHEs and some molecular pathways in glioma. NHEs, including NHE1, NHE5, and NHE9 affect apoptosis, tumor-associated macrophage inflammatory pathways, matrix metalloproteinases, cancer-cell growth, invasion, and migration of glioma. Also, inhibition of NHEs contributes to increased survival in animal models of glioma. Limited studies, however, have assessed the relationship between NHEs and molecular pathways in glioma. This review summarizes current knowledge and evidence regarding the relationship between NHEs and glioma, and the mechanisms involved.

Background: Early detection of apoptosis is very important for therapy and follow-up treatment in various pathologic conditions. Annexin V interacts strongly and specifically with phosphat...

A novel coronavirus emerged in Wuhan, China; in December 2019 and has widely affected the global community. After months of extensive effort, much remains to be understood of the pathogenesis of Coronavirus Disease 2019 (COVID-19). The available evidence raises a critical question : Is COVID-19 a lung disorder leading to circulatory problems, or a systemic disorder that leads to lung problems?. If the latter scenario is correct, investigations on hypoxia conditions and the development of anti-hypoxia agents may lead to potential front-line treatments in combination with antivirals for hypoxemic COVID-19 patients. Hence, anti-hypoxic agents may become a potential part of combination therapy in hypoxemic respiratory failure and COVID-19.

A systematic review and meta-analysis was carried out to examine the role of hydroxychloroquine (HCQ) in the treatment of COVID-19.We performed a systematic search in PubMed, Scopus, Embase, CochraneLibrary, Web of Science, Google Scholar, and medRxiv pre-print databases using available MeSH terms for COVID-19 and hydroxychloroquine. Data from all studies that focused on the effectiveness of HCQ with or without the addition of azithromycin (AZM) in confirmed COVID-19 patients, which were published up to 12 September 2020, were collated for analysis using CMA v.2.2.064.Our systematic review retrieved 41 studies. Among these, 37 studies including 45,913 participants fulfilled the criteria for subsequent meta-analysis. The data showed no significant difference in treatment efficacy between the HCQ and control groups (RR: 1.02, 95% CI, 0.81-1.27). Combination of HCQ with AZM also did not lead to improved treatment outcomes (RR: 1.26, 95% CI, 0.91-1.74). Furthermore, the mortality difference was not significant, neither in HCQ treatment group (RR: 0.86, 95% CI, 0.71-1.03) nor in HCQ plus AZM treatment group (RR: 1.28, 95% CI, 0.76-2.14) in comparison to controls. Meta-regression analysis showed that age was the factor that significantly affected mortality (The meta-analysis found that there was no clinical benefit of using either HCQ by itself or in combination with AZM for the treatment of COVID-19 patients. Hence, it may be prudent for clinicians and researchers to focus on other therapeutic options that may show greater promise in this disease.

Mg2+ is an important cation in our body. It is an essential cofactor for many enzymes. Despite many works, nothing is known about the protective effects of MgSO4 against hypoxia-induced lethality and oxidative damage in brain mitochondria. In this study, antihypoxic and antioxidative activities of MgSO4 were evaluated by three experimental models of induced hypoxia (asphyctic, haemic, and circulatory) in mice. Mitochondria protective effects of MgSO4 were evaluated in mouse brain after induction of different models of hypoxia. Antihypoxic activity was especially pronounced in asphyctic hypoxia, where MgSO4 at dose 600 mg/kg showed the same activity as phenytoin, which used as a positive control ( P < 0.001 ). In the haemic model, MgSO4 at all used doses significantly prolonged latency of death. In circulatory hypoxia, MgSO4 (600 mg/kg) doubles the survival time. MgSO4 significantly decreased lipid peroxidation and protein carbonyl and improved mitochondrial function and glutathione content in brain mitochondria compared to the control groups. The results obtained in this study showed that MgSO4 administration has protective effects against lethality induced by different models of hypoxia and improves brain mitochondria oxidative damage.

Objective: A systematic review and meta-analysis was carried out to examine the role of hydroxychloroquine (HCQ) in the treatment of COVID-19. Methods: We performed a systematic search in PubMed, Scopus, Embase, Cochrane- Library, Web of Science, Google Scholar, and medRxiv pre-print databases using available MeSH terms for COVID-19 and hydroxychloroquine. Data from all studies that focused on the effectiveness of HCQ with or without the addition of azithromycin (AZM) in confirmed COVID-19 patients, which were published up to 12 September 2020, were collated for analysis using CMA v.2.2.064. Results: Our systematic review retrieved 41 studies. Among these, 37 studies including 45,913 participants fulfilled the criteria for subsequent meta-analysis. The data showed no significant difference in treatment efficacy between the HCQ and control groups (RR: 1.02, 95% CI, 0.81–1.27). Combination of HCQ with AZM also did not lead to improved treatment outcomes (RR: 1.26, 95% CI, 0.91–1.74). Furthermore, the mortality difference was not significant, neither in HCQ treatment group (RR: 0.86, 95% CI, 0.71–1.03) nor in HCQ plus AZM treatment group (RR: 1.28, 95% CI, 0.76–2.14) in comparison to controls. Meta-regression analysis showed that age was the factor that significantly affected mortality (P

Objectives Breast cancer is known as one of the deadliest forms of cancer, and it is increasing globally. There are a variety of proven and controversial risk factors for this malignancy. Herein, we aimed to undertake a systematic review and meta-analysis focus on the epidemiology of breast cancer risk factors in Iran. Methods We performed a systematic search via PubMed, Scopus, Web of Science, and Persian databases for identifying studies published on breast cancer risk factors up to March 2019. Meta-analyses were done for risk factors reported in more than one study. We calculated odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using a fixed/random-effects models. Results Thirty-nine studies entered into the meta-analysis. Pooling of ORs showed a significant harmful effect for risk factors including family history (OR: 1.80, 95%CI 1.47–2.12), hormonal replacement therapy (HRT) (OR: 5.48, 95%CI 0.84–1.74), passive smokers (OR: 1.68, 95%CI 1.34–2.03), full-term pregnancy at age 30 (OR: 3.41, 95%CI 1.19–5.63), abortion (OR: 1.84, 95%CI 1.35–2.33), sweets consumption (OR: 1.71, 95%CI 1.32–2.11) and genotype Arg/Arg (crude OR: 1.59, 95%CI 1.07–2.10), whereas a significant protective effect for late menarche (OR: 0.58, 95%CI 0.32–0.83), nulliparity (OR: 0.68, 95%CI 0.39–0.96), 13–24 months of breastfeeding (OR: 0.68, 95%CI 0.46–0.90), daily exercise (OR: 0.59, 95%CI 0.44–0.73) and vegetable consumption (crude OR: 0.28, 95%CI 0.10–0.46). Conclusions This study suggests that factors such as family history, HRT, passive smokers, late full-term pregnancy, abortion, sweets consumption and genotype Arg/Arg might increase risk of breast cancer development, whereas late menarche, nulliparity, 13–24 months breastfeeding, daily exercise and vegetable consumption had an inverse association with breast cancer development.

BackgroundEvidence recommends that vitamin D might be a crucial supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a systematic review and meta-analysis in order to maximize the use of everything that exists about the role of vitamin D in the COVID-19.MethodsA systematic search was performed in PubMed, Scopus, Embase, and Web of Science up to December 18, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review.ResultsTwenty-three studies containing 11901participants entered into the meta-analysis. The meta-analysis indicated that 41% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 29%-55%), and in 42% of patients, levels of vitamin D were insufficient (95% CI, 24%-63%). The serum 25-hydroxyvitamin D concentration was 20.3 ng/mL among all COVID-19 patients (95% CI, 12.1-19.8). The odds of getting infected with SARS-CoV-2 is 3.3 times higher among individuals with vitamin D deficiency (95% CI, 2.5-4.3). The chance of developing severe COVID-19 is about five times higher in patients with vitamin D deficiency (OR: 5.1, 95% CI, 2.6-10.3). There is no significant association between vitamin D status and higher mortality rates (OR: 1.6, 95% CI, 0.5-4.4).ConclusionThis study found that most of the COVID-19 patients were suffering from vitamin D deficiency/insufficiency. Also, there is about three times higher chance of getting infected with SARS-CoV-2 among vitamin D deficient individuals and about 5 times higher probability of developing the severe disease in vitamin D deficient patients. Vitamin D deficiency showed no significant association with mortality rates in this population.

Edaravone has been recently used for the treatment of acute cerebral infarction. However, there is no data on the protective effects of this drug against hypoxia-induced lethality. Here, we aimed to evaluate the protective effects of edaravone against hypoxia-induced lethality and oxidative stress in mice through three experimental models of hypoxia.Materials and Methodsmale Swiss albino mice were randomly housed in groups of 10. Mice received single i.p. injections of edaravone for four consecutive days. Three experimental models of hypoxia: asphyctic, circulatory, and haemic were applied in this study. Oxidative stress, lipid peroxidation and glutathione content were assessed after hypoxia induction.ResultsSignificant protective activities were observed in all models of hypoxia. Antihypoxic activities were highly significant in asphytic and circulatory hypoxia. These effects were dose-dependent. Edaravone, at 5 mg kg−1, showed statistically significant activities concerning the control groups. Edaravone significantly prolonged the latency for death. At 2.5 mg kg−1, it prolonged survival time (26.08 ± 0.79 min). This effect was statistically significant (PConclusionsEdaravone showed an excellent protective effect against hypoxia in all tested models and decreased the oxidative stress in the brain tissue of hypoxic mice. Notably, results showed significant and dose-dependent effects on the models of asphytic and circulatory hypoxia. The antioxidant activity itself might be a proposed mechanism for the antihypoxic activities of this drug.Impact statementThis study provides a novel proof-of-concept for a FDA approved drug, which will open a new area of research in the field and drug repurposing.

BackgroundCoronavirus Disease 2019 (COVID-19) has become a major global issue with rising the number of infected individuals and mortality in recent months. Among all therapeutic approaches, arguments have raised about hydroxychloroquine (HCQ) efficacy in the treatment of COVID-19. We carried out a systematic review and meta-analysis overcome the controversies regarding the effectiveness of hydroxychloroquine in the treatment of COVID-19.MethodsA systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, Google Scholar and medRxiv pre-print database using all available MeSH terms for COVID-19 and hydroxychloroquine up to July 19, 2020. Studies focused on the effectiveness of HCQ with/without azithromycin (AZM) in confirmed COVID-19 patients were entered into the study. Two researchers have independently evaluated quality assessment of the studies and abstracted data for data extraction. Extracted data were analyzed using CMAv. 2.2.064. Heterogeneity was assessed using theI-squared (I2) test, and fixed/random-effects model was used when appropriate for pooling of studies.ResultsOut of 26 studies entered into our systematic review, 21 studies including 14 comparative studies with control group and seven observational studies containing 103,486 participants have entered into the meta-analysis. The results of the meta-analysis on comparative studies indicated no significant clinical effectiveness (negative in RT-PCR evaluation) for HCQ regimen in the treatment of COVID-19 in comparison to control group (RR: 1.03, 95% CI, 0.79-1.34). The same result was observed for the combination of HCQ+azithromycin (RR: 1.26, 95% CI, 0.91-1.74). No significant differences were found for both HCQ (RR: 0.92, 95% CI, 0.72-1.16) and HCQ+AZM (RR: 1.72, 95% CI, 0.86-3.42) mortality rate; however, mortality was affected by age differences according to meta-regression analysis (PConclusionThis systematic review and meta-analysis showed no clinical benefits regarding HCQ treatment with/without azithromycin for COVID-19 patients. Although mortality rate was not significantly different between cases and controls, frequency of adverse effects was substantially higher in HCQ regimen group. However, due to that most of the studies were non-randomized and results were not homogenous, selection bias was unavoidable and further large randomized clinical trials following comprehensive meta-analysis should be taken into account in order to achieve more reliable findings. Also, it is worth mentioning that if this work does not allow to quantify a “value” of the HCQ, it allows at least to know what is not the HCQ and that it would be prudent not to continue investing in this direction.

This study was performed to systematically asses the risk of secondary malignancies in patients with ovarian cancer. We conducted a systematic search in PubMed, Web of Science, and Scopus databases up to September 2019 to find target studies. In this study, the overall SIR has been calculated with fixed/random-effects models. Sixteen cohort studies including 122715 ovarian cancer patients with 4458 secondary malignancies have been included in this meta-analysis. Combined SIRs showed an increased risk of secondary malignancies prevalence (SIR: 1.81, 95%CI 1.58-2.03). The most prevalence diagnosed malignancies were as follows: breast cancer (1.34, 95%CI 1.5-1.18), intestine (2.36, 95%CI 1.11-3.61), colorectal (1.73, 95%CI 1.44-2.02), pancreatic (1.42, 95%CI 1.13-1.71), cervical cancer (11.57, 95%CI 6.94-16.21), renal (1.43, 95%CI 1.11-1.74), bladder (2.13, 95%CI 1.77-2.50), leukemia (3.33, 95%CI 2.23-4.43), connective tissue (2.61, 95%CI 1.56-3.66), and thyroid (1.59, 95%CI 1.13-2.04). In regards to the results, various malignancies have a greater prevalence in patients with ovarian cancer in comparison to the general public. Corpus cancer, leukemia cancer, endometrium cancer, connective tissue malignancy, and bladder cancer are among the high risks in these patients and need to be considered for them. Hence, the survival rate of the patients can be increased through prevention and early diagnosis.

To systematically investigate the epidemiology of breast cancer risk factors in Iran, we performed a systematic search via PubMed, Scopus, Web of Science and Persian databases for identifying studies published on breast cancer risk factors up to March 2019. Meta-analyses were done for risk factors reported in more than one study. We calculated odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using a fixed/random-effects models.Thirty-nine studies entered into the meta-analysis. Pooling of ORs showed a significant harmful effect for risk factors including family history (OR: 1.80, 95%CI 1.47-2.12), HRT (OR: 5.48, 95%CI 0.84-1.74), ER positive (OR: 1.87, 95%CI 1.41-2.33), PR positive (OR: 1.84, 95%CI 1.38-2.29), stress condition (OR: 2.67, 95%CI 1.84-3.50), passive smokers (OR: 1.68, 95%CI 1.34-2.03), full-term pregnancy at age 30 (OR: 3.41, 95%CI 1.19-5.63), abortion (OR: 1.84, 95%CI 1.35-2.33), sweets consumption (OR: 1.71, 95%CI 1.32-2.11) and genotype Arg/Arg (crude OR: 1.59, 95%CI 1.07-2.10), whereas a significant protective effect for late menarche (OR: 0.58, 95%CI 0.32-0.83), nulliparity (OR: 0.68, 95%CI 0.39-0.96), 13 to 24 months of breastfeeding (OR: 0.68, 95%CI 0.46-0.90), daily exercise (OR: 0.59, 95%CI 0.44-0.73) and vegetable consumption (crude OR: 0.28, 95%CI 0.10-0.46).This study suggest that factors such as family history, HRT, ER and PR positive status, stress condition, passive smokers, late full-term pregnancy, abortion, sweets consumption and genotype Arg/Arg might increase risk of breast cancer development, whereas late menarche, nulliparity, 13-24 months breastfeeding, daily exercise and vegetable consumption had an inverse association with breast cancer development.

IMPORTANCEProstate cancer (PC) is the second most common cancer among males globally, however, the survival rate is favorable in most patients. In a small number of patients, who suffer from advanced or invasive cancer, various side effects such as secondary malignancies or treatment-related secondary malignancies (SMs) may be seen.OBJECTIVETo systematically asses the risk of secondary malignancies in patients with prostate cancer.DATA SOURCESWe have searched for longitudinal studies through databases of Web of Science, Scopus and PubMed for all available data up to September 2019.STUDY SELECTIONStudies with longitudinal design on prostate cancer patients that declared the results in SIR or those that the SIR could be calculated were eligible.DATA EXTRACTION AND SYNTHESISThe heterogeneity was evaluated using the I2 test. According to the results and in case of I2 ≥ 50%, the random effect model was used to combine the results. To identify the cause of heterogeneity in the studies, the analysis of sub-groups was performed based on the site of secondary malignancy, the treatment procedure, and duration of follow-up. Data were analyzed using STATA version 11.MAIN OUTCOMES AND MEASURESOverall SIR and based on treatment of prostate cancer and duration of follow-up.RESULTSTwenty-six studies involving more than 2223,704 patients with PC and more than 86034 cases of SMs were entered into this study. The meta-analysis showed that the risk of cancer after PC was 1.03 (95% CI 0.90 - 1.15) and the SIRs of some cancers such as the bladder 1.52 (1.06 - 1.99) and melanoma 1.32 (0.78 - 1.87) were higher than expected. While, malignancies such as rectum 0.92 (0.85 - 1.00), lung 0.85 (0.74 - 0.96) and liver 0.76 (0.54 - 0.98) showed lower incidence in compare to general population.CONCLUSIONS AND RELEVANCEThe overall risk of SMs in patients with prostate cancer is not significantly different from general population, and even in patients undergoing prostatectomy or brachytherapy, the risk is lower. But the incidence of some cancers such as melanoma, bladder, and urinary tract appears to be higher than the public in all types of treatment approaches.Key PointsQuestioIs the risk of secondary malignancy in patients with prostate cancer higher than the general population?FindingsThis systematic review and meta-analysis of 26 unique trials including 2223,704 patients, showed that the SIRs of some cancers such as the bladder and melanoma were higher than expected.MeaningThese findings suggest that the overall risk of some cancer such as bladder and melanoma in patients with prostate cancer were higher than the general population.

IntroductionRecently, a new strain of coronaviruses, which originated from Wuhan City, Hubei Province, China has been identified. According to the high prevalence of new coronavirus, further investigation on the clinical and paraclinical features of this disease seems essential. Hence, we carried out this systematic review and meta-analysis to figure out the unknown features.MethodsThis study was performed using databases of Web of Science, Scopus and PubMed. We considered English cross-sectional and case-series papers which reported clinical, radiological, and laboratory characteristics of patients with COVID-19. We used STATA v.11 and random effect model for data analysis.ResultsIn the present meta-analysis, 32 papers including 49504 COVID-19 patients were studied. The most common clinical symptoms were fever (84%), cough (65%) and fatigue (42%), respectively. The most common radiological and paraclinical features were bilateral pneumonia (61%), ground-glass opacity (50%), thrombocytopenia (36%) and lymphocytopenia (34%). The study also showed that the frequency of comorbidities and early symptoms was higher in critically severe patients. Moreover, we found the overall mortality rate of three percent.ConclusionAccording to that there are many cases without Computed Tomography Scan findings or clear clinical symptoms, it is recommended to use other confirming methods such RNA sequencing in order to identification of suspicious undiagnosed patients. Moreover, while there is no access to clinical and paraclinical facilities in in public places such as airports and border crossings, it is recommended to consider factors such as fever, cough, sputum and fatigue.

Glioma is the oneof the most prevalent primarybrain tumors. There is a variety of oxidative stresses, inflammatory pathways, apoptosis signaling, and Na

BACKGROUND: Integrins are interesting targets in oncology. RGD sequence has high affinity for α(V)β(3) integrin receptors. Diagnostic/therapeutic agents can be selectively delivered into cancer cells overexpressing α(V)β(3) integrin by using RGD as a carrier. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown anticancer properties in in vitro and in vivo studies. The anti-cancer properties of NSAIDs occur though COX-2 inhibition. Regarding the anti-cancer properties of NSAIDs and overexpression of COX-2 enzyme in cancer cells, targeted delivery of NSAIDs into cancer cells to maximize their efficiency and minimize their side effects may gain increased clinical interest. OBJECTIVES: In this study, RGD was conjugated to ketoprofen/Naproxen to selectively transfer these non-selective COX inhibitors into cancer cells. METHODS: Keto/Nap-RGD-N4 peptides were synthesized based on solid phase fmoc peptide synthesis. Radiolabeling with [(99m)Tc] via N4 (GGAG) ligand was done for biological evaluation. Affinity and specificity of Keto/Nap-RGD-N4 to integrin was determined using A2780, OVCAR-3, SKOV-3 and HT-1080 cell lines. Percentage of Intenalization was measured in A2780 cells. Biodistriburion was studied in normal and tumor model mice. RESULTS: Radiolabeled compounds showed high affinity to cells expressing α(V)β(3) integrin in comparison to cells not expressing α(V)β(3). The affinity to A2780 was significantly higher than OVCAR-3 cells. The %internalization into A2780 cells was quite low. Compounds showed more than 50% inhibition on A2780 and OVCAR-3 cells, less than 10% on MCF-7 and HT-1080 cells and no cytotoxicity on fibroblast cells after 48 h incubation. Although uptake of radiolabeled compounds in tumor was high at 1 h post-injection, the tumor/blood ratio was less than 1.5 which made SPECT imaging impossible. CONCLUSION: Provided that NSAID drugs are conjugated to RGD, there will be a selective delivery to target tissues as well as synergetic anti-tumor effects which reduce systemic doses and toxicity. [Figure: see text]

Objective: This study was performed to systematically assess the risk of secondary malignancies in patients with ovarian cancer. Methods: A systematic search was conducted in PubMed, Web of Science, and Scopus databases up to September 2019. In this study, the overall standardized incidence ratio (SIR) was calculated applying fixed/random-effects models. Sixteen cohort studies, including 122715 ovarian cancer patients with 4458 secondary malignancies were included. Results: Combined SIRs showed an increased risk of secondary malignancies prevalence (SIR = 1.81, 95% CI 1.58-2.03). The most common malignancies were cervical cancer 11.57 (6.94- 16.21), endometrium 6.31 (4.18-8.44), leukemia 3.33 (2.23-4.43), connective tissue 2.61 (1.56-3.66), bladder 2.13 (1.77-2.50), renal 1.43 (1.11-1.74), intestine 2.36 (1.11-3.61), colorectal 1.73 (1.44-2.02), pancreatic 1.42 (1.13-1.71), breast 1.34 (1.5-1.18), and thyroid 1.59 (1.13- 2.04) cancers. Conclusion: Some malignancies were found to be highly prevalent in patients with ovarian cancer compared to the general population, including endometrial cancer, leukemia, connective tissue malignancy, and bladder cancer. Therefore, efforts for early detection, which could lead to improved survival should be taken in these patients.

Background Measurement of serum human epidermal growth factor receptor-2 (HER-2/neu) levels for breast cancer is still controversial and not recommended in any clinical procedures. However, it seems that HER-2 measuring can plays an important role as a diagnostic marker for early selection of therapeutic approach as well as predict of prognosis in breast cancer patients. We aimed to undertake a systematic review and meta-analysis focuses on the diagnostic value of serum HER-2 level measures by ELISA in compare to other methods due to its ease of implementation and cost-effectiveness for HER-2 positive two plus in IHC. Methods We performed a systematic search via PubMed, Scopus, Cochrane Library and Web of Science databases for human diagnostic studies reported the levels of serum HER2 in breast cancer patients, which was confirmed using histopathological examination such as immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Meta-analyses were carried out for sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR). Results Fourteen studies entered into the study. The meta-analysis indicated that serum HER2 levels had sensitivity 53.05 (95%CI 40.82-65.28), specificity 79.27 (95%CI 73.02-85.51), accuracy 72.06 (95%CI 67.04-77.08), PPV 56.18 (95%CI 44.16-68.20), NPV 76.93 (95%CI 69.56-84.31), PLR 2.10 (95%CI 1.69-2.50) and NLR 0.58 (95%CI 0.44-0.71). Conclusions Our findings revealed that, although serum HER2 levels showed a low sensitivity for breast cancer diagnosis, its specificity is significantly high in this regard. Hence, it seems that measurement of serum HER2 levels can play a significant role as a verification test for initial negative screening test results, especially in low-income regions due to its cost-effectiveness and ease of implementation in comparison with monitoring of tissue HER-2. Legal entity responsible for the study Amir Shamshirian and Reza Alizadeh-Navaei. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Melanocortin-1 (MC1) receptor is an attractive melanoma-specific target for the development of α-MSH peptide based imaging and therapeutic agents. In this work a new lactam bridge α-MSH analogue was synthesized and radiolabeled with 99mTc via HYNIC chelator and tricine as co-ligand. Also, stability in human serum, receptor bound internalization and tissue biodistribution in tumor bearing nude mice were thoroughly investigated. Radiolabeling with 99mTc was performed at high specific activities (163MBq/nmol) with an acceptable labeling yield (>98%). The radioligand showed specific internalization into B16/F10 cells (13.35 ± 0.9% at 4 h). In biodistribution studies, a receptor-specific uptake was observed in MC1 receptor positive organ so that after 4 h the tumor uptake was 4.51 ± 0.11 % ID/g. Predominant renal excretion pathway with a highest accumulation of activity in tumor was observed for this radiopeptide. Obtained results show that the new designed labeled peptide conjugate can be a suitable candidate for diagnosis of metastatic melanomas.

The quantitative relationship between molecular properties and pharmaceutical activities of 19 antimalarial 3-hydroxypyridinones is studied using B3LYP/6-311++G** structural, electronic, and thermochemical characteristics. In this QSAR study, stepwise-multilinear regression (MLR) and principle component regression (PCR) are utilized based on volume, HOMO, nCrH2, and nHDon descriptors selected from a number of descriptor sets calculated and examined. The MLR coefficients are evaluated by cross-validation and external test sets methods. Regression coefficients of R2 = 0.882 and R2 = 0.874 are obtained, respectively, for the MLR and PCR predicted pIC50 values as referenced to their experimental values. Results of PCR predict the same trend for the predicted IC50 approving validity of the MLR results. Based on the present MLR and PCR analyses, pIC50 value is calculated for six candidate antimalarial drugs designed in this work, two of which are found to have promising antimalarial activity as high as that of the two best already synthesized and examined drugs.

Multiple linear regression (MLR), factor analysis in combination with multiple linear regression (FA-MLR), and genetic algorithm subset selection partial least square (GA-PLS) regression methods were used for quantitative structure–activity relationships (QSAR) model building. These approaches were employed to investigate the correlation between pIC50 and various physicochemical descriptors of 28 compounds of 1-aminocyclopentyl-3-carboxyamides including substituted tetrahydropyran moieties as CCR2 inhibitors. The obtained models were validated using cross-validation and external test set. The predictability and robustness of the developed models were considered by some figures of merit such as RMSEP and Y-randomization. MLR, FA-MLR, and GA-PLS have R 2 equal to 0.84, 0.69, and 0.93, respectively. Predicted variance by MLR, FA-MLR, and GA-PLS (R 2 test) is 78, 75, and 78%, respectively. Furthermore, the domain of applicability which indicates the area of reliable predictions is defined. The prediction results by models are in good agreement with the experimental value.

Melanocortin-1 (MC1) receptor is an attractive melanoma-specific target which has been used for melanoma imaging and therapy. In this work, a new lactam bridge α-MSH analog was labeled with 99mTc via HYNIC and EDDA/tricine as coligands including gamma aminobutyric acid (GABA) as a three carbon chain spacer between HYNIC and the N-terminus of the cyclic peptide. Also, stability in human serum, receptor bound internalization, in vivo tumor uptake, and tissue biodistribution were thoroughly investigated. HYNIC-GABA-Nle-CycMSHhept was synthesized using a standard Fmoc strategy. Labeling was performed at 95 °C and analysis involved instant thin layer chromatography and high performance liquid chromatography methods. The receptor bound internalization rate was studied in MC1 receptor expressing B16/F10 cells. Biodistribution of radiopeptide was studied in nude mice bearing B16/F10 tumor. Labeling yield of >98 % (n = 3) was obtained corresponding to a specific activity of 81 MBq/nmol. Peptide conjugate showed efficient stability in the presence of human serum. The radioligand showed specific internalization into B16/F10 cells (12.45 ± 1.1 % at 4 h). In biodistribution studies, a receptor-specific uptake was observed in MC1 receptor-positive organs so that after 2 h the uptake in mouse tumor was 5.10 ± 0.08 % ID/g, while low accumulation in the kidney uptake was observed (4.58 ± 0.68 % ID/g at 2 h after injection). The obtained results show that the presented new designed labeled peptide conjugate may be a suitable candidate for diagnosis of malignant tumors.