Updates on Overcoming Bicalutamide Resistance: A Glimpse into Resistance to a Novel Antiandrogen.

The standard androgen deprivation therapy for advanced prostate cancer includes the use of bicalutamide, which is a well-known antagonist of androgen receptors. Despite numerous benefits of the drugs in prostate cancer treatment, there is always a risk of developing a resistant phenotype, which paves the way for a more aggressive and low-survival type of prostate cancer. Over the years, many studies have investigated the candidate mechanisms of such resistance and have managed to find possible therapeutic solutions. In this Review, we shed light on the heterogeneous dynamics of progression to resistance against bicalutamide treatment, referring to the most recent studies and the approaches that have been so far discussed. This Review tries to offer a deep and comprehensive understanding about how the resistant cells become sensitive to the drug and what corresponding pathways lead to an appropriate solution for the antiandrogen resistance challenge.

A digital image colorimetry system based on smart devices for immediate and simultaneous determination of enzyme-linked immunosorbent assays.

Standard enzyme-linked immunosorbent assays based on microplates are frequently utilized for various molecular sensing, disease screening, and nanomedicine applications. Comparing this multi-well plate batched analysis to non-batched or non-standard testing, the diagnosis expenses per patient are drastically reduced. However, the requirement for rather big and pricey readout instruments prevents their application in environments with limited resources, especially in the field. In this work, a handheld cellphone-based colorimetric microplate reader for quick, credible, and novel analysis of digital images of human cancer cell lines at a reasonable price was developed. Using our in-house-developed app, images of the plates are captured and sent to our servers, where they are processed using a machine learning algorithm to produce diagnostic results. Using FDA-approved human epididymis protein of ovary IgG (HE4), prostate cancer cell line (PC3), and bladder cancer cell line (5637) ELISA tests, we successfully examined this mobile platform. The accuracies for the HE4, PC3, and 5637 tests were 93%, 97.5%, and 97.2%, respectively. By contrasting the findings with the measurements made using optical absorption EPOCH microplate readers and optical absorption Tecan microplate readers, this approach was found to be accurate and effective. As a result, digital image colorimetry on smart devices offered a practical, user-friendly, affordable, precise, and effective method for quickly identifying human cancer cell lines. Thus, healthcare providers might use this portable device to carry out high-throughput illness screening, epidemiological investigations or monitor vaccination campaigns.

The 15-year national trends of urinary cancers incidence among Iranian men and women; 2005-2020.

BACKGROUND: Urinary tract cancers including bladder, kidney, ureter, and pelvis are a common malignancy worldwide with high mortality ratio. Aimed to investigate the prevalence of these cancers, we conducted this study. METHODS: In this study, all the information related to ICD10 codes, gender, age and province of residence of individuals were obtained from the data of Iran's cancer registry by the Ministry of Health, Medicine and Medical Education and demographic evidence for each sub-country from the reports of Statistics Center of Iran (SCI). Also, the data of two Iranian national survey studies CASPIAN-III, IV, and V (information related to the care and prevention of non-communicable diseases (NCD) in childhood and adolescence) and STEPs (including information on NCD in adults over 18 years old) were used. The data was analyzed using Poisson regression with mixed effects to estimate the incidence of cancers. RESULTS: Bladder and kidney neoplasm are the most common cancers of the urinary system in Iran. The prevalence of bladder cancer has increased from 5.82 to 11.50 per 100,000 individuals. The increasing trend is growing faster in men compared with women. The incidence of kidney neoplasm has increased over the years (2.03 in 2005 vs. 7.02 in 2020 per 100,000). Having a higher incidence ratio compared with bladder cancer, kidney cancer is responsible for 35.06% of all urinary cancers in 2020 compared with 23.71% in 2005. Both neoplasms of the ureter and renal pelvis were recorded rarely and with lower incidence in both sexes during this period. CONCLUSION: Considering the increasing trend in the incidence of urinary neoplasms in Iran during these years, the advantage of focusing on the risk of urinary cancers is highlighted. Therefore, investigating the prevalence and incidence of urinary cancers to plan and manage these cancers will result in prevention and reduction of the disease burden on the Iranian society. Future studies in this field can help in the prevention and well-timed diagnosis of these cancers.

A Simple Aptamer-Based Nanoconjugate Assay for Diagnosis of Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) as a bone marrow stem cell clonal disease appears from the proliferation of granulocyte cells at all stages of maturation. If the disease diagnosis is not early, patients enter the blastic phase, which decreases their survival rate to 3-6 months. It implies the significance of the early diagnosis of CML. In this study, we introduce a simple array for diagnosis of the K562 cells as the human immortalized myeloid leukemia cell line. The developed aptamer-based biosensor (aptasensor) includes the T2-KK1B10 aptamer strands attached to the surface of mesoporous silica nanoparticles (MSNPs) with the cavities accumulated from rhodamine B and coated by both Ca2+ ions and ATP aptamer. The aptamer-based nanoconjugate can enter the K562 cells through the complexation of the T2-KK1B10 aptamer with the cells. The ATP in the cells and low level of intracellular Ca2+ ion release both the aptamer and ion from the surface of the MSNPs. The liberated rhodamine B results in an increased fluorescence intensity. Fluorescence microscope imaging and flow cytometry histogram display a strong fluorescence emission for the K562 cells (CML cells) exposed to the nanoconjugate in comparison with that for MCF-7 cells. The aptasensor possesses good performance in the blood samples with the advantages of high sensitivity, rapidness, and cost-effectiveness, making it an appropriate tool for the diagnosis of CML disease.

PTEN promoter methylation and expression in endometrial cancer tissues.

Introduction: Some gene expression regulation in cancers can be controlled by epigenetic change like methylation. PTEN promoter methylation and expression were evaluated in endometrial cancer. Methods: The study was run on 39 tumor tissues of endometrial cancer patients and 41 normal endometrial tissues. After total RNA extraction, cDNA synthesis was done by reverse transcription of the total (real-time PCR) using SYBER Green master mix. DNA extraction and bisulfite treatment were conducted and methylation was semiquantified by the methylation-sensitive high-resolution melting method. Finally, promoter methylation quantification of the total number of 25 tumors and 22 non-neoplastic tissues was done. Results: PTEN gene expression showed a significant decrease in endometrial cancer tissues. Promoter methylation was significantly lower in the non-neoplastic group (7.2; p < 0.001). In addition, PTEN promoter methylation was observed in 52.0% of tumor tissues compared with 13.6% in the non-neoplastic group (p = 0.06). There were no significant correlations between PTEN expression and methylation and clinicopathological features in endometrial cancer patients (p > 0.05). Conclusion: PTEN gene expression in endometrial cancer tissues decreased because of its promoter hypermethylation.

Whole Exome Sequencing to Find Candidate Variants for the Prediction of Kidney Transplantation Efficacy.

INTRODUCTION: Kidney transplantation is the optimal treatment strategy for some end-stage renal disease (ESRD); however, graft survival and the success of the transplantation depend on several elements, including the genetics of recipients. In this study, we evaluated exon loci variants based on a high-resolution Next Generation Sequencing (NGS) method. METHODS: We evaluated whole-exome sequencing (WES) of transplanted kidney recipients in a prospective study. The study involved a total of 10 patients (5 without a history of rejection and 5 with). About five milliliters of blood were collected for DNA extraction, followed by whole-exome sequencing based on molecular inversion probes (MIPs). RESULTS: Sequencing and variant filtering identified nine pathogenic variants in rejecting patients (low survival). Interestingly, in five patients with successful kidney transplantation, we found 86 SNPs in 63 genes 61 were variants of uncertain significance (VUS), 5 were likely pathogenic, and five were likely benign/benign. The only overlap between rejecting and non-rejecting patients was SNPs rs529922492 in rejecting and rs773542127 in non-rejecting patients' MUC4 gene. CONCLUSIONS: Nine variants of rs779232502, rs3831942, rs564955632, rs529922492, rs762675930, rs569593251, rs192347509, rs548514380, and rs72648913 have roles in short graft survival.

Salivary and serum periostin in kidney transplant recipients.

INTRODUCTION: End-stage renal disease (ESRD) treatment includes dialysis and kidney transplantation. Transplant rejection is a major barrier to transplant success. One of the markers mentioned in previous studies on renal function in patients with renal failure for various reasons is periostin (POSTN). The expression of POSTN correlates with interstitial fibrosis and reduced renal function. One of the limitations in this regard is the effect of oral lesions on the POSTN level. This study was conducted aimed to measure the relationship between salivary and serum POSTN and renal function in patients with a history of a kidney transplant, taking into account all the conditions affecting POSTN. METHODS: In this study, serum and saliva samples were taken from 23 transplant patients with normal function (NF) and 29 transplant patients with graft failure (GF). At least one year had passed since the transplant. Before sampling, a complete oral examination was performed. Salivary and serum POSTN was examined by ELISA. The results were analyzed by SPSS software. RESULTS: The POSTN level in the serum of the NF group (191.00 ± 33.42) was higher than GF patients (178.71 ± 25.68), but the difference was not significant (P = 0.30). Salivary POSTN in NF patients (2.76 ± 0.35) was significantly higher than GF patients (2.44 ± 0.60) (P = 0.01). CONCLUSIONS: The superiority of saliva as a diagnostic fluid includes ease of collection and storage, and non-invasiveness, all of which can lead to the replacement of blood with this bio-fluid. The significant results of salivary POSTN may be due to the lack of serum disturbing factors. Saliva is an ultra-filtered fluid from serum and therefore there are fewer proteins and polysaccharides attached to biomarkers in saliva and the accuracy of measuring these biomarkers in the saliva is more valuable than serum.

The 15-year national trends of genital cancer incidence among Iranian men and women; 2005-2020.

BACKGROUND: Cancer is a major health problem and cause of mortality worldwide. Despite the prevalence of other cancers in males and females, genital cancers are especially important because of their psychological effects on individuals. Currently, cervical cancer, corpus uteri neoplasm, and ovarian cancer are the most common gynecological cancers in Iran. Prostate cancer has increased in Iranian men in the last decade. Therefore, this study aimed to investigate the 15-year national trend in the incidence of genital cancers in the Iranian population. METHODS: In this study, we used Iranian cancer registration data collected by the Ministry of Health and Medical Education, demographic information from the reports of the Statistics Center of Iran, STEPs (STEPwise approach to non-communicable diseases risk factor surveillance), and Caspian (childhood and adolescence surveillance and prevention of adult non-communicable disease). A list of potential auxiliary variables and secondary variables at all levels of the province-age-sex were evaluated during the years. We used mixed-effects Poisson regression to model the data and calculate the incidence of each cancer. RESULTS: Our results show an enhancement in the outbreak of all types of male cancers, but the most important are prostate (11.46 in 2005 to 25.67 in 2020 per 100,000 males) and testicular cancers (2.39 in 2005 to 5.05 per 100,000 males). As for female cancers, there has been an increase in ovarian and corpus uteri neoplasm incidence with 6.69 and 4.14 incidences per 100,000 females in 2020, making them the most occurring female genital neoplasms. While the occurrence of cervical cancer has decreased over the years (4.65 in 2005 to 3.24 in 2020). In general, the incidence of genital cancers in men and women has amplified in the last 15 years. CONCLUSIONS: Our study examined the trend of change for each malignant genital neoplasm for 15 years in Iranian men and women in each province. Considering the growing trend of the elderly population in Iran, patient awareness and early screening are essential in reducing mortality and costs imposed on patients and the health care system.

The Impact of Covid-19 Pandemic on Genitourinary Cancers Stage and Grade.

INTRODUCTION: Our study aims to evaluate the impact of the COVID-19 pandemic on the number of uro-oncological surgeries (cystectomy, nephrectomy, prostatectomy, orchiectomy, and transurethral resection of bladder tumor (TURBT)) and pathological staging and grading. MATERIALS AND METHODS: The present study is a retrospective study on patients with genitourinary cancers treated from 2018 to 2021 in a referral tertiary center. The data were obtained from the hospital records with lengths of 22 and 23 months, labeled hereafter as non-COVID and COVID pandemic, respectively (2018/3/21-2020/1/20 and 2020/1/21-2021/12/21). The total number of registered patients, gender, age, stage, and grade were compared in the targeted periods. Moreover, all the pathologic slides were reviewed by an expert uropathologist before enrolling in the study. The continuous and discrete variables are reported as mean (standard deviation (SD)) and number (percent) and the χ2 test for the comparison of the discrete variables' distribution. RESULTS: In this study total number of 2077 patients were enrolled. The number of procedures performed decreased during the Covid pandemic. The tumors' distribution stage and grade and patients' baseline characteristics were not significantly different in non-COVID and COVID pandemic periods for Radical Nephrectomy, Radical Cystectomy, Radical Prostatectomy, and orchiectomy. For TURBT only, the tumor stage was significantly different (P-value<.001) from the higher stages in the COVID pandemic period. CONCLUSION: Among urinary tract cancers, staging of bladder cancer and TURBT are mainly impacted by the COVID-19 pandemic with higher stages compared to the non-COVID period. We evaluate the impact of the COVID-19 pandemic on the number of uro-oncological surgeries based on pathological staging and grading. Total number of 2077 patients were enrolled. Among urinary tract cancers, staging of bladder cancer and TURBT are mainly impacted by the COVID-19 pandemic with higher stages compared to the non-COVID period.

The effect of mesenchymal stem cells-derived exosomes on the prostate, bladder, and renal cancer cell lines.

We aimed to explain the role of mesenchymal stem cells (MSC-exosomes) on gene expressions of epithelial to mesenchymal transition (EMT), angiogenesis, and apoptosis. Four different cell lines were employed, including ACHN, 5637, LNCaP, and PC3, as well-known representatives for renal, bladder, hormone-sensitive, and hormone-refractory prostate cancers, respectively. Cell lines were exposed to diverse concentrations of mesenchymal stem cells-derived exosomes to find IC50 values. Percentages of apoptotic cells were evaluated by Annexin/P.I. staining. Micro Culture Tetrazolium Test assessed proliferative inhibitory effect; and prostate biomarker (KLK2), EMT (E-cadherin and Snail), angiogenesis genes (VEGF-A/VEGF-C), apoptosis genes (BAX/BCL2, P53) and Osteopontin variants (OPNa/b, and c) mRNA levels were studied by realtime PCR method. All 5637, LNCaP, and PC3 following treatment with exosomes illustrated specific responses with changes in expression of different genes. The increased TP53 and decreased BCL2 expressions were seen in 5637, LNCaP, and PC3. In PC3, OPNb and OPNc have raised more than P53; in LNCap, the increase was in VEGF-c. In 5637 cells, more than TP53 and BCL2 changes, two other genes, VEGFa and B.A.X., have decreased, suggesting exosomes' anti-apoptotic and anti-angiogenic effects. The kidney tumor cell line saw no significant gene expression change in ten targeted genes. MSC-exosomes therapy has augmented some interesting antitumor effects on prostate, bladder, and kidney cancer cell lines. This effect which originates from exosomes' potency to persuade apoptosis and prevent the proliferation of cancer cells simultaneously, was more substantial in bladder cancer, moderate in prostate cancer, and mild in renal cancer.

The Gene Manipulation and Cellular Immunotherapy Combination in the Treatment of Cancer.

Context: The immune system is directly linked to the tumors, from tumor formation to the tumor's development and metastasis. So, the interest of scientists over the protective immunological mechanisms has increased and shown gifted strategy in cancer treatment. Evidence acquisition: Genetic engineering and cellular immunotherapy are two different advanced molecular mechanisms to modify the immune responses and genome. Gene manipulation is the bioengineering technology that allows vectors to transfer new genetic information into the target cells. Cellular immunotherapy is an excellent strategy that connects the body's immune system to fight cancer. Results & Conclusions: This review described that combination of genetic engineering and cellular immunotherapy has brought the novel antitumor repressive molecules stopping the tumor tissue immune tolerance and significantly expanding cancer therapy's effectiveness. Usually, cell immunotherapy and genetic engineering are considered two independent processes, and, in this review, we believe them in combinations. Here, we review these two novel approaches, and they are both combinations in terms of technological advances and clinical experience.

Genetic Polymorphisms and Kidney Stones Around the Globe: A Systematic Review and Meta-Analysis.

Objective: This study explores associations between recurrent kidney stones and genetic polymorphisms. Methods: Meta-analysis of polymorphisms in renal stone cases versus control groups. Four electronic databases (PubMed, SCOPUS, EMBASE, and Web of Science) were searched up to 30 May 2021, using the keywords: "kidney stone" or "kidney calculi," or "urolithiasis" or "nephrolithiasis" or "urinary calculi" and "genome" or "genetic" or "mutation" or "single nucleotide polymorphism." Forrest plots, ORs, 95% CI, Chi-square (χ2)-test, and index of heterogeneity (I2) were calculated. Only studies with Newcastle-Ottawa scale (NOS) ≥ 6 were included for quality control, and Funnel, Begg's, and Eager's plots assessed publication bias. PROSPERO: CRD42022250427. Results: Among 7,671 searched articles, 72 were included. Polymorphisms in VDR (OR: 1.20; 95% CI: 1.06-1.36), CASR (OR = 1.24; 95% CI: 1.01-1.52), Osteopontin (OR = 1.38; 95% CI: 1.09-1.74), and Urokinase genes (OR = 1.52; 95% CI: 1.02-2.28) showed a significant association with risk of urinary stone formation, while Klotho gene showed a protective effect (OR = 0.75; 95% CI: 0.57-0.99). The VDR gene polymorphism was frequent in Asians, whereas CASR polymorphism was frequent in European and North American populations. Conclusion: Multifactorial nature of the stone formation, emphasizing the role of environmental factors, might explain contradictory results in the literature. While polymorphisms in VDR, CASR, Osteopontin, and Urokinase genes were associated with urinary stone formation, the Klotho gene showed a protective effect.

Diagnostic Accuracy of Predictive Models in Prostate Cancer: A Systematic Review and Meta-Analysis.

Aim: Accurate diagnosis of prostate cancer (PCa) has a fundamental role in clinical and patient care. Recent advances in diagnostic testing and marker lead to standardized interpretation and increased prescription by clinicians to improve the detection of clinically significant PCa and select patients who strictly require targeted biopsies. Methods: In this study, we present a systematic review of the overall diagnostic accuracy of each testing panel regarding the panel details. In this meta-analysis, using a structured search, Web of Science and PubMed databases were searched up to 23 September 2019 with no restrictions and filters. The study's outcome was the AUC and 95% confidence interval of prediction models. This index was reported as an overall and based on the WHO region and models with/without MRI. Results: The thirteen final articles included 25,691 people. The overall AUC and 95% CI in thirteen studies were 0.78 and 95% CI: 0.73-0.82. The weighted average AUC in the countries of the Americas region was 0.73 (95% CI: 0.70-0.75), and in European countries, it was 0.80 (95% CI: 0.72-0.88). In four studies with MRI, the average weighted AUC was 0.88 (95% CI: 0.86-0.90), while in other articles where MRI was not a parameter in the diagnostic model, the mean AUC was 0.73 (95% CI: 0.70-0.76). Conclusions: The present study's findings showed that MRI significantly improved the detection accuracy of prostate cancer and had the highest discrimination to distinguish candidates for biopsy.

Precision medicine journey through omics approach.

It has been well established that understanding the underlying heterogeneity of numerous complex disease process needs new strategies that present in precision medicine for prediction, prevention and personalized treatment strategies. This approach must be tailored for each individual's unique omics that lead to personalized management of disease. The correlation between different omics data should be considered in precision medicine approach. The interaction provides a hypothesis which is called domino effect in the present minireview. Here we review the various potentials of omics data including genomics, transcriptomics, proteomics, metabolomics, pharmacogenomics. We comprehensively summarize the impact of omics data and its major role in precision medicine and provide a description about the domino effect on the pathophysiology of diseases. Each constituent of the omics data typically provides different information in associated with disease. Current research, although inadequate, clearly indicate that the information of omics data can be applicable in the concept of precision medicine. Integration of different omics data type in domino effect hypothesis can explain the causative changes of disease as it is discussed in the system biology too. While most existing studies investigate the omics data separately, data integration is needed on the horizon of precision medicine by using machine learning.

The importance of personalized medicine in urological cancers.

A better understanding of key regulatory pathways involved in cancers has led to the development of molecularly targeted therapies. Molecular profiling based on genomics, proteomics, and metabolomics in tumors provides clinicians with the necessary information to maintain a personalized therapeutic regimen according to the patient's needs. for example, androgen deprivation therapy (ADT) for advanced prostate cancer is one of the earliest forms of targeted therapy and has remained a choice of treatment by physicians. Unfortunately, most patients will eventually become non-responsive to ADT and succumb to the disease. Since the emergence of ADT, the understanding of androgen receptor (AR) signaling and mechanisms driving the resistance to ADT has been significantly improved. Inactivation of the PTEN gene is a common occurrence in prostate cancers and is associated with metastatic potential, androgen independence, and poor prognosis. Several studies over personalized medicine for muscle-invasive and metastatic bladder cancer discussed potential molecular biomarkers which are currently under investigation and based on the excision repair cross-complementing group 1 (ERCC1) gene and its role in tumor development and therapeutic resistance to cytotoxic DNA-damaging chemotherapy and ionizing radiation. In this review, we consider personalized medicine for four urological cancers.

Genomic medicine on the frontier of precision medicine.

Genomic medicine has created a great deal of hope since the completion of the Human Genome Project (HGP). Genomic medicine promises disease prevention and early diagnosis in the context of precision medicine. Precision medicine as a scientific discipline has introduced as an evolution in medicine. The rapid growth of high-development technologies permits the assessment of biological systems. Study of the integrated profiles of omics, such as genome, transcriptome, proteome and other omics information lead to significant advances in personalized and precision medicine. In the context of precision medicine, pharmacogenomics can play an important role in order to discriminate responders and non-responders to medications and avoiding toxicity and achieving the optimum dose. So precision medicine in accordance with genomic medicine will transform medicine from conventional evidence-based medicine in the diagnosis and treatment towards precision based-medicine. In this review, we have summarized the related issues for genomic medicine and precision medicine.

The correlation between promoter hypermethylation of VDR, CLDN, and CasR genes and recurrent stone formation.

OBJECTIVES: Recurrent Kidney stone formation is a main medical problem imposing a significant burden on both healthcare and the economy worldwide. Environmental and genetic factors have been linked to a bigger risk of kidney stone formation. We aim to assess the role of methylation on recurrent stone formation in three target genes. METHODS: We aimed to check the association between promoter hypermethylation vitamin D receptor (VDR), calcium-sensing receptor (CaSR), and claudin 14 (CLDN14) genes in recurrent kidney stones. We enrolled 30 consecutive recurrent kidney stone formers (age 18-60 years) (cases) and 30 age and gender-matched controls.3. To identify promoter methylation, two target regions from each candidate gene were bisulfited after blood collection and DNA extraction. Methylation quantification was done through methylation-specific high resolution melting (MS-HRM). RESULTS: The mean age of the patients and controls (mean ± SD) was 49.58 ± 14.23 years and BMI 36.12 ± 2.72. The methylation status in all six target regions was meaningfully different between the stone-former group and controls when methylation was considered in three clusters of unmethylated, methylated, and hypermethylated. A higher effect in VDR and CLDN was observed compare to CasR (p-value < 0.001, and < 0.005 versus p-value < 0.256). CONCLUSIONS: Methylation as an important epigenetic mechanism should be considered more in recurrent stone formations. Promoter hypermethylation of VRD and CLDN genes may have an essential role in recurrent kidney stones formations.

Smartphone-Based Electrochemiluminescence for Visual Simultaneous Detection of RASSF1A and SLC5A8 Tumor Suppressor Gene Methylation in Thyroid Cancer Patient Plasma.

Visual one-step simultaneous detection of low-abundance methylation is a crucial challenge in early cancer diagnosis in a simple manner. Through the design of a closed split bipolar electrochemistry system (BE), detection of promoter methylation of tumor suppressor genes in papillary thyroid cancer, RASSF1A and SLC5A8, was achieved using electrochemiluminescence. For this purpose, electrochemiluminescence of luminol loaded into the Fe3O4@UiO-66 and gold nanorod-functionalized graphite-like carbon nitride nanosheet (AuNRs@C3N4 NS), separately, on the anodic and cathodic pole bipolar electrodes (BPEs) in two different chambers of a bipolar cell were recorded on a smartphone camera. To provide the same electric potential (ΔEelec) through the BPEs to conduct simultaneous light emission, as well as to achieve higher sensitivity, anodic and cathodic poles BPEs were separately connected to ruthenium nanoparticles electrodeposited on nitrogen-doped graphene-coated Cu foam (fCu/N-GN/RuNPs) to provide a hydrogen evolution reaction (HER) and polycatechol-modified reduced graphene oxide/pencil graphite electrode (PC-rGO/PGE) to provide electrooxidation of hydrazine. Moreover, taking advantages of the strong cathodic ECL activity due to the roles of AuNRs, as well as the high density of capture probes on the UiO-66 and Fe3O4 roles in improving the signal-to-background ratio (S/B) in complicated plasma media, a sensitive visual ECL immunosensor was developed to detect two different genes as model target analytes in patient plasma samples. The ability of discrimination of methylation levels as low as 0.01% and above 90% clinical sensitivity in thyroid cancer patient plasma implies that the present strategy is able to diagnose cancer early, as well as monitor responses of patients to therapeutic agents.

Oncologic outcomes of Bacillus Calmette-Guérin therapy in elderly patients with non-muscle-invasive bladder cancer: A meta-analysis.

INTRODUCTION: There is a challenge on the medical efficacy of intravesical Bacillus Calmette-Guérin (BCG) therapy and the power of the immune system boosting, which can be influenced by the age of the non-muscle-invasive bladder cancer (NMIBC) patients. This meta-analysis evaluates the efficacy of BCG therapy among aged (>70) and younger patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: The central database of PubMed, Scopus, and Web of Science were queried until August 4, 2021, by using "BCG," "Bladder Cancer," "AGE," and "efficacy" keywords. After excluding duplicated results, titles and abstracts were evaluated by two independent reviewers. The exclusion criteria included non-English studies, conference abstracts, reviews, editorials, letters, and comments. Three main outcomes, disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS), were considered. The statistical analysis was performed using STATA (version 14; Stata Corp, College Station, Texas, USA). RESULTS: From 1115 found documents, the 24 research articles were recruited in the systematic review, and 10 were the candidate for meta-analysis. The overall estimate of H.R. revealed that BCG therapy in those over age 70 is significantly associated with an improved risk of progression and cancer-specific death in studied patients. However, this association was not statistically significant for DFS (1.04 (95% CI: 0.85,1.26)). CONCLUSION: The BCG maintenance therapy improved CSS and PFS oncological outcomes in elderly patients with NMIBC. BCG therapy did not significantly change the DSF.

Combined anticancer effects of simvastatin and arsenic trioxide on prostate cancer cell lines via downregulation of the VEGF and OPN isoforms genes.

Arsenic trioxide (ATO) and statins have been demonstrated to have anti-neoplastic properties; however, the data regarding their combination therapy is limited. Thus, we aimed to study the effects of ATO, Simvastatin and their combination in proliferation, apoptosis and pathological angiogenesis in prostate cancer cell lines. The human prostate cell lines were treated with different concentrations of Simvastatin and ATO alone and combined to find effective doses and IC50 values. In addition, the percentage of apoptotic cells was evaluated by annexin/PI staining, and mRNA expression levels of the apoptotic gene, including OPN isoforms and VEGF, were investigated using real-time PCR. Our data displayed that Simvastatin (12 and 8 µM in PC3 and LNCaP cell lines respectively), ATO (8 and 5 µM in PC3 and LNCaP cell lines respectively), and also their combination (12 µM Simvastatin and 8 µM ATO in PC3, 8 µM Simvastatin and 5 µM ATO in LNCaP cell lines respectively) significantly increased the percentage of apoptotic cells. Also, we showed that the combination therapy by Simvastatin and ATO increased cell apoptosis and inhibited cell proliferation, providing anti-proliferative and anti-angiogenic properties, possibly via downregulation of the expression of VEGF and OPN genes. These results provide new perceptions regarding the anticancer roles of ATO and statins' combination therapy in prostate cancer.