Cardiovascular disease risk assessment and multidisciplinary care in prostate cancer treatment with ADT: recommendations from the APMA PCCV expert network.

PURPOSE: Androgen deprivation therapy (ADT) is the mainstay approach for prostate cancer (PCa) management. However, the most commonly used ADT modality, gonadotropin-releasing hormone (GnRH) agonists, has been associated with an increased risk of cardiovascular disease (CVD). METHODS: The PCa Cardiovascular (PCCV) Expert Network, consisting of multinational urologists, cardiologists and oncologists with expertise in managing PCa, convened to discuss challenges to routine cardiovascular risk assessment in PCa management, as well as how to mitigate such risks in the current treatment landscape. RESULTS: The experts identified several barriers, including lack of awareness, time constraints, challenges in implementing risk assessment tools and difficulties in establishing multidisciplinary teams that include cardiologists. The experts subsequently provided practical recommendations to improve cardio-oncology care for patients with PCa receiving ADT, such as simplifying cardiovascular risk assessment, individualising treatment based on CVD risk categories, establishing multidisciplinary teams and referral networks and fostering active patient engagement. A streamlined cardiovascular risk-stratification tool and a referral/management guide were developed for seamless integration into urologists' practices and presented herein. The PCCV Expert Network agreed that currently available evidence indicates that GnRH antagonists are associated with a lower risk of CVD than that of GnRH agonists and that GnRH antagonists are preferred for patients with PCa and a high CVD risk. CONCLUSION: In summary, this article provides insights and guidance to improve management for patients with PCa undergoing ADT.

Management of patients with high-risk and advanced prostate cancer in the Middle East: resource-stratified consensus recommendations.

PURPOSE: Prostate cancer care in the Middle East is highly variable and access to specialist multidisciplinary management is limited. Academic tertiary referral centers offer cutting-edge diagnosis and treatment; however, in many parts of the region, patients are managed by non-specialists with limited resources. Due to many factors including lack of awareness and lack of prostate-specific antigen (PSA) screening, a high percentage of men present with locally advanced and metastatic prostate cancer at diagnosis. The aim of these recommendations is to assist clinicians in managing patients with different levels of access to diagnostic and treatment modalities. METHODS: The first Advanced Prostate Cancer Consensus Conference (APCCC) satellite meeting for the Middle East was held in Beirut, Lebanon, November 2017. During this meeting a consortium of urologists, medical oncologists, radiation oncologist and imaging specialists practicing in Lebanon, Syria, Iraq, Kuwait and Saudi Arabia voted on a selection of consensus questions. An additional workshop to formulate resource-stratified consensus recommendations was held in March 2019. RESULTS: Variations in practice based on available resources have been proposed to form resource-stratified recommendations for imaging at diagnosis, initial management of localized prostate cancer requiring therapy, treatment of castration-sensitive/naïve advanced prostate cancer and treatment of castration-resistant prostate cancer. CONCLUSION: This is the first regional consensus on prostate cancer management from the Middle East. The following recommendations will be useful to urologists and oncologists practicing in all areas with limited access to specialist multi-disciplinary teams, diagnostic modalities and treatment resources.

Vitamin D status and its correlates in Saudi male population.

BACKGROUND: Vitamin-D deficiency is a universal health problem caused primarily by inadequate exposure to sunlight. This study aimed to assess the vitamin D status and investigate the factors affecting vitamin D distribution among Saudi males. METHODS: A cross-sectional study was conducted at the King Saud University Medical City from December 2015 to August 2016. Saudi males attending the outpatient primary health care clinics were invited to participate in the study. Data were collected on the current and past health status along with biochemical investigations for total 25-hydroxyvitamin D (25OHD), blood sugar, and cholesterol. RESULTS: Majority of the participants (76.1%) had vitamin D deficiency. Blood sugar level, age, and cholesterol level were the most significant factors associated with vitamin D status. The highest percentage of deficiency was observed in the youngest age group (30-40 years). With increasing age, the percentage of deficiency decreased significantly. Those with normal blood sugar and cholesterol level had higher serum vitamin D levels compared to those with diabetes and hypercholesterolemia. CONCLUSIONS: Vitamin D deficiency is still endemic in Saudi Arabia, particularly among younger males and those with diabetes and hypercholesterolemia. Vitamin D screening, supplementations, and vitamin D-fortified foods should be provided especially for these groups.

Age-Specific Reference Ranges of Prostate-Specific Antigen among Saudi Men as a Representation of the Arab Population.

OBJECTIVE: To describe the reference ranges of serum prostate-specific antigen (PSA) in Saudi men. Materials/Subjects and Methods: Saudi males, aged 30 and above, were invited to participate in the study. Blood samples were taken from each subject to determine serum levels of PSA. Blood sugar levels, lipid profile, and anthropometric measurements were also obtained. RESULTS: Our cohort consisted of 7,814 men; their mean PSA level was 1.24 ng/mL. The majority (90.5%) had PSA values between 0 and 2.5 ng/mL. The median PSA and the 95th percentile increased steadily with age. There was a sharp increase in the 95th percentile, from 3.8 ng/mL in men between 60 and 70 years old to 6.9 ng/mL in men over 71 years old. The 95th percentiles of PSA serum levels were lower in Saudi men than in the general population. CONCLUSIONS: PSA serum levels in Saudi men are lower than in other communities. Creating age-specific reference ranges could improve the sensitivity of the PSA tests by allowing the detection of treatable tumors in younger men if the threshold of 4.0 ng/mL is lowered. Furthermore, unnecessary biopsies among older men may be avoided if the threshold is increased.

Association of Interleukin-6 and Other Cytokines with Self-Reported Pain in Prostate Cancer Patients Receiving Chemotherapy.

Background: Pain is a common and dose-limiting side effect of many potentially curative cancer chemotherapeutic agents. This chemotherapy-induced pain (CIP) affects the quality of life of cancer patients and survivors and hampers the optimal clinical management of chemotherapy in cancer patients. The underlying mechanisms remain largely unknown, but changes in levels of cytokines/chemokines may contribute to the pathophysiology of CIP. Objective: This retrospective study was aimed at examining whether plasma levels of various cytokines change in prostate cancer patients after chemotherapy treatment and whether such changes (if any) are associated with their pain intensity. Methods: Using a Luminex assay, plasma levels of 27 cytokines/chemokines were measured in 78 men: 30 patients with metastatic prostate cancer who received chemotherapy (Docetaxel, 75 mg/m2 intravenously), 29 untreated patients with nonmetastatic prostate cancer, and 19 healthy controls. Subjective pain was assessed in chemotherapy-treated cancer patients using the 11-point numeric rating scale (NRS) pain scores. Results: Chemotherapy-treated patients with pain (NRS ≥ 3) exhibited significantly increased levels of the pro-inflammatory cytokines (IL-6, IL-8) and chemokines (Eotaxin, VEGF, and IP-10) compared with untreated cancer patients or with patients without pain (NRS = 0). Of the 27 cytokines examined, only IL-6 was positively correlated with pain intensity in the chemotherapy-treated patients with pain. Conclusions: These findings suggest that the cytokines, particularly IL-6, whose levels were elevated in the chemotherapy-treated patients may be involved in the pathophysiology of CIP, and that they might be potential new targets for pain control in cancer patients receiving chemotherapy.

Prostate cancer small non-coding RNA transcriptome in Arabs.

BACKGROUND: Prostate cancer (PCa) is a complex disorder resulting from the combined effects of multiple environmental and genetic factors. Small non-coding RNAs (sRNAs), particularly microRNAs (miRNAs), regulate several cellular processes and have an important role in many human malignancies including PCa. We assessed the sRNA profiles associated with PCa in Arabs, a population that has rarely been studied. METHODS: We used next generation sequencing technology to obtain the entire sRNA transcriptome of primary prostate tumor formalin-fixed paraffin-embedded tissues, and their paired non-tumor tissues, collected from Bedouin patients (Qatari and Saudi). The miRNA and the target gene expression were evaluated by real-time quantitative PCR. miRNA KEGG pathway and miRNA target genes were subsequently analyzed by starBase and TargetScan software. RESULTS: Different expression patterns of several sRNA and miRNA editing were revealed between PCa tumor and their paired non-tumor tissues. Our study identified four miRNAs that are strongly associated with prostate cancer, which have not been reported previously. Differentially expressed miRNAs significantly affect various biological pathways, such as cell cycle, endocytosis, adherence junction and pathways involved in cancer. Prediction of potential targets for the identified miRNAs indicates the overexpression of KRAS, BCL2 and down-regulation of PTEN in PCa tumor tissues. CONCLUSION: These miRNAs, newly associated with prostate cancer, may represent not only markers for the increased risk of PCa in Arabs, but may also reflect the clinical and pathological diversity as well as the ethno-specific heterogeneity of prostate cancer.

Hematuria: Is it useful in predicting renal or ureteral stones in patient presenting to emergency department with flank pain?

Objectives: The objective of the study was to evaluate hematuria as a diagnostic test for renal and ureteral stones compared with a noncontrast-enhanced computed tomography (CT) scan (gold standard test) in emergency room patients with acute flank pain. Patients and Methods: In total, 604 patients treated in our emergency department from 2006 to 2011, with a history of flank pain and suspected urolithiasis were included in a retrospective review. All patients were evaluated with a noncontrast-enhanced CT scan and urine analysis. Using the noncontrast CT scan as the gold standard for the evaluation of the presence, number, size, and site (renal or ureteral [upper, middle, and lower]) of the stones, we calculated the sensitivity, specificity, and positive and negative predictive values of hematuria for diagnosing both renal and ureteral stones. Results: Urolithiasis was diagnosed in 388 patients (64%) and 216 patients (36%) had no stones on a noncontrast-enhanced CT scan. The sensitivity, specificity, positive predictive value, and negative predictive value for microhematuria were 77%, 33%, 67%, and 45%, respectively. Microhematuria was more common in patients with ureteral stones only (139 patients) and had a sensitivity of 85% compared to patients with renal stones only (32 patients), with a sensitivity of 55% (P < 0.001). There were no significant differences in the specificity or positive or negative predictive values. Conclusion: Although microhematuria is more sensitive to ureteral stones, the absence of microhematuria does not exclude the possibility of urolithiasis and a noncontrast-enhanced CT scan should be the gold standard diagnostic tool.

Snake (Walterinnesia aegyptia) venom-loaded silica nanoparticles induce apoptosis and growth arrest in human prostate cancer cells.

Prostate cancer (PCa) is the most commonly diagnosed cancer in men. The progression and invasion of PCa are normally mediated by the overexpression of chemokine receptors (CKRs) and the interaction between CKRs and their cognate ligands. We recently demonstrated that venom extracted from Walterinnesia aegyptia (WEV) either alone or in combination with silica nanoparticles (WEV+NP) mediated the growth arrest and apoptosis of breast cancer cells. In the present study, we evaluated the impact of WEV alone and WEV+NP on the migration, invasion, proliferation and apoptosis of prostate cancer cells. We found that WEV alone and WEV+NP decreased the viability of all cell types tested (PCa cells isolated from patient samples, PC3 cells and LNCaP cells) using an MTT assay. The IC(50) values were determined to be 10 and 5 µg/mL for WEV alone and WEV+NP, respectively. WEV+NP decreased the surface expression of the CKRs CXCR3, CXCR4, CXCR5 and CXCR6 to a greater extent than WEV alone and subsequently reduced migration and the invasion response of the cells to the cognate ligands of the CKRs (CXCL10, CXCL12, CXCL13 and CXCL16, respectively). Using a CFSE proliferation assay, we found that WEV+NP strongly inhibited epidermal growth factor-mediated PCa cell proliferation. Furthermore, analysis of the cell cycle indicated that WEV+NP strongly altered the cell cycle of PCa cells and enhanced the induction of apoptosis. Finally, we demonstrated that WEV+NP robustly decreased the expression of anti-apoptotic effectors, such as B cell Lymphoma-2 (Bcl-2), B cell Lymphoma-extra large (Bcl-(XL)) and myeloid cell leukemia sequence-1 (Mcl-1), and increased the expression of pro-apoptotic effectors, such as Bcl-2 homologous antagonist/killer (Bak), Bcl-2-associated X protein (Bax) and Bcl-2-interacting mediator of cell death (Bim). WEV+NP also altered the membrane potential of mitochondria in the PCa cells. Our data reveal the potential of nanoparticle-sustained delivery of snake venom as effective treatments for prostate cancer.

Genome scan study of prostate cancer in Arabs: identification of three genomic regions with multiple prostate cancer susceptibility loci in Tunisians.

BACKGROUND: Large databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans. Arab populations, however, have been only rarely studied. METHODS: Using Affymetrix Genome-Wide Human SNP Array 6, we conducted a genome-wide association study (GWAS) in which 534,781 single nucleotide polymorphisms (SNPs) were genotyped in 221 Tunisians (90 prostate cancer patients and 131 age-matched healthy controls). TaqMan SNP Genotyping Assays on 11 prostate cancer associated SNPs were performed in a distinct cohort of 337 individuals from Arab ancestry living in Qatar and Saudi Arabia (155 prostate cancer patients and 182 age-matched controls). In-silico expression quantitative trait locus (eQTL) analysis along with mRNA quantification of nearby genes was performed to identify loci potentially cis-regulated by the identified SNPs. RESULTS: Three chromosomal regions, encompassing 14 SNPs, are significantly associated with prostate cancer risk in the Tunisian population (P = 1 × 10-4 to P = 1 × 10-5). In addition to SNPs located on chromosome 17q21, previously found associated with prostate cancer in Western populations, two novel chromosomal regions are revealed on chromosome 9p24 and 22q13. eQTL analysis and mRNA quantification indicate that the prostate cancer associated SNPs of chromosome 17 could enhance the expression of STAT5B gene. CONCLUSION: Our findings, identifying novel GWAS prostate cancer susceptibility loci, indicate that prostate cancer genetic risk factors could be ethnic specific.

Enhanced anticancer efficacy of snake venom combined with silica nanoparticles in a murine model of human multiple myeloma: molecular targets for cell cycle arrest and apoptosis induction.

Multiple myeloma (MM) is a clonal disease of plasma cells that reside in the bone marrow (BM). MM is an incurable disease; thus, screening for novel anti-myeloma drugs remains critically important. We recently described a silica nanoparticle-based snake venom delivery model that targets cancer cells, but not normal cells. Using this model, we demonstrated a strong enhancement of the antitumor activity of snake venom extracted from Walterinnesia aegyptia (WEV) in two breast carcinoma cell lines when the venom was combined with silica nanoparticles (WEV+NP). In the present study, we aimed to delineate the in vivo therapeutic efficacy of WEV+NP in an MM-bearing experimental nude mouse model. We found that treatment with WEV+NP or WEV alone significantly inhibited tumor growth compared to treatment with NP or vehicle. WEV+NP- and WEV-treated cancer cells exhibited marked elevations in oxidative stress and robust reductions in the levels of interleukin-6 (IL-6) and B cell-activating factor (BAFF). WEV+NP also decreased the surface expression of the chemokine receptors CXCR3, CXCR4 and CXCR6 to a greater extent than WEV alone, and WEV+NP subsequently reduced migration in response to the cognate ligands CXCL10, CXCL12 and CXCL16. Furthermore, we found that WEV+NP strongly inhibited insulin-like growth factor 1 (EGF-1)- and IL-6-mediated MM cell proliferation, altered the cell cycle and enhanced the induction of apoptosis of MM cells. In addition, the results of treatment with WEV+NP or WEV alone revealed that the combination of WEV with NP robustly decreased the expression of cyclin D1, Bcl-2 and the phosphorylation of AKT; increased the expression of cyclin B1; altered the mitochondrial membrane potential; increased the activity of caspase-3, -8 and -9; and sensitized MM cells to growth arrest and apoptosis. Our data reveal the therapeutic potential of the nanoparticle-sustained delivery of snake venom to fight cancer cells.

Maternal supplementation of diabetic mice with thymoquinone protects their offspring from abnormal obesity and diabetes by modulating their lipid profile and free radical production and restoring lymphocyte proliferation via PI3K/AKT signaling.

BACKGROUND: Epidemiological studies have shown that the offspring of mothers who experience diabetes mellitus during pregnancy are seven times more likely to develop health complications than the offspring of mothers who do not suffer from diabetes during pregnancy. The present study was designed to investigate whether supplementation of streptozotocin (STZ)-induced diabetic pregnant mice with thymoquinone (TQ) during pregnancy and lactation improves the risk of developing diabetic complications acquired by their offspring. METHODS: Three groups of pregnant female mice were used: non-diabetic control dams (CD), diabetic dams (DD), and diabetic dams supplemented with TQ (DD + TQ) during pregnancy and lactation (n = 10 female mice in each group). RESULTS: Our data demonstrated a marked decrease in the number of neonates born to DD, and these neonates showed a marked increase in their mean body weight (macrosomic pups) compared to those born to CD and DD + TQ. The induction of diabetes during pregnancy and lactation resulted in macrosomic pups with several postpartum complications, such as a marked increase in their levels of blood glucose, free radicals, plasma pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), and lipids, and a tendency toward abnormal obesity compared to the offspring of CD. By contrast, macrosomic offspring born to DD exhibited a marked reduction in plasma cytokine levels (IL-2, -4 and -7), an obvious reduction in the number of circulating lymphocytes, decreased proliferation of superantigen (SEB)-stimulated lymphocytes and aberrant AKT phosphorylation. Interestingly, the supplementation of DD with TQ during pregnancy and lactation had an obvious and significant effect on the number and mean body weight of neonates. Furthermore, TQ significantly restored the levels of blood glucose, insulin, free radicals, plasma cytokines, and lipids as well as lymphocyte proliferation in the offspring. CONCLUSIONS: Our data suggest that the nutritional supplementation of DD with the natural antioxidant TQ during pregnancy and lactation protects their offspring from developing diabetic complications and preserves an efficient lymphocyte immune response later in life.

False-positive magnetic resonance imaging prostate cancer correlates and clinical implications.

Background: False-positive (FP) multiparametric magnetic resonance imaging (MPMRI) obscures and swift needless biopsies in men with a high prostate-specific antigen. Materials and Methods: This was a retrospective study, in which all patients who had been exposed to consecutive MP-MRI of the prostate combined with transrectal ultrasound-guided-magnetic resonance imaging fusion-guided prostate biopsy between 2017 and 2020 were involved in the study. The FP was measured as the number of biopsies that did not encompass prostate cancer divided by the whole number of biopsies. Results: The percentage of FP cases was 51.1%, the highest percentage was found in Prostate Imaging-Reporting and Data System (PI-RADs) 3 (37.7%) and the lowest was detected in PI-RAD 5 (14.5%). Those with FP biopsies are younger, and their total prostate antigen (PSA) and PSA density (PSAD) are significantly lesser. The area under the curve PSAD, age, and total PSA are 0.76, 0.74, and 0.69, respectively. An optimum PSAD value of 0.135 was chosen as a cutoff because it showed the highest sum of sensitivity and specificity, 68% and 69%, respectively. Conclusion: FP results of mpMRI were detected in more than half of our sample, more than one-third were presented in Pi-RAD3, improved imaging techniques to decrease FP rates are highly needed.

Prostate-specific Antigen Density as a Proxy for Predicting Prostate Cancer Severity: Is There Any Difference between Systematic and Targeted Biopsy?

Background: Prostate cancer screening with prostate-specific antigen (PSA) can result in unnecessary biopsies and overdiagnosis. Alternately, PSA density (PSAD) calculation may help support biopsy decisions; however, evidence of its usefulness is not concrete. Objective: To evaluate the predictive value of PSAD for clinically significant prostate cancer detection by systematic and MRI-targeted biopsies. Methods: This prospective study was conducted at two tertiary hospitals in Riyadh, Saudi Arabia, between December 2018 and November 2021. Patients suspected of prostate cancer were subjected to multi-parametric MRI, and for those with positive findings, systematic and targeted biopsies were performed. Clinically non-significant and significant prostate cancer cases were classified based on histopathology-defined ISUP grade or Gleason score. The PSAD was measured using the prostate volume determined by the MRI and categorized into ≤0.15, 0.16-0.20, and >0.20 ng/ml2 subgroups. Results: Systematic and targeted biopsies were carried out for 284 patients. The discriminant ability of PSAD is higher in MRI-targeted biopsy compared with systematic biopsy (AUC: 0.77 vs. 0.73). The highest sensitivity (97%) and specificity (87%) were detected at 0.07 ng/ml2 in targeted biopsy. More than half of the clinically significant cases were detected in the >0.2 ng/ml2 PSAD category (systematic: 52.4%; targeted: 51.1%). The CHAID methodology found that the probability of having clinically significant cancer (CSC) in patients with PSAD >0.15 ng/ml2 was more than threefold than that in patients with PSAD ≤0.15 ng/ml2 (64% vs. 20.2%). When considered by age, in PSAD ≤0.15 ng/ml2 subgroup, the percentage of CSC detection rate increased from 20.2% to 24.6% in patients aged ≥60 years. Conclusion: PSAD has good discriminant power for predicting clinically significant prostate cancer. A cutoff of 0.07 ng/ml2 should be adopted, but should be interpreted with caution and by considering other parameters such as age.

Are There Any Developments in the Attitudes and Practices of Oncologists Regarding Fertility Preservation in Saudi Arabia After 12 Years?

INTRODUCTION: The current practice of offering fertility preservation (FP) counseling and treatment has become one of the focal points in patient care throughout cancer treatment. The turning point was the approval of the Council of Senior Religious Scholars four years ago to freeze tissues from the ovarian membrane, the entire ovary, and the eggs for later use in reproduction to preserve the offspring. Thus, we aimed to assess any development in oncologists' knowledge, attitude, and referral practices regarding FP in Saudi Arabia. METHODS: This is a cross-sectional survey using a self-administered questionnaire. We assessed oncologists' opinions on the importance of FP, their perception of the patient's preferences, and factors to consider when discussing the subject. Then, we assessed the knowledge and referral practices, including the timing of referral before starting cancer treatment. RESULTS: Most oncologists showed good knowledge and positive attitudes toward FP; however, their referral practices could be better. Most were familiar with FP options. The most significant factors influencing the oncologist-patient FP discussion were the number of existing children, marital status, cost, and type of cancer (96.6%, 76.7%, 65.7%, and 58.9%, respectively). CONCLUSIONS: There is a significant improvement in the knowledge and attitude of oncologists toward FP. However, patients' counseling and referral to fertility services still need to be improved. There is a shortfall in the clinical practice guidelines for FP in cancer patients in Saudi Arabia. The implementation of clinical practice guidelines would enhance FP. However, patients' counseling and referral to fertility services still need to be improved. The lack of proper guidelines on FP is affecting oncologists' practice.

Treatment of diabetic mice with undenatured whey protein accelerates the wound healing process by enhancing the expression of MIP-1α, MIP-2, KC, CX3CL1 and TGF-ß in wounded tissue.

BACKGROUND: Continuous diabetes-associated complications are a major source of immune system exhaustion and an increased incidence of infection. Diabetes can cause poor circulation in the feet, increasing the likelihood of ulcers forming when the skin is damaged and slowing the healing of the ulcers. Whey proteins (WPs) enhance immunity during childhood and have a protective effect on some immune disorders. Therefore, in this study, we investigated the effects of camel WP on the healing and closure of diabetic wounds in a streptozotocin (STZ)-induced type I diabetic mouse model. RESULTS: Diabetic mice exhibited delayed wound closure characterized by a significant decrease in an anti-inflammatory cytokine (namely, IL-10) and a prolonged elevation of the levels of inflammatory cytokines (TNF-α, IL-1ß and IL-6) in wound tissue. Moreover, aberrant expression of chemokines that regulate wound healing (MIP-1α, MIP-2, KC and CX3CL1) and growth factors (TGF-ß) were observed in the wound tissue of diabetic mice compared with control nondiabetic mice. Interestingly, compared with untreated diabetic mice, supplementation with WP significantly accelerated the closure of diabetic wounds by limiting inflammatory stimuli via the restoration of normal IL-10, TNF-α, IL-1ß and IL-6 levels. Most importantly, the supplementation of diabetic mice with WP significantly modulated the expression of MIP-1α, MIP-2, KC, CX3CL1 and TGF-ß in wound tissue compared with untreated diabetic mice. CONCLUSION: Our data demonstrate the benefits of WP supplementation for improving the healing and closure of diabetic wounds and restoring the immune response in diabetic mice.

Induction of apoptosis and growth arrest in human breast carcinoma cells by a snake (Walterinnesia aegyptia) venom combined with silica nanoparticles: crosstalk between Bcl2 and caspase 3.

We recently demonstrated that the snake venom extracted from Walterinnesia aegyptia (WEV) either alone or combined with silica nanoparticles (WEV+NP) enhanced the proliferation of mice immune cells and simultaneously decreased the proliferation of human breast carcinoma cell line (MDA-MB-231). However, the molecular mechanism of how this venom induced growth arrest of breast cancer cells has not been studied. In this context, we extended our study to evaluate the anti-tumor potential of WEV and WEV+NP on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as their effects on non-tumorigenic normal breast epithelial cells (MCF-10). The IC(50 )values of WEV alone and WEV+NP in these cell lines were determined to be 50 ng/ml and 20 ng/ml, respectively. Interestingly, at these concentrations, the venom did not affect the viability of normal MCF-10 cells and treatment of all these cell lines with NP alone did not affect their viability. Using annexin-V binding assay followed by flow cytometry analysis, we found that combination of WEV with NP strongly induced apoptosis in MDA-MB-231 and MCF-7 cancer cells without significant effect on normal MCF-10 cells. Furthermore, we found that WEV+NP decreased the expression of Bcl2 and enhanced the activation of caspase 3 in MDA-MB-231 and MCF-7 cells. Most importantly, WEV+NP-treated breast cancer cells, but not normal MCF-10 cells, exhibited a significant (P<0.05) reduction in actin polymerization and cytoskeletal rearrangement in response to CXCL12. Our data reveal biological effects of WEV or WEV+NP and the underlying mechanisms to fight breast cancer cells.

Survival among men with clinically localized prostate cancer treated with radical prostatectomy or radiation therapy in the prostate specific antigen era.

PURPOSE: Radical prostatectomy, external beam radiotherapy and brachytherapy are accepted treatments for localized prostate cancer. However, it is unknown if survival differences exist among treatments. We analyzed the survival of patients treated with these modalities according to contemporary standards. MATERIALS AND METHODS: A total of 10,429 consecutive patients with localized prostate cancer treated with radical prostatectomy (6,485), external beam radiotherapy (2,264) or brachytherapy (1,680) were identified. Multivariable regression analyses were used to model the disease (biopsy grade, clinical stage, prostate specific antigen) and patient specific (age, ethnicity, comorbidity) parameters for overall survival and prostate cancer specific mortality. Propensity score analysis was used to adjust for differences in observed background characteristics. RESULTS: The adjusted 10-year overall survival after radical prostatectomy, external beam radiotherapy and brachytherapy was 88.9%, 82.6% and 81.7%, respectively. Adjusted 10-year prostate cancer specific mortality was 1.8%, 2.9% and 2.3%, respectively. Using propensity score analysis, external beam radiotherapy was associated with decreased overall survival (HR 1.6, 95% CI 1.4-1.9, p<0.001) and increased prostate cancer specific mortality (HR 1.5, 95% CI 1.0-2.3, p=0.041) compared to radical prostatectomy. Brachytherapy was associated with decreased overall survival (HR 1.7, 95% CI 1.4-2.1, p<0.001) but not prostate cancer specific mortality (HR 1.3, 95% CI 0.7-2.4, p=0.5) compared to radical prostatectomy. CONCLUSIONS: After adjusting for major confounders, radical prostatectomy was associated with a small but statistically significant improvement in overall and cancer specific survival. These survival differences may arise from an imbalance of confounders, differences in treatment related mortality and/or improved cancer control when radical prostatectomy is performed as initial therapy.

Fertility cryopreservation for female cancer patients: attitudes and clinical practices of oncologists in Riyadh, Saudi Arabia.

OBJECTIVE: To study and report on the attitudes and clinical practices of oncologists regarding fertility cryopreservation for female cancer patients. STUDY DESIGN: Data was collected using a self administered questionnaire distributed to oncologists in different institutions in Riyadh, Saudi Arabia, during the period May through August 2010. The questionnaire covered their attitudes and clinical practices regarding fertility cryopreservation for female cancer patients. RESULTS: Almost half of the respondents (45.6%) were not familiar with any female fertility preservation options. Although most of the respondents had a positive attitude toward the topic, their referral practice was very poor. About three-quarters (76%) perceived that fertility preservation was very important, and 90% thought that patients would benefit from referral to an infertility specialist for counseling, yet 80% believed that cryopreservation was a complicated process. Almost half of respondents (55.3%) mentioned that they always discuss future fertility with their patients. The most prominent reasons for not discussing this issue were the emergent need to start therapy (50.5%) and the concern about the well-being of future children (34.5%). The majority (86.4%) did not refer their cancer patients to an infertility specialist. CONCLUSION: Oncologists' knowledge about female cryopreservation was lacking, and their attitudes and clinical practice on the topic needed enhancement.

Nutritional Related Knowledge of Cancer Prevention among Primary Health Care Physicians.

OBJECTIVES: To explore the cancer prevention-related nutrition knowledge of primary health care physicians towards nutrition and its relation to the development of cancer. MATERIALS AND METHODS: a cross-sectional study was conducted among family physicians in Riyadh, between November 2019 and April 2020. The participants in the current study were surveyed using a self-administered questionnaire. The questionnaire included socio-economic data and data related to the association between nutrition and cancer. RESULTS: The mean correct knowledge score for physicians is good but less than expected (26.5+5.8) 73.6%. Multiple regression revealed that age, position, and nationality to be significantly associated with knowledge of cancer prevention (P<0.05) among physicians. CONCLUSIONS: Primary care physicians have good knowledge about the relation between nutrition and cancer but not sufficient, they should have continuous nutrition educational training programs to ensure safe and sound nutritional advice to patients and for the public about the relation of nutrition and cancer.

Saudi Urological Association consensus guidelines on the use of robotic surgery in urology.

Over the past three decades, minimally invasive robotic technology has evolved substantially in urological practice, replacing many open procedures and becoming part of routine clinical practice. The Health Sector Transformation Program for the Kingdom's Vision 2030 aims to restructure the health sector and optimize its status and prospects as an effective and integrated ecosystem centered on the patient's health. Therefore, this consensus seeks to endorse the clinical practice guidelines for robotic surgery (RS) in the KSA, highlighting its effectiveness, safety, and favorable outcomes compared to open and laparoscopic surgeries in certain procedures when used by trained surgeons in well-structured RS programs.