An In Vitro Investigation of the Antiproliferative and Antimetastatic Effects of Levosimendan: Potential Drug Repurposing for Cervical Cancer.

Cervical cancer presents a significant challenge to the global health of women. Despite substantial advances in human papillomavirus (HPV)-related cervical cancer vaccines, non-HPV-related cervical cancer is still waiting novel therapeutic options. Drug repurposing has provided a promising approach to improve cancer therapy in recent years. Our study aimed to explore the potential in vitro antineoplastic effects of levosimendan on cervical cancer cells. The antiproliferative effects of levosimendan were investigated on cervical cancer cells using a standard MTT assay. Fluorescent double staining was performed to identify its ability to induce apoptosis and necrosis. The possible mechanism of action of levosimendan was explored using cell-cycle analysis. Furthermore, antimetastatic effects were investigated using a wound-healing assay and a Boyden chamber assay. Our results revealed that levosimendan exhibited the highest growth-inhibitory effect in the HPV-negative C33A cell line. However, the effects were modest compared to the standard agent, cisplatin. Cell-cycle analysis detected that levosimendan can induce cell-cycle arrest in C33A cells by increasing the G1 and G2/M phases, decreasing the S phase, and enhancing the hypodiploid subG1 population. Levosimendan inhibited cell migration and invasion in a concentration-dependent manner. As levosimendan showed antimetastatic efficacy, it could be considered for repurposing to contribute to overcoming resistance to therapy in cervical cancer.

Impact of V9302, a Competitive Antagonist of Transmembrane Glutamine Flux on Reversal of Resistance in Breast Cancer Cell Lines.

Chemotherapy is a known treatment modality that improves the long-term survival of breast cancer patients. However, due to the resistance to numerous anticancer drugs, alternative chemotherapeutic strategies are required. Regarding antimetabolic drugs, several compounds have proven anticancer properties, such as statins. The present study aimed to investigate the in vitro effects of V9302, a competitive antagonist of glutamine flux, on different subtypes of breast cancers (estrogen, progesterone, and HER2 receptor-positive or negative, and Pgp-negative and Pgp-overexpressing). The interactions of V9302 with standard chemotherapeutic drugs (doxorubicin and cisplatin) were also determined by MTT staining on breast cancer cell lines. Furthermore, the influence of V9302 on the cell cycle of MCF-7 and its Pgp-overexpressing counterpart KCR was monitored by flow cytometry. It was shown that V9302 exerted synergistic interactions with doxorubicin in all breast cancer cell lines. In cell cycle analysis, the KCR cell line was more sensitive to V9302. After 48 h, cell proliferation was completely blocked, and elevated G1, suppressed S, and decreased G2/M could be detected. Inhibition of glutamate transport can be assumed to block resistance related to Pgp.

Telepharmacy in Indonesia: Navigating Knowledge, Perception, and Readiness Among 6,000 Pharmacists and Related Sociodemographic Determinants.

Introduction: Telepharmacy can improve the delivery of pharmaceutical care services to patients. However, there are limited data regarding the knowledge, perceptions, and readiness (KPR) for telepharmacy in Indonesia. In this cross-sectional survey study, we assessed KPR and associated factors among Indonesian pharmacists, aiming to implement telepharmacy services in the future. Methods: Eligible participants were recruited from all provinces of Indonesia through a 24-item instrument. KPR scores were classified as low, moderate, and high. Sociodemographic characteristics and KPR of participants were summarized using descriptive statistics. Bivariate/multivariate ordinal logistic regression analyses were conducted to identify independent determinants of KPR. An adjusted odds ratio (AOR) with a 95% confidence interval (CI) was calculated for each determinant. Results: A total of 6,059 pharmacists provided responses. Overall, 58.28% had a high knowledge score, and 63.51% expressed moderate perceptions toward telepharmacy services. Moreover, 70.21% showed a moderate level of readiness. Gender (male; AOR: 1.21 [95% CI: 1.06-1.39]), stable internet access (AOR: 0.75 [95% CI: 0.64-0.86]), and central region (AOR: 1.13 [95% CI: 0.99-1.29]) were significantly associated with perception toward telepharmacy. Readiness was significantly associated with age (17-25 years; AOR: 0.73 [95% CI: (0.60-0.89]), gender (male; AOR: 0.83 [95% CI: 0.72-0.95]), stable internet access (AOR: 0.75 [95% CI: 0.64-0.89]), education level (master/doctoral; AOR: 1.33 [95% CI: 1.06-1.67]), and central region (AOR: 1.29 [95% CI: 1.12-1.49]). Interestingly, knowledge levels were not significantly correlated with specific factors. Conclusions: Participants demonstrated high knowledge, without significant influencing factors. However, they showed moderate perceptions and readiness levels, influenced by sociodemographic factors, including gender, age, education level, internet access, and regional disparities. Therefore, targeted interventions (e.g., telepharmacy training and regional outreach) are imperative to enhancing perceptions and readiness, fostering the effective integration of telepharmacy services, and advancing pharmaceutical care in Indonesia.

Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance.

Efflux pump (EP)-mediated multidrug resistance (MDR) seems ubiquitous in bacterial infections and neoplastic diseases. The diversity and lack of specificity of these efflux mechanisms raise a great obstacle in developing drugs that modulate efflux pumps. Since developing novel chemotherapeutic drugs requires large investments, drug repurposing offers a new approach that can provide alternatives as adjuvants in treating resistant microbial infections and progressive cancerous diseases. Hydroxy-methyl-glutaryl coenzyme-A (HMG-CoA) reductase inhibitors, also known as statins, are promising agents in this respect. Originally, statins were used in the therapy of dyslipidemia and for the prevention of cardiovascular diseases; however, extensive research has recently been performed to elucidate the functions of statins in bacterial infections and cancers. The mevalonate pathway is essential in the posttranslational modification of proteins related to vital eukaryotic cell functions. In this article, a comparative review is given about the possible role of HMG-CoA reductase inhibitors in managing diseases of bacterial and neoplastic origin. Molecular research and clinical studies have proven the justification of statins in this field. Further well-designed clinical trials are urged to clarify the significance of the contribution of statins to the lower risk of disease progression in bacterial infections and cancerous diseases.

Optimal Medical Therapy for Secondary Prevention of Acute Coronary Syndrome: A Retrospective Study from a Tertiary Hospital in Sudan.

Background: Five-medication regimen is recommended for patients after acute coronary syndrome (ACS) as a secondary prevention strategy at discharge to reduce recurrence and improve mortality. Objective: This study aimed to assess prescribing of optimal medical therapy (OMT) as five-medication regimens for secondary prevention at discharge after ACS in Sudan. Methods: A retrospective cohort study was performed at a tertiary hospital located in Wad Medani, Sudan, in the period between January and December 2019. Data were collected from patients' files. OMT was defined as a combination of five medications; aspirin and P2Y12 inhibitors, statins, beta-blockers (BBs), and angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) or if a valid contraindication was documented. Results: Of the 619 patients throughout the study period, 591 were selected based on inclusion and exclusion criteria. The median age of patients was 60 years, and 58.9% of patients were male. Diabetes (44.5%) and hypertension (42%) were the most common risk factors. Most patients (58.4%) were diagnosed with ST-segment elevation myocardial infarction. About 99.7% of patients were on aspirin, 99.5% on statins, 97% on clopidogrel, 96.8% on dual antiplatelet therapy, 70.4% on BBs, and 57.9% on ACEIs/ARBs. OMT for secondary prevention was prescribed to 267 (45.2%) patients with ACS at discharge. Conclusion: Although prescriptions for all five guideline-recommended medications after ACS were suboptimal, the study showed a positive trend in prescribing most individual medications.

Survival Outcomes of Breast Cancer in Sudanese Women: A Hospital-Based Study.

PURPOSE: Breast cancer (BC) is the leading malignancy among Sudanese women. Yet, data on survival are limited. This study aimed to determine 5-year overall survival (OS) of BC in Sudanese women, and identify prognostic demographic and clinicopathologic factors. PATIENTS AND METHODS: A hospital-based retrospective study was conducted by reviewing data of women with BC diagnosed and treated at the National Cancer Institute-University of Gezira during 2012, and followed up to end of August 2018. Data were retrieved from medical records and analyzed, OS was determined, and the prognostic factors were explored. RESULTS: A total of 225 cases were recruited. The median age at presentation was 45 years (range, 22-85 years). Clinical stage I, II, III, and IV represented 3.1%, 31.6%, 48%, and 17.3%, respectively. Most women (81.3%) were treated with curative intent. Of those, 25.1% received neoadjuvant chemotherapy. Mastectomy was the commonest (61.7%) type of surgery. The median follow-up period was 59.8 months with mean OS time of 55.7 months. The 5-year cumulative survival rate was 58%. The 5-year OS rates for stages I, II, III, and IV were 71.5%, 82.4%, 56.5%, and 8.4%, respectively. For lymph node (LN)-positive cases, 5-year OS rate was 63% and for LN-negative was 83.5%. Presenting with advanced-stage disease and positive LN status associated with short OS times (P < .005). CONCLUSION: OS of women with BC in Central Sudan is worse than in the developed world, but similar to African countries. Our findings indicate that advanced stage at diagnosis and lymph nodal involvement are strong predictors of short survival times. Raising awareness and introducing early detection programs are critical for better survival of these patients.