Aamir Ahmed

Penile carcinoma is a rare malignancy in developed countries but is more common in South America and East Africa. The small number of cases means there are limited resources to investigate disease pathogenesis. This report describes a method of generating primary cell lines from freshly isolated human penile tissue using a clonal expansion approach on mitotically inactivated fibroblasts. Matched normal and penile cancer cell lines from two patients were generated and characterised. Molecular karyotyping and targeted sequencing were performed to compare their genomic landscape. Gains in 8q13.3, 10q23.2, 10q25.1, 10q26.13,12p13.33, 20q13.33, Xq21.1 or losses in Yq11.23 were consistent in both tumour cell lines. Gains in 8q13.3 and Xq21.1 cytobands positively correlated with changes in the expression of nearby genes. The top 20 differentially expressed genes are involved in immune responses like interferon alpha/beta signalling. Additionally, there was an increase in integrin β1, transglutaminase 1, keratins 5, 10, 14 and 16, and a decrease in involucrin protein expression. The cell lines described in this study can provide an invaluable platform for new insights and testing of therapies for penile carcinoma.

Purpose: Beta-blockers, originally developed for cardiovascular conditions, have been explored for their potential role in cancer treatment. Propranolol, a non-selective beta-blocker, has shown promise in inhibiting stress-induced signalling pathways associated with cancer progression. This systematic review aims to assess the evidence for the repurposing of propranolol as a treatment for various cancers, particularly breast cancer to answer the research question: Does propranolol improve cancer outcomes, including survival and recurrence? Methods: We conducted a systematic search of MEDLINE, EMBASE, Global Health, Web of Science, and the Cochrane Library, including studies up to July 2024. Randomised Controlled Trials (RCTs), systematic reviews, and meta-analyses were included if they assessed the effects of propranolol on cancer outcomes such as mortality, survival, recurrence, or biomarkers of tumour regression. A narrative synthesis was performed to summarise the findings. Results: Thirty-one studies were included, consisting of 7 RCTs, 4 systematic reviews and 20 meta-analyses. The evidence suggests that propranolol may improve cancer outcomes, especially when administered perioperatively, by reducing recurrence risk. However, the results remain inconclusive regarding its use in combination with chemotherapy or radiotherapy, as studies showed mixed results. The timing of propranolol administration, alongside its combination with other cancer therapies, appears to be a key factor in its effectiveness. Conclusion: Propranolol has potential as an adjunctive therapy in cancer treatment, particularly in reducing recurrence risk during the perioperative period. However, further clinical trials are needed to better define its role in cancer therapy, particularly regarding optimal treatment regimens and patient populations.

Pakistan faces tremendous challenges in providing healthcare due to a lack of consistent policymaking, increasing expenditure and exponential growth in population since its inception in 1947. These challenges are not just driven by politics, policy and allocation of resources but also by healthcare, environment and characteristics of the population biology. Clinical trials provide the best way to find population-specific, cost-effective treatments that do not merely mimic those used in wealthier nations. This article analyzes all clinical studies conducted with at least one site in Pakistan listed on ClinicalTrials.gov, combined with a short overview that considers new therapeutic approaches that can be investigated in future clinical trials. Therapies using repurposed medicines are of particular interest as they use affordable drugs that are already widely available.

Endocytosis, an important macromolecule uptake process in cells, is known to be dysregulated in cancer. Clathrin and caveolin-1 proteins play a major role in receptor-mediated endocytosis. We have used a quantitative, unbiased and semi-automated method to measure in situ protein expression of clathrin and caveolin-1 in cancerous and paired normal (cancer adjacent, non-cancerous) human prostate tissue. There was a significant (p < 0.0001) increase in the expression of clathrin in prostate cancer samples (N = 29, n = 91) compared to normal tissue (N = 29, n = 67) (N = number of patients, n = number of cores in tissue arrays). Conversely, there was a significant (p < 0.0001) decrease in expression of caveolin-1 in prostate cancer tissue compared to normal prostate tissue. The opposite change in expression of the two proteins was highly correlated to increasing cancer aggressiveness. There was also a concurrent increase in the expression of epidermal growth factor receptor (EGFR), a key receptor in carcinogenesis, with clathrin in prostate cancer tissue, indicating recycling of EGFR through clathrin-mediated endocytosis (CME). These results indicate that in prostate cancer, caveolin-1-mediated endocytosis (CavME) may be acting as a brake and increase in CME may facilitate tumorigenicity and aggressiveness of prostate cancer through recycling of EGFR. Changes in the expression of these proteins can also potentially be used as a biomarker for prostate cancer to aid in diagnosis and prognosis and clinical decision-making.