Predicting treatment responses in advanced prostate cancer (PCa) currently centres on prostate-specific antigen (PSA) kinetics and on being able to visualize measurable changes in imaging modalities. New molecular markers have emerged as potential diagnostic and prognostic indicators; these were summarized in Part I of this review in the Asian Journal of Andrology. A number of molecular markers are now being used to enhance PCa imaging and staging. However, management options for advanced and hormone-resistant PCa (HRPC) are limited and additional therapeutic options are needed. Molecular markers have been proposed as potential therapeutic targets using gene therapy and immunomodulation. Additionally, markers identified in early PCa and precursor lesions may offer novel targets for chemoprevention and vaccine development. This review summarizes the current advances regarding the roles of these markers in the management of PCa.
Antineoplastic Agents ; therapeutic use ; Biomarkers, Tumor ; genetics ; metabolism ; Cancer Vaccines ; therapeutic use ; Genetic Therapy ; Humans ; Immunologic Factors ; therapeutic use ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; metabolism ; therapy

Carcinomas arising from an exstrophic urinary bladder are rare entities, and only seven such cases have been reported in the literature. We present the eighth case of advanced squamous cell carcinoma arising from an exstrophic bladder, with a pertinent review of the literature. The mean age of the patients was 54.9 years, with a male to female ratio of 3:1. The average duration of symptoms was 18.6 months. The appearance of a new growth was the most common symptom. Three patients had stage I disease, one patient each had stage II and III disease, two patients had stage IV disease, and the disease stage was not known in one patient. Five out of these eight patients underwent surgery. Four patients in the treatment group remained disease-free, with a mean survival period of 30 months. In conclusion, regular surveillance with cystoscopy is advised in all cases that had primary closure of the exstrophic bladder.
Adult ; Biopsy ; Bladder Exstrophy ; complications ; diagnosis ; surgery ; Carcinoma, Squamous Cell ; complications ; diagnosis ; surgery ; Diagnosis, Differential ; Humans ; Male ; Pelvic Exenteration ; methods ; Urinary Bladder Neoplasms ; complications ; diagnosis ; surgery

Pigmented villonodular synovitis (PVNS) is a rare benign condition that is locally aggressive and may destructively invade the surrounding soft tissues and bone causing functional loss of the joint and the limb. The knee is the most affected joint (range, 28% to 70%) but involvement of the bone is not a common feature seen at this site. We present a rare case of diffuse PVNS of the knee associated with subchondral cyst of the lateral femoral condyle. This posed a diagnostic dilemma because of bone invasion. The radiological image of synovitis was pathognomonic of PVNS but etiology of the osteolytic lesion was confirmed only on histopathology. The large osteochondral defect was eventually managed in a staged manner with bone grafting and osteochondral autograft transfer.
Autografts ; Bone Cysts ; Bone Transplantation ; Cartilage ; Extremities ; Joints ; Knee ; Synovitis ; Synovitis, Pigmented Villonodular

There is a lack of evidence regarding the use of betel quid (BQ) and its potential contribution to oral cancer. Limited attention has been directed towards investigating the involvement of BQ-derived organic acids in the modulation of metabolic-epigenomic pathways associated with oral cancer initiation and progression. We employed novel protocol for preparing saliva-amalgamated BQ filtrate (SABFI) that mimics the oral cavity environment. SABFI and saliva control were further purified by an in-house developed vertical tube gel electrophoresis tool. The purified SABFI was then subjected to liquid chromatography-high resolution mass spectrometry analysis to identify the presence of organic acids. Profiling of SABFI showed a pool of prominent organic acids such as citric acid. malic acid, fumaric acid, 2-methylcitric acid, 2-hydroxyglutarate, cis-aconitic acid, succinic acid, 2-hydroxyglutaric acid lactone, tartaric acid and β-ketoglutaric acid. SABFI showed anti-proliferative and early apoptosis effects in oral cancer cells. Molecular docking and molecular dynamics simulations predicted that SABFI-derived organic acids as potential inhibitors of the epigenetic demethylase enzyme, Ten-Eleven Translocation-2 (TET2). By binding to the active site of α-ketoglutarate, a known substrate of TET2, these organic acids are likely to act as competitive inhibitors. This study reports a novel approach to study SABFI-derived organic acids that could mimic the chemical composition of BQ in the oral cavity. These SABFI-derived organic acids projected as inhibitors of TET2 and could be explored for their role oral cancer.

Cancer drug resistance is associated with metabolic adaptation. Cancer cells have been shown to implicate acetylated polyamines in adaptations during cell death. However, exploring the mimetic of acetylated polyamines as a potential anticancer drug is lacking.We performed intracellular metabolite profiling of human breast cancer MCF-7 cells treated with doxorubicin (DOX), a well known anticancer drug. A novel and in-house vertical tube gel electrophoresis assisted procedure followed by LC-HRMS analysis was employed to detect acetylated polyamines such as N1-acetylspermidine. We designed a mimetic N1-acetylspermidine (MINAS) which is a known substrate of histone deacetylase 10 (HDAC10). Molecular docking and molecular dynamics (MDs) simulations were used to evaluate the inhibitory potential of MINAS against HDAC10. The inhibitory potential and the ADMET profile of MINAS were compared to a known HDAC10 inhibitor Tubastatin A. N1-acetylspermidine, an acetylated form of polyamine, was detected intracellularly in MCF-7 cells treated with DOX over DMSO-treated MCF-7 cells. We designed and curated MINAS (PubChem CID 162679241). Molecular docking and MD simulations suggested the strong and comparable inhibitory potential of MINAS (–8.2 kcal/ mol) to Tubastatin A (–8.4 kcal/mol). MINAS and Tubastatin A share similar binding sites on HDAC10, including Ser138, Ser140, Tyr183, and Cys184. Additionally, MINAS has a better ADMET profile compared to Tubastatin A, with a high MRTD value and lower toxicity. In conclusion, the data show that N1-acetylspermidine levels rise during DOX-induced breast cancer cell death. Additionally, MINAS, an N1-acetylspermidine mimetic compound, could be investigated as a potential anticancer drug when combined with chemotherapy like DOX.