Background: Oxaliplatin is a 3rd generation platinum analogue, which is active in a broad spectrum of tumours. Clinical trials using this drug in bladder cancer are underway, but not yet reported. There are currently no in vitro data regarding oxaliplatin in bladder cancer. Therefore, this study compares the efficacy of oxaliplatin with cisplatin and carboplatin, which are both used widely in this tumour type, in bladder cancer cell lines. Method: The efficacy of oxaliplatin, carboplatin and cisplatin were compared in 4 bladder cancer cell lines (5637, J82, HT1197 and 253J). Cell parameters including cell number, viability and apoptosis were assessed after 3 days of drug exposure. The effects of the drugs on the cell cycle were also observed. Results: Overall cisplatin was the most potent at inducing cell death (IC50 11.5–70.6 µM). Oxaliplatin was the 2nd most potent drug (IC50 15.2–126.3 µM) and carboplatin the least effective (IC50 75.4–137.8 µM). Carboplatin was significantly less potent at inducing cell death than the other two drugs in all 4 cell lines. Carboplatin was also inferior at inducing apoptosis in 3 of the 4 cell lines. All three drugs had a similar effect on the cell cycle, causing an initial G2 block. Conclusions: These data suggest that oxaliplatin is a potent agent in bladder cancer cell lines and is superior to carboplatin in this in vitro setting. It justifies the clinical studies using oxaliplatin that are underway.
Nonseminomatous germ cell cancers (NSGCC) have a varied response to chemotherapy, some melting away with resultant cure, some have tumour stem cell necrosis and residual benign disease whilst others are resistant to treatment. The latter two require surgical excision in order to identify those needing high intensity chemotherapy. Objective: The aim of this study was to investigate whether it was possible to give an earlier prediction of need for surgery after chemotherapy on the basis of a limited CT scan performed after the first course. Materials and Methods: Twenty-three patients with metastatic NSGCC undergoing induction chemotherapy were studied. The site of the maximum disease was noted before treatment and only this area was rescanned at day 21. The change in disease bulk, measured as maximum transverse diameter (MTD), was compared with appearances on a CT scan immediately after chemotherapy and post-treatment response. Results: Of those patients showing a poor response on the day 21 scan (i.e. no change, or less than 50% reduction in MTD), 70% required early surgical excision of residual disease, while none of the good responders (i.e. greater than 50% reduction in MTD), required immediate surgery (p < 0.001). Conclusion: It is concluded that a limited day 21 CT scan may represent an independent predictor of good and poor response to chemotherapy, thus enabling reduction in chemotherapy and its toxicity in good responders and early identification of those who may need surgical excision, thereby permitting easier scheduling of these often difficult surgical procedures.
e13606 Background: The sun-sensitive microaerophylic bacterium C. acnes, is linked with prostate cancer (PC) in 9 studies 3 of which are cohort studies of 289,043 men followed for 30 years from puberty. That circumcision reduces PC risk further supports a role for anaerobes as they are reduced on the circumcised glans penis. A 1988 study linked anaerobes with PC but considered them opportunists. Reports that H. pylori, linked to stomach cancer, is also a microaerophilic bacterium led us to reinvestigate the association of PC and anaerobes. Methods: The MOLDI-TOF methodology for analysing anaerobes in 18 post rectal exam urine samples has been previously reported ( https://www.nature.com/articles/s41598-017-13782-6 ). This report analyses outcome after a further 21 patients were recruited and follow up was extended from 1 month to a median of 43 months. In total there were 21 diagnosed as PC and 18 BPH. Results: Of the 29 anaerobic isolates, 19 were Chlostridiales family, 2 Prevotella and 7 Actinomycoses (includes C.acnes) family. 12 cases had obligate anaerobes, 7 microaerophylic bacteria and 20 none of these. In 27 patients with PSA > 1.5, 56% had anaerobes, while in 12 with PSA = < 1.5 it was 17% (p < 0.037 Fisher’s exact test) In the 21 with prostate cancer, 7 (64%) of 11 without anaerobes and 2 of 10 (20% ) with anaerobes remain on Active Surveillance (p = 0.08 Fisher’s exact test) vs in 18 without cancer, 10/11 (91%) without and 5/7 (71%) with anaerobes remain without the need of TURP intervention. Conclusions: This is a small study and needs expanding. Given the rising incidence of antibiotic resistance more resources should be focused on the immune deficiency associated with chronic bacterial infection. Expansion of technology used to produce bacterial vaccines to treat women with recurrent cystitis could offer new approaches to prevention of PC and to treat patients with raised PSA and negative biopsy. Modern approaches to immunotherapy against these bacteria with checkpoint inhibitors could be used in combination with androgen suppression and chemotherapy.
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