Production of simian virus 40 large tumor antigen in bacteria: altered DNA-binding specificity and dna-replication activity of underphosphorylated large tumor antigen

A bacterial expression system was used to produce simian virus 40 large tumor antigen (T antigen) in the absence of the extensive posttranslational modifications that occur in mammalian cells. Wild-type T antigen produced in bacteria retained a specific subset of the biochemical activities displayed by its mammalian counterpart. Escherichia coli T antigen functioned as a helicase and bound to DNA fragments containing either site I or the wild-type origin of replication in a manner identical to mammalian T antigen. However, T antigen purified from E. coli did not efficiently bind to site II, an essential cis element within the simian virus 40 origin of replication. It therefore could not unwind origin-containing plasmids or efficiently replicate simian virus 40 DNA in vitro. The ability of protein phosphorylation to modulate the intrinsic preference of full-length T antigen for either site I or site II is discussed

Initial management of low-risk localized prostate cancer in the UK : analysis of the British Association of Urological Surgeons Cancer Registry

OBJECTIVE: To assess the patterns of care for low-risk localized prostate cancer. Management of this condition is highly controversial, with a range of treatment options, but there are no published UK data. METHODS Data from the British Association of Urological Surgeons (BAUS) Cancer Registry were linked to the UK Association of Cancer registries postcode directory. The demographic and clinical characteristics, and the initial management of men diagnosed with low-risk localized prostate cancer in the UK between 2000 and 2006 were analysed. RESULTS: In all, 43 322 cases of localized prostate cancer were recorded in the BAUS Registry between 2000 and 2006, of which 8861 (20%) met the criteria for low-risk disease. The proportion classified as low risk ranged from 16% in 2000 to 21% in 2006. The proportion of men with low-risk disease opting for 'watchful waiting' increased from 0% to 39% over the same period. Treatment choice was associated with socio-economic status. For example, radical prostatectomy was chosen by 34% of patients in the most affluent quintile, compared with 19% in the most deprived quintile (P = 0.01). CONCLUSION: The management of low-risk localized prostate cancer in the UK has changed markedly in recent years, and contrasts with that in the USA. The association observed between socio-economic status and choice of treatment deserves further study.4 page(s

Abnormal hCG levels in a patient with treated stage I seminoma: a diagnostic dilemma

<p>Abstract</p> <p>Background</p> <p>We report the case of a patient with treated Stage Ia seminoma who was found to have an elevated beta human chorionic gonadotrophin (hCG) on routine follow – up. This instigated restaging and could have lead to commencement of chemotherapy.</p> <p>Case presentation</p> <p>The patient was a bodybuilder, and following a negative metastatic work – up, admitted to injecting exogenous beta hCG. This was done to reduce withdrawal symptoms from androgen abuse. The patient remains well eight years post diagnosis.</p> <p>Conclusion</p> <p>This case highlights the need for surgical oncologists to conduct vigilant screening of young male patients with a history of testicular germ cell tumours and who may indulge in steroid abuse.</p

The curative management of synchronous rectal and prostate cancer

Objective: Neoadjuvant &amp;quot;long-course&amp;quot; chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. Results: Pelvic external beam radiotherapy (RT) 45-50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2-6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45-50.4Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort. Advances in knowledge: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients

The curative management of synchronous rectal and prostate cancer

Objective: Neoadjuvant &amp;quot;long-course&amp;quot; chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. Results: Pelvic external beam radiotherapy (RT) 45-50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2-6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45-50.4Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort. Advances in knowledge: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients