Biomedical subjects

S N Datta

Publications and source records attributed to S N Datta.

13 recordsLinked to original sources

PubMed2004

Investigation of sequential mitomycin C and photodynamic therapy in a mitomycin-resistant bladder cancer cell-line model.

OBJECTIVES: To investigate the hypothesis that sequential mitomycin C and 5-aminolaevulinic acid (ALA)-mediated photodynamic therapy (PDT) interact additively in both the J82 bladder cancer cell line and its mitomycin-C-resistant derivative, J82/MMC, and to assess the theoretical basis of this interaction by measuring the relative mitochondrial density of the respective cell lines, on the basis that the mitochondria are the intracellular site where ALA is metabolized to the active photosensitizer, protoporphyrin IX. MATERIALS AND METHODS: Cell survival was assayed in J82 cell line and the J82/MMC derivative after treating them with sequential ALA-mediated PDT and mitomycin C, and with the sequence of treatments reversed. Cell survival was estimated using the tetrazolium assay. The relative mitochondrial density of the two cell lines was estimated using flow cytometry to measure 123rhodamine fluorescence. RESULTS: The effect of sequential mitomycin C followed by ALA-mediated PDT enhanced the effect of PDT in both cell lines. In J82/MMC this effect was marginally supra-additive. When ALA-mediated PDT was administered before mitomycin C, the combined effect was 'sub-additive'. 123Rhodamine fluorescence was > 10 times greater in J82/MMC than J82, suggesting a significantly higher mitochondrial density in the former than the latter. CONCLUSION: Mitomycin C appears to enhance ALA-mediated PDT when administered first. This appears to be particularly so in J82/MMC. This phenomenon may have clinical significance in recurrent superficial bladder cancer.

Aminolevulinic Acid↗

PubMed2002

Urinary tract ultrasonography in the evaluation of haematuria--a report of over 1,000 cases.

Over a 5-year period, 1007 patients with haematuria were investigated, using a protocol based on ultrasonography as the upper tract imaging modality of choice. Intravenous urography (IVU) was only used in selected individuals, including those patients with bladder cancer suspected on cystoscopy, suspicious or malignant cytology, previous investigation for haematuria, on-going haematuria at the time of their clinic visit, a history of flank pain or hydronephrosis on ultrasonography. Of this series, 840 (83%) had visible haematuria, 158 (15%) had microscopic or chemical haematuria and 9 (0.9%) had unspecified haematuria. A total of 133 bladder transitional cell tumours, 21 renal cell cancers and 2 upper tract transitional cell cancers (TCC) were diagnosed. The sensitivity of ultrasound with respect to bladder cancer was 63% and the specificity 99%. The odds ratio of diagnosing cancer in patients with visible haematuria compared to microscopic or unspecified haematuria was 3.3. No upper tract tumours were missed using this investigational protocol. An ultrasonography-based protocol could miss fewer upper tract TCCs than a standard IVU-based service would miss renal cell cancer. Provided there is no history of flank pain, no malignant cytology, no hydronephrosis and no previously investigated haematuria, IVU could be safely omitted.

Carcinoma, Renal Cell↗

PubMed1998

Quantitative studies of the kinetics of 5-aminolaevulinic acid-induced fluorescence in bladder transitional cell carcinoma.

Photodynamic therapy is a potential treatment for superficial bladder cancer that utilizes photosensitizer drugs, which are activated by light to cause tissue destruction. However, first-generation photosensitizers cause prolonged phototoxicity, have poor tumour specificity and can accumulate within detrusor muscle, resulting in permanent loss of bladder capacity following treatment. A newer drug, called 5-aminolaevulinic acid (ALA), generates a sensitizer called protoporphyrin IX (PpIX) in situ and has been shown, qualitatively, to be more tumour specific. The fluorescence kinetics of ALA-induced PpIX was investigated in patient biopsies of bladder tumour, normal urothelium and detrusor muscle, both in vitro after incubation of specimens in ALA-rich culture medium for various times and in vivo after instillation of intravesical ALA before endoscopic resection. The fluorescence in tumour tissue was twice that of normal urothelium in vitro and up to tenfold in vivo. There was little ALA-induced fluorescence in detrusor muscle, both in vitro and in vivo. Most importantly, no patients experienced phototoxicity or other adverse events following intravesical instillation of ALA.

Administration, Intravesical↗

PubMed1997

Effect of photodynamic therapy in combination with mitomycin C on a mitomycin-resistant bladder cancer cell line.

Photodynamic therapy is a method for treating cancer using drugs activated by light. A new compound, 5-aminolaevulinic acid (ALA), is a precursor of the active photosensitizer protoporphyrin IX (PpIX) and has fewer side-effects and much more transient phototoxicity than previous photosensitizers. Cell survival of ALA-mediated photodynamic therapy was measured in the J82 bladder cancer cell line, along with its mitomycin C-resistant counterpart J82/MMC. This demonstrated that mitomycin resistance is not cross-resistant to photodynamic therapy. There was also a suggestion that the mitomycin-resistant cells were more susceptible to photodynamic therapy than the parent cell line. Photodynamic therapy appeared to enhance the effect of mitomycin C, when mitomycin C was given first. This phenomenon was apparent for both drug-resistant and drug-sensitive cell lines. This suggests a possible role for combined mitomycin C and photodynamic therapy in superficial bladder tumours that have recurred despite intravesical cytotoxic drug treatment.

Aminolevulinic Acid↗

PubMed1997

Photodynamic therapy of bladder cancer cell lines.

OBJECTIVE: To determine the effect of photodynamic therapy mediated by 5-aminolevulinic acid (ALA) on a range of bladder cancer cell lines, including a squamous cancer cell line and a multi-drug resistant cell line. MATERIALS AND METHODS: Experiments were performed on cells growing in culture: the cell lines studied were the transitional cell cancer lines RT112, T24 and EJ138, the squamous cancer cell line, SCaBER, and the multi-drug resistant transitional cancer cell line, MGH-U1(R), together with its non-resistant parent line, MGH-U1. The kinetics of the ALA-mediated generation of fluorescent photosensitizer were determined using flow cytometry. Photodynamic therapy was performed by incubating cells in ALA followed by exposure to various doses of white light. RESULTS: The response of the various transitional cancer cell lines to photodynamic therapy depended on dose. The squamous cell line was relatively resistant to photodynamic therapy. There was some cross-resistance of the MGH-U1(R) cell line to photodynamic therapy, although the mechanism of cross-resistance appeared not to be necessarily a property of the drug-resistant phenotype. CONCLUSION: This study suggests that ALA-mediated photodynamic therapy may be effective in transitional cell carcinoma of the bladder. Based on these findings, this therapeutic method should be further evaluated clinically.

Aminolevulinic Acid↗

PubMed1997

Is prednisolone as good as flutamide in hormone refractory metastatic carcinoma of the prostate?

PURPOSE: There are no generally accepted rules for the second line treatment of prostate cancer and few prospective studies have attempted to compare 2 therapeutic strategies with different modes of action. MATERIALS AND METHODS: We describe a prospective, randomized study of 40 patients comparing the second line response of flutamide to prednisolone in patients with known hormone refractory stage M1 prostate cancer. RESULTS: The median survival of patients receiving either treatment was 32.9 weeks, with no difference between the 2 groups. In terms of biological response 11 of 20 patients (55%) receiving prednisolone and 10 of 20 (50%) receiving flutamide exhibited prostate specific antigen (PSA) suppression. Average minimum PSA was 54 and 52% of the initial PSA in patients receiving prednisolone and flutamide, respectively. There was no difference between the 2 treatment groups in terms of long-term survival, although 35% of all patients survived beyond 1 year and 3 survived beyond 2 years. CONCLUSIONS: More patients taking prednisolone described better pain relief, although both medications were well tolerated and there was no difference in terms of performance status or analgesic requirements.

Aged↗

PubMed1997

Surgeons' follow-up practice after resection of colorectal cancer.

Consultant surgeons in two United Kingdom Health Regions were invited to complete a questionnaire on details of their personal management of patients with colon and rectal cancer, with particular emphasis on follow-up. Replies from 140 (94%) were analysed by the surgeon's subspecialty of colorectal and gastrointestinal surgery (group 1) and all others (group 2). There was a wide variation in the duration of followup, but no difference between the two groups. More group 1 surgeons carried out investigations as a routine after colonic (P < 0.01) and rectal (P < 0.01) resection. Colonoscopy was used more frequently by group 1 (P < 0.0001) and barium enema by group 2 surgeons (P < 0.05). Investigations to detect asymptomatic metastases were used as a routine by 33.3% of surgeons, in whom there was no concordance over the choice or combination of tests and no difference between the two groups of surgeons. There is no consensus among surgeons as to the ideal duration, intensity and method of follow-up after resection for colorectal cancer and little difference between the practice of colorectal and gastrointestinal surgeons and that of other specialists, except in the use of colonoscopy and barium enema. These results reflect the continuing lack of evidence on which to base the follow-up of patients after surgery for colorectal cancer.

Colonic Neoplasms↗

PubMed1996

Problematic renal calculi presenting during pregnancy.

Urinary tract calculi presenting during pregnancy are rare, with less than 0.1% of pregnancies being associated with stones, the vast majority being asymptomatic and a chance finding. We outline six cases treated over an 8-year period. They presented with combinations of pain, sepsis and obstruction. Intervention was required in four cases: insertion of antegrade nephrostomy, double-J stent, Dormia basket stone extraction, open pyelolithotomy and induction of labour. In each case the pregnancy had a successful outcome. Renal colic can precipitate premature labour. Delayed diagnosis and intervention can result in permanent renal impairment. Ionising radiation and anaesthetic agents may be harmful during pregnancy. The problem is rarely encountered and we therefore present information on the relative risks in each trimester of exposure to the mother and fetus and present a clinical algorithm for the management of these patients.

Adult↗

PubMed1994