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Biomedical subjects

D Raghavan

Publications and source records attributed to D Raghavan.

At least 109 records · Page 6Linked to original sources
PubMed1990

Testis cancer: the way forward.

The past decade has been an exciting time in the evolution of management of testicular cancer. A disease that once ranked as one of the major causes of cancer deaths in young men has now been transformed into one of the curable cancers. Having achieved this happy situation, clinicians have turned their attention to the reduction of the side effects of treatment. Surgical protocols have been simplified, with less extensive dissection, and schedules of chemotherapy have been attenuated. In our haste to achieve further benefits for the patients with testicular cancer, we must not sacrifice their chance of cure by poorly conceived or unevaluated clinical programmes. In the 1990s, the greatest cause of deaths from testicular cancer could be the well-intentioned, but inadequately trained or insufficiently cautious clinician. Testicular cancer should be treated in specialist centres with the best facilities by clinicians with a specific interest in the biology and management of the disease.

Animals↗
PubMed1990

Towards the earlier diagnosis of testicular cancer.

There is little public awareness that testicular cancer is the commonest malignancy in men aged 20 to 44 years. Early diagnosis correlates with an improved chance of cure and a reduction in the severity of treatment. There have been major advances in treatment in the past decade, so that 80 per cent of patients with metastases can expect a cure. The family practitioner must be active in the management of this disease by educating his or her patients, by remaining vigilant to the possible diagnosis of this entity, and by referring patients to specialist urologists or to cancer centres with a specific interest and expertise in the management of this disease. With the vast improvement in techniques of management, when applied in specialist centres, errors of clinical judgment by inexperienced practitioners could now become the commonest cause of death from this disease.

Adult↗
PubMed1989

Elastase activities of human bladder cancer cell lines derived from high grade invasive tumours.

Elastase activities in intact human bladder cancer cell lines, established from three patients, were measured using a fluorogenic substrate highly specific for elastase, under conditions of physiological pH and ionic strength. This method allowed separation of cell-associated from secreted enzyme activity. As secreted elastase accounted for only 8% of the total, we concluded that the elastases were present at the cell surface. Inhibition studies using extracts of cell-surface elastases showed them to be serine proteinases which were also inhibited by alpha 1-antitrypsin. Partially purified fractions showing the highest specific activity towards the fluorogenic substrate hydrolysed insoluble elastin thus confirming the presence of elastases. This is the first time that elastase activity has been demonstrated in human bladder cancer cells and may represent a mechanism involved in tumour invasion.

Alanine↗
PubMed1989

Site-specific growth of the prostate xenograft line UCRU-PR-2.

A xenografted small-cell, undifferentiated prostate (SCUCP) cancer line, UCRU-Pr-2, was implanted at different sites within nude mice to examine the effect of local environmental factors on tumor growth and behavior. All tumors that grew were small-cell carcinomas. Fragments implanted within muscle and under the kidney capsule were locally invasive; however, tumors that grew subcutaneously or intraperitoneally showed no invasion. UCRU-Pr-2 did not grow in the spleen or the liver. No induced metastases were observed in the lung after intravenous injection. The sites of implantation did not allow the outgrowth of subpopulations as detected by the parameters used: light and electron microscopy, expression of tumor markers, levels of hormone production, and DNA flow cytometry. Electron microscopy, which showed both glandular and neuroendocrine differentiation within the same cell, does not support a dual-cell origin of SCUCP.

Animals↗
PubMed1989

A phase I study of trimetrexate (NSC 352122) administered by 5-day continuous intravenous infusion.

Trimetrexate (TMTX) is a potent inhibitor of dihydrofolate reductase that circumvents the transport resistance seen with methotrexate and has a wide spectrum of preclinical activity. A total of 18 patients with advanced cancer were treated in a clinical and pharmacological phase I trial with TMTX given as a continuous 5-day intravenous infusion. Neutropenia, thrombocytopenia and stomatitis were the dose-limiting toxicities at the maximum tolerated dose of 50 mg/m2 per 120 h (10 mg/m2 per day for 5 days). There was one septic death associated with neutropenia. Other toxicities were mild rash, mild nausea and transiently raised serum transminase levels. Significant relationships between the dose given and the AUC of plasma TMTX and the steady-state plasma level were established. Significant, although weak, relationships between the percentage of change in neutrophils and platelets and both the AUC and steady-state plasma level of TMTX were also observed. No objective tumour responses were seen, although six patients had stable disease. The recommended phase II dose for a continuous infusion of trimetrexate is 40 mg/m2 per 120 h.

Adult↗
PubMed1989

Detection of tumor-associated membrane proteins in prostate and bladder carcinomas by means of protein blotting.

Analysis of membrane proteins by Western blotting has revealed both overexpression of proteins of molecular weight 10-200 kD (in particular, of proteins of MW less than 43 kD) and increased glycosylation in a xenografted human small cell undifferentiated prostatic carcinoma, and in two xenografted human bladder tumor cell lines compared with preparations from normal human tissue. Of potential functional significance were: a) a 43 kD protein in the bladder line, UCRU-BL-13, which demonstrated increased synthesis and a marked increase in the degree of glycosylation, and b), a 28 kD ConA-binding protein in prostatic tissue which was absent in normal tissue, present in intermediate quantity in a benign hyperplasia and greatly overexpressed in small cell carcinoma. This study demonstrates the utility of the protein blotting/autoradiography technique for the investigation of tumor membrane proteins.

Autoradiography↗
PubMed1989

Dose intensity and outcome with combination chemotherapy for germ cell carcinoma. Australasian Germ Cell Trial Group.

Two hundred and fifty-three patients with advanced stage germ cell carcinoma received induction chemotherapy with vinblastine, bleomycin and cisplatin, sometimes with subsequent surgical resection of residual masses. Overall, 191 patients (76%) achieved complete remission or no evidence of disease after surgery (CR + NED). With 64 months median follow-up only 24 patients have relapsed (13%) and 68% of all patients treated are long-term survivors and 84% of patients entering CR + NED are alive. Toxicity with this chemotherapy was considerable, including seven deaths from leukopenia and septicaemia and eight deaths from bleomycin lung toxicity. Dose reductions or omissions of the drug from the treatment programme was necessary with cisplatin in 8% of patients, with vinblastine in 37% and with bleomycin in 35% of patients. Analysis of these alterations in dose intensity for each drug revealed that initial treatment response and subsequent survival were not compromised by reductions in intended doses of drug administered for either vinblastine or bleomycin. Too few patients had dose reductions of cisplatin for meaningful analysis. This apparent lack of major dose-response effect for either vinblastine or bleomycin in the present treatment programme for germ cell carcinoma has prompted the initiation of a randomized study to determine whether deletion of bleomycin from treatment for patients with good prognostic pretreatment characteristics improves the therapeutic index of this very successful therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Detection of malignant cells in voided urine from patients with bladder cancer, a novel monoclonal assay.

A simple assay is described for detecting malignant cells in the voided urine from patients with transitional cell carcinoma of the bladder. Agarose-embedded urothelial cells from 24 biopsy-proven cancer patients and 10 controls were stained for surface immunofluorescence with four monoclonal antibodies reactive with human bladder cancer and three monoclonals reactive with blood group A. Reactivity was assessed by fluorescence microscopy. One antibody, BLCA-8 appeared to have particular diagnostic utility. Thus, 24.3 +/- 5.8 percent of outer layer and 27.0 +/- 4.6 percent of inner layer urothelial cells reacted with BLCA-8 in patient samples, compared to 2.9 +/- 1.0 and 0.8 +/- 0.5 percent of similar cells from control urines. BLCA-8 antigen expression was found to be relatively stable even after prolonged exposure to urine. In a comparison with conventional cytology, samples from 4/8 patients were considered positive by standard methods, whereas, 8/8 were BLCA-8 positive. This new technique may thus be a useful adjunct to conventional methods.

Animals↗
PubMed1989

A randomized trial of cisplatin versus cisplatin plus methotrexate in advanced cancer of the urothelial tract.

One hundred eight patients with recurrent or metastatic transitional cell carcinoma of the urothelial tract were randomized to receive cisplatin (C) 80 mg/m2 on day 1 every 4 weeks, or methotrexate (M) 50 mg/m2 on days 1 and 15 plus C 80 mg/m2 on day 2 every 4 weeks (C + M). Fifty-three eligible patients were randomized to C + M and 55 to C. In the C + M arm, 45% of patients responded (complete response [CR], 9%) and 31% (CR, 9%) in the C arm (P = .18). In the C arm, 20 patients failing or relapsing after C received M. Two patients responded, and four with progressive disease (PD) and one with a previous partial response (PR) showed no change. The median survival was 8.7 months (C + M arm) and 7.2 months (C arm), P = .7. Relapse-free survival was not significantly different, but C + M was associated with a significantly increased time to disease progression (median, 5.0 months, v 2.8 months for C arm). The response of untreated patients (37%) was not different from those with prior treatment (39%). On the C + M arm, 92% of patients and 96% of patients on the C arm received 85% or more of the scheduled C dose. Significantly more grade 3 or 4 hematological toxicity (27% v 2%; P = .01) and mucositis (20% v 0%; P = .0005) occurred in patients on the C + M arm. Although the initial response rates seen on the combination arm look superior, and the time to disease progression is increased, these effects have not translated into a clinically important increase in the duration of survival and were associated with increased toxicity.

Adult↗
PubMed1988

Establishment and characterization of a new human bladder cancer cell line showing features of squamous and glandular differentiation.

Tumour-cell heterogeneity has been studied in a continuous cell line, UCRU-BL-17CL, established from a xenografted human primary bladder carcinoma. The cell line, grown in vitro for more than 30 generations, reflects the pathology of both the xenograft from which it was derived and the original human tumour. It comprises mainly adenocarcinoma cells which secrete mucin in vitro, as well as squamous and transitional carcinoma cells. Features of both adenocarcinomatous and squamous differentiation have been observed within the same cell. The line expresses ABH blood group isoantigens, binds to peanut lectin and reacts with monoclonal antibodies (MAbs) raised against keratin and against normal and malignant epithelial cells. It also reacts with MAbs against ras p21 proteins and the epidermal growth factor receptor (EGFR). It shows high levels of lactic acid dehydrogenase isozyme 5, consistent with a high-grade tumour, forms colonies in methylcellulose and is tumorigenic in nude mice. The karyotype (human) shows many marker chromosomes, consistent with expression of EGF receptors and ras p21 proteins, and an 11:13 translocation. DNA content, as studied by flow cytometry, reveals a shift from tetraploid to near triploid. This line may provide a useful model for studies of the histogenesis of bladder cancer and the relationship between transitional-cell carcinoma and the other histological subtypes of this disease.

Aged↗
PubMed1988

A phase II trial of oral 4'demethoxydaunorubicin (DMDR) in inoperable non small cell lung cancer.

4'Demethoxydaunorubicin, an orally active daunorubicin analogue, was administered to 22 patients with inoperable non small cell lung cancer (NSCLC). Patients were stratified into good and poor risk categories and received doses of 45 mg/m2 and 40 mg/m2 respectively at 28 day intervals. All 22 patients were evaluable for response: No tumour responses occurred. Therapy was well tolerated. Mild gastrointestinal toxicity occurred in 41% of patients. Leucopenia with a wcc less than 3 x 10(9)/L occurred in 33% of patients and thrombocytopenia less than 100 x 10(9)/L in 9%. Severe marrow toxicity was rare and there appeared to be no difference in terms of toxicity between the different dose levels. DMDR appears to have no useful clinical activity in NSCLC.

Administration, Oral↗
PubMed1988

Features of squamous and adenocarcinoma in the same cell in a xenografted human transitional cell carcinoma: evidence of a common histogenesis?

Ultrastructural features of squamous differentiation have been found in adenocarcinomatous cells in a xenografted line (UCRU-BL-17) established in nude mice from a primary human bladder transitional cell carcinoma (grade III, stage T4) with a tetraploid DNA component. The line has been characterized by light and electron microscopy, flow cytometry and immunocytochemistry. The initial xenograft showed predominantly adenocarcinomatous differentiation with mucin secretion, whilst the subsequent passages also contained cells showing squamous differentiation. A xenograft subline established from a cell culture of the initial xenograft shows the emergence of a population of cells with near triploid DNA, which are less differentiated, grow more quickly, show decreased expression of carcinoembryonic antigen, and a change in the distribution of staining with peanut lectin from cell surface to cytoplasm. These lines offer an unusual opportunity to study the histogenetic relationships between the histological subtypes of bladder cancer.

Adenocarcinoma↗