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Biomedical subjects

D Raghavan

Publications and source records attributed to D Raghavan.

177 records · Page 10Linked to original sources
PubMed1981

Fibronectin from human germ-cell tumors resembles amniotic fluid fibronectin.

Three human germ-cell tumors established as xenografts in immunosuppressed mice were shown to produce fibronectin. Immunoperoxidase tissue staining with a specific antiserum revealed human fibronectin in some tumor cells. The cyst fluid which accumulated in the tumors contained human fibronectin as shown by a species-specific radioimmunoassay. Human fibronectin was isolated from two of the tumor fluids and compared to previously characterized fibronectins. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis and gel electrofocusing showed that the germ-cell fibronectins resembled amniotic fluid fibronectin with regard to subunit molecular weight and isoelectric point. The distinct features of the amniotic fluid and germ-cell tumor fibronectin suggest that such fibronectins may provide new oncodevelopmental markers.

Amniotic Fluid↗
PubMed1981

Localization of human tumour xenografts after i.v. administration of radiolabeled monoclonal antibodies.

A mouse monoclonal antibody (LICR-LON/HT13) has been developed to a cell-surface antigen carried on a human germ-cell tumour xenograft (HX39). After radioiodination, the antibody localized in vivo preferentially in xenografted tumours as opposed to normal mouse tissue, whereas tumor uptake did not occur with normal mouse IgG or nonspecific monoclonal IgG. This selective localization could be abolished by simultaneous injection of an excess of the unlabelled LICR-LON/HT13. The kinetics of and factors influencing localization have been examined. Tumour weight was important in that the smaller the tumour the better the localization. LICR-LON/HT13 was found to localize also in other xenografted germ-cell tumours, but not in non-germ-cell tumour xenografts. Thus monoclonal antibodies are capable of selective in vivo localization of human tumours in an animal model, and their clinical value should now be assessed.

Animals↗
PubMed1981

Non-seminoma germ cell tumours (malignant teratoma) of the testis. Results of treatment and an analysis of prognostic factors.

The results of treatment of 126 patients with non-seminoma germ cell tumours (malignant teratoma) of the testis are presented. Of this group 81% are alive and 70% disease-free. Of 98 patients who had had no prior treatment 83% are alive and 76.5% disease-free. Of 43 early-stage patients 41 (95%) are alive and tumour-free despite a 21% relapse rate after radiotherapy. The disease-free rate in patients with advanced disease treated with chemotherapy, and in some cases radiotherapy and/or surgery, ranged from 100 to 9% and was strongly dependent upon the volume of metastatic tumour and the histology. Patients with malignant teratoma undifferentiated (embryonal carcinoma) showed a significantly higher disease-free survival rate than those with malignant teratoma intermediate (teratocarcinoma). Twenty-six men with advanced disease received radiotherapy after chemotherapy and of these 23 (88%) are alive and 21 (81%) are disease-free. No difference in disease-free survival rate was seen between advanced-stage patients receiving vinblastine and bleomycin and those receiving, in addition, cis-platinum. The overall drug-related mortality was 4.5%. Serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotrophin (beta-HCG) levels were valuable monitors in advanced disease but not prognostically significant if allowance was made for tumour volume. Fifteen patients had surgical resection of residual masses and one died post-operatively.

Castration↗
PubMed1981

Hypothesis: when is a seminoma not a seminoma?

A xenograft line, HX 53, has been established in immune-suppressed mice from a specimen of a lymph node metastasis in a patient with a histological diagnosis of seminoma but with markedly raised circulating levels of alpha-fetoprotein. Histological, immunocytochemical, and ultrastructural studies of this xenograft line have suggested that a solid variant of yolk sac carcinoma may exist, which morphologically resembles seminoma, or that a continuum of differentiation exists between seminoma and yolk sac carcinoma.

Adult↗
PubMed1981

Monoclonal antibodies to detect human tumours: an experimental approach.

The use of monoclonal antibodies which can be raised to antigens of choice offers a selective and specific approach for the detection of tumours both in vivo and at a cellular level in biopsy specimens. We demonstrate that a monoclonal antibody raised to human teratoma will localise in a teratoma, growing as a xenograft in immune-suppressed mice.

Animals↗
PubMed1981

Role of laboratory chemosensitivity testing in the selection of cancer chemotherapy for individual patients.

Recently several assays have been developed which allow the growth of colonies from cell suspensions prepared from human tumour biopsy specimens. It has been suggested that such assays will provide a reliable means of measuring the chemosensitivity of human tumours for predicting the response to treatment in patients. We have briefly reviewed the previous, largely unsuccessful, attempts at chemosensitivity testing and the potential place of the new assays. The measurement of the survival of clonogenic tumour cells after cytotoxic treatment probably reflects to some extent the survival of cells which in vivo are capable of proliferating to repopulate and regrow the tumour. This endpoint therefore has advantages over alternatives that do not directly measure reproductive cell death, and the assays also have the advantage of suppressing the growth of many non-malignant cells found in tumours. However, technical problems such as the preparation of cell suspensions and the artificial nature of the drug exposure phase of the assays have not been completely overcome and the plating efficiencies remain low in most systems. Work with model systems such as human tumour xenografts tends to support the usefulness of the assays but also highlights some difficulties. Clinical studies of chemosensitivity testing are in progress and initial results are encouraging but inconclusive.

Antineoplastic Agents↗
PubMed1980

Mediastinal seminomas.

A series of malignant seminomas of the mediastinum is presented and compared with previously reported series. The difficulty of conclusively excluding occult primary gonadal disease is noted. Primary mediastinal seminomas are associated with a better prognosis than teratomas of this site, mainly because of their radiosensitivity. A case report of a patient with mediastinal seminoma and two congenital abnormalities (ventricular septal defect and congenital absence of a thoracic hemivertebra) is presented and its relationship to the possible origin of these tumors discussed.

Adolescent↗
PubMed1980

Father-son testicular malignancy. Does genetic anticipation occur?

Testicular malignancy in a father and son is reported. The father had sequential bilateral seminomas while the son had embryonal cell carcinoma and seminoma. Reported cases of father-son testicular malignancy are reviewed and a predominance of seminomas in the fathers is apparent while the sons' tumors are highly malignant teratomas, choriocarcinomas and embryonal cell carcinomas. The possibility of genetic anticipation in father-son testicular malignancy is discussed.

Adult↗
PubMed1980

The interpretation of marker protein assays: a critical appraisal in clinical studies and a xenograft model.

Although useful in the management of malignant testicular tumours, alphafoetoprotein and human chromonic gonadotrophin are not perfect parameters of tumour bulk. In a series of 65 patients with marker-positive advanced disease, 23 showed the phenomenon of discordance of markers or dissociation from tumour response. Transplantable human malignant teratoma xenografts were established in immune-suppressed mice as models of the human disease. In the model system, it was demonstrated that tumour AFP concentration was reflected by AFP titres in the blood, but that tumour AFP (or blood AFP) did not correlate well with tumour size. One xenograft line illustrated the evolution of marker-negative tumour cells from a patient who was initially AFP-positive.

Animals↗
PubMedDate not supplied

Experimental models of histogenesis and tumor cell heterogeneity in bladder cancer.

The histogenetic relationships between the subtypes of bladder cancer are not known. Each common pattern (transitional cell carcinoma, adenocarcinoma, and squamous carcinoma) can exist independently, although they may coexist in primary or metastatic bladder cancers, and tumors that are predominantly composed of transitional cell carcinoma may have regions of squamous or glandular differentiation. Morphologically identical tumors exhibit marked variation in their natural history and response to treatment. To study these aspects of the biology of human bladder cancer, a series of cell lines have been established and characterized as xenografts and in tissue culture. These studies have shown a likely common origin for transitional cell carcinoma, adenocarcinoma, and squamous carcinoma of the bladder. Morphologically similar xenografts and cell lines in vitro have shown a broad range of functional heterogeneity, including ultrastructure, tumor marker production, ploidy, cell surface characteristics, and response to chemotherapy. These are useful models of heterogeneity of response to treatment with established and new cytotoxic agents.

Animals↗
PubMedDate not supplied

Progress in the management of metastatic bladder cancer.

BACKGROUND: Inadequate survival results from single agents in the management of advanced bladder cancer have prompted several trials involving multidrug combinations to increase response rates and survival. METHODS: Since the development of the MVAC regimen (methotrexate, vinblastine, doxorubicin, and cisplatin) and the CMV regimen (cisplatin, methotrexate, and vinblastine), other regimens have been tested. We evaluate results from regimens that include cisplatin combined with gemcitabine, paclitaxel, or docetaxel, and paclitaxel combined with gemcitabine or carboplatin. RESULTS: Objective results observed with various new combinations are promising. Objective response (OR) rates of 41%, 59%, and 71% are reported with a regimen of gemcitabine plus cisplatin. Paclitaxel plus cisplatin produced OR rates of 65% and 72%. CONCLUSIONS: The use of combination cytotoxic chemotherapy regimens in treating patients with metastatic bladder cancer has nearly doubled median survival to 12 months, with a 3-year survival of approximately 20% to 25%. Caution must be exercised in using some of the newer regimens as survival may be inferior compared with the MVAC regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Management of bladder cancer.

Bladder cancer is a paradigm of malignancy, representing the spectrum from localized to metastatic disease, and manifesting varied histologic types, including transitional cell carcinoma, squamous cell carcinoma, and adenocarcinoma. Preclinical and clinical data suggest that a common stem cell of origin gives rise to the different histologic types and that these patterns are of clonal origin. Localized bladder cancer is managed optimally by transurethral resection, with or without adjuvant intravesical chemotherapy. Invasive cancer or relapsed superficial disease may require more radical surgery or radical radiotherapy. In recent years, the evolution of techniques of continent urinary diversion or of bladder replacement has revolutionized the management of invasive disease. However, the 5-year survival for invasive bladder cancer is still approximately 50%, and innovative strategies have been developed, combining definitive local treatment and systemic chemotherapy, in an attempt to improve survival. For patients with metastatic disease, the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (the MVAC regimen) has achieved response rates as high as 70% but with a median survival of only 12 months. Until cure rates are improved, one of the hallmarks of effective management of metastatic disease will remain the provision of thorough and well-structured palliative treatment programs. Recently, the introduction of new agents (such as paclitaxel, gallium, ifosfamide, and gemcitabine) has led to promising response rates, and further clinical trials of these agents alone and in combination are in progress. In addition, an improved understanding of the mechanisms of resistance to treatment, including the implications of the expression of p-glycoprotein, p53 proteins, and other biochemical predictors of outcome, and of strategies to overcome such resistance, may lead to more effective management of advanced disease. Furthermore, real progress will be made only through the application of well-designed clinical trials to test the efficacy and toxicity of the new strategies of treatment.

Administration, Intravesical↗