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Biomedical subjects

R R Weichselbaum

Publications and source records attributed to R R Weichselbaum.

At least 325 records · Page 18Linked to original sources

Proliferation kinetics of a human breast cancer line in vitro following treatment with 17beta-estradiol and 1-beta-D-arabinofuranosylcytosine.

The effect of 17beta-estradiol on an estrogen receptor-positive human breast cancer cell line (MCF-7) was studied. Low concentrations (10(-9) M) of 17beta-estradiol enhanced the rate of cell proliferation; the overall cell cycle time was shortened; and the proportion of cells in the S phase increased. Higher concentrations (10(-7) M) suppressed proliferation and slightly decreased the proportion of the cells in DNA synthesis. When combined with 1-beta-D-arabinofuranosylcytosine, an S-phase-specific chemotherapeutic agent, 10(-9) M 17beta-estradiol enhanced cell killing. This enhancement was not observed with 10(-7) M 17beta-estradiol. Kinetic changes caused by hormones have profound implications in clinical therapy, since the efficacy of cycle active agents may be altered.

Breast Neoplasms↗

Preliminary results of aggressive multimodality therapy for metastatic osteosarcoma.

Ten patients with metastatic osteosarcoma were treated at the Joint Center for Radiation Therapy, the Sidney Farber Cancer Institute, and the Children's Hospital Medical Center from 1973 to 1976. Patients were treated with an aggressive multimodality approach with included surgery, chemotherapy, and radiation therapy. Three of 10 patients are alive with no evidence of disease, five are alive, with disease, and two are dead of disease. The median survival is 12+ months. Local control data for radiation combined with high dose methotrexate in metastatic osteosarcoma is shown.

Adolescent↗

Characterization and radiobiologic parameters of medulloblastoma in vitro.

Cultured cells from human medulloblastomas were demonstrated to have distinctive features and a "glial" potential from the morphological and ultrastructural parameters. The in vitro radiobiological survival curve parameters of cultured human medulloblastoma and non-malignant skin fibroblasts obtained under the same conditions of exponential growth were similar. In vitro conditions may underestimate the shoulder region of the survival curve. Since the shoulder region is the most important in clinical fractionated radiotherapy, multiple dose experiments might be useful in examining this portion of the survival curve more closely.

Brain Neoplasms↗

The role of postoperative irradiation in carcinoma of the breast.

Chest wall and regional nodal recurrences, and survival following postmastectomy radiation therapy, were analyzed in 352 patients. Patients with T1 and T2 central and medial breast lesions, negative axillary nodal findings, and no evidence of skin or chest wall extension received irradiation to the peripheral lymphatics alone. There were no chest wall recurrences among these patients. The remainder of the patients, including those with axillary nodal involvement, regardless of the site of the primary breast lesion received irradiation by a three-field technique directed to both chest wall and regional nodes. The chest wall recurrence rate was 1.9% when axillary nodes were negative for metastatic disease, 1.3% when the axillary nodes showed less than 50% positivity, and 14.2% when axillary nodes showed greater than 50% involvement. The overall chest wall recurrence rate was 5.1%. A possible mechanism of chest wall recurrence is discussed. Cumulative 5-year survival for stage I is 76%, for stage II, 79%, and for stage III, 57%. If chemotherapy proves to be effective in controlling distant microscopic disease local control may become an equally critical issue in long-term survival of patients with breast carcinoma.

Axilla↗

In vitro radiosensitivity of human dipliod fibroblasts derived from patients with unusual clinical responses to radiation.

Four diploid cell strains were derived from skin biopsies from patients exhibiting unusually sensitive or resistant clinical responses to ionizing radiation during radiotherapy. The in vitro x-ray survival curve parameters for these strains were determined and compared with those of two normal human skin fibroblast strains. No systematic correlation could be demonstrated between these single dose survival parameters in vitro, and the clinical radiation response in vivo of the normal tissue or the tumor.

Aged↗

Inherent cellular radiosensitivity of human tumors of varying clinical curability.

It is well known that radiation therapy can be successfully used to cure or control some types of human tumors, while consistently failing in others. This has been ascribed to several factors including differences in the intrinsic sensitivity of the tumor cells and in their ability to recover from radiation damage. In this study, human tumor cells from an osteogenic sarcoma, a glioblastoma, and two medulloblastomas, as well as cells from human skin, were established in tissue culture, and the in vitrox x-ray survival and DNA repair parameters determined. No significant differences in either clonogenic survival or DNA strand rejoining ability could be detected among these human tumors or skin cells, despite the wide variability in their radiocurability in vivo. In addition, skin cell strains derived from patients exhibiting markedly sensitive or resistant skin reactions during fractionated radiotherapy showed no differences in survival characteristics from normal controls. It is therefore suggested that the wide range of radiocurabilities seen among various human tumors cannot be explained on the basis of inherent cellular factors responsible for the survival of tumor cells after x-irradiation.

Adolescent↗

Genetically engineered HSV in the treatment of glioma: a review.

Central nervous system malignancies, particularly glioblastoma multiforme, pose significant problems for the development of novel therapeutics. In the absence of advances with standard surgical and chemotherapeutic approaches, the utilisation of genetically engineered viruses, both as direct oncolytic agents as well as for the delivery of foreign proteins, represents a significant advance in the experimental approach to management of patients with these incurable tumours. Among other viruses, HSV offers an opportunity to directly influence the replication of tumour cells within the central nervous system. Because of its propensity to replicate in neuronal tissue as well as its large coding capacity, it provides an experimental model for the development of novel therapeutics. The status of these experimental approaches will be summarised in this review.

Animals↗

Radioresistant tumor cell lines derived from head and neck radiation failures.

We studied the in vitro radiobiological parameters of 16 human head and neck squamous cell carcinoma tumor cell lines cultured from patients who suffered local failure after a curative course of radiotherapy. The radiobiological parameters determined included D0, n, and D. When compared with in vitro radiobiological parameters of tumor cells cultured from head and neck cancer patients prior to radiotherapy, human sarcoma cell lines, and normal human diploid fibroblasts studied in our laboratory (as well as other human tumor cell lines reported in the literature), tumor cells derived from radiotherapy failures on average are resistant to the cytotoxic effects of ionizing radiation.

Carcinoma, Squamous Cell↗

Epidermal growth factor receptor gene amplification and expression in head and neck cancer cell lines.

We studied epidermal growth factor receptor (EGFR) gene amplification and expression in 11 early passage human head and neck carcinoma cell lines. Three cell lines demonstrated EGFR gene amplification and 10 lines showed an increase in EGFR mRNA when compared with normal keratinocytes, placenta, and a human skin carcinoma cell line. The effects of EGF on growth in 6 head and neck carcinoma cell lines was also studied. Growth inhibition at a concentration of 20 ng/mL was observed in one cell line but had no effect on growth in 5 cell lines. An increase in EGFR may be important in the etiology of, or progression of, head and neck carcinoma although the mechanisms need to be elucidated by further study.

Carcinoma, Squamous Cell↗

Radiation or surgery for chemodectoma of the temporal bone: a review of local control and complications.

For a presentation to the American College of Surgeons in November 1988, we reviewed the literature concerning primary management of glomus tympanicum and jugulare tumors. From the published series, we examined the local control and treatment-related morbidity for three therapeutic approaches: surgery alone, radiation before or after surgery, and radiation alone. The local control rates were similar, 86%, 90%, and 93%, respectively. Among the surgical series reporting complications, new cranial nerve deficits were common, especially with advanced lesions. Serious sequelae from radiation therapy were rare (2% to 3%). We feel radiation therapy should be considered as primary treatment for glomus jugulare.

Combined Modality Therapy↗

Investigation of the cytotoxic effects of DNA damaging agents on neurofibromatosis cells.

Cells cultured from individuals with neurofibromatosis, a genetic syndrome associated with a predisposition to malignancy, were studied. We examined survival as measured by colony formation in skin fibroblasts from 5 patients with neurofibromatosis after exposure to X-rays, ultraviolet light and an alkylating agent. We did not observe mutagen hypersensitivity in neurofibromatosis cells as compared to normal controls.

Adolescent↗

Radiation-inducible gene therapy.

The radiation-inducible chimeric genetic construct Egr-TNF alpha introduced into human xenografts produces cytotoxicity of infected tumor cells resulting in tumor growth inhibition. The interaction between Egr-TNF and radiation is selectively cytotoxic for the tumor microvasculature resulting in vascular thrombosis and tumor necrosis. Gene therapy combined with radiation therapy offers great potential for the treatment of localized human cancers.

Adenoviridae↗