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Biomedical subjects

R R Weichselbaum

Publications and source records attributed to R R Weichselbaum.

At least 271 records · Page 15Linked to original sources
PubMed1984

Repair of fractionated radiation in plateau phase cultures of human tumor cells and human multicellular tumor spheroids.

We have measured potentially lethal damage repair (PLDR) after fractionated radiation, delivered at 24-h intervals in density-inhibited plateau phase cultures of four human tumor cell lines derived from tumors of differing radiocurability (two melanoma and two breast). The repair of potentially lethal damage conferred significant radioresistance on the human melanoma cells but not on the breast carcinoma cells. We examined the effects of fractionated radiation on human tumor cells adapted to become multicellular tumor spheroids (MTS). MTS derived from a human neuroblastoma were "cured" by a total fractionated radiation dose about 50% of that required for MTS derived from a human melanoma.

Breast Neoplasms↗
PubMed1984

Protease inhibitor antipain reduces nuclear binding of estrogen-receptor complex in MCF-7 breast tumor cells.

We have initiated studies to ascertain the effects of protease inhibitors on specific steroid hormonal-related events as they occur in cultured cells, in an attempt to identify hormone-related processes perturbed by these inhibitors. We report here that the presence of antipain during incubation of cultured MCF-7 breast tumor cells with estradiol-containing medium considerably reduces the extent of nuclear binding of the estradiol-receptor complex.

Antipain↗
PubMed1984

Incidence of hypothyroidism following multimodality treatment for advanced squamous cell cancer of the head and neck.

The incidence of chemical hypothyroidism, as manifested by elevated thyroid stimulating hormone (TSH) levels, has been estimated to be as high as 25% after radiation therapy and 45% after radiation therapy and surgery to the neck for treatment of nodal metastases from squamous carcinoma of the head and neck. We prospectively evaluated 43 previously untreated patients seen in the Dana Farber Cancer Institute Interdisciplinary Head and Neck Service who were treated with aggressive combination chemotherapy in addition to standard surgery and/or radiotherapy. All patients were serially monitored for serum TSH, serum T4, and clinical evidence of hypothyroidism. Following cis-platinum, bleomycin, and methotrexate chemotherapy and subsequent surgery and/or radiotherapy, decreased thyroid reserve appeared in 37% of patients at a median follow-up of 9 months. Thirty percent of patients receiving radiotherapy alone and 43% of patients receiving surgery and radiotherapy developed elevated TSH levels. Only one patient developed clinical symptoms. Other patients were asymptomatic despite persistently elevated TSH levels. Abnormalities appeared within the first 4 months after completion of all therapy and were slowly progressive. The addition of combination chemotherapy does not appear to increase the incidence or severity of thyroid dysfunction following radiation therapy and surgery to the neck. In view of the extended survival seen in patients treated with interdisciplinary regimens, we recommend that all patients receiving irradiation to the neck--particularly those patients having neck dissections or total laryngectomies--have routine thyroid function studies performed following the cessation of treatment.

Adolescent↗
PubMed1984

Response of human fibroblasts to low dose rate gamma irradiation.

Cells from 11 human strains, including fibroblasts from patients with the genetic diseases of ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Fanconi's anemia (FA), were exposed to gamma radiation at high (1.6-2.2 Gy/min) and at low (0.03-0.07 Gy/min) dose rates. Survival curves reveal an increase in the terminal slope (D0) when cells are irradiated at low dose rates compared to high dose rates. This was true for all cell lines tested, although the AT, FA, and XP cells are reported or postulated to have radiation repair deficiencies. From the response of these cells, it is apparent that radiation sensitivities differ; however, at low dose rate, all tested human cells are able to repair injury.

Ataxia Telangiectasia↗
PubMed1983

Radiobiologic research for head and neck cancer therapy. Therapeutic implications.

Hypoxic cell sensitizers, particle therapy, hyperthermia, and combinations of chemotherapy and radiotherapy have potential to increase the therapeutic ratio in future clinical radiotherapy treatment regimens. The biologic bases of these investigations are beginning to appear as avenues of clinical investigation.

Head and Neck Neoplasms↗
PubMed1983

Estrogen receptor-mediated cytotoxicity using iodine-125.

Auger effects from 125I decay are singularly damaging if localized in DNA as the thymidine analogue 125I-iododeoxyuridine (125IUdR). Recent experience with steroid sex hormones extends these observations by demonstrating cytotoxicity in sites other than the DNA backbone. We have compared the cytotoxicity in human MCF-7 breast cancer cells of 125IUdR, 125I-iodotamoxifen, a nonsteroidal antiestrogen that is translocated from the cytoplasm to the nucleus of receptor containing cells, and 125I-iodoantipyrine, a biological indicator of the body water space. Cytotoxicity is critically dependent upon subcellular localization.

Antipyrine↗
PubMed1983

Repair of potentially lethal X ray damage and possible applications to clinical radiotherapy.

The relationship of potentially lethal damage repair (PLDR) to clinical radiotherapy has not been studied in great detail. We have therefore examined the cellular and molecular basis of PLDR in bacterial, animal and human tumor systems and attempted to relate laboratory data to clinical fractionation schemes. We also have examined how the repair of potentially lethal damage may alter the therapeutic ratio by altering tumor radiocurability and normal tissue tolerance.

Animals↗
PubMed1983

In vitro radiosensitivity of fibroblasts derived from patients with retinoblastoma and abnormalities of chromosome 13.

In vitro x-ray survival experiments were performed on fibroblast strains derived from nine patients with sporatic unilateral retinoblastoma and 26 patients with hereditary retinoblastoma. Fibroblasts derived from patients with hereditary retinoblastoma were significantly more radiosensitive than those derived from patients with sporatic retinoblastoma. The authors hypothesize that the increased in vitro radiosensitivity observed in some hereditary retinoblastoma cell strains is a reflection of an, as yet, uncharacterized defect in DNA repair or post-irradiation DNA replication. X-ray sensitivity was also measured in 19 fibroblast strains derived from patients bearing deletions, trisomies, inversions, or translocations of all or part of chromosome 13. These results are compared with data from individuals trisomic for three other autosomes. The results suggest an association between abnormalities of chromosome 13 and the cytotoxic effects of x-irradiation.

Adult↗
PubMed1983

Small cell carcinomas of the larynx: results of combined modality treatments.

Four cases of primary small cell carcinoma of the larynx are described. Two patients presented with extensive metastatic disease and two with tumor limited to the larynx. All four cases responded (3PR, 1CR) to systemic combination chemotherapy. Long-term remission was achieved in one patient with limited disease who underwent chemotherapy with a complete response followed by definitive radiotherapy. Treatment results are compared with previously reported cases. The importance of early diagnosis through staging, and combined treatment in small cell carcinoma of the larynx is discussed.

Aged↗
PubMed1982

Chemotherapy of advanced salivary gland neoplasms.

Fourteen patients with advanced salivary gland malignancies were treated with combination chemotherapy. Five of 13 patients responded to cyclophosphamide and adriamycin and two patients in the responding groups underwent further potentially curable treatment, rendering them disease-free. Three patients with mucoepidermoid carcinoma failed to respond to this regimen, but two of three patients treated with a combination of cisplatinum, bleomycin and methotrexate responded. The potential role for chemotherapy in the treatment of salivary gland malignancies is discussed.

Adult↗
PubMed1982

Effects of serum-free defined medium on MCF-7 cell nuclear estrogen-receptor levels.

We have examined the effects of serum-free defined medium on filled and unfilled nuclear estrogen-receptor levels in the MCF-7 breast tumor cell line. Transfer of the cells to defined medium resulted in an initial increase in nuclear receptor levels, primarily of unfilled receptors, followed by a decrease of both receptor types to starting levels. Cells maintained in 10% fetal calf serum-containing medium, and sampled identically to those transferred to defined medium, exhibited a gradual but continuous increase in filled nuclear receptor levels accompanied by a decrease in unfilled receptors occurring toward the end of the 1-week experimental period. These results suggest that experiments requiring maximal depletion of endogenous MCF-7 nuclear estrogen will be optimized by repeated washing with estrogen-depleted medium, while limited washing with the same medium may be counter-productive.

Breast Neoplasms↗
PubMed1982

Toxicity of aggressive multimodality therapy including cisplatinum, bleomycin and methotrexate with radiation and/or surgery for advanced head and neck cancer.

A combined modality regimen employing induction chemotherapy with cisplatinum, bleomycin and methotrexate followed by surgery and/or radiation therapy was initiated in patients with advanced squamous cell carcinoma of the head and neck. In the first 23 patients treated with this program there was a 90% response rate to induction chemotherapy (9% CR and 81% PR). Toxicity associated with radiotherapy, but not surgery, was increased with 11 of 23 patients (48%) who experienced some toxicity during or immediately after radiotherapy. Mucositis was worse than expected and severe delayed mucositis was seen in 2 patients, one or whom required hospitalization. Late complications, possibly related to therapy included one myocardial infarction and one episode of hypoglycemia, both of which were fatal. One other patient voluntarily failed to take prescribed oral leucovorin, dying of unrescued methotrexate toxicity during adjuvant therapy, a questionable suicide. Further follow-up and analysis of failure will be necessary to determine if the value of a combined modality regimen in producing an increased cure rate and long term survival will out weight increased toxicity.

Adolescent↗
PubMed1982

Radiation therapy in the management of patients with mesothelioma.

The results of radiation therapy in the management of 27 patients with malignant mesothelioma were reviewed. Eight patients were treated with a curative intent combining attempted surgical excision of tumor (thoracic in 6 and peritoneal in 2), aggressive radiation therapy, and combination chemotherapy using an adriamycin-containing regimen. One patient achieved a 2-year disease-free interval followed by recurrence of tumor above the thoracic irradiation field. This patient was retreated with localized irradiation and is disease-free after 5 years of initial diagnosis. One patient has persistent abdominal disease at 18 months; the other 6 patients suffered local recurrence within 8-13 months of initiation of treatment. Radiation therapy was used in 19 other patients who received 29 courses for palliation of dyspnea, superior vena cava syndrome, dysphagia, or neurological symptoms of brain metastasis. A palliation index was used to determine the effectiveness of irradiation and revealed that relief of symptoms was complete or substantial in 5 treatment courses, moderately effective in 6 courses and inadequate in 18 treatment courses. Adequate palliation strongly correlated with a dose at or above 4,000 rad in 4 weeks. The management of patients with mesothelioma requires new and innovative approaches to increase the effectiveness of radiation therapy and minimize the significant potential combined toxicity of pulmonary irradiation and adriamycin.

Adult↗
PubMed1982

Cellular repair factors influencing radiocurability of human malignant tumours.

We have studied the repair of X-ray-induced, potentially lethal damage (PLD) in 9 human tumour lines derived from tumours of varying radiocurability. Cells derived from 3 tumours considered non-radiocurable (1 osteosarcoma, 2 melanoma) repaired significantly more X-ray PLD than cells from 3 tumours considered radiocurable (2 breast, 1 neuroblastoma). The remaining tumour lines were intermediate in their ability for repair, and included cells from another osteosarcoma, a hypernephroma and a glioblastoma. We conclude that the repair of X-ray PLD may be an important cellular determinant of clinical radiocurability.

Cell Line↗
PubMed1982

The differential response of human tumours to fractionated radiation may be due to a post-irradiation repair process.

We have measured post-irradiation recovery (potentially lethal damage repair) after fractionated radiation in plateau-phase cultures of two human tumour cell lines derived from tumours of different radiocurabilities (melanoma and breast). Although the radiation survival-curve parameters of these cell lines are similar, the repair of potentially lethal X-ray damage after fractionated X-ray treatment conferred significant radioresistance on the human melanoma cells but not the human breast carcinoma cells. We suggest that the repair of potentially lethal damage may correlate with clinical radiocurability.

Breast Neoplasms↗