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Biomedical subjects

L Helson

Publications and source records attributed to L Helson.

At least 73 records · Page 4Linked to original sources

Ocular tumors react with anti-neuroblastoma monoclonal antibodies.

The reactivities of mouse monoclonal antibodies directed against human neuroblastoma and peripheral melanoma associated antigens, with human retinoblastoma and choroidal melanoma cell lines were tested. Segregation of antigenic determinants according to each tumor class and cell line were observed. Three retinoblastoma cell lines and one fresh tumor explant showed determinants detected by two human neuroblastoma antisera, while the choroidal melanoma showed one determinant present on a peripheral melanoma but not neuroblastomas nor retinoblastomas, suggesting certain potential distinctive tumor related determinants.

Animals↗

Malignant schwannoma--clinical characteristics, survival, and response to therapy.

One hundred and sixty-five cases of malignant schwannoma were reviewed. Sixty-five (40%) of the patients had evidence of disseminated neurofibromatosis. Patients with neurofibromatosis were younger, had malignant schwannomas that were centrally rather than peripherally located, and had a shorter five-year survival (23%) than patients with solitary malignant schwannomas (47%). Histologically, tumors developing in patients with neurofibromatosis had a collagenous appearance, while tumors in patients without neurofibromatosis were undifferentiated and highly cellular. The clinical course of both groups of patients tended to be that of multiple local recurrences, although local recurrence had a more ominous prognosis in patients with neurofibromatosis. Chemotherapy responses in all these patients were extremely poor; however, the results of adjuvant therapy after surgery appeared encouraging. Fourteen patients (8.5%) had a malignant schwannoma in an area of prior radiation therapy and died of disease a median of 14 months after diagnosis. Malignant schwannoma should be considered in the differential diagnosis of tumors developing in areas previously treated with radiation.

Adolescent↗

Growth pattern and differentiation of human soft tissue sarcomas in nude mice.

Tumor suspensions prepared from 62 human soft tissue sarcomas were injected into the peritoneal cavity and subcutis of 124 nude mice. The sarcomas included were ten malignant fibrous histiocytomas, 15 fibrosarcomas, six tendosynovial sarcomas, five liposarcomas, nine myosarcomas, six angiosarcomas, six malignant schwannomas, and five miscellaneous sarcomas. Sixty-two percent of the sarcomas showed progressive growth in nude mice either subcutaneously (46%), intraperitoneally (14%), or at both sites (40%). Fifty-one percent of the primary sarcomas, 71% of the recurrent tumors, and 78% of the sarcomas that were metastatic grew in the animals. Sarcomas that were grafted into the subcutis appeared as solitary nodules and showed a more accelerated growth as well as better differentiation than those that were injected into the peritoneal cavity. The intraperitoneal tumors were multifocal and dedifferentiated growths. It appears that simultaneous subcutaneous and intraperitoneal grafting of human sarcomas into nude mice offers a model to study the histogenesis and morphologic variations of soft tissue sarcomas.

Animals↗

Malignant fibrous histiocytoma of the temporal bone with intracranial extension.

An 18-year-old male presented with a right temporal bone tumour; histology revealed malignant fibrous histiocytoma. Following surgical excision and radiation the tumour recurred. The patient was treated with Vindesine (desacetyl vinblastine amide sulphate) with marked response. Malignant fibrous histiocytomas of the temporal bone are extremely rare; this report suggests that the occasional dramatic response may be obtained by combined modality treatment.

Adolescent↗

Human hematopoietic tumors in nude mice.

Despite the difficulty in establishing human hematopoietic tumors in nude mice, four human lymphomas were successfully heterotransplanted and passaged serially in our laboratory. Additional immunosuppression with chemotherapy, whole-body radiation or splenectomy was not required for establishment of these tumors. All four of these tumors were of the non-Hodgkin's lymphoma type. In each case the tumors in the nude mice were histologically identical to the biopsy specimens from the patient in whom they were derived. Attempts to transplant tumor from 17 patients with Hodgkin's disease or 4 patients with immunoblastic lymphadenopathy were unsuccessful. Tumors from 2 patients with chronic myelogenous leukemia and 1 with hairy cell leukemia could be grown in nude mice conditioned with whole-body radiation or cytosine arabinoside, but these tumors could not be passaged to other nude mice. Cell surface markers were determined on the four serially passaged lymphomas. These surface markers were similar to the markers on the original tumors, even after long periods of mouse-to-mouse passage. In 1 patient with fevers, night sweats and mediastinal mass in whom a diagnosis had not been made after several biopsies, examination of tumor tissue that had been transplanted from the patient to the nude mouse clearly established the diagnosis of lymphoma.

Animals↗

High-dose cyclophosphamide chemotherapy for recurrent CNS tumors in children.

A Phase Ii chemotherapy trial was conducted in 18 children with recurrent brain tumors, using high doses (80 mg/kg or greater) of intravenous cyclophosphamide cyclophosphamide. All eight patients with medulloblastomas responded; two patients with systemic metastases had complete responses and six others had partial responses. In seven patients with gliomas, there were one complete and four partial responses. In a third group, all three patients with intracranial germ-cell tumors had partial responses. The overall response rate was, therefore, 89% (16 of 18 patients), and the mean duration of response was 7 months (range 2 to 24 or more months). The hematological toxicity was considerable, with two deaths possibly related to chemotherapy: one patient, a recipient of unirradiated packed cells, died from a graft versus host reaction, and the other died from an intracranial hemorrhage during a thrombocytopenic episode. Four patients had prior chemotherapy, and 10 patients had prior neuraxis radiation therapy. These patients tolerated aggressive chemotherapy reasonably well. The results are sufficiently encouraging to justify a Phase III trial in patients with newly diagnosed disease.

Adolescent↗

Flow cytometric analysis of bone marrow in a patient with resistant neuroblastoma.

Using flow cytometric analysis, we followed changes in a patient's bone marrow which was infiltrated with cells resistant to chemotherapy. Samples taken prior to, during, and after treatment with dianhydrogalactitol (2 days), cytosine arabinoside and hydroxyurea (2 days), and Adriamycin (2 days) contained an aneuploid population of cells which exhibited changes in ploidy, viability, and distribution in cell cycle compartment. The restricted changes in cell ploidy and viability of tumor cells encountered as well as limited increases in S phase on day 4 and G2 phase on day 6 with a rebound on day 9 of G1 phase cells suggest the tumor to be sensitive to dianhydrogalactitol but not to the other agents used.

Antineoplastic Agents↗

DOPA metabolism in neuroblastoma.

Blood plasma samples from 60 neuroblastoma patients prior to, during, and following treatment were studied for their content of circulating DOPA using a radioenzymatic assay. Normal values were established from children who were tumor-free or had other nonneurogenic tumors. The highest plasma DOPA concentration in tumor-free or nonneuroblastoma controls was 5.3 ng/ml with a mean of 2.15 ng/ml. Most neuroblastoma patients (28/31) with active disease had DOPA values above this level. Only one out of 30 "successfully" treated patients without evidence of disease was encountered with an abnormally high level. In treated patients, elevated values forewarned of impending clinical recurrence or persistent tumor. Cerebrospinal fluid DOPA levels in one patient with cerebral neuroblastoma were extraordinarily high and suggests that this assay may prove useful to distinguish neuroblastoma from other central neuroectodermal or metastatic tumors. Plasma DOPA appears to be a reliable predictive and diagnostic test for neuroblastoma.

Adolescent↗

Statistical methods for measuring and comparing treatment efficacies: applications to nude mice experimentation.

A method is proposed for measuring and comparing the growth over time of a sample of tumors subjected to a number of different therapies. The procedure, which is illustrated by means of an example, does not require explicit parametric modelling of the growth curve itself and is particularly useful when the comparison of treatment efficacies is of chief interest. In addition, an ad hoc approach to the estimation of required sample sizes is delineated.

Animals↗

Evaluation of 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA, NSC 249992) on human tumors in nude mice.

The nude mouse human tumor-bearing system is a useful model for studying the efficacy of new drugs against human tumors. A panel of six selected human tumor heterotransplants was used to assess the activity of m-AMSA. No effect was seen against malignant schwannoma, malignant lymphoma, liposarcoma, neuroblastoma, or malignant melanoma. A testicular carcinoma appeared to respond to m-AMSA: however, statistical evaluation demonstrated that this was not significant. No evidence was found to support the use of m-AMSA as a sensitizing agent for radiation.

Aminoacridines↗

Effect of desacetyl vinblastine amide (DVA) against human sarcomas heterotransplanted in nude mice.

The efficacy of desacetyl vinblastine amide (DVA) was tested against five human sarcomas heterotransplanted into nude mice. Marked antitumor effect was found against a lipoblastic liposarcoma, including complete regressions of tumor in some animals. A lesser, though statistically significant, antitumor effect was observed with a malignant schwannoma. No antitumor activity was seen against a leiomyosarcoma, epithelioid sarcoma, or Ewing's sarcoma. We conclude that DVA deserves study in the treatment of human patients with malignant sarcomas.

Animals↗

Dianhydrogalactitol and neural tumors: an in vitro, in vivo preclinical evaluation.

The effects of dianhydrogalactitol on human neuroblastomas in vitro and in vivo as heterotransplants in nude mice were determined. Four neuroblastoma lines and three primitive neuroectodermal tumor lines were found, in vitro, to have different sensitivities to the drug. The most sensitive in in vitro assays was the neuroblastoma line SK-N-Mc. Tumors from patients resistant to cyclophosphamide were sensitive to dianhydrogalactitol in vitro and in nude mice. The lack of increased cytotoxicity in vitro with concentrations greater than 12 micrograms/ml and the lowered degree of weight loss in mice treated with 6 mg/kg/day x 5 consecutive days compared to 15 mg/kg/day x 2 days (either in sequence or with a 3-day interval) suggest that clinical trials with 5-day courses or constant infusions may be more effective than intermittent pulsed doses.

Animals↗

Tumour promoter alone induces neoplastic transformation of fibroblasts from humans genetically predisposed to cancer.

Neoplastic transformation is a multi-phase process apparently caused by carcinogens and subject to the influence of promoters. The naturally occurring phorbol esters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA) are potent tumour promoting agents. Through the use of phorbol esters a two-stage process of malignant transformation has been demonstrated in the mouse skin model and, more recently, in cell culture systems. Studies in vitro suggest that TPA reversibly inhibits terminal differentiation in most, but not all model systems, and that its function is presumably to increase the probability of expression of the malignant phenotype. We have studied the effects of TPA on mutant human fibroblast cell strains derived from individuals with hereditary adenomatosis of the colon and rectum (ACR), an autosomal dominant trait. We have previously demonstrated in these fibroblasts abnormal phenotypic expressions which often appear in transformed cells. In these studies, we have assumed that the ACR cell exists in an "initiated state" due to a dominant mutation and that expression of the malignant state might only require treatment with a promoting agent. This single experimental protocol provided a novel system for the study of cancer promotion in vitro. We have now demonstrated, for the first time, the growth in vivo of human mutant cells exposed to TPA alone.

Animals↗

Metastasizing extradural ependymoma of the sacrococcygeal region: case report and review of literature.

A case is discussed in which the patient presented with a primary extradural sacrococcygeal ependymoma and synchronous pulmonary metastasis. The clinical course has been characterized by recurrent pulmonary metastases. Management has consisted of repeated surgical resections of the pulmonary metastases and the tumor at the primary site; and the use of a wide spectrum of chemotherapeutic agents. Transplantation of this tumor into nude mice initially resulted in rapid growth but there was spontaneous regression in the second transplants. A general discussion of the management of such lesions is presented, and the literature pertaining to this tumor is discussed.

Adult↗

Phytohemagglutinin effects on cultured human neural crest tumors.

Two human melanoma lines, RPMI-7931 and HS-294, respond to mitogenic stimulation by PHA. A dose-response curve for these lines can be demonstrated with maximal stimulation at 16 and 32 micrograms per ml and inhibition at 75 to 250 micrograms per ml PHA. The mitogenic effects of PHA were inhibited by N-acetyl-D-galactosamine. Neuroblastoma cells also exhibits a similar but less important dose-response to PHA. These data indicate that human melanomas and neuroblastomas may have PHA receptors or mechanisms for mitogenic stimulation which are analogous to those observed with normal lymphocytes.

Acetylgalactosamine↗