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Biomedical subjects

L Helson

Publications and source records attributed to L Helson.

At least 91 records · Page 5Linked to original sources

Effects of murine tumor necrosis factor on heterotransplanted human tumors.

A partially purified glycoprotein fraction (the G-200 II fraction) obtained from sera of CD-1 mice sensitized with Corynebacterium parvum and treated with endotoxin was designated as tumor necrosis factor (TNF). Human melanoma cells exposed to this factor in vitro had decreased tumorigenicity when injected into nude mice. Human melanoma, embryonal adenocarcinoma of the testis and colon carcinoma heterotransplanted in nude mice exhibited regressions in size following intraperitoneal injections of TNF. The responses were related to dose and duration of exposure.

Adenocarcinoma↗

Circulating immune complexes in sera of children with neuroblastoma: correlation with stage of disease.

The presence of circulating immune complexes (ICS) in freshly drawn sera of 67 children with neuroblastoma was studied by the Raji cell radioimmunoassay of Theofilopoulos et al. (J. Clin. Invest. 57: 169--182), with particular emphasis on the correlation of levels of ICS with stage of disease and changes attributable to treatment. There was a close correlation between amount of complexes and stage of disease and treatment. Levels of ICS increased as the stage of the disease advanced, and were significantly higher (P less than 0.005) in stage IV than in all other stages combined. When patients with stage IV disease were subdivided into "before," "during," and "after" treatment groups, there was a significant decrease in ICS levels as treatment progressed. Studies of complement and complement components did not give such a clear relationship. A significant decrease of hemolytic C1 values was found in patients with "active disease" compared to normal age-matched controls. Some high C3 levels, determined immunochemically, were associated with low hemolytic levels of C3, which were attributed to C3 cleavage detected by immunoelectrophoresis. Based on our survival data, ICS, which were significantly different in 20 patients now decreased when compared to those of other patients, are very valuable in the prognosis of neuroblastoma.

Antigen-Antibody Complex↗

cis-Platinum ototoxicity.

The incidence and spectrum of ototoxicity secondary to cis-platinum administration in 104 cancer patients ranging in age from 8-78 years were determined. Pure tone thresholds from 500 to 8000 Hz were evaluated prior to and following cis-platinum administration. The most sensitive frequencies were 6000 and 8000 Hz. Younger patients had lower threshold increases per administered dose than older patients. High drug dosages caused larger threshold elevations and extended to lower frequencies. Prehydration and mannitol infusion did not alter ototoxicity. Audiographic evaluation appears necessary for monitoring the treatment of cancer patients with cis-platinum.

Adolescent↗

High dose cis-platinum diammine dichloride: amelioration of renal toxicity by mannitol diuresis.

A clinical trial was undertaken to improve the therapeutic index of cis-platinum diammine dichloride with a concomitantly administered mannitol induced diuresis. Sixty patients, heavily pretreated, were entered; fifty-one are evaluable. The technique of concomitant osmotic diuresis and CPDD administration is described in detail. Doses ranged from 3 mg/kg to 5 mg/kg. At 5 mg/kg, dose-limiting renal, marrow and ototoxicity were seen, and resulted in one drug death. Marrow toxicity was moderate. Renal toxicity was limited to transient elevations in serum creatinine levels, except in some patients who had renal impairment prior to CPDD treatment. These patients had moderate renal toxicity. Serial treatments as frequently as once every 3 weeks were used to maintain responses. Serial high dose CPDD produced only mild renal dysfunction. Ototoxicity, usually subclinical, was quantitated audiometrically, and found to be dose related, but not clinically prohibitive at 4 mg/kg or less. The overall response rate (PR/MR) was 42%. Clinically significant responses in epidermoid carcinoma of the head and neck, adenocarcinoma of the ovary, and germ cell tumors of the testis were seen. All six responding patients with germ cell tumor of the testis, had been resistant to low dose (1mg/kg) CPDD. Two responding patients with ovarian adenocarcinoma had been resistant to alkylating agents.

Adenocarcinoma↗

The clinical and physiological implications of hepatoma B12-binding proteins.

A serum B12-binding protein with increased sialic acid content (termed hepatoma B12-binding protein) that causes elevations of serum B12 and unsaturated B12-binding capacity has been found in some patients with hepatocellular carcinoma (hepatoma). We now report another patient with hepatoma with initial near-normal, unsaturated B12-binding capacity that increased 400-fold as the disease progressed and then fell 50% with response to chemotherapy. A perfusate of the tumor in the liver had 5 times more B12-binding protein than did the serum and was immunologically the same as the serum hepatoma B12-binding protein isolated from previous cases. A cell line derived from hepatoma produced significant amounts of B12-binding protein similar to hepatoma B12-binding protein, whereas cell lines from normal liver and other neoplasia did not. The hepatoma sera, perfusate, and media from the hepatoma cell line contained elevated sialyltransferase activity. These data suggest that some hepatomas produce increased hypersialylated B12-binding protein that is cleared slowly from the plasma and accumulates there as hepatoma B12-binding protein.

Adolescent↗

Lymphocyte transformation in children with neuroblastoma.

Using a simple fingerstick-whole blood technique, we demonstrated that patients with disseminated neuroblastoma have diminished lymphocyte responses to phytohemagglutinin (PHA) and that their sensitivity to antilymphocyte serum inhibition of PHA responses was increased over that of tumor-free controls. These altered immunologic reactivities led us to question the chronologic sequence between the occurrence of the tumor and the lymphocyte defect. Tumor-bearing patients had serum substances that exerted an inhibitory effect on the transformation responses of lymphocytes from unrelated normal individuals; these substances may be present in sera for long periods after the tumor is eliminated.

Antilymphocyte Serum↗

Reactions to dinitrochlorobenzene in patients with neuroblastoma and survival.

To determine the relationship of cell-mediated immunity (CMI) to survival, I studied 67 children with the histologically confirmed diagnosis of neuroblastoma. CMI was measured by testing the ability of patients to develop sensitization to dinitrochlorobenzene (DNCB) and to respond to challenge. Reactions at the challenge sites were considered positive only when induration and swelling were present. Ninety percent of the patients with localized neuroblastoma and 27% of those with disseminated neuroblastoma were DNCB reactive. This suggested that patients with DNCB-positive reactions have a better chance of survival than those who are DNCB negative. Some patients with disseminated disease were evaluated in longitudinal studies, and alterations in reactivity did occur with changes in disease status and/or chemotherapy. The suggestion was made that this test systme is potentially useful in estimating survival in children with neuroblastoma.

Child↗

Carcinoembryonic antigen in children with neuroblastoma.

Plasma carcinoembryonic antigen (CEA) was assayed with a radioimmune procedure in 27 healthy control children. The upper limit of plasma CEA (mean +2 SD) was derived from healthy controls and was 3.35 ng/ml. This value was compared with those obtained from 15 children with active neuroblastoma, 7 with active embryonal rhabdomyosarcoma, 16 with treated neuroblastoma and without evidence of disease, 14 disease-free patients with embryonal rhabdomyosarcoma, and 17 patients still on therapy. The neuroblastoma and embryonal rhabdomyosarcoma patients with active disease had higher CEA values than did the successfully treated neuroblastoma and embryonal rhabdomyosarcoma patients. CEA plasma values greater than 3.35 ng/ml were found in 35% and 24% of patiens with neuroblastoma and embryonal rhabdomyosarcoma, respectively.

Carcinoembryonic Antigen↗

A rationale for the treatment of metastatic neuroblastoma.

In developing a chemotherapeutic program for children with disseminated neuroblastoma, we established three human neuroblastoma lines in cell culture to study the effects of dibutyryl cyclic AMP, papaverine, 5-trifluoromethyl-2'-deoxyuridine, and cyclophosphamide on cell growth, biochemical behavior, and morphology. Based upon our studies, a clinical treatment program was designed. We have treated 15 patients with disseminated neuroblastoma and have established the optimum dose range and sequence of these drugs. Early results were promising; plans for continuation of clinical and experimental studies were discussed.

Antineoplastic Agents↗