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Biomedical subjects

R E Falk

Publications and source records attributed to R E Falk.

At least 109 records · Page 6Linked to original sources
PubMed1980

Adjuvant chemoimmunotherapy for gastric carcinoma.

Between July 1974 and August 1978, 78 patients were entered into a study to assess the effect of immune stimulation with bacille Calmette Guérin (BCG) on gastric carcinoma. Patients were selected in random fashion for the two treatment regimens; 41 received BCG and 5-fluorouracil and 37 received 5-fluorouracil alone. Initial results, after a mean follow-up of 72 weeks, are presented. Immunotherapy as used in this study did not affect survival. However, 5-fluorouracil given as an adjuvant to palliative resection did improve survival when compared with a matched control group in which patients received no additional treatment after palliative resection. Although this finding will have to be studied further by multicentre randomized prospective trials, our experience indicates that incurable gastric carcinoma should be managed more aggressively.

Adult↗
PubMed1980

Comparison of the antitumor effects of a synthetic biopolymer and standard adjuvants.

The synthetic biopolymer NED 137 is capable of stimulating an immune response to tumor antigen. This article compares the efficacy of NED 137 to bacille Calmette-Guerin, Corynebacterium parvum, pyran, levamisole, and Freund's complete adjuvant in a rat tumor model where adjuvant treatment is administered after excision of subcutaneous tumor implants. A single intraperitoneal injection of NED 137 at 30 mg/kg body weight prolonged survival beyond 60 days with no evidence of recurrent or metastatic disease, whereas with the other adjuvants, animals survived a mean of 30 to 40 days with 100% local recurrence and a 60% to 90% incidence of pulmonary metastases. Use of NED 137 resulted in a greater lysis of tumor cells compared to other adjuvants when assessed in an in vivo 51Cr release assay. A phase I clinical study of high-risk gastrointestinal cancer patients treated with NED 137 is reported at a median survival time of 23 weeks (103 patients). This group is compared to a historical control group from the same institution. No NED 137-related toxicity has been noted to date.

Adenocarcinoma↗
PubMed1980

Reversal of toxic and anoxic induced hepatic failure by syngeneic, allogeneic, and xenogeneic hepatocyte transplantation.

This report describes the efficacy of syngeneic hepatocyte transplantation in an anoxic model and of xenogeneic (rabbit and porcine) hepatocyte transplantation in a toxic model of fulminant hepatic failure in the rat. Lewis strain rats that received 4 X 10(7) hepatocytes intraperitoneally at 48 hours after hepatic artery ligation had a significantly improved survival rate (79%, n = 14) when compared with control animals (38%, n = 21, P less than 0.05). Xenogeneic hepatocytes (4 X 10(7) cells/rat) given intraperitoneally to D-galactosamine-poisoned Lewis rats at 48 hours after toxin administration were able to significantly improve survival rate as compared with controls (71% versus 14%, n = 14, P less than 0.01 for rabbit; and 75%, n = 14 versus 12.5%, n = 16, P less than 0.001 for porcine). Although an increase in in vivo cytotoxicity could be demonstrated after procine hepatocyte transplantation, no adverse clinical effects were observed. The methodology for the harvest and storage of large numbers of hepatocytes from a large animal liver has been developed, and it is now feasible to proceed to the clinical application of hepatocyte transplantation for human fulminant hepatic failure.

Animals↗
PubMed1979

Modulation of the immune response and control of tumour spread by a new synthetic compound.

A small molecular weight biofunctional polymer, NED 137, has been investigated for its anti-neoplastic effect. Through its effect on the immune system, particularly the induction of B cell differentiation to antibody producing cells, this synthetic compound can retard tumour growth and prevent the development of distant metastases. Reactivity to tumour developed following administration of the NED 137. No toxicity has been observed. The polymer NED 137 is now being tested in phase I and phase II clinical trials.

Adjuvants, Immunologic↗
PubMed1978

Effective antitumor immunity following elimination of suppressor T cell function.

An increased resistance to a transplantable tumor was demonstrable in Fischer (F344) strain rats after thymectomy and high doses of total body irradiation, followed by bone marrow cell repopulation if the animals were allowed to recover for 6 to 8 weeks. Further experiments demonstrated that removal of a subpopulation of T cells by lower doses of radiation plus thymectomy could (1) reduce recurrences after surgical excision, and (2) prolong survival of animals with established pulmonary metastases. It was found that thymectomy + 50 leads to 100 R total body irradiation could eliminate a T cell-mediated suppression of effective antitumor immunity. The removal of the suppressor cell component by lower doses of irradiation was dependent on pre-exposure of the animals to tumor antigen. These experiments indicate the specificity of suppressor T cells to tumor antigen and their exquisite sensitivity to radiation in appropriate circumstances.

Animals↗
PubMed1977

Combined treatment with BCG and chemotherapy for metastatic gastrointestinal cancer.

The survival of patients who have cancers of the gastrointestinal tract is poor even after surgical resection of all gross disease. In an initial consecutive series of patients with metastatic or recurrent cancers, an attempt to improve survival with combined nonspecific immunostimulation by the intraperitoneal administration of BCG followed by oral BCG cycled with chemotherapy was studied. The results suggested that a population of patients with gastric and colonic cancers showed improved survival with this treatment. A randomized trial of combined chemoimmunotherapy versus chemotherapy alone was begun on November 1, 1974, for all cancers of the stomach and pancreas and all colorectal cancers beyond stage C by Dukes' classification. The initial results with patients entered by December 31, 1975, and followed until March 1, 1976, are reported.

BCG Vaccine↗
PubMed1977

Conversion of incomplete antibodies to direct agglutinins by mild reduction: evidence for segmental flexibility within the Fc fragment of immunoglobulin G.

Reduction of interchain disulfide bonds converted some IgG incomplete antibodies to direct hemagglutinins. This conversion occurred whether antibody was free in solution or bound to the red-cell surface. Reduced antibody permitted to reoxidize in air no longer behaved as a direct agglutinin; reversion to an incomplete antibody did not occur when reoxidation was prevented by S-alkylation. These results suggest that mild reduction of the antibody imparts sufficient freedom to permit bridging between cells and are interpreted as evidence that the interheavy-chain disulfide bonds restrict segmental flexibility within the Fc fragment of IgG.

Binding Sites↗
PubMed1977

Adjuvant immunostimulation in malignant melanoma with oral Bacille Calmette-Guérin.

Results of the administration of oral bacille Calmette-Guérin (BCG) as an adjunct to standard treatment in 62 patients with malignant melanoma indicate that this drug is of value in preventing distant spread of the disease when it is limited to one region and in its early stages. BCG increases survival in patients with visceral metastases. In those in whom these metastases are surgically resectable, it inhibits the development of further metastases. Oral BCG treatment does not affect the course of the disease in patients with massive hepatic or intracranial metastases.

Administration, Oral↗
PubMed1976

Nonspecific complement activation by streptococcal structures. I. Re-evaluation of HLA cytotoxicity inhibition.

A number of experiments have suggested that there is an antigenic relationship between the HLA complex and streptococcal bacterial structures. Using inhibition of cytotoxicity of HLA antisera as our assay system, it was demonstrated that the inhibitory effect on HLA cytotoxicity by streptococcal antigens is, in reality, due to activation and consumption of components of the alternate complement pathway. In addition, antisera prepared against streptococcal membrane antigens had no cytotoxic effect on a large panel of human lymphocytes, nor did these antisera exhibit immunofluorescent staining of lymphocytes directly. These experiments are compatible with our concept that the HLA complex may have evolved through selective evolutionary pressure as a means of escaping bacterial mimicry.

Antibodies, Bacterial↗
PubMed1976

Canine small bowel transplantation. A study of the immunological responses.

A canine small bowel allograft model was used to determine the effects of radiation to the graft in modifying the immunological effects of the passenger leukocytes. When untreated allografts were transplanted, death of the recipient animals occurred at a mean of nine days. The allograft was well-preserved and showed no signs of rejection. The reasons for attributing death to graft-versus-host (GVH) disease are discussed. When allografts were treated with 150 rads prior to transplantation, allograft rejection occurred, with death of the recipient animals at a mean of 9.2 days. This was the only group in which cell-mediated immunity developed. When allografts were treated with 50 rads, prolonged survival of the recipients to a mean of 28 days was noted. It is postulated that in this group a balance was struck between the allograft rejection reaction and GVH disease, with prolongation of allograft survival.

Animals↗