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Biomedical subjects

D W Weiss

Publications and source records attributed to D W Weiss.

At least 19 recordsLinked to original sources
PubMed1992

Chemo-adoptive immunotherapy of nude mice implanted with human colorectal carcinoma and melanoma cell lines.

The antitumor effects of chemotherapy, recombinant human interleukin-2 (IL-2), recombinant human interferon alpha A/D (IFN alpha), allogeneic human lymphokine-activated killer (LAK) cells, and antitumor monoclonal antibody (mAb), administered alone and in various combinations, were tested in athymic nude mice carrying human tumor xenografts. Treatment began 6-18 days after i.v. or i.p. inoculation of colorectal carcinoma or melanoma cell lines, when macroscopic growths were evident. Chemotherapy consisted of two or three courses of 5-fluorouracil (5-FU) or dacarbazine. IL-2 and/or IFN alpha were administered three to five times weekly for 1-3 weeks, usually starting 2-5 days after chemotherapy. Human LAK cells were infused once or twice weekly for 2 or 3 weeks concurrently with IL-2. In some experiments, murine anticolorectal carcinoma mAb (SF25) was administered. In both tumor systems, chemotherapy alone or immunotherapy alone (IL-2, IL-2 + LAK cells, IFN alpha, IL-2 + IFN alpha +/- LAK cells) had little or no therapeutic effects. Additive effects were obtained by combining chemotherapy with IL-2 and LAK cells or with IL-2 and IFN alpha. In the majority of the experiments, the most effective combination was chemotherapy + IL-2 + IFN alpha + LAK cells. Treatment with mAb was beneficial in the colorectal carcinoma system when combined with 5-FU + IL-2 or 5-FU + IL-2 + IFN alpha. Homing experiments with radiolabeled human and mouse LAK cells injected i.v. showed increased early accumulation in the liver and lungs, whereas freshly explanted mouse splenocytes localized mostly in the spleen and liver. The tissue distribution pattern of human LAK cells was similar in normal and tumor-bearing mice (with lung metastases). These findings suggest that combination of chemotherapy with cytokines and LAK cells can be partially effective for advanced solid human tumors even in the absence of the host's T-cell immune response. Preliminary experiments showed that tumor-specific, anti-melanoma T-cell clones were effective in local (s.c.) tumor growth inhibition (Winn assay) following coinjection with the autologous tumor cells.

Animals↗
PubMed1991

Registration of three-dimensional MR and PET images of the human brain without markers.

Axial and sagittal magnetic resonance (MR) sections and contiguous sections of axial positron emission tomographic (PET) images obtained with fludeoxyglucose F-18 were used to evaluate a new method of registering three-dimensional images of the brain. The users specified the interhemispheric fissure plane in three dimensions for both the MR and PET data sets by specifying its endpoints within several axial sections. A transformation matrix aligning the interhemispheric fissure plane in MR and PET space was calculated and used to create one resectioned PET image on the resectioned PET image, and the user specified the remaining translations and rotation by moving the overlaid outline of the MR image. MR and PET data sets in four subjects were registered. The three-dimensional error on average was less than 3.8 mm and never exceeded 7.5 mm. Less than 1 hour per patient was required for registration. The method is accurate unless the interhemispheric fissure deviates significantly from a planar configuration. It does not need thin or contiguous MR sections and provides an estimate of the total registration error for every case.

Brain↗
PubMed1979

In vitro induction of cytotoxic effector cells against human neoplasms. I. Sensitization conditions and effect of cryopreservation on the induction and expression of cytotoxic responses to allogeneic leukemia cells.

Peripheral blood lymphocytes (PBL) from normal human donors were sensitized in vitro against allogeneic human acute myelocytic leukemia (AML) cells by means of an unidirectional mixed lymphocyte-tumor cell culture (MLTC) technique. The cytotoxic responsiveness of the sensitized lymphocytes, as determined in vitro by the 51Cr-release assay, varied among individual lymphocyte donors and was greatly dependent on the sensitization culture conditions. Induction of cytotoxic effector cells was augmented appreciably by adding to the cultures minute amounts of the immunopotentiating agent MER-BCG. Responding lymphocytes and stimulating leukemia cells cryopreserved for several weeks in liquid nitrogen were as effective as fresh cells in generating effector lymphocytes; the cytotoxic capacity of already sensitized lymphocytes was fully retained by cryopreservation. The implications of these findings for possible clinical employment of in vitro sensitized lymphocytes in adoptive immunotherapy of cancer are discussed.

Adult↗
PubMed1979

Effect of the MER tubercle bacillus fraction on the responsiveness of mice to T-independent antigens.

The effect of treatment with the methanol extraction residue (MER) mycobacterial fraction on the immunological responsiveness of BALB/c mice to the T-independent antigens pneumococcal polysaccharide type III (SIIII) and trinitrophenyl-lipopolysaccharide conjugate (TNP-LPS) was ascertained. Pretreatment with MER prevented the establishment of immunological paralysis by threshold doses (10 or 15 microgram) of SIII and by a paralyzing dose of 100 microgram TNP-LPS. The induction of immunological paralysis by SIII was unaffected by treatment with the bacterial adjuvant Corynebacterium parvum and with the B cell mitogens PPD, LPS (Escherichia coli lipopolysaccharide), and dextran sulfate.

Animals↗
PubMed1978

In vitro induction of cell-mediated immunity to murine leukemia cells. III. Effect of methanol extraction residue fraction of BCG on the generation of cytotoxic lymphocytes against leukemia.

Effects of the methanol extraction residue (MER) fraction of tubercle bacilli (BCG) on the generation of cytotoxic lymphoid cells were studied in vitro with the use of unidirectional mixed lymphocyte-tumor cell cultures. These cultures consisted of splenocytes of lymph node cells from normal donor C57BL/6, BALB/c, and strain A mice and mitomycin C-inactivated leukemia cells of both syngeneic and allogeneic origin. Addition of small amounts of MER (0.2-5 microgram/ml) to the cultures potentiated appreciably the elicitation of cytotoxic reactivity (as measured by the 51Cr-release assay) of the sensitized cells, whereas higher quantities (10-40 microgram/ml) had a strong suppressive effect. MER also induced some cytotoxic capacity in normal murine and human lymphoid cells not exposed to specific tumor cell stimulation. The stimulatory and suppressive effects were noted only when MER was present during the initial 24-48 hours of the 6-day culture. With the nylon wool fractionation technique, it was apparent that MER affected primarily the nonadherent cell population. MER could also prevent the generation of nonspecific suppressor cells by splenocytes maintained for 3-6 days in tissue culture.

Animals↗
PubMed1978

Effects of prophylactic treatment with the methanol extraction residue fraction of tubercle bacilli (MER) on the development of Rous sarcomas of chickens following challenge with the Rous sarcoma virus.

Three-month-old chickens were treated with the methanol extraction residue fraction of tubercle bacilli (MER) under different conditions, and subsequently challenged with living Rous sarcoma virus. The birds developed progressively growing sarcomas following viral challenge. A substantial proportion of the hosts which had been pretreated with MER under optimal circumstances (38 to 58%) showed complete and long-lasting regression of the neoplasms, and the survival of many of the animals that did succumb to progressively growing tumors was prolonged. An absolute condition for prophylactic efficacy of MER treatment in this model system was injection of the agent into the same body area (wing) into which subsequent viral challenge was introduced. The quantity of MER employed and the timing of the prophylactic administration were also decisive variables.

Animals↗
PubMed1977

Potentiation of mouse peritoneal macrophage antibacterial functions by treatment of the donor animals with the methanol extraction residue fraction of tubercle bacilli.

Administration to inbred mice of the methanol extraction residue fraction of tubercle bacilli by some, but not by all, routes affected markedly the in vitro phagocytic and antibacterial capacities of their peritoneal macrophages harvested several days to weeks after treatment. Phagocytosis of living [3H]thymidine- labeled Staphylococcus albus and Staphylococcus aureus organisms, but not of Listeria monocytogenes, was markedly enhanced. Uptake of the deoxyribonucleic acid precursor thymidine by the phagocytized staphylococci was consistently and significantly inhibited in macrophages taken from methanol extraction residue-treated donors. Such macrophages also displayed a significant facility to reduce the viability of intracellular S. albus and L. monocytogenes, but not of S. aureus, under the present experimental conditions.

Animals↗
PubMed1976

Stimulation of anti-tumour immunity in guinea-pigs by methanol extraction residue of BCG.

The immunoprophylactic effects of the methanol extraction residue (MER) of BCG were investigated in Strain 2 guinea-pigs injected with cells of the transplantable, diethylnitrosamine-induced, Line 10 hepatocarcinoma. Pretreatment with MER at times ranging from 18 to 182 days prior to tumour implantation protected approximately 40% of guinea-pigs from progressive neoplastic disease. In addition, MER-treated animals developed specific cell-mediated anti-tumour immunity both more rapidly and at higher levels than did non-MER-treated tumour-bearing controls. It was not possible, however, to prognosticate from the results of such laboratory studies to the outcome of immunoprophylaxis.

Animals↗
PubMed1976

Chemoimmunotherapy of syngeneic mouse mammary carcinomas employing methanol extraction residue.

Isografts of two mammary carcinomas, one spontaneously arising in a BALB/cfC3H female infected with MTV and one free of MTV (tumor D7T4S), were removed surgically from Balb/c (MTV free) female hosts, and fragments of each tumor were immediately reimplanted in situ (simulated local recurrence challenge). The animals were then subjected to treatment with the MER fraction of tubercle bacilli, with one of three chemotherapeutic drugs (5-FU, cyclophosphamide, and methotrexate), or with both MER and one of the chemotherapeutic agents (chemoimmunotherapy). The incidence of progressively developing recurrence tumors and the longevity of the animals were determined. The therapeutic effects of treatment with MER alone were ascertained by comparing groups of mice that received the fraction by various schedules with saline-injected control groups; the efficacy of chemoimmunotherapy was assassed by comparing groups that received MER plus one of the drugs with groups subjected to drug intervention by itself. MER administered alone did not reduce the incidence of recurrent tumors but was consistently efficacious in prolonging the lives of animals challenged with the MTV (+) carcinoma, although considerably less so in animals tested with the weakly immunogenic tumor D7T4S. A negative effect by MER on tumor frequency did not occur and was seen only once with regard to host life duration. Combined intervention with MER and 5-FU proved to be significantly and consistently superior to similar treatment with only 5-FU in animals challenged with the MTV(+) carcinoma. No such additive action by MER plus 5-FU was seen in mice challenged with D7T4S, however, nor did the other two chemoimmunotherapeutic regimens differ significantly in therapeutic efficacy from the corresponding chemotherapy alone in most of the trials with both tumors.

Adenocarcinoma↗