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Biomedical subjects

M D Lieberman

Publications and source records attributed to M D Lieberman.

27 records · Page 2Linked to original sources
PubMed1990

Tumor immunization. Improved results after vaccine modified with recombinant interferon gamma.

The purpose of this study was to determine if a 3-day in vitro culture of the murine neuroblastoma C1300 with 500 U/mL of recombinant interferon gamma resulted in a protective crossreactivity to parent C1300. Twenty A/J mice received either a vaccine of 1 x 10(6) irradiated C1300 tumor cells intradermally or an equivalent inoculum of C1300 that had been incubated in recombinant interferon gamma (C1300*). One week later, all animals were rechallenged with 1 x 10(6) viable C1300. Animals immunized with C1300* had a significantly delayed early tumor incidence that translated into a survival advantage for the group. At the time of tumor rechallenge, a significantly increased level of nonspecific systemic immunity was conferred by the C1300* immunization. Thus, modification of tumor with recombinant interferon gamma before introduction as a vaccine may improve that vaccine's protective capability.

Animals↗
PubMed1990

Transfusion-induced immunosuppression results in diminished host survival in a murine neuroblastoma model.

Perioperative blood transfusion has been associated with decreased survival in cancer patients. The immunologic consequences of H-2 incompatible blood transfusion as related to neoplasia are unclear. This report examined the effect of multiple allogeneic blood transfusions, compared to syngeneic transfusions and saline infusion, on cellular immunity, tumor growth, and host survival in a murine C1300 neuroblastoma model. A/J mice were randomized to receive two weekly transfusions of washed whole blood cells from C57 Bl/6 or A/J donors or saline. Animals transfused with allogeneic blood, compared to syngeneic transfusions or saline infusions, had a significantly diminished lymphocyte response to mitogen (P less than 0.001), reduced donor-specific (P less than 0.001) and third party alloantigen (P less than 0.01) MLR, and reduced cytotoxicity against a natural killer (NK) cell-sensitive target (P less than 0.001). These in vitro deficits in cellular immunity correlated with a significantly greater Day 21 tumor weight to total body weight ratio in the allogeneic group (0.33) compared with the syngeneic (0.25) and saline (0.28) groups P less than 0.05). Median host survival was reduced in the allogeneic group (24 days) compared with the syngeneic (30 days) and saline (31 days) groups. There were no significant differences in cellular immunity, tumor growth, or survival between syngeneic and saline control groups. Allogeneic blood transfusion had an adverse affect on NK and T-lymphocyte function which was associated with enhanced tumor growth and reduced survival in tumor-bearing mice.

Animals↗
PubMed1990

Protein-calorie malnutrition inhibits antitumor response to interleukin-2 immunotherapy.

The efficacy of systemic interleukin-2 (IL-2) immunotherapy is dependent on a competent host immune response. This study demonstrated that protein-calorie malnutrition (PCM) inhibited the generation of an antitumor response to IL-2. A/J mice received an isocaloric diet of 2.5% or 24% casein 8 weeks before inoculation with C1300 neuroblastoma cells. Three weeks later lymphocytes from tumor-bearing mice were harvested for determination of cytotoxic T-lymphocyte generation and natural killer cell cytotoxicity. PCM produced a significant reduction in total body weight (p less than 0.001) and serum albumin concentration (p less than 0.001). PCM inhibited generation of cytotoxic T lymphocytes (p less than 0.001), T-lymphocyte response in mixed lymphocyte reaction (p less than 0.001), and in vitro activation of natural killer cell cytotoxicity with IL-2 (p less than 0.001). A second experiment was performed to evaluate whether the in vitro deficits in tumor-specific and natural immunity in the animal model of PCM would diminish the efficacy of systemic high-dose IL-2 (3 x 10(6) units/kg three times daily for 5 days). The mean percent inhibition of C1300 growth with IL-2 was only 15% in mice with PCM compared with 60% in well-nourished mice (p less than 0.01). Median host survival time was greater in well-nourished animals (55 days) compared with animals with PCM (39 days) that received IL-2 (p less than 0.05). These data suggest that nutritional status is a critically important variable in tumoricidal response to systemic IL-2.

Animals↗
PubMedDate not supplied

Immunonutrition: the role of arginine.

Clearly, arginine has great potential as an immunomodulator and may prove useful in catabolic conditions such as severe sepsis and postoperative stress. there is a body of evidence suggesting that supplemental arginine upregulates immune function and reduces the incidence of postoperative infection. More modest improvements in nitrogen balance have been observed. Tumor response to arginine appears to depend on the immunogenicity of the particular tumor and on the requirement of arginine by the tumor as a growth substrate. Of note, ornithine shares the thymotrophic, immunostimulatory and secretagogue effects of arginine. It is, therefore, likely that these compounds share the same cellular mechanism of action or that arginine acts via increasing the concentration of available ornithine. The role of arginine in the injured patient and in the tumor-bearing host demands additional study based on the promising experimental evidence regarding the supplemental use of arginine.

Animals↗
PubMedDate not supplied

Regional treatment of hepatic micrometastasis by adenovirus vector-mediated delivery of interleukin-2 and interleukin-12 cDNAs to the hepatic parenchyma.

We hypothesize that adenovirus (Ad) vector-mediated delivery of the human interleukin-2 (IL-2) cDNA (AdIL2) or the murine IL-12 cDNA heterodimer (AdIL12) would produce high concentrations of cytokines in the local hepatic milieu to induce host responses sufficient to inhibit the growth of experimental colon carcinoma-derived hepatic metastases. Ad vectors administered intravenously, which is a route known to deliver >90% of the vector to the hepatic parenchyma, achieved significant levels of each cytokine locally, with minimal levels in the sera. To examine the therapeutic effect, the AdIL2 and AdIL12 vectors were evaluated in a hepatic metastasis model that was established by injecting 3 x 10(4) cells from the poorly immunogenic syngeneic C26 colon carcinoma cell line into the right lobe of the livers of BALB/c mice. Animals received AdIL2, AdIL12, or control virus (10(8) plaque-forming units each) intravenously for 2 days after tumor implantation, and tumor growth was compared with naive controls. The AdNull control tumors measured 116 +/- 25 mm2 at 2 weeks. The control virus showed no significant antitumor effect. In marked contrast, both AdIL2 and AdIL12 vectors that were delivered regionally had significant antitumor effects, with AdIL2-treated animals having an average tumor size of 16 +/- 8 mm2; AdIL12-treated tumors measured 6 +/- 6 mm2 (P < .01, both compared with control). Both the AdIL2 and AdIL12 vectors provided a significant survival advantage by log-rank analysis (P < .01), but only AdIL12 translated into an increase in mean survival from 27 (naive control) to 37 days. To evaluate whether these antitumor effects were T-cell-mediated, splenocytes from AdIL2-treated, AdIL12-treated, and naive control groups were stimulated in vitro with gamma-irradiated C26 tumor cells for 5 days and tested for C26 tumor cell cytolysis by an in vitro cytotoxicity assay. Splenocytes from both AdIL2- and AdIL12-treated animals showed a dose-dependent, T-cell-mediated, specific cytolysis of CT26 cells. AdIL12 and to a lesser extent AdIL2 induced natural killer cell activity, as determined by a dose-dependent increase in lysis of the natural killer-specific target cell YAC-1. Overall, these data suggest that regional Ad-mediated delivery of IL-2 and IL-12 cDNAs may be useful for local tumor control and may warrant further investigation as a potentially useful adjuvant for the treatment of hepatic micrometastasis.

Adenoviridae↗
PubMedDate not supplied

Comparison of acute and chronic protein-energy malnutrition on host antitumor immune mechanisms.

Protein-calorie malnutrition (PCM) is prevalent in cancer patients. However, the effect of PCM on anti-tumor immunity is unclear and critically important in an era of improving results with adoptive immunotherapy. This study examined the effect of short- and long-term PCM on tumor-specific and natural immune effector mechanisms in a murine neuroblastoma (C1300 NRB) model. A/J mice received an isocaloric 2.5% or 24% casein diet for 3 or 8 weeks before inoculation with tumor. Three weeks later lymphocytes from tumor-bearing mice were harvested for determination of cytotoxic T lymphocyte (CTL) generation and natural killer (NK) cell cytotoxicity. Both 3 and 8 weeks of PCM significantly reduced mean total body weight by 25% (p less than 0.001) and 41% (p less than 0.001), respectively, compared with regularly nourished mice. Short-term PCM did not inhibit CTL or NK cytotoxicity, whereas long-term PCM significantly diminished CTL generation (p less than 0.001) but preserved NK cytotoxic function. These results indicate that CTL development against autologous tumor, in contrast to basal NK function, is dependent on host nutritional status. Mean tumor growth, determined by tumor-weight to carcass-weight ratio, was unchanged for both short- and long-term protein-energy deprived groups compared with results in regularly nourished mice. These findings suggest that NK function is the predominant effector mechanism inhibiting C1300 NRB growth and that NK tumoricidal capacity is preserved during PCM.

Acute Disease↗
PubMedDate not supplied

Dietary manipulation of methotrexate-induced enterocolitis.

Administration of chemotherapy is limited by host toxicity, which is often manifested by severe enterocolitis. This study evaluated the effects of a liquid, elemental, chemically defined diet (ED) supplemented with 2% glutamine (Glu-ED) compared with a polypeptide diet (PPD) on the morbidity and mortality after methotrexate (MTX) administration. Fischer 344 rats (n = 80) were fed either a regular rat chow diet (RD), a 2% glycine supplemented elemental diet (Gly-ED), a 2% glutamine-supplemented elemental diet (GLU-ED), and a glycine-supplemented polypeptide diet(Gly-PPD) for 7 days prior to administration of MTX (20 mg/kg, ip). After 72 hours, eight rats per group were killed; portal vein and vena cava blood, mesenteric lymph nodes (MLN), liver, small intestine, and cecum were sampled for bacterial culture. Remaining animals were followed to calculate survival. One hundred percent of the Gly-PPD and 25% of the Glu-ED animals survived compared with 0% of the Gly-ED animals. Our data showed that ED resulted in an increased quantity of intestinal Gram-negative bacteria and diminished intestinal mucosal height and mucosal DNA/protein content. The polypeptide diet prevented intestinal mucosal atrophy, avoided MTX-induced enterocolitis and significantly improved animal survival compared with an elemental diet with or without glutamine supplementation.

Animals↗
PubMedDate not supplied

Nutritional support of the cancer patient.

Malnutrition, a common problem in cancer patients, adversely affects survival and quality of life. It results from several factors that alter nutritional intake and cause massive metabolic disturbances. Anticancer therapies may compound the malnutrition. Optimal nutrition improves therapeutic modalities and the clinical course and outcome. Oral nutrition should be used whenever possible; in patients unable to ingest adequate amounts orally, enteral and parenteral feedings are safe and effective.

Energy Metabolism↗