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S S Joshi

Publications and source records attributed to S S Joshi.

At least 37 records · Page 2Linked to original sources
PubMed1999

The cytotoxic effects of a novel IH636 grape seed proanthocyanidin extract on cultured human cancer cells.

Grape seed proanthocyanidins are natural antioxidants which possess a broad spectrum of chemoprotective properties against free radicals and oxidative stress. In this study, we have assessed the cytotoxicity of a novel IH636 grape seed proanthocyanidin extract (GSPE) against MCF-7 human breast cancer cells, A-427 human lung cancer cells, CRL-1739 human gastric adenocarcinoma cells and K562 chronic myelogenous leukemic cells at 25 and 50 mg/lit concentrations for 0-72 h using cytomorphology and MTT cytotoxicity assay. In addition, we compared the effects on normal human gastric mucosal cells and normal J774A.1 murine macrophage cells with the effects on the cancer cell lines. Concentration- and time-dependent cytotoxic effects of GSPE were observed on the MCF-7 breast cancer, A-427 lung cancer and gastric adenocarcinoma cells. Following incubation of the MCF-7 cells with 25 mg/lit of the GSPE approximately 6.5, 30 and 43% inhibitions in cell growth were observed at 24, 48 and 72 h of incubation, respectively, while incubation of the MCF-7 cells with 50 mg/lit of the GSPE resulted in 11, 35 and 47% inhibition in cell growth at these same points, respectively. Similar results were observed in the A-427 and gastric adenocarcinoma cells. GSPE exhibited no cytotoxicity toward the neoplastic K562 myelogenous leukemic cells. However, GSPE enhanced the growth and viability of the normal human gastric mucosal cells and J774A.1 murine macrophage cells. These data demonstrate that GSPE exhibited cytotoxicity towards some cancer cells, while enhancing the growth and viability of the normal cells which were examined.

Adenocarcinoma↗
PubMed1998

Lymphocyte reconstitution after allogeneic blood stem cell transplantation for hematologic malignancies.

Forty-one patients were studied at set times after allogeneic blood stem cell transplantation (alloBSCT) for recovery of lymphocyte numbers and function. Cells were mobilized with G-CSF from HLA-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate; G-CSF was administered post-transplant. Median time to absolute lymphocyte count (ALC) >500/microl was 17 days vs 41 and 49 days in historical alloBMT patients with G-CSF (n = 23) or no cytokine (n = 29) post-transplant, respectively (P < 0.0001). CD4/CD8+ ratio was 1.9 on day 28 after alloBSCT, then gradually declined to 0.8 at 1 year due to more rapid CD8+ cell recovery. Mean phytohemagglutinin-induced T cell responses were lower than normal on day +28 (P < 0.05), then tended to recover towards normal values. Natural-killer cytotoxicity remained low from day +28 to 1 year post-alloBSCT, but considerable lymphokine-activated killer cytotoxicity was induced from cells already obtained on day +28. Faster lymphocyte recovery correlated with better survival in alloBSCT patients (median follow-up 287 days, P = 0.002), ALC recovery was not affected by acute GVHD, CMV infections or doses of infused cells. ALC recovery did not correlate with survival in either historical alloBMT group. These data suggest that after alloBSCT lymphocyte reconstitution is faster than after alloBMT, and that quicker lymphocyte recovery predicts better survival in the alloBSCT setting.

Adult↗
PubMed1998

Antitumor activity of human umbilical cord blood cells: A comparative analysis with peripheral blood and bone marrow cells.

Although the hematopoietic reconstituting ability of human umbilical cord blood cells (UCBC) is well documented, their antitumor cytotoxic potential has not been well studied. Therefore, UCBC were compared to normal peripheral blood stem cells (PBSC) and bone marrow (BM) stem cell harvests for cytomorphology, antitumor cytotoxic activity before and after ex vivo cytokine manipulation, response to T and B cell mitogens, expression of adhesion molecules and immunophenotypes using flow cytometry, cytokine production and in vivo antitumor activity. BM and PBSC, but not UCBC, did not form cellular clusters in culture. More cytotoxic granules were present in the cytoplasm of UCBC than PBSC following activation in vitro. Ex vivo manipulation of UCBC with cytokines produced more cytotoxicity to K562 and Raji tumor cells than PBSC or BM (p<0.001). Most cytotoxic cells in UCBC cultures were T lymphocytes, and a correlation existed between the number of CD56+ cells and cytotoxicity levels, particularly after in vitro activation with interleukin-2. No significant difference in adhesion molecule expression was noted among UCBC, PBSC and BM cells. However, there was a significantly decreased expression of CD54 molecules (ICAM) on UCBC compared to PBSC (p<0.05). IL-2 activated UCBC showed significant antitumor effects against K562 leukemic cells grown in SCID mice. Thus UCBC contained more antitumor effector cells and precursors than cells from marrow or peripheral blood cells which might be capable of providing a therapeutic effect.

Animals↗
PubMed1998

Cell cycle-based purging of lymphoma cells from bone marrow harvests using radioiodinated 5-iodo-2'-deoxyuridine.

Minimal residual disease in lymphoma patients is a major problem in the clinical management of their cancer. High-dose chemotherapy followed by autologous bone marrow transplantation has been used to treat the disease. However, residual lymphoma may be reintroduced along with the marrow if it is present in the bone marrow harvest. In this report we describe results of experiments testing the efficacy of 5-[125I]-iodo-2'-deoxyuridine (125IdU) for purging murine RAW117 large cell lymphoma cells (Joshi et al., Oncology 44, 180-185, 1987; Cancer Res. 47, 3551-3557, 1987) from bone marrow in a relevant animal model. Donor BALB/c mice were injected with murine RAW117 cells and euthanized on day 13, and their bone marrow that had been contaminated with tumor cells was harvested and treated in vitro with 125IdU or nonradioactive 127IdU (control). Nine of 10 mice receiving 127IdU-treated bone marrow contaminated with tumor cells died at an average of 17 days after injection. In comparison, 9 of 10 mice injected with 125IdU-treated bone marrow contaminated with tumor cells were still alive after 82 days. In addition, the 125IdU treatment did not diminish the formation of hematopoietic progenitor cell colonies in normal mouse and human peripheral blood stem cells.

Animals↗
PubMed1997

A hexameric phosphorothioate oligonucleotide telomerase inhibitor arrests growth of Burkitt's lymphoma cells in vitro and in vivo.

A phosphorothioate oligonucleotide (PS-ODN) with sequence identical to the repeat sequence of the mammalian telomere, 5'-d(TTAGGG)-3', was incubated with a Burkitt's lymphoma-derived (OMA-BL1) cell line. This hexanucleotide inhibits telomerase activity in cell lysates, lengthens cell doubling time, and induces apoptosis. Concatenated repeats (12-, 18-, and 24-mers) of the 5'-d(TTAGGG)-3' motif induce similar cellular responses. Scrambled sequences do not efficiently inhibit telomerase activity or significantly alter cell growth and viability. The in vivo efficacy of this PS-ODN was evaluated in a xenograft human-nude mouse model. Once tumors were established these animals were administered the telomere mimic, 5'-d(TTAGGG)-3', a control scrambled sequence 5'-d(TGTGAG)-3', or saline for 14 days via a subcutaneous osmotic pumps in a blinded study monitoring tumor size with dose and time. A significant decrease in tumor size was observed in animals given 50 micrograms/mouse/day 5'-d(TTAGGG)-3', but not following 5'-d(TGTGAG)-3', relative to the saline-treated animals. The antitumor activity of the 6-mer telomere mimic demonstrated a dose dependency including a reduction in metastatic nodules in the spleen. No activity was observed with the scrambled controls. In addition to antitumor activity we observed an increase in the mouse hematopoietic progenitor cell populations, BFU-e and CFU-GM. These results demonstrated the effects of a short hexameric oligonucleotide telomere mimic in vitro and in vivo and the potential utility of short oligonucleotides as telomerase inhibitors.

Animals↗
PubMed1997

Combination of antisense oligonucleotide and low-dose chemotherapy in hematological malignancies.

Current conventional chemotherapy for the treatment of hematological malignancies, although quite effective, has associated toxicities to normal tissue and organs, which is still a major dose limiting factor. In addition, high dose chemotherapy followed by autologous stem cell transplantation is limited by tumor cell contamination in the stem cell harvest. The use of conventional chemotherapy alone to purge these tumor cell contaminants is known to damage normal hematopoietic progenitor cells, resulting in delayed engraftment. The combination of antisense oligodeoxynucleotides (ODN) and low doses of chemotherapy offer a potential regiment which may lower the doses of conventional therapeutics required to effectively combat disease, thus lowering cytotoxicity experienced by normal cells. Transient downregulation of genes by ODN treatment, which are involved in the transformation or perpetuation of the cancerous disease state, can remove the growth and survival advantages exploited by tumor cells. Many groups are currently investigating this combination and have produced intriguing results. This review article discusses the current research investigating the combination of antisense ODN therapy with conventional chemotherapy in the treatment of hematological malignancies. Although further improvements in this strategy are required, the results thus far support a future for this strategy in clinical management of hematological malignancy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Increased hematopoietic progenitor cell maintenance in long-term bone marrow cultures containing minimal numbers of contaminating breast cancer cells.

The maintenance of hematopoietic progenitor cells as assayed in the mixed colony (CFU-GEMM) assay in human long-term bone marrow cultures was compared between normal allogeneic marrow transplantation donor collections and those from candidates for high-dose therapy and autologous bone marrow transplantation (ABMT). To be eligible for ABMT, patients were required to have a histologically normal appearing bone marrow and therefore any tumor contamination was at minimal levels and detectable only after evaluation of the cultured harvests. Marrow from 15 normal donors, 36 patients with breast cancer, and 30 patients with Hodgkin's disease was evaluated. The number of mononuclear cells placed in culture was standardized. In all groups, significantly more progenitor cells were recovered at 4-6 weeks of culture that at 12-14 weeks. At 4-6 and 12-14 weeks, there were no significant differences in the number of progenitor cells recovered from the cultures of normal donors and tumor negative cultures of breast cancer or Hodgkin's disease patients. However, following 4-6 and 12-14 weeks of culture, progenitor cell numbers of cultures which contained breast cancer cells were significantly higher than the pooled values for cultures from the concurrent normal controls, and those from breast cancer and Hodgkin's disease patients with tumor negative cultures. These results suggest that minimal breast cancer cell contamination of the bone marrow can influence the production of marrow progenitor cells. Exposure to prior chemotherapy or radiation therapy does not appear to be the cause of this effect. The most likely mechanism is the local production of cytokines by the tumor cells, although a process involving direct adhesive contact of the tumor cells with hematopoietic cells, which is sometimes observed in semisolid cultures, cannot be excluded.

Bone Marrow Cells↗
PubMed1997

Immunosuppression by metastatic lymphoma derived altered retroviral gp70 molecule.

In this report we describe the characteristics of an immunosuppressive molecule from an Abelson Leukemia Virus transformed highly malignant and metastatic RAW117-H10 murine large cell lymphoma cells. Our studies have shown that the mitomycin-c treated or irradiated RAW117-H10 cells very significantly (p < 0.001) inhibited the nitrogen induced proliferation of normal Balb/c splenocytes. The cell surface extracts from the immunosuppressive RAW117-H10 lymphoma cells significantly inhibited the in vitro T cell or NK/LAK cell functions. Our in vivo studies demonstrated that there was a significant suppression of immune response in the Balb/c mice bearing RAW117-H10 cells when compared with mice bearing low metastatic parental RAW117-P cells or control mice. Subsequently we isolated and purified the main molecule responsible for this immunosuppression and found that the molecule is a glycoprotein with a molecular weight of 70 kD with an isoelectric point of 4.3, which cross reacted with antibodies to murine leukemia virus envelope gp70 molecules. Further analysis using immunoelectrophoresis, molecular probing techniques, and mannose specific lectin binding assay revealed that the immunosuppressive 70 kD molecule, is different from the wild type MLV envelope gp70 molecule and thus appears to be an altered gp70 molecule. These studies demonstrate that the metastatic lymphoma associated immunosuppression may facilitate the growth and metastasis of tumor cells. Our results also elucidate the possible mechanism(s) of retrovirus induced immunosuppression and the molecular basis of this retroviral envelope-mediated process in viral pathogenesis and tumor progression.

Abelson murine leukemia virus↗
PubMed1996

In vivo therapeutic effects of interleukin-12 against highly metastatic residual lymphoma.

Despite considerable advancement in anticancer therapy, minimal residual disease (MRD) is still a major problem in the clinical management of cancer, including lymphoma. In this report, we have studied the antitumor effects of interleukin-12 (IL-12) against an aggressive liver metastatic murine RAW117-H10 lymphoma. Our results using three different doses of IL-12 (0.175, 0.35 and 0.7 micrograms/mouse) showed that a 0.35 micrograms dose is the most efficacious against lymphoma grown in intact mice. Furthermore, we have evaluated the therapeutic effects of IL-12 against residual lymphoma in a transplantation setting. BALB/c mice were treated with high-dose therapy (HDT) and transplanted with syngeneic bone marrow cells added with a known number of RAW117-H10 lymphoma cells to mimic the clinical situation of MRD. The mice were then treated with IL-12 (0.25 micrograms/mouse/day) alone or IL-12 plus activated cytotoxic effector cells. Our results showed that IL-12 had a significant (P < 0.05) antitumor therapeutic effect against liver metastatic lymphoma grown in intact mice as well as in lymphoma-bearing mice treated with HDT followed by stem cell transplantation as determined by survival period. The therapeutic effect of IL-12 was also demonstrated by a very significant decrease (P < 0.05) in the tumor burden in livers from the IL-12-treated mice. Mice that were treated with IL-12 following HDT and hematopoietic stem cell transplantation had a significant decrease in circulating white blood cells (P < 0.05), a significant increase in spleen weight and cellularity (P < 0.05), and hematopoietic progenitor cells (P < 0.05), a significant increase in the number of splenocytes expressing IL-2 alpha-chain receptor (P < 0.05), and an increase in the frequency of natural killer cells in their spleens. These studies suggest that cytokines such as IL-12 may have the potential to mediate antitumor effects against residual lymphoma without compromising lymphohematopoietic recovery.

Animals↗
PubMed1996

Assessment of genotoxic effect of piperine using Salmonella typhimurium and somatic and somatic and germ cells of Swiss albino mice.

Piperine (CAS 94-62-2) is a constituent of various spices and is used as a common food additive all over the world. The genotoxic potential of piperine was assessed using four different test systems, namely, Ames test using Salmonella typhimurium, micronucleus test, sperm shape abnormality test and dominant lethal test using Swiss albino mice. In the Ames test, six different doses of piperine, in the range of 0.005-10 mumol/plate, did not induce his+ revertants, with or without metabolic activation, indicating its nonmutagenic nature. In the bone narrow micronucleus test using two doses in the range of therapeutic usage (10 and 20 mg/kg body weight), piperine itself was non-mutagenic. Like in somatic cells, piperine (10 and 50 mg/kg body weight) failed to induce mutations in male germ cells of mouse as assessed by using the sperm shape abnormality and dominant lethal tests. Piperine thus appears to be a non-genotoxic chemical.

Alkaloids↗
PubMed1995

Functional and phenotypic characterization of human peripheral blood stem cell harvests: a comparative analysis of cells from consecutive collections.

A considerable number of patients with malignancies who are treated with high-dose therapy and hematopoietic stem cell transplantation subsequently relapse. Analyses of peripheral blood stem cell (PBSC) harvests obtained from 49 cancer patients showed that the PBSC harvest contained precursors for antitumor effector cells. Ex vivo manipulation of these harvests to maximize the antitumor effector cell activity may provide a new therapeutic approach to decrease or eliminate any minimal residual disease that remains after high-dose therapy. Characterization of PBSC from consecutive collections determined the collections best suited for ex vivo augmentation of antitumor cytotoxic effector cells. We report the results of a functional and phenotypical characterization of PBSC obtained from six consecutive collections from 18 cancer patients receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) for hematopoietic stem/progenitor cell mobilization. The PBSC were evaluated for their cytotoxicity using the 51Cr-release assay. The frequency and subsets of lymphocytes were determined using flow cytometry with appropriate specific marker antibodies and differential cell counts. The content of hematopoietic progenitor cells in each collection was determined using a colony-forming unit granulocyte-macrophage (CFU-GM) culture assay. The frequency of cytotoxic effector cells including lymphokine-activated killer (LAK) cell precursors and lymphocytes was significantly greater (P < .05) in the early collections, whereas the later collections contained significantly (P < .05) more CFU-GM progenitor cells and fewer cytotoxic effector cells. Thus, our results show that PBSC obtained from advanced cancer patients do contain considerable levels of precursor cells for the generation of LAK cell populations. These results suggest that cells from the earlier collections are best suited for ex vivo manipulation to augment the antitumor effects.

Adolescent↗
PubMed1995

Effects of BCR-ABL antisense oligonucleotides (AS-ODN) on human chronic myeloid leukemic cells: AS-ODN as effective purging agents.

We examined phosphorothioate oligodeoxyribonucleotides (ODNs) directed against bcr in exon 3 or exon 2, which are rearranged with exon 2 of abl (B3A2 and B2A2) at t(9;22) of chronic myelogenous leukemia (CML). Since these ODNs are designed to be CML cell specific, we studied their effects on the human CML cell line K562, which is known to have B3A2 rearrangement, and leukemic cells from patients, as well as normal hematopoietic stem cells in vitro. In vitro experiments were performed to determine a potential role of these two ODNs as ex vivo purging agents. Incubation of B3A2 antisense at 40, 80, and 120 micrograms/ml with K562 CML cells for 72 hours at 37 degrees C resulted in 44%, 56%, and 63% reduction of CFU-L as compared to controls. In contrast, B3A2 sense and B2A2 antisense had no significant growth inhibitory effect on K562 cells. Incubation of B3A2 and B2A2 antisense ODNs at concentration of 80 micrograms/ml at 37 degrees C for 36 hours with normal peripheral blood stem/progenitor cells (PBSC) resulted in 124% and 98% CFU-GM formation as compared to untreated controls, respectively. However, incubation of PBSC with B3A2 and B2A2 sense-ODNs resulted in a 22% and 44% reduction in CFU-GM, respectively. In order to determine the ex vivo purging effects of bcr-abl ODNs, the K562 cells were mixed with PBSC from normal donors at a ratio of 1:20 (CML:PBSC). The mixture of cells was then incubated with B3A2 antisense at 80 micrograms/ml for 36 hrs at 37 degrees C. After incubation, no CML cells were detected by fluorescence in situ hybridization (FISH) as compared to untreated controls. These results were confirmed by RT-PCR using bcr-abl primers and mRNA isolated from the mixture of cells. Further, these results support the hypothesis that bcr-abl antisense ODNs are potentially effective agents for ex vivo purging of autologous stem cells before transplantation to eliminate/reduce the burden of leukemic cells. No significant toxicity to normal hematopoietic stem/progenitor cell population by the bcr-abl antisense ODNs was observed. Although unanticipated reductions in normal hematopoietic progenitor cells (CFU-GM) were observed with sense ODNs, no reduction in CFU-GM was observed with unrelated phosphorothioate ODN controls.

Base Sequence↗
PubMed1995

Altered in vivo and in vitro behavior of butanol-modified bone marrow cells.

Cell-surface molecules, particularly glycoconjugates, appear to be involved in the in vivo homing of hematopoietic stem and progenitor cells and in their interactions with hematopoietic stromal cells. To study the role of cell-surface molecules of hematopoietic stem cells, the expression of some surface molecules was altered using n-butanol treatment. We examined the in vivo and in vitro colony-forming abilities, in vivo homing patterns, and cell-surface lectin receptor expression of butanol-treated bone marrow cells (BMC) from BDF1 mice. The butanol-treated/-modified BMC formed an increased number of significantly larger spleen colonies (CFU-S) in lethally irradiated (1050 rad) mice. The butanol-treated BM formed significantly larger in vitro granulocyte-macrophage progenitor cell colonies (CFU-C) and in vitro fibroblastic colonies (CFU-F), although the number of such colonies was not significantly altered. The homing pattern of butanol-treated BMC was studied by comparing the distribution in lethally irradiated mice of intravenously injected 51Cr-labeled butanol-treated BMC with that of untreated cells. The butanol treatment altered the in vivo homing pattern of these cells, with increased homing to liver, spleen, and bone marrow and decreased homing to thymus, lung, and mesenteric lymph nodes. Flow-cytometric analyses of butanol-treated BMC showed an increased expression of receptors for the lectins concanavalin A (conA) and wheat germ agglutinin (WGA), indicating an increased expression of mannosyl and galactosyl residues, which are known sugar moieties in hematopoietic stem/progenitor cell homing. These results indicate that cell surface modifications can influence homing and growth of transplanted BMC and that butanol treatment is a useful tool for studying the mechanisms of hematopoietic stem/progenitor cell homing in vivo and for further characterizing the molecules involved in this process.

Animals↗
PubMed1994

Interleukin-2 therapy of lymphoma-bearing immunosuppressed mice.

In the present study, the immune status of syngeneic Balb/c animals bearing a poorly metastatic RAW117-P lymphoma and the highly malignant liver metastatic variant RAW117-H10 lymphoma were measured and compared to control animals with no known tumor. The immune status was evaluated by performing various analyses of spleen cells for the frequencies of immune cells using flow cytometry, in vitro mitogen response and in vitro NK cell-mediated cytotoxicity assays on days 6, 9 and 12 after tumor transplantation. The results of these studies indicated that from day 9 onwards, some of the immune response of the RAW117 lymphoma-bearing animals appeared to decrease compared to control animals. In order to boost the immune response of the tumor-bearing immunosuppressed animals, recombinant interleukin-2 (rIL-2) was administered to RAW117-H10 lymphoma-bearing animals. The immune status of tumor-bearing animals treated with rIL-2 was evaluated on days 5, 10 and 15 after tumor transplantation using similar analyses of spleen cells as described above. The results of these experiments indicated that IL-2 treatment increased splenic levels of cytotoxic cells, and decreased the in vivo tumorigenicity/metastasis of metastatic RAW117-H10 lymphoma cells. rIL-2 administration resulted in a significant increase in survival of tumor-bearing animals, and histological studies showed significantly lower tumor burdens in treated animals: it appears that rIL-2 has a beneficial therapeutic effect on immunosuppressive metastatic RAW117 lymphoma.

Animals↗
PubMed1994

Genotoxicity assessment of the antifungal antibiotic aureofungin in Salmonella typhimurium and Swiss albino mice.

The widely used agricultural antifungal agent aureofungin (ARF) was subjected to genotoxicity assessment using the Ames Salmonella assay as well as the in vivo micronucleus test and dominant lethal test in Swiss mice. In the Ames Salmonella spot test, ARF slightly elevated the number of histidine revertants after metabolic activation over a wide dose range (1-1000 micrograms/plate) in TA102 but not in TA97a, TA98 or TA100. In the preincubation plate incorporation assay with TA102, ARF increased the number of revertants in a dose-dependent manner only after metabolic activation. ARF failed to significantly elevate the frequency of micronucleated polychromatic erythrocytes (PE) in the bone marrow of Swiss mice. It elevated the frequency of dominant lethal mutations in the 7th and 8th weeks at 30 mg/kg body weight, a concentration much higher than the actual concentration used in the field. We conclude that ARF is non-mutagenic in somatic cells in vivo at doses used in the present study, probably mutagenic in stem-cell spermatogonia and may be classified as an equivocal promutagen, possibly acting as a cross-linker.

Animals↗
PubMed1994

From ill-defined extracts to the immunomodulatory lectin: will there be a reason for oncological application of mistletoe?

There is an obvious discrepancy between the popularity of mistletoe extracts and their classification as a non-conventional treatment modality with unproven efficacy in oncology. The commercial preparations suffer from several major drawbacks: lack of precise declarations for the molecular characteristics and the concentrations of diverse extract constituents; the composition of extracts can even be influenced by the different methods of preparation, the time of harvest, and the type of host tree; lack of experimentally substantiated instructions for the dose of supposedly effective substance(s) and the schedule of applications to clinically trigger an undisputably documented antitumoral activity; lack of thorough clinical studies according to the generally accepted criteria as the measure for responsible recommendations. To provide the indispensable set of data for a rational decision, the immunomodulatory galactoside-specific lectin was biochemically characterized and its antitumoral/antimetastatic activity was documented in three murine tumor model systems, occurring within a narrow dose range. Biweekly treatment with s.c. injections of a lectin dose of 1 ng/kg caused no notable harmful side-effects in patients, who showed modulation of selected immune parameters. In a group of 23 patients with advanced cancer no at least partial remission was seen. In principle, enhancement of factors like cytokine availability or NK-cell activity is not necessarily linked to therapeutic benefit. Factors such as growth promotion of certain tumor cell lines by cytokines, occurrence of respective insensitivity in advanced stages or varying levels of target sensitivity to cell-mediated cytotoxicity with significant interindividual differences deserve attention. Each tumor class has to be considered separately for its responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1993

Enhanced immunosuppressive activity associated with metastatic lymphoma cells.

Earlier reports from our laboratory showed that Abelson virus-induced, highly malignant and liver metastatic RAW117-H10 cells, but not the parental, less metastatic RAW117-P cells, inhibited both T-cell and B-cell mitogen-induced proliferation of syngeneic normal murine spleen cells. Similar inhibition was also noted when RAW117-H10 cell surface molecules extracted with butanol were used instead of whole tumor cells. In this report we describe the suppressive properties of the butanol-extracted RAW117-H10 cell surface molecules on other immune functions and the isolation/purification of a molecule from RAW117-H10 cell butanol extract which shows inhibitory activity. The immunosuppressive molecules also inhibit natural killer cell-mediated cytotoxicity, lymphokine-activated killer cell-mediated cytotoxicity, and bone marrow colony-forming unit-granulocyte-macrophage colony formation, but not colony-forming unit-fibroblast colony formation. The suppressive molecules inhibit interleukin 2 production by the T-lymphocytes. One of the molecules responsible for some of the immunosuppressive activity has been isolated and purified from butanol extracts of the metastatic RAW117-H10 cells by preparative isoelectrofocusing techniques. The suppressive molecule has an isoelectric point of 4.3 with an approximate molecular weight of 70,000. Metastatic RAW117-H10 lymphoma cells therefore express immunosuppressive molecules, which may facilitate their growth and metastasis in vivo.

Animals↗