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R M Bukowski

Publications and source records attributed to R M Bukowski.

At least 19 recordsLinked to original sources
PubMed2002

A phase I trial of weekly gemcitabine and subcutaneous interferon alpha in patients with refractory renal cell carcinoma.

INTRODUCTION: Recombinant human interferon-a2b (rHuIFN-alpha2b) and Interleukin-2 have limited effectiveness in the treatment of metastatic renal cell carcinoma (MRCC). Gemcitabine (Gemzar) is also reported to have activity against MRCC, and recent in vitro, in nude mice xenografts, and human data suggests increased activity of gemcitabine (Gemzar) when combined with IFN-alpha2b. PURPOSE: A phase I clinical trial utilizing gemcitabine (Gemzar and rHuIFN-alpha2b was conducted in patients with metastatic renal cell carcinoma. METHODS: Treatment consisted of: gemcitabine (Gemzar) 600 mg/m2 I.V. weekly and rHuIFN-alpha2b 1.0 MU/m2 (dose level A) or 3.0MU/m2 S.C. (dose level B) three times a week for 6 weeks with a 2 weeks rest period. RESULTS: Thirteen patients were entered into the trial and were evaluated. Dose limiting toxicity was predominantly hematologic, and was seen at dose level B. This included grade 3 anemia (1 patient), neutropenia (1 patient), and nausea (1 patient) and grade 4 neutropenia (1 patient). The maximal tolerated dose was gemcitabine (Gemzar) 600 mg/m2 I.V. weekly and rHuIFN-alpha2b 1.0 MU/m2 three times a week. CONCLUSION: This combination of gemcitabine (Gemzar) and rHuIFN-alpha2b has significant hematologic toxicity despite low doses of each agent. Further investigation of this combination using this schedule is not recommended.

Adult↗
PubMed2001

Cell cycle phase specificity in the potentiation of etoposide-induced DNA damage and apoptosis by KN-62, an inhibitor of calcium-calmodulin-dependent enzymes.

The cell cycle phase-dependent induction of DNA damage and apoptosis by etoposide (VP-16) and its modulation by 1-[N,O-bis(1, 5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-piperazine (KN-62), an inhibitor of calcium-calmodulin-dependent enzymes, were examined in sensitive (HL-60/S) and VP-16-resistant (HL-60/DOX0.05) HL-60 cells. Cells from exponential-phase cultures were enriched by centrifugal elutriation into G(1), S, and G(2)+M fractions. Modulation of VP-16-induced apoptosis by KN-62 in HL-60/S cells was apparent only in the S phase at the IC(50) concentration. However, in the HL-60/DOX0.05 cells, significant (P < 0.001) potentiation of VP-16-induced apoptosis by a non-cytotoxic concentration of 2 microM KN-62 was apparent in cells in the G(1), S, and G(2)+M phases, as well as over the entire concentration range tested. VP-16-induced apoptosis and its potentiation by a non-cytotoxic concentration of 2 microM KN-62 were correlative with drug-stabilized DNA cleavable complex formation based on a band depletion assay. In agreement with the results on apoptosis in the resistant HL-60/DOX0.05 cells, the enhanced depletion of the alpha and beta isoforms of topoisomerase II by VP-16 + KN-62 was observed in G(1), S, and G(2)+M cells. Results suggest that the effects of KN-62 in reversing resistance are based on its role as a potent sensitizer of VP-16-induced DNA damage and apoptosis in a cell cycle phase-independent manner.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Phase I and II trials of subcutaneously administered rIL-2, interferon alfa-2a, and fluorouracil in patients with metastatic renal carcinoma.

PURPOSE: A phase I followed by a phase II trial utilizing rIL-2, IFN alpha, and 5-FU were conducted in patients with unresectable and/or metastatic renal cell carcinoma. METHODS: Treatment consisted of: rIL-2 at 5.0 x 10(6) IU/m2 SQ on days 1-5 for 4 weeks, rHUIFN alpha-2a at 5.0 x 10(6) U/m2 SQ on days 1, 3, and 5 for 4 weeks, and 5-FU by IV bolus on days 1-5 during week 1. In the phase I study, patients were treated at varying doses of 5-FU: I-none, II-250 mg/m2, III-300, and IV 375. A phase II trial was then conducted utilizing the same schedule and maximum tolerated dose (MTD) for 5-FU. RESULTS: Twenty patients were entered into the phase I trial. Dose-limiting toxicity included grade III nausea and vomiting, and one sudden cardiac death. The MTD for 5-FU was determined to be 300 mg/m2. In the phase II trial, a median of two cycles of therapy was administered to 25 evaluable patients. Toxicity was moderate and consisted primarily of fevers, chills, fatigue, nausea/vomiting, and anorexia. Grade IV thrombocytopenia, consistent with ITP, developed in one patient each on the phase I and phase II trial. Seven partial responses were seen among 25 patients treated in the phase II trial for a 28% (CI 12-49%) response rate. CONCLUSIONS: The addition of 5-FU to rIL-2 and rHuIFN alpha-2a appears to increase the toxicity of this therapy. Randomized trials will be required to determine if efficacy is enhanced.

Adult↗
PubMed2001

Phase I trial of simultaneously administered GM-CSF and IL-6 in patients with renal-cell carcinoma: clinical and laboratory effects.

BACKGROUND: Metastatic renal-cell carcinoma is a neoplasm that is minimally responsive to cytotoxic chemotherapy. Tumor regression following therapy with cytokines such as interferon alpha and or interleukin-2 is seen in selected subsets of patients. Investigations with other immunomodulatory cytokines, such as GM-CSF and IL-6 are therefore of interest. PATIENTS AND METHODS: A phase I trial of concomitantly administered granulocyte macrophage-colony stimulating factor (3.0 mcg/kg/day s.c. d1-14) and escalating doses of interleukin-6 (1.0, 5.0 or 10.0 microg/kg/day d1-14) was conducted in patients with metastatic renal-cell carcinoma to explore the toxicity of the combination and its hematologic effects. RESULTS: The most common side effects seen were fever, fatigue and arthralgias. Dose limiting toxicity included thrombocytosis and hyperbilirubinemia in patients receiving 10 microg/kg/day of IL-6. The hematologic effects of IL-6 and GM-CSF included leukocytoses and thrombocytosis, with increases in peripheral blood progenitors (BFU-E, CFU-GM, and CFU-GEMM). Evidence of platelet activation demonstrated by increased platelet expression of CD62 was found. No clinical responses were observed. CONCLUSIONS: The combination of IL-6 and GM-CSF has pleotropic hematologic effects. Further studies with this combination for the treatment of renal-cell carcinoma are not recommended.

Adult↗
PubMed2001

Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-alpha 2a for patients with advanced renal cell carcinoma.

Recombinant human interleukin-12 (rHuIL-12) is a pleiotropic cytokine with anticancer activity against renal cell carcinoma (RCC) in preclinical models and in a phase I trial. A randomized phase II study of rHuIL-12 compared with interferon-alpha (IFN-alpha) evaluated clinical response for patients with previously untreated, advanced RCC. Patients were randomly assigned 2:1 to receive either rHuIL-12 or IFN-alpha2a. rHuIL-12 was administered by subcutaneous (s.c.) injection on days 1, 8, and 15 of each 28-day cycle. The dose of IL-12 was escalated during cycle 1 to a maintenance dose of 1.25 microg/kg. IFN was administered at 9 million units by s.c. injection three times per week. Serum concentrations of IL-12, IFN-gamma, IL-10, and neopterin were obtained in 10 patients treated with rHuIL-12 after the first full dose of 1.25 microg/kg given on day 15 (dose 3) of cycle 1 and again after multiple doses on day 15 (dose 6) of cycle 2. Thirty patients were treated with rHuIL-12, and 16 patients were treated with IFN-alpha. Two (7%) of 30 patients treated with rHuIL-12 achieved a partial response, and the trial was closed to accrual based on the low response proportion. IL-12 was absorbed rapidly after s.c. drug administration, with the peak serum concentration appearing at approximately 12 h in both cycles. Serum IL-12 concentrations remained stable on multiple dosing. Levels of IFN-gamma, IL-10, and neopterin increased with rHuIL-12 and were maintained in cycle 2. rHuIL-12 is a novel cytokine with unique pharmacologic and pharmacodynamic features under study for the treatment of malignancy and other medical conditions. The low response proportion associated with rHuIL-12 single-agent therapy against metastatic RCC was disappointing, given the preclinical data. Further study of rHuIL-12 for other medical conditions is underway. For RCC, the study of new cytokines is of the highest priority.

Adult↗
PubMed2001

Tumor-induced sensitivity to apoptosis in T cells from patients with renal cell carcinoma: role of nuclear factor-kappaB suppression.

Antitumor immunity fails to adequately develop in many cancer patients, including those with renal cell carcinoma (RCC). A number of different mechanisms have been proposed to explain the immune dysfunction observed in cancer patient T cells. Here we show that T cells from RCC patients display increased sensitivity to apoptosis. Tumor-infiltrating lymphocytes (TILs) display the most profound sensitivity, because 10-15% of those cells are apoptotic when assessed by terminal deoxynucleotidyltransferase-mediated nick end labeling in situ, and the number of apoptotic TILs further increases after 24 h of culture. Peripheral blood T cells from RCC patients are not directly apoptotic, although T lymphocytes derived from 40% of those individuals undergo activation-induced cell death (AICD) upon in vitro stimulation with phorbol myristate acetate and ionomycin. This is in contrast to T cells from normal individuals, which are resistant to AICD. TILs and peripheral blood T cells from RCC patients also exhibit impaired activation of the transcription factor, nuclear factor (NF)-kappaB. Additional findings presented here indicate that the heightened sensitivity of patient T cells to apoptosis may be tumor induced, because supernatants from RCC explants sensitize, and in some instances directly induce, normal T cells to apoptosis. These same supernatants also inhibit NF-kappaB activation. RCC-derived gangliosides may represent one soluble tumor product capable of sensitizing T cells to apoptosis. Pretreatment with neuraminidase, but not proteinase K, abrogated the suppressive effects of tumor supernatants on both NF-kappaB activation and apoptosis. Additionally, gangliosides isolated from tumor supernatants not only inhibited NF-kappaB activation but also sensitized T cells to AICD. These findings demonstrate that tumor-derived soluble products, including gangliosides, may contribute to the immune dysfunction of T cells by altering their sensitivity to apoptosis.

Apoptosis↗
PubMed2001

Cytokine therapy for metastatic renal cell carcinoma.

Cytokine therapy for patients with metastatic renal cancer is based on observations suggesting this neoplasm may be responsive to immunotherapy. Two cytokines, interferon-alpha (IFN-alpha) and interleukin 2 (IL-2) produce tumor regressions in 10% to 15% of patients with metastatic disease. Randomized trials demonstrate a modest survival advantage for patients treated with IFN-alpha. Combinations of IL-2 and IFN-alpha appear to be associated with improved response rates, but no demonstrable effect on survival. Additions of other cytokines (eg, GM-CSF) or chemotherapy to this combination has been investigated, but results do not suggest they enhance the outcome. Patient selection remains an important issue in this patient population. Individuals who are asymptomatic and have limited pulmonary or soft-tissue disease are most likely to benefit. The roles of immune dysregulation and the addition of novel cytostatic agents to these regimens are under investigation.

Antineoplastic Agents↗
PubMed2000

Roles of NF-kappaB and 26 S proteasome in apoptotic cell death induced by topoisomerase I and II poisons in human nonsmall cell lung carcinoma.

Activation of signaling pathways after DNA damage induced by topoisomerase (topo) poisons can lead to cell death by apoptosis. Treatment of human nonsmall cell lung carcinoma (NSCLC-3 or NSCLC-5) cells with the topo I poison SN-38 or the topo II poison etoposide (VP-16) leads to activation of NF-kappaB before induction of apoptosis. Inhibiting the degradation of IkappaBalpha by pretreatment with the proteasome inhibitor MG-132 significantly inhibited NF-kappaB activation and apoptosis but not DNA damage induced by SN-38 or VP-16. Transfection of NSCLC-3 or NSCLC-5 cells with dominant negative mutant IkappaBalpha (mIkappaBalpha) inhibited SN-38 or VP-16 induced transcription and DNA binding activity of NF-kappaB without altering drug-induced apoptosis. Regulation of apoptosis by mitochondrial release of cytochrome c and activation of pro-caspase 9 followed by cleavage of poly(ADP-ribose) polymerase by effector caspases 3 and 7 was similar in neo and mIkappaBalpha cells treated with SN-38 or VP-16. In contrast to pretreatment with MG-132, exposure to MG-132 after SN-38 or VP-16 treatment of neo or mIkappaBalpha cells decreased cell cycle arrest in the S/G2 + M fraction and enhanced apoptosis compared with drug alone. In summary, apoptosis induced by topoisomerase poisons in NSCLC cells is not mediated by NF-kappaB but can be manipulated by proteasome inhibitors.

Apoptosis↗
PubMed2000

A phase II pharmacodynamic study of pyrazoloacridine in patients with metastatic colorectal cancer.

PURPOSE: To perform a phase II trial of pyrazoloacridine (PZA), a novel DNA intercalator, in patients with metastatic colorectal carcinoma and no previous therapy. METHODS: PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 21 days. Pharmacokinetic studies to determine PZA plasma concentrations were performed. RESULTS: No responses were seen in 14 response-evaluable patients. Patients received a median of two cycles of PZA (range 1-6). Toxicity included neutropenia and neurologic side-effects, which were > or = grade III in 73% and 14%, respectively. High plasma concentrations of PZA (Cmax) correlated with low neutrophil counts (P = 0.04). CONCLUSIONS: PZA is inactive at this dose and schedule in colorectal cancer, and produces moderately severe toxicity.

Acridines↗
PubMed2000

Tumor-induced dysfunction in interleukin-2 production and interleukin-2 receptor signaling: a mechanism of immune escape.

PURPOSE: The development of an effective antitumor immune response is compromised in patients with renal cell carcinoma. Despite significant infiltration by T lymphocytes into renal tumors, no detectable induction of gene expression is associated with the generation of an antitumor immune response. Tumor-induced down-regulation of interleukin (IL)-2 expression may contribute to the impaired development of the T cell-mediated antitumor immune response. Within renal tumors, there is no detectable expression of IL-2 or the IL-2 receptor alpha chain, and only low levels of interferon gamma (IFN-gamma) mRNA are detected. Products in the tumor environment may suppress the expression of these genes, thus inhibiting production of type 1 helper T cell cytokines. METHODS: Peripheral blood lymphocytes obtained from healthy volunteers were exposed to supernatants from renal cell carcinoma explants, and the immunologic consequences of this were assessed using a variety of molecular assays. RESULTS: Soluble products from renal tumor explants can inhibit the production of IL-2 and IFN-gamma by peripheral blood lymphocytes and can suppress T-cell proliferation. Soluble products from renal cell carcinoma explants appear to block the nuclear translocation of nuclear factor kappa B (NFkappaB) proteins p50 and RelA without affecting cytoplasmic levels of these proteins. In some experiments, a reduction in the nuclear translocation of other transcription factors involved in IL-2 gene expression, including nuclear factor of activated T cells and accessory protein-1, was observed. Gangliosides isolated from tumor supernatants blocked the production of IL-2 and IFN-gamma in response to ionomycin plus phorbol myristate acetate stimulation. These gangliosides also inhibited stimulus-dependent activation and nuclear accumulation of NFkappaB. Coculture experiments demonstrated that renal cell carcinoma lines known to express gangliosides could inhibit the activation of NFkappaB in normal T cells and the Jurkat T-cell line. Supernatants from renal cell carcinoma explants and renal cell carcinoma cell lines can also suppress the proliferation of normal T cells, thus reproducing another defect observed in tumor-infiltrating lymphocytes. Supernatants from renal cell carcinoma tumors also appear to inhibit signaling through the IL-2 receptor. Although tumor supernatants had little effect on IL-2 receptor (alpha, beta or gamma) expression, they did block expression of JAK3, a key kinase involved in signaling through the IL-2 receptor pathway. Moreover, downstream events in IL-2 receptor signaling linked to JAK3 were impaired in T cells treated with tumor supernatants. CONCLUSION: These findings suggest that soluble products from renal tumors may suppress T-cell responses by blocking both IL-2 production and normal IL-2 receptor signaling.

Carcinoma, Renal Cell↗
PubMed2000

Cytokine combinations: therapeutic use in patients with advanced renal cell carcinoma.

Treatment of metastatic renal cell carcinoma (RCC) remains unsatisfactory. To enhance the antitumor effects of various cytokines, combinations of these agents have been investigated. Interleukin-2 (IL-2) and interferon-alfa (IFN-alpha) have been combined based on data from preclinical studies suggesting synergism. A review of available phase I and II trials in more than 1,400 patients indicates that response rates are approximately 20%. Complete regressions are seen in 3% to 5% of patients. To demonstrate that this combination increases overall response rates, randomized trials were required. The results of a phase III study demonstrate a significantly improved response rate (18.6%) and 1-year event-free survival (20.9%) for patients treated with continuous infusion recombinant (r) IL-2 and subcutaneous IFN-alpha compared with either cytokine alone. The toxicity of rlL-2 and IFN-alpha is related to cytokine dose and schedule, but appears less than that reported with high-dose rIL-2. Analysis of prognostic factors and surrogate marker changes have been conducted. Performance status and number of disease sites predict response. rIL-2 and IFNalpha were then combined with fluorouracil, with initial reports suggesting response rates greater than 40%. Recent reports indicate 1% to 39% of patients responding. In a group of 836 patients with metastatic RCC receiving this therapy, 25.3% responded. Randomized trials comparing chemoimmunotherapy to rIL-2 and/or IFN-alpha are now required. The biologic basis and rationale for utilization of cytokines are strong. Clinical results are consistent with improved response rates in patients receiving rIL-2 and IFN-alpha. Continued investigation of novel and new treatment approaches remains a priority.

Adjuvants, Immunologic↗
PubMed1999

T-cell adoptive immunotherapy of metastatic renal cell carcinoma.

OBJECTIVES: To determine the feasibility and toxicity of the adoptive transfer of ex vivo-activated T lymphocytes that have been sensitized to autologous tumor vaccine in vivo. METHODS: Twenty patients with extensive metastatic renal cell carcinoma received systemic adoptive immunotherapy with autologous T cells in the absence of conjunctional interleukin-2 (IL-2) administration. Patients were vaccinated intradermally with irradiated autologous tumor cells and granulocyte-macrophage colony-stimulating factor as an adjuvant to stimulate an immune response. Inguinal lymph nodes draining the vaccine site were surgically removed, and the cells were stimulated with staphylococcal enterotoxin A followed by expansion in 60 IU/mL IL-2, and in some cases additionally stimulated with anti-CD3 monoclonal antibody and IL-2, to obtain a large number of cells. RESULTS: The staphylococcal enterotoxin A/IL-2 activation induced vigorous proliferation of T cells (median expansion 26-fold) that were a mixture of CD4 and CD8 T lymphocytes. Activated cells were infused intravenously at doses ranging from 2x10(9) to 9.5x10(10). There was minimal toxicity consisting of grade 1 or 2 fever and nausea, and the entire treatment was delivered as outpatient therapy. One patient had a partial response, one had a mixed response, and 8 had stable disease lasting at least 5 months. CONCLUSIONS: Adoptive transfer of ex vivo-activated, tumor vaccine-primed lymph node cells is feasible and is associated with minimal toxicity when used alone. These results warrant further study in a Phase II trial.

Adult↗
PubMed1999

Recent advances in systemic therapy for gastrointestinal neuroendocrine tumors.

Neuroendocrine tumors of the gastrointestinal tract are rare tumors which can be classified as amine precursor uptake and decarboxylation tumors (APU-Domas). Although the majority of clinically apparent tumors are malignant, they are frequently slow growing. Despite this characteristic, they may generate disabling hormonal syndromes requiring aggressive treatment to achieve palliation. Recent advances in understanding the pathophysiology of these tumors has led to better medical therapy with chemotherapeutic agents, somatostatin analogues, and biologic therapies. This review will update the recent efforts in systemic therapies of the gastrointestinal neuroendocrine tumors.

3-Iodobenzylguanidine↗
PubMed1999

Interferon-gamma production by T lymphocytes from renal cell carcinoma patients: evidence of impaired secretion in response to interleukin-12.

Interleukin-12 (IL-12) is a heterodimeric cytokine that enhances the cytolytic activity, proliferation, and interferon-gamma (IFN-gamma) production by T lymphocytes and natural killer cells, and has significant antitumor activity in a variety of murine tumor models. The induction of interferon (IFN)-gamma by IL-12 in tumor-bearing mice plays an important role in its antitumor activity. We therefore examined the effects of IL-12 on IFN-gamma production by T cells derived from patients with renal cell carcinoma (RCC), including freshly isolated tumor infiltrating lymphocytes (T-TIL), matched peripheral blood T cells (T-PBL), and RCC-specific TIL lines. IL-12 alone induced IFN-gamma secretion by T cells from normal individuals and appeared to act synergistically with either IL-2 or anti-CD3 antibody. In contrast, it failed to stimulate significant IFN-gamma secretion by T-PBL and T-TIL from RCC patients. This unresponsive state in T-PBL appeared selective because IFN-gamma was produced when cells were stimulated with either phytohemagglutinin or anti-CD3 antibody. Moreover, costimulation through the T-cell receptor (TCR)/CD3 complex or with IL-2 made T-PBL from RCC patients responsive to IL-12, possibly secondary to the upregulation of IL-12R (beta chain). A selective loss of IL-12-dependent production of IFN-gamma was also consistently observed in two of three established RCC-specific TIL lines. Although these cell lines did not respond to any concentration of IL-12, they did produce IFN-gamma after ligation of the TCR/CD3 or stimulation with IL-2, IL-12 also acted either syngeristically or additively with IL-2, anti-CD3 antibody, or autologous tumor cells to induce IFN-gamma production. The observed decreases in IFN-gamma production in response to IL-12 may have a negative effect on the development of T-cell immunity. The clinical importance of these findings during in vivo administration of IL-12 remains to be determined.

Carcinoma, Renal Cell↗
PubMed1999

Altered drug interaction and regulation of topoisomerase IIbeta: potential mechanisms governing sensitivity of HL-60 cells to amsacrine and etoposide.

Topoisomerase II (topo II), an enzyme essential for cell viability, is present in mammalian cells as the alpha- and beta-isoforms. In human leukemia HL-60/S or HL-60/doxorubicin (DOX)0.05 cells, the levels of topo IIalpha- or beta-protein were similar in either asynchronous exponential or synchronized cultures. Although topo IIalpha was hypophosphorylated in HL-60/DOX0.05 compared with HL-60/S cells, both overall and site-specific hyperphosphorylation of topo IIbeta was apparent in HL-60/DOX0.05 compared with HL-60/S cells. The phosphorylation of topo IIalpha and not beta was enhanced in the S and G(2) + M phases of HL-60/S cells. In contrast, an increase in the phosphorylation of topo IIbeta compared with alpha was apparent in the G(1) and S phases of HL-60/DOX0.05 cells. The cytotoxicity and depletion of topo IIalpha or beta in cells treated with drug for 1 h revealed that mole-for-mole, amsacrine was 2-fold more effective than etoposide in killing HL-60/S or HL-60/DOX0.05 cells and in depleting the beta versus alpha topo II protein. Present results demonstrate that: 1) hyperphosphorylation of topo IIbeta in HL-60/DOX0.05 cells may be a compensatory consequence of the hypophosphorylation of topo IIalpha to maintain normal topo II function during proliferation, and 2) enhanced sensitivity of HL-60/S or HL-60/DOX0.05 cells to amsacrine may be due to the preferential interaction and depletion of topo IIbeta.

Amsacrine↗
PubMed1999

Renal cell carcinoma-derived gangliosides suppress nuclear factor-kappaB activation in T cells.

Activation of the transcription factor nuclear factor-kappaB (NFkappaB) is impaired in T cells from patients with renal cell carcinomas (RCCs). In circulating T cells from a subset of patients with RCCs, the suppression of NFkappaB binding activity is downstream from the stimulus-induced degradation of the cytoplasmic factor IkappaBalpha. Tumor-derived soluble products from cultured RCC explants inhibit NFkappaB activity in T cells from healthy volunteers, despite a normal level of stimulus-induced IkappaBalpha degradation in these cells. The inhibitory agent has several features characteristic of a ganglioside, including sensitivity to neuraminidase but not protease treatment; hydrophobicity; and molecular weight less than 3 kDa. Indeed, we detected gangliosides in supernatants from RCC explants and not from adjacent normal kidney tissue. Gangliosides prepared from RCC supernatants, as well as the purified bovine gangliosides G(m1) and G(d1a), suppressed NFkappaB binding activity in T cells and reduced expression of the cytokines IL-2 and IFN-gamma. Taken together, our findings suggest that tumor-derived gangliosides may blunt antitumor immune responses in patients with RCCs.

Carcinoma, Renal Cell↗