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41.
Robin L. Miller M.D. Leslie R. Sheeler M.D. Thomas W. Bauer M.D. Ph.D. Ronald M. Bukowski M.D. 《The American journal of medicine》1986,80(6):1230-1236
Erdheim-Chester disease is a distinctive pathologic and radiographic entity characterized by bilateral, symmetric sclerosis of the metaphyseal regions of long bones and infiltration of foamy, lipid-laden histiocytes. Clinically, it ranges from an asymptomatic, focal process to a fatal, systemic disease. All previously reported cases of ErdheimChester disease are reviewed and a new case with diabetes insipidus, partial hypopituitarism, histiocytic skin lesions, and retro-orbital tumors is presented. An 11-year follow-up reveals progression from a benign, limited process to a progressive, systemic disease. Patients with Erdheim-Chester disease show markedly disparate clinical courses and some features similar to Hand-Schüller-Christian disease. They need careful monitoring and further attempts at treatment. 相似文献
42.
Storkus WJ Herrem C Kawabe M Cohen PA Bukowski RM Finke JH Wesa AK 《Critical reviews in immunology》2007,27(5):485-493
Tumors represent an altered self cell type that can be recognized by both the host humoral (B cells, antibodies) and cellular (T cells) adaptive immune systems. Because most known tumor-associated antigens (TAA) recognized by T cells represent overexpressed or aberrantly expressed proteins, which are not mutated and to which tolerance has been developed, the anti-TAA T-cell repertoire available to the cancer patient is of moderate-to-low avidity. Specific vaccinations typically amplify the absolute number of such T cells, but may have little consequence on improving their functional avidity, which may fall below a critical threshold required for effective recognition of tumor cells in situ. This review will discuss methods to improve low-avidity T-cell recognition of cancer cells by manipulating the tumor cells themselves to conditionally express higher levels of TAA-derived peptide epitopes presented in major histocompatibility (MHC) complexes. This may facilitate the design and performance of novel combinational therapies for the effective treatment of a broad range of cancer types. 相似文献
43.
Rowe CA Nantz MP Bukowski JF Percival SS 《Journal of the American College of Nutrition》2007,26(5):445-452
OBJECTIVE: Determine if a specific formulation of Camellia sinensis (CSF) can prevent illness and symptoms due to cold and flu, and enhance gammadelta T cell function METHODS: Design: Randomized, double-blind, placebo-controlled study. Subjects: Healthy adults 18-70 years old. Intervention: Proprietary formulation of Camellia sinensis (green tea) capsules, or a placebo, twice a day, for 3 months. Measures of Outcome: As assessed by daily symptom logs, percentage of subjects experiencing cold and flu symptoms, number of days subjects experienced symptoms, and percentage of subjects seeking medical treatment. Mean in vivo and ex vivo proliferative and interferon gamma responses of subjects' peripheral blood mononuclear cells to gammadelta T cell antigen stimulation. RESULTS: Among subjects taking CSF there were 32.1% fewer subjects with symptoms (P = 0.035), 22.9% fewer overall illnesses of at least 2 days duration (P = 0.092), and 35.6% fewer symptom days (P < 0.002), compared to subjects taking placebo. gammadelta T cells from subjects taking CSF proliferated 28% more (P = 0.017) and secreted 26% more IFN-gamma (P = 0.046) in response to gammadelta T cell antigens, as compared to gammadelta T cells from subjects taking placebo. CSF was well-tolerated. CONCLUSIONS: This proprietary formulation of CSF is a safe and effective dietary supplement for preventing cold and flu symptoms, and for enhancing gammadelta T cell function. 相似文献
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45.
Vaziri SA Hill J Chikamori K Grabowski DR Takigawa N Chawla-Sarkar M Rybicki LR Gudkov AV Mekhail T Bukowski RM Ganapathi MK Ganapathi R 《Molecular cancer therapeutics》2005,4(12):1880-1890
Proteasome inhibition following DNA damage results in the synergistic induction of apoptosis via a nuclear factor-kappaB-independent mechanism. In this study, we identify the role of p53 in mediating apoptosis by the sequence-specific treatment involving the DNA-damaging, topoisomerase I-targeting drug SN-38 followed by the proteasome inhibitor PS-341 (SN-38-->PS-341). The p53-dependent sensitization of DNA damage-induced apoptosis by PS-341 is accompanied by persistent inhibition of proteasome activity and increased cytosolic accumulation of p53, including higher molecular weight forms likely representing ubiquitinated species. In contrast, pretreatment with PS-341 followed by treatment with SN-38 (PS-341-->SN-38), which leads to an antagonistic interaction, results in transient inhibition of proteasome activity and accumulation of significantly lower levels of p53 localized primarily to the nucleus. Whereas cells treated with PS-341-->SN-38 undergo G2 + M cell cycle arrest, cells treated with SN-38-->PS-341 exhibit a decreased G2 + M block with a concomitant increase in the sub-G1 population. Decreased accumulation of cells in the G2 + M phase of the cell cycle in SN-38-->PS-341-treated cells compared with PS-341-->SN-38-treated cells correlates with enhanced apoptosis and reduced expression of two p53-modulated proteins, 14-3-3sigma and survivin, both of which play critical roles in regulating G2 + M progression and apoptosis. The functional role of 14-3-3sigma or survivin in regulating the divergent function of p53 in response to SN-38-->PS-341 and PS-341-->SN-38 treatment in inducing apoptosis versus G2 + M arrest/DNA repair, respectively, was confirmed by targeted down-regulation of these proteins. These results provide insights into the mechanisms by which inhibition of proteasome activity modulates DNA damage-induced apoptosis via a p53-dependent pathway. 相似文献
46.
Garcia JA Mekhail T Elson P Wood L Bukowski RM Dreicer R Rini BI 《BJU international》2012,109(1):63-69
Study Type – Therapy (individual cohort) Level of Evidence 2b
OBJECTIVE
? To determine, in a phase I/II trial, the maximum tolerated dose (MTD), clinical activity and safety of concurrent subcutaneous (s.c.) interleukin‐2 (IL‐2), interferon‐α2b (IFN‐α) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF).PATIENTS AND METHODS
? Patients with metastatic renal cell carcinoma (RCC) received on a 3+3 trial design escalating doses of s.c. GM‐CSF, IL‐2 and IFN‐α. ? Dose‐limiting toxicities (DLTs) during the first 6‐week cycle were used to determine the MTD. ? A phase II trial was then initiated to determine clinical activity.RESULTS
? A total of sixty patients were enrolled in the study (phase I = 31; phase II = 29). ? Two DLTs were observed (G3 nausea/vomiting and fatigue) and the MTD was determined to be GM‐CSF 5.0 µg/kg/day, IL‐2 9.0 mIU/m2/day and IFN‐α 5.0 mU/m2/day. ? Patients received a median (range) of four (one to 11) cycles of therapy. G3 adverse events were reported in 10 of 31 (32%) patients. ? The overall response rate was 20% (one complete response and 11 partial responses), including patients who were rendered free of disease with surgery. ? The median progression‐free survival and overall survival were 6.0 and 23.4 months, respectively.CONCLUSIONS
? Immunotherapy with concurrent s.c. GM‐CSF, IL‐2 and IFN‐α is generally well tolerated. ? The overall response rate observed with this combination continues to show the efficacy of immunotherapy in a selected group of metastatic RCC patients. 相似文献47.
Gingival biopsy in thrombotic thrombocytopenic purpura 总被引:1,自引:0,他引:1
A Goodman R Ramos M Petrelli S A Hirsch R Bukowski J W Harris 《Annals of internal medicine》1978,89(4):501-504
Gingival biopsy has been advocated as a readily available, safe, rapid histologic confirmation of the clinical diagnosis of thrombotic thrombocytopenic purpura. Eighteen gingival biopsies from 16 patients with proven thrombotic thrombocytopenic purpura were reviewed. Seven (39%) showed characteristic histologic changes: [1] subendothelial hyalinelike deposits; [2] intraluminal deposits; [3] lack of inflammatory change in vessels and stroma. To assess specificity, gingival sections from 154 patients with oral pathology only and from 50 unselected autopsies were reviewed: 10% to 20% of biopsies from patients with oral pathology only (primarily inflammation) and three of 50 autopsy specimens showed occasional intraluminal deposits but no subendothelial deposits. In addition, other histologic features permitted them to be distinguished from thrombotic thrombocytopenic purpura. We conclude that gingival biopsy in thrombotic thrombocytopenic purpura, although helful in confirming the diagnosis, is less often positive than has been suggested. Biopsy of grossly inflamed gingiva should be avoided. 相似文献
48.
Hussein MA Sandstrom K Elson P Finke J McLain D Rayman P Rybicki LA Bukowski RA 《Journal of cancer research and clinical oncology》2001,127(10):619-624
PURPOSE: Some limitations of effective therapy in multiple myeloma include the low growth fraction of the malignant plasma cells, multi-drug resistance, and the presence of other concurrent diseases in this patient population. A phase I study was conducted to evaluate the toxicity of granulocyte macrophage colony stimulating factor (GM-CSF) in myeloma patients as well as the potential effect on the plasma cell labeling index (PCLI). Relapsed patients with multiple myeloma were eligible. METHODS: The first phase of this trial assessed the toxicity (including the effect on disease progression) of escalating doses (125-500 microg/m2 SC, days 1-5) of GM-CSF, and the effects of this cytokine on PCLI. Patients whose PCLI doubled and increased to > or = 1.7% were treated with chemotherapy including cyclophosphamide, vincristine, prednisone, and GM-CSF. Twenty-two patients were enrolled. RESULTS: The toxicity of GM-CSF was mild, and no dose-limiting side effects were seen. Twenty-five percent of patients (5/20) achieved the target PCLI, and 4/5 proceeded to receive chemotherapy. No relationship of GM-CSF dose to increases of the PCLI was noted. All patients who received chemotherapy responded. CONCLUSIONS: GM-CSF has acceptable toxicity in patients with multiple myeloma and produced increases of PCLI in selected individuals. Further studies of GM-CSF alone or in combination with chemotherapy are indicated. 相似文献
49.
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