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21.
Phase II trial of pegylated interferon and thalidomide in malignant metastatic melanoma 总被引:2,自引:0,他引:2
Pegylated interferon and thalidomide demonstrate immunomodulatory and antiangiogenic activity, and efficacy in melanoma. The combination was evaluated in a phase II trial. Eligibility included biopsy-confirmed malignant melanoma with metastases and progression, maximum of two earlier systemic therapies, performance status of 0-2, and adequate hepatic, bone marrow and renal function. Pegylated interferon was administered at a dose of 0.5 microg/kg subcutaneously weekly and thalidomide 200 mg orally daily. Toxicity was evaluated every 2 weeks and response every 8 weeks. Eighteen patients were enrolled in this trial. Median age was 55.5 years (range: 29-80 years). Seventeen patients had visceral metastases and one had lymph node-only metastases. Two patients had brain metastases. Nine patients had received earlier adjuvant therapy and 16 patients had received earlier therapy for metastatic disease. Performance status was 0, 1 and 2 in 11, six and one patients, respectively. Severe (grade 4) toxicities observed were anemia in two patients and thrombocytopenia in one patient. No treatment-related deaths occurred. Dose escalation of thalidomide to 300 mg daily was feasible in four patients. One therapy-related hospitalization for nausea and dehydration occurred. No objective responses were noted; three patients demonstrated disease stabilization. The regimen of pegylated interferon and thalidomide was well tolerated. The combination, however, failed to demonstrate clinical efficacy in pretreated metastatic malignant melanoma. 相似文献
22.
Matrix metalloproteinase activity and osteoclasts in experimental prostate cancer bone metastasis tissue
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Dong Z Bonfil RD Chinni S Deng X Trindade Filho JC Bernardo M Vaishampayan U Che M Sloane BF Sheng S Fridman R Cher ML 《The American journal of pathology》2005,166(4):1173-1186
Previously, we and others showed that broad spectrum pharmaceutical inhibition of matrix metalloproteinase (MMP) activity reduces intraosseous tumor burden and bone degradation in animal models of bone metastasis. Herein, we used specific assays to measure net enzymatic activities of individual MMPs during colonization of bone by prostate cancer cells. PC3 cells were injected into the marrow of human fetal femurs previously implanted in SCID mice. Net MMP-9 activity in bone tissues peaked 2 weeks after injection, coinciding with a wave of osteoclast recruitment. In contrast, MMP-2 and MT1-MMP activity did not change. In vitro, co-culture of PC3 cells with bone tissue led to activation of pro-MMP-9 and increases in secreted net MMP-9 activity. Activation of pro-MMP-9 was prevented by metalloprotease inhibitors but not by inhibitors of other classes of proteases. Ribozyme suppression of MMP-9 expression in PC3 cells did not affect pro-MMP-9 activation or net MMP-9 activity and did not affect the phenotype of bone tumors. siRNA targeting of MMP-9 expression in preosteoclasts in vitro demonstrated that tumor-induced preosteoclast motility was dependent on MMP-9 expression. These data suggest that osteoclast-derived MMP-9 may represent a potential therapeutic target in bone metastasis and provide a rationale for the development of MMP-9-specific inhibitors. 相似文献
23.
Background
Nivolumab is an important new therapy option for patients with advanced renal cell carcinoma, and has a different mechanism of action compared with vascular endothelial growth factor -targeted therapies. It is a programmed death 1 immune checkpoint inhibitor antibody with response patterns, efficacy, and safety profiles that differ from those of conventional antiangiogenic or mammalian target of rapamycin inhibition therapy.Methods and Purpose
This commentary discusses and evaluates the clinical experience with nivolumab from the available literature and presents practical considerations for the use of nivolumab immunotherapy in aRCC to optimize clinical management. 相似文献24.
Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study
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Amishi Y. Shah Jose A. Karam Gabriel G. Malouf Priya Rao Zita D. Lim Eric Jonasch Lianchun Xiao Jianjun Gao Ulka N. Vaishampayan Daniel Y. Heng Elizabeth R. Plimack Elizabeth A. Guancial Chunkit Fung Stefanie R. Lowas Pheroze Tamboli Kanishka Sircar Surena F. Matin W. Kimryn Rathmell Christopher G. Wood Nizar M. Tannir 《BJU international》2017,120(6):782-792
25.
Prajakta Vaishampayan Clara Curiel-Lewandrowski Sally E. Dickinson 《Molecular carcinogenesis》2023,62(1):52-61
Recent advances in the understanding and targeting of immune checkpoints have led to great progress in immune therapies against many forms of cancer. While many types of immune checkpoints are currently targeted in the clinic, this review will focus on recent research implicating the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) axis as an emerging focus for the treatment of keratinocytic tumors. PD-L1 is of particular interest in nonmelanoma skin cancer (NMSC), as it is not only upregulated in these tumors but is stimulated by environmental ultraviolet exposure. This response may also make PD-L1 an excellent target for photochemoprevention using topically applied small molecule inhibitors. Here, we summarize recent investigations on PD-L1 expression and clinically relevant immune checkpoint inhibitor treatment in cutaneous squamous cell carcinoma, basal cell carcinoma, and head and neck squamous cell carcinoma, as well as small molecule agents targeting PD-L1 that may be useful for clinical development aiming at treatment or prevention of NMSC. 相似文献
26.
Heng DY Mackenzie MJ Vaishampayan UN Bjarnason GA Knox JJ Tan MH Wood L Wang Y Kollmannsberger C North S Donskov F Rini BI Choueiri TK 《Annals of oncology》2012,23(6):1549-1555
BackgroundA subset of patients treated with initial anti-vascular endothelial growth factor (VEGF) therapy exhibit progressive disease (PD) as the best response per RECIST criteria.MethodsData from patients with metastatic renal cell carcinoma (mRCC) treated with anti-VEGF therapy were collected through the International mRCC Database Consortium from 12 centers.ResultsOne thousand and fifty-six assessable patients received initial VEGF inhibitors and 272 (26%) of these patients had PD as best response. Initial treatment included sunitinib (n = 203), sorafenib (n = 51), or bevacizumab (n = 18). Six percent of patients were at favorable risk, 55% at intermediate risk, and 39% at poor risk. On multivariable analysis, predictors of PD were Karnofsky performance status < 80% [odds ratio (OR) = 2.3, P < 0.0001], diagnosis to treatment < 1 year (OR = 2.1, P < 0.0001), neutrophilia (OR = 1.9, P = 0.0021), thrombocytosis (OR = 1.7, P = 0.0068), and anemia (OR = 1.6, P = 0.0058). Median progression-free survival (PFS) in patients with PD versus without PD was 2.4 versus 11 months (P < 0.0001) and overall survival (OS) was 6.8 versus 29 months (P < 0.0001), respectively. One hundred and eight (40%) VEGF-refractory patients proceeded to receive further systemic therapies. Response rate, PFS, and OS for subsequent therapy were 9%, 2.5 months, and 7.4 months, respectively, with no statistical differences between patients who received VEGF versus mammalian target of rapamycin (mTOR) inhibitors.ConclusionsPrimary anti-VEGF-refractory mRCC patients have a dismal prognosis. Second-line anti-mTOR and anti-VEGF agents produce similar outcomes. 相似文献
27.
28.
Iftekhar U. Ahmad Jeffrey D. Forman Fazlul H. Sarkar Gilda G. Hillman Elisabeth Heath Ulka Vaishampayan 《Nutrition and cancer》2013,65(7):996-1000
Soy isoflavones sensitize prostate cancer cells to radiation therapy by inhibiting cell survival pathways activated by radiation. At the same time, soy isoflavones have significant antioxidant and anti-inflammatory activity, which may help prevent the side effects of radiation. Therefore, we hypothesized that soy isoflavones could be useful when given in conjunction with curative radiation therapy in patients with localized prostate cancer. In addition to enhancing the efficacy of radiation therapy, soy isoflavones could prevent the adverse effects of radiation. We conducted a pilot study to investigate the effects of soy isoflavone supplementation on acute and subacute toxicity (≤6 mo) of external beam radiation therapy in patients with localized prostate cancer. Forty-two patients with prostate cancer were randomly assigned to receive 200 mg soy isoflavone (Group 1) or placebo (Group 2) daily for 6 mo beginning with the first day of radiation therapy, which was administered in 1.8 to 2.5 Gy fractions for a total of 73.8 to 77.5 Gy. Adverse effects of radiation therapy on bladder, bowel, and sexual function were assessed by a self-administered quality of life questionnaire at 3 and 6 mo. Only 26 and 27 patients returned completed questionnaires at 3 and 6 mo, respectively. At each time point, urinary, bowel, and sexual adverse symptoms induced by radiation therapy were decreased in the soy isoflavone group compared to placebo group. At 3 mo, soy-treated patients had less urinary incontinence, less urgency, and better erectile function as compared to the placebo group. At 6 mo, the symptoms in soy-treated patients were further improved as compared to the placebo group. These patients had less dripping/leakage of urine (7.7% in Group 1 vs. 28.4% in Group 2), less rectal cramping/diarrhea (7.7% vs. 21.4%), and less pain with bowel movements (0% vs. 14.8%) than placebo-treated patients. There was also a higher overall ability to have erections (77% vs. 57.1%). The results suggest that soy isoflavones taken in conjunction with radiation therapy could reduce the urinary, intestinal, and sexual adverse effects in patients with prostate cancer. 相似文献
29.
Nikita P. Panpaliya Prasanna T. Dahake Yogesh J. Kale Mahesh V. Dadpe Shrikant B. Kendre Ayesha G. Siddiqi Ulka R. Maggavi 《Saudi Dental Journal》2019,31(1):76-83
Introduction
Numerous antimicrobial agents are used to eliminate oral biofilm. However due to emergence of multi drug resistant microorganisms, the quest to find out biologically safe and naturally available antimicrobial agents continues.Aim
To evaluate antimicrobial efficacy of silver nano-particles against five common oral pathogenic bacteria.Objective
To determine antimicrobial activity of silver nanoparticles and chlorhexidine gluconate against oral pathogenic bacteria.Material and Method
We used strains of Streptococcus mutans (MTCC 497), Streptococcus oralis (MTCC 2696), Lactobacillus acidophilus (MTCC 10307), Lactobacillus fermentum (MTCC 903), and Candida albicans (MTCC 183). We used commercially available silver nanoparticles (experimental group) and chlorhexidine gluconate (positive control). We determined minimum inhibitory concentration (MIC) minimum bactericidal concentration (MBC) of both agents and analyzed the data using paired ‘t’ test, one way ANOVA and Tucky’s post Hoc HSD.Result
Silver nanoparticles inhibited bacterial growth moderately. The mean MIC of AgNP against S. mutans was 60?±?22.36?μg/ml, S. oralis – 45?±?11.18?μg/ml, L. acidophilus – 15?±?5.59?μg/ml, L. fermentum – 90?±?22.36?μg/ml, Candida albicans – 2.82?±?0.68?μg/ml respectively. For chlorhexidine gluconate, mean MIC for S. mutans was 300?±?111.80?μg/ml, S. oralis – 150?±?55.90?μg/ml, L. acidophilus – 450?±?111.80?μg/ml, L. fermentum – 450?±?111.80?μg/ml and Candida albicans – 150?±?55.90?μg/ml. MIC and MBC values of AgNP were significantly lower than chlorhexidine gluconate and statistically significant (p?<?0.05).Conclusion
Silver nanoparticles exhibited better bacteriostatic and bactericidal effect with concentration less than five folds as compared to chlorhexidine. Silver nanoparticles when used in appropriate concentration as safe alternative to present chemically derived other antimicrobial agents. 相似文献30.
Verma R Jaiswal AK Vaishampayan SS Baveja S 《Indian journal of dermatology, venereology and leprology》1999,65(5):232
A case of lichenoid epidermal naevus with unusual clinical presentation is reported. 相似文献