共查询到20条相似文献,搜索用时 15 毫秒
1.
Barrio MM de Motta PT Kaplan J von Euw EM Bravo AI Chacón RD Mordoh J 《Journal of immunotherapy (Hagerstown, Md. : 1997)》2006,29(4):444-454
We investigated whether recombinant human granulocyte-monocyte-colony-stimulating factor (rhGM-CSF) increased the immunogenicity of VACCIMEL, a vaccine consisting of 3 irradiated allogeneic melanoma cell lines. A phase I clinical trial was performed on 20 melanoma patients in stages IIB (n=2), III (n=10), and IV (n=8), who were disease free after surgery (n=16) or had minimal disease (n=4). Cohorts of 4 patients were vaccinated 4 times with VACCIMEL and bacillus Calmette Guerin (BCG) as adjuvant. Besides, the patients received placebo (group 1) or GM-CSF: 150 microg (group 2), 300 microg (group 3), 400 microg (group 4), and 600 microg (group 5) per vaccine. The combination of VACCIMEL and GM-CSF had low toxicity. Only in group 5, grade 2 thoracic pain (3/4 patients) and abdominal cramps (2/4 patients) were observed. Delayed-type hypersensitivity increased after vaccination and it was highest in group 4. Phytohemagglutinin stimulation of peripheral blood lymphocytes was analyzed in 9 patients: 4/9 had normal stimulation; 3/9 had low basal stimulation, which recovered after vaccination; and 2/9 were not stimulated. Antimelanoma antibodies preexisted in 9/19 patients; in 3/19 patients, antibodies anti-33 kd, 90 kd, and 100 kd antigens were induced by vaccination. IgG2 but not IgG1 antibodies were detected. Anti-BCG antibodies, mostly IgG2, reached the highest post/prevaccination ratio in group 4. Median serum interleukin-12 was lower in progressing patients (61.6 pg/mL) than in those without evident disease (89 pg/mL). Thus, its low toxicity and the induction of a predominantly cellular immune response suggest that the addition of 300 to 400 microg GM-CSF to VACCIMEL is useful in increasing the immune response. 相似文献
2.
3.
A phase I vaccine trial with peptides reflecting ras oncogene mutations of solid tumors 总被引:3,自引:0,他引:3
Khleif SN Abrams SI Hamilton JM Bergmann-Leitner E Chen A Bastian A Bernstein S Chung Y Allegra CJ Schlom J 《Journal of immunotherapy (Hagerstown, Md. : 1997)》1999,22(2):155-165
Mutations in the ras genes occur in 20% of all human cancers. These genes, in turn, produce mutated proteins that are unique to cancer cells, rendering them distinguishable from normal cells by the immune system. Thus, mutated Ras proteins may form potential targets for immune therapy. We conducted a phase I/pilot clinical trial in patients with advanced cancers to test the toxicity and the ability to induce an immune response by vaccination with 13-mer mutated Ras peptides reflecting codon 12 mutations. These peptides corresponded to each of the patient's own tumor Ras mutation. Patients were vaccinated monthly x3 subcutaneously with the specific Ras peptide along with Detox adjuvant (RiBi ImmunoChem Research, Inc., Hamilton, MT, U.S.A.) at one of five different peptide dose levels (100, 500, 1,000, 1,500, and 5,000 micrograms). Three out of 10 evaluable patients generated a mutant Ras specific CD4+ and/or CD8+ T-cell immune response. The CD8+ cytotoxic cells specific for Gly to Val mutation at codon 12 were capable of lysing an HLA-A2-matched tumor cell line carrying the corresponding mutant but not the wild-type ras gene. The treatment has been well tolerated with no evidence of serious acute or delayed systemic side effects on any of the five dose levels. We demonstrated that we can generate in cancer patients specific T-lymphocyte responses that detect single amino acid differences in Ras oncoproteins. Neither the immune responses nor the minor side effects seen were found to be dose dependent. This approach may provide a unique opportunity for generating a tumor-directed therapy. Also, in vitro stimulation of these cells with the corresponding peptide generated specific T-cell lines that could be used for adoptive immune therapy. 相似文献
4.
Jelena Kasapović Snežana Pejić Vesna Stojiljković Ana Todorović Ljiljana Radošević-Jelić Zorica S. Saičić Snežana B. Pajović 《Clinical biochemistry》2010,43(16-17):1287-1293
ObjectivesBreast carcinoma is related to the increase of lipid peroxidation in plasma with concomitant decrease of antioxidant (AO) defense capacity in blood cells, which becomes more pronounced during aging of the patients. This work evaluated the potential age-related effect of chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) on the level of lipid hydroperoxides (LP), glutathione (GSH), AO enzyme activities of copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in breast cancer patients. The level of CuZnSOD protein was assessed after the FAC therapy and radiotherapy of breast cancer.Design and methodsAO parameters were measured in the blood of 58 breast cancer patients and 60 healthy age-matched healthy subjects by biochemical and Western blot analyses.ResultsIncreased oxidative stress (LP: p < 0.05) and decreased AO enzyme activities (CuZnSOD: p < 0.01, GPx: p < 0.05, GR: p < 0.01) and GSH level (p < 0.01) in the blood of breast cancer patients in response to FAC chemotherapy seem not to be age-dependent. CuZnSOD enzyme expression decreased after the FAC chemotherapy (p < 0.05), while it increased after the radiotherapy of breast cancer (p < 0.05).ConclusionFAC chemotherapy and radiotherapy promote further oxidative shift, which potentiate already existing chronic oxidative stress linked to breast cancer. In these effects, impaired capacity for H2O2 detoxification (CAT, GPX and GSH) seems to have major contribution. 相似文献
5.
Tahir Hakami 《Clinical Case Reports》2022,10(5)
Acute liver failure developed in a 48‐year‐old woman within days after she received adjuvant chemotherapy for breast cancer. On arrival at ED, she had severe encephalopathy and jaundice. Serum analyses demonstrated coagulopathy and markedly increased transaminases. She was admitted to the ICU for supportive treatment but died several days later. 相似文献
6.
7.
8.
《中华临床医师杂志(电子版)》2015,(21)
目的探讨吡柔比星和环磷酰胺联合多西他赛在乳腺癌新辅助化疗中的临床应用价值。方法选取2012年6月至2014年6月期间我院所收治的100例乳腺癌患者作为临床研究对象,采用区组化随机分组法将入选研究对象随机分为研究组50例和对照组50例。研究组乳腺癌患者采用吡柔比星、环磷酰胺、多西他赛的化疗方案,对照组乳腺癌患者采用吡柔比星、环磷酰胺、氟尿嘧啶的化疗方案,并分别对两组患者的临床治疗情况、不良反应发生情况进行比较和分析。结果与对照组相比,研究组CR 34.00%和PR 48.00%均有所提升,但差别均不具有统计学意义(P>0.05);研究组总缓解率显著增加(82.00%),白细胞下降(52.00%)、血小板减少(24.00%)、恶性呕吐(60.00%)、腹泻(10.00%)、脱发(18.00%)等各项不良反应的总发生率均显著降低,差别均具有统计学意义(P<0.05)。治疗后两组TNM分期均较治疗前明显下降(P<0.05),研究组0期和Ⅰ期的比率与对照组比较显著提高,差异均有统计学意义(P<0.05)。结论吡柔比星和环磷酰胺联合多西他赛的新辅助化疗方案在改善乳腺癌临床治疗效果,以及降低因化疗所引起的相关毒性不良反应方面均呈现出明显的优势作用,可作为乳腺癌患者较为理想的新辅助化疗方案予以临床推广。 相似文献
9.
Lin JT Zhang JS Su N Xu JG Wang N Chen JT Chen X Liu YX Gao H Jia YP Liu Y Sun RH Wang X Yu DZ Hai R Gao Q Ning Y Wang HX Li MC Kan B Dong GM An Q Wang YQ Han J Qin C Yin WD Dongs XP 《Antiviral therapy》2007,12(7):1107-1113
BACKGROUND: Emergence of severe acute respiratory syndrome (SARS) from the winter of 2002 to the spring of 2003 has caused a serious threat to public health. METHODS: To evaluate the safety and immunogenicity of the inactivated SARS coronavirus (SARS-CoV) vaccine, 36 subjects received two doses of 16 SARS-CoV units (SU) or 32 SU inactivated SARS-CoV vaccine, or placebo control. RESULTS: On day 42, the seroconversion reached 100% for both vaccine groups. On day 56, 100% of participants in the group receiving 16 SU and 91.1% in the group receiving 32 SU had seroconverted. The geometric mean titre of neutralizing antibody peaked 2 weeks after the second vaccination, but decreased 4 weeks later. CONCLUSION: The inactivated vaccine was safe and well tolerated and can elicit SARS-CoV-specific neutralizing antibodies. 相似文献
10.
Immune monitoring in a phase 1 trial of a PSA DNA vaccine in patients with hormone-refractory prostate cancer 总被引:3,自引:0,他引:3
Miller AM Ozenci V Kiessling R Pisa P 《Journal of immunotherapy (Hagerstown, Md. : 1997)》2005,28(4):389-395
Prostate cancer remains a leading cause of cancer illness and death among men in Europe. No curative treatment exists when the disease has spread beyond the prostate. Immunotherapy with DNA vaccines has emerged as a potential therapeutic approach for the induction of antitumor specific cytotoxic T lymphocytes. In this study six patients with hormone-refractory prostate cancer were monitored for their ability to mount PSA-specific cellular responses after receiving a pVAX/PSA DNA vaccine (patients 1-3, 100 microg; patients 7-9, 900 microg) with recombinant GM-CSF and IL-2 as adjuvants. IFNgamma ELISPOT showed that naturally processed PSA protein and PSA peptides are recognized by T cells in the blood of some prostate cancer patients after a PSA DNA vaccine. Analysis of other cytokines showed the production of IL-4 and IL-6 but importantly did not show an increase in the number of IL-10-producing cells after vaccination in any of the patients. The authors conclude that a pVAX/PSA DNA vaccine can induce PSA-specific cellular immune responses in patients with hormone-refractory prostate cancer, thus emphasizing the potential for PSA as a target molecule for the immunotherapy of prostate cancer. 相似文献
11.
Elizabeth L. Strevel Colin Newman Gregory R. Pond Martha MacLean Lillian L. Siu 《Supportive care in cancer》2007,15(7):829-840
Goals of work The quality of informed consent in phase I trials is controversial, partially due to gaps in patient understanding. We assessed
an educational DVD’s impact on knowledge and satisfaction in cancer patients newly referred to a phase I clinic.
Materials and methods Forty-nine patients were randomly assigned to view an educational DVD (n = 22) which explained phase I trials or a placebo DVD (n = 27). Patients completed a questionnaire assessing knowledge of phase I studies and satisfaction with the DVD. The blinded
interviewing physician (n = 8) rated the patient’s understanding of phase I trials.
Main results The mean patient age was 56; 61% were male. Patients who viewed the educational DVD were less likely to believe that phase
I trials determine drug efficacy (p = 0.019), more likely to know that phase I drugs have not been thoroughly studied in humans (p = 0.003), and less likely to believe that these agents have proven activity against human cancers (p = 0.008). More patients who viewed the educational DVD agreed/strongly agreed that the DVD provided useful information (p < 0.001), were confident in their knowledge of phase I trials (p = 0.031), felt aided in their decision to enter a phase I study (p = 0.011), and would have more questions for their physicians because of the DVD (p = 0.017). No statistically significant difference in physician perception of patient understanding or phase I trial accrual
was observed between the educational and placebo DVD groups.
Conclusions An educational DVD increased patient knowledge and satisfaction regarding participation in phase I clinical trials. 相似文献
12.
13.
14.
Ragini Singh Binayak Kumar Ram Krishna Sahu Soni Kumari Chandan Bhogendra Jha Nahar Singh Rashi Mathur Suresh T. Hedau 《RSC advances》2021,11(53):33723
Exploration of an efficient dual-drug based nanocarrier with high drug loading capacity, specific targeting properties, and long-term stability is highly desirable in cancer therapy. Metal–organic frameworks (MOFs) have proven to be a promising class of drug carriers due to their high porosity, crystalline properties with defined structure information, and their potential for further functionalization. To enhance the drug efficacy as well as to overcome the burst effect of drugs, here we synthesized a pH responsive folic acid (FA) and graphene oxide (GO) decorated zeolitical imidazolate frameworks-8 (GO–FA/ZIF-8), for targeted delivery of doxorubicin (DOX) and cyclophosphamide (CP), simultaneously. In this system, DOX molecules were encapsulated in the pores of ZIF-8 during in situ synthesis of ZIF-8 and CP molecules have been captured by the GO surface via hydrogen bonding and π–π interactions as well. Furthermore, the resulting pH-responsive nanocarrier (DOX@ZIF-8/GO–FA/CP) showed in vitro sustained release characteristics (76% of DOX and 80% of CP) by cleavage of chemical bonding and disruption of the MOFs structure under acidic condition (at pH 5.6). Moreover, DOX@ZIF-8/GO–FA/CP has synergistic cytotoxic effects as compared to the combination of both the drugs without ZIF-8/GO–FA when treating MCF-7 and MDA-MB-231 breast cancer cell lines (with a combination index of 0.29 and 0.75 for MCF-7 and MDA-MB-231 cell-lines, respectively). Hence this system can be applied as an effective platform for smart dual drug delivery in breast cancer treatment through its remarkable manageable multidrug release.Exploration of an efficient dual-drug based nanocarrier with high drug loading capacity, specific targeting properties, and long-term stability is highly desirable in cancer therapy. 相似文献
15.
目的:比较乳腺癌患者术后应用TEC方案与EC-T方案化疗对空腹的血糖影响.方法:回顾性研究TEC方案患者114例,EC-T方案患者99例,统计每例患者每周期化疗前空腹血糖,分析两种化疗方案对患者血糖的影响.结果:EC-T方案组有4例患者空腹血糖水平异常增高,TEC组有12例患者空腹血糖水平异常增高,两者比较差异有显著性.结论:EC-T方案升高患者空腹血糖水平的作用小于TEC方案,在病情允许情况下,尽可能将TEC方案改为EC-T方案,以降低患者化疗导致血糖升高甚至糖尿病的风险. 相似文献
16.
17.
Kojiro Shimozuma Yasuo Ohashi Ayano Takeuchi Toshihiko Aranishi Satoshi Morita Katsumasa Kuroi Shozo Ohsumi Haruhiko Makino Hirohumi Mukai Noriyuki Katsumata Yoshihide Sunada Toru Watanabe Frederick H. Hausheer 《Supportive care in cancer》2009,17(12):1483-1491
Goals
The aim of the study was to determine the feasibility and validity of a newly developed patient-based instrument—the Patient Neurotoxicity Questionnaire (PNQ)—for grading chemotherapy-induced peripheral neuropathy (CIPN).Patients and methods
We prospectively collected data from 300 female patients who were treated with taxane chemotherapy for primary breast cancer as part of a national multicenter phase III randomized trial (N-SAS BC 02). We evaluated patient compliance with the PNQ and several validation parameters, including concordance between CIPN grades noted by physicians (National Cancer Institute Common Toxicity Criteria) and patients (PNQ), and the concurrent validity and responsiveness of the PNQ versus the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) utilizing data at pre-treatment and before three, five, and seven treatment cycles.Main results
The questionnaire completion rate was >90% at all assessments. Evaluation by physicians always resulted in lower neuropathy assessment scores compared with those reported directly by patients (weighted kappa coefficients, 0.02–0.06). Both PNQ sensory and motor scores were significantly correlated with the FACT/GOG-Ntx (r?=?0.66 and 0.51, respectively). In the repeated measures analysis of variance model, PNQ grades increased considerably as treatment continued, indicating progressively worsening CIPN over time.Conclusions
The PNQ has an applicable degree of feasibility and validity, useful for the diagnosis of CIPN as well as for clinical treatment decision-making, where the development of CIPN is a potential treatment-limiting consideration. Physicians underreport and underestimate the severity of CIPN symptoms compared with patients, thereby supporting the importance of assessing patient-reported outcomes using the PNQ. 相似文献18.
19.
Mehnert JM Tan AR Moss R Poplin E Stein MN Sovak M Levinson K Lin H Kane M Gounder M Lin Y Shih WJ White E Rubin EH Karantza V 《Molecular cancer therapeutics》2011,10(8):1509-1519
In the preclinical setting, phosphorylation and subsequent proteosomal degradation of the proapoptotic protein BIM confers resistance to paclitaxel in solid tumors with RAS/RAF/MAPK pathway activation. Concurrent administration of the proteasome inhibitor bortezomib enables paclitaxel-induced BIM accumulation, restoring cancer cell apoptosis in vitro and producing tumor regression in mice in vivo. A phase I study was conducted to determine the maximum tolerated dose (MTD) of paclitaxel and bortezomib combinatorial treatment. Sixteen patients with refractory solid tumors commonly exhibiting mitogen-activated protein kinase (MAPK) pathway activation were treated weekly with paclitaxel and bortezomib. Starting doses were 40 mg/m(2) for paclitaxel and 0.7 mg/m(2) for bortezomib. A modified continual reassessment method adapted for 2-drug escalation was used for MTD determination with 3-patient cohorts treated at each dose level. MTD was reached at 60 mg/m(2) paclitaxel and 1.0 mg/m(2) bortezomib, the recommended phase II dose. Therapy was overall well tolerated. Most frequently observed toxicities included anemia (in 43.75% of patients, one grade 3 event), fatigue (in 43.75% of patients, one grade 3 event beyond cycle 1), and neuropathy (in 31.25% of patients, one grade 3 event after cycle 1). Of 15 evaluable patients, one non-small-cell lung carcinoma (NSCLC) patient with paclitaxel exposure at the adjuvant setting had a partial response and five patients had stable disease (SD); median disease stabilization was 143.5 days; three NSCLC patients had SD lasting 165 days or longer. Thus, rationally designed weekly treatment with paclitaxel and bortezomib in solid tumors with MAPK pathway activation, including previously taxane-treated malignancies, is a tolerable regimen with preliminary signals of antitumor activity worthy of further investigation. 相似文献
20.
Innocenti F Undevia SD Ramírez J Mani S Schilsky RL Vogelzang NJ Prado M Ratain MJ 《Clinical pharmacology and therapeutics》2004,76(5):490-502
The anticancer agent irinotecan has been demonstrated to improve the survival rate in patients with metastatic colorectal cancer. Its usage has been limited by severe toxicity. To modulate irinotecan pharmacokinetics and reduce the prevalence of severe toxicity, patients were treated with cyclosporine (INN, ciclosporin) and the irinotecan dose was increased from 25 to 72 mg/m2 weekly. Phenobarbital was then added, allowing dose escalation to 144 mg/m2. Dose-limiting toxicities were neutropenia and diarrhea. Irinotecan was well tolerated at the recommended phase II dose of 120 mg/m2, with a 6% prevalence of grade 4 neutropenia and an 18% prevalence of grade 3 diarrhea. Cyclosporine increased 7-ethyl-10-hydroxycamptothecin (SN-38) area under the concentration-time curve (AUC) by 23% to 630% and reduced irinotecan clearance by 39% to 64% when compared with historical controls. Phenobarbital increased irinotecan clearance by 27% (P < or =.001) and reduced SN-38 AUC by 75% (P < or =.001) when compared with patients treated with cyclosporine alone. Five partial responses were observed. Pharmacokinetic modulation of irinotecan with cyclosporine and phenobarbital has been demonstrated; further studies are necessary to evaluate whether this strategy improves the therapeutic index. 相似文献