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1.
Oncologist ; 23(10): 1137-1143, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30018134

RESUMO

BACKGROUND: This SafeHer subgroup analysis assessed the safety of fixed-dose subcutaneous trastuzumab (H SC) as an adjuvant therapy in HER2-positive early breast cancer (EBC) by body weight. PATIENTS AND METHODS: Patients with HER2-positive EBC not previously treated with anti-HER2 therapy received H SC 600 mg (every 3 weeks for 18 cycles), with neoadjuvant or adjuvant chemotherapy or without adjuvant chemotherapy. Adverse events (AEs) were assessed throughout treatment and at final follow-up (28 ±5 days after last treatment). Subgroups were categorized by body weight, Asian origin, and chemotherapy administration. All analyses were descriptive. RESULTS: Of 2,577 patients enrolled, 2,573 received ≥1 dose of study medication and were included in this safety analysis. Median body weight at baseline was 67.0 kg (range 33.6-150.0 kg). Any-grade AEs occurred in 88.7% (2,282/2,573) of the overall population, versus 87.1% (590/677) of the lowest bodyweight quartile (≤59 kg), 90.0% (561/623) of the highest quartile (>77 kg), and 86.5% (327/378) of the Asian population. Grade ≥3 AEs occurred in 23.2% (596/2,573) of the overall population, 17.9% (121/677) of the lowest bodyweight quartile, 26.8% (167/623) of the highest quartile, and 15.3% (58/378) of the Asian population. The highest bodyweight quartile had the highest incidence of medical conditions at baseline (highest quartile, 75.6%; lowest quartile, 56.1%). CONCLUSION: These data support the use of fixed-dose H SC as an adjuvant therapy in HER2-positive EBC and confirm the comparable safety profile of H SC in patients with low body weight or of Asian origin versus the overall population in SafeHer. ClinicalTrials.gov: NCT01566721. IMPLICATIONS FOR PRACTICE: The safety profile of fixed-dose subcutaneous trastuzumab (H SC) was comparable between patients in the lowest bodyweight subgroup and the overall patient population, and also between patients of Asian origin (of whom a higher proportion often fall within the lower bodyweight quartiles) and the overall population. The safety data from this SafeHer subgroup analysis therefore support the use of fixed-dose H SC 600 mg administered every 3 weeks as an adjuvant therapy for patients with HER2-positive early breast cancer across different bodyweight subgroups and in the Asian patient population.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Peso Corporal , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Adulto Jovem
2.
BMC Cancer ; 18(1): 295, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29544445

RESUMO

BACKGROUND: Trastuzumab (Herceptin® [H]) is the standard of care for HER2-positive locally advanced/metastatic breast cancer and gastric/gastroesophageal junction (GEJ) cancer. However, there is a paucity of data available on long-term H treatment of patients. The Rollover Protocol (ROP) Study was conducted to report safety data for patients with HER2-positive locally advanced/metastatic breast and gastric/GEJ cancer who have received long-term H therapy (≥ 5 years and ≥ 3 years for breast and gastric/GEJ cancer, respectively). METHODS: The ROP Study was a single-arm, multicenter, international continuation trial of H in patients who had previously completed a global Roche-sponsored trial with H therapy, had stable disease, and were receiving H at the end of the lead-in trial. Patients with chronic heart failure during the lead-in trial could be included following a risk-benefit analysis. The primary objectives were to provide H therapy to patients with HER2-overexpressing locally advanced/metastatic breast or gastric/GEJ cancer at the end of the lead-in study, and to follow the long-term outcomes and long-term overall safety in these patients. RESULTS: Twenty-five of 69 patients enrolled in the ROP Study received long-term H therapy (19 breast cancer and 6 gastric/GEJ cancer). The median duration of H treatment for patients with breast cancer was 8 years 7 months, and 5 years 2 months for patients with gastric/GEJ cancer. The cardiac status of the patients remained stable over time, with no serious cardiac adverse events or marked changes in left ventricular ejection fraction (LVEF). The median overall worst LVEF measurement was 57.0%, and no patients experienced an LVEF of < 45% (range 47-63%). There were no serious adverse events related to study treatment. CONCLUSIONS: These results suggest that H has an acceptable safety profile and was well tolerated in patients who received long-term H therapy (≥ 5 years and ≥ 3 years for breast and gastric/GEJ cancer, respectively). Further investigation and reporting of long-term H therapy would be valuable. TRIAL REGISTRATION: This study was retrospectively registered on March 24, 2016 with Clinicaltrials.gov, number NCT02721641 .


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Taxa de Sobrevida
3.
J Clin Oncol ; 35(22): 2558-2567, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28574779

RESUMO

Purpose To compare standard-of-care (SoC) trastuzumab plus chemotherapy with higher-dose (HD) trastuzumab plus chemotherapy to investigate whether HD trastuzumab increases trastuzumab serum trough concentration (Ctrough) levels and increases overall survival (OS) in first-line human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. Patients and Methods Patients with Eastern Cooperative Oncology Group performance status 2, no prior gastrectomy, and ≥ two metastatic sites were randomly assigned at a one-to-one ratio to loading-dose trastuzumab 8 mg/kg followed by SoC trastuzumab maintenance 6 mg/kg every 3 weeks or loading-dose trastuzumab 8 mg/kg followed by HD trastuzumab maintenance 10 mg/kg every 3 weeks until progression; treatment in each arm was combined with cisplatin 80 mg/m2 plus capecitabine 800 mg/m2 twice per day in cycles 1 to 6. The primary objective was HD trastuzumab OS superiority (all randomly assigned patients [full-analysis set]). Final results are from an interim analysis for futility (boundary hazard ratio [HR] ≥ 0.95) at 125 deaths. Results At clinical cutoff, 248 patients had been randomly assigned. A marked increase in mean trastuzumab Ctrough was observed after the first HD trastuzumab cycle versus SoC trastuzumab. In the full-analysis set, median OS was 12.5 months in the SoC trastuzumab arm and 10.6 months in the HD trastuzumab arm (stratified HR, 1.24; 95% CI, 0.86 to 1.78; P = .2401). Results were similar in the per-protocol set (cycle 1 trastuzumab Ctrough < 12 µg/mL). Safety was comparable between arms. Conclusion HD trastuzumab maintenance dosing was associated with higher trastuzumab concentrations, no increased efficacy, and no new safety signals. HELOISE confirms standard-dose trastuzumab (loading dose of 8 mg/kg followed by 6 mg/kg maintenance dose every 3 weeks) with chemotherapy as the SoC for first-line treatment of human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Junção Esofagogástrica , Padrão de Cuidado , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/administração & dosagem , Adenocarcinoma/química , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Capecitabina/administração & dosagem , Cisplatino/administração & dosagem , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Trastuzumab/sangue
4.
Eur J Cancer ; 62: 62-75, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27208905

RESUMO

BACKGROUND: In the phase III, open-label, randomised HannaH study, fixed-dose neoadjuvant-adjuvant subcutaneous trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer was non-inferior to standard weight-based intravenous infusion in terms of serum trough concentration and pathological complete response (pCR). Evidence suggests that pCR, particularly total pCR (tpCR), is likely to predict clinical benefit. We report associations between tpCR and event-free survival (EFS) from HannaH (the largest population from a single study of patients presenting with newly diagnosed HER2-positive breast cancer treated with neoadjuvant-adjuvant trastuzumab to date) plus long-term efficacy and safety. METHODS: Eligible patients received four cycles of neoadjuvant docetaxel followed by four cycles of fluorouracil/epirubicin/cyclophosphamide administered concurrently with 3-weekly subcutaneous (600 mg fixed dose) or intravenous trastuzumab (8 mg/kg loading, 6 mg/kg maintenance doses). Post-surgery, patients received adjuvant trastuzumab as randomised to complete 1 year of standard treatment. In exploratory analyses, we used Cox regression to assess associations between tpCR and EFS. EFS rates per subgroup were estimated using the Kaplan-Meier method. FINDINGS: Three-year EFS rates were 76% for subcutaneous and 73% for intravenous trastuzumab (unstratified hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69-1.30; intention-to-treat population). Three-year overall survival rates were 92% for subcutaneous and 90% for intravenous trastuzumab (unstratified HR 0.76, 95% CI 0.44-1.32). tpCR was associated with a reduced risk of an EFS event: subcutaneous arm HR 0.38 (95% CI 0.22-0.65); intravenous arm HR 0.32 (95% CI 0.18-0.60). Results were similar for subgroups, including oestrogen receptor status. The few additional adverse events occurring during treatment-free follow-up were balanced between arms. INTERPRETATION: Long-term efficacy supports the established non-inferiority of subcutaneous trastuzumab, and its safety profile remains consistent with the known intravenous profile. In each of HannaH's treatment arms, tpCR was associated with improved EFS, adding to evidence that tpCR is associated with clinical benefit in HER2-positive early breast cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Terapia Neoadjuvante , Adulto Jovem
5.
PLoS One ; 10(4): e0123444, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25844871

RESUMO

There is unequivocal evidence that alpha-synuclein plays a pivotal pathophysiological role in neurodegenerative diseases, and in particular in synucleinopathies. These disorders present with a variable extent of cognitive impairment and alpha-synuclein is being explored as a biomarker in CSF, blood serum and plasma. Considering key events of aging that include proteostasis, alpha-synuclein may not only be useful as a marker for differential diagnosis but also for aging per se. To explore this hypothesis, we developed a highly specific ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels correlated strongly with age, revealing much lower concentrations in older (avg. 58.1 years) compared to younger (avg. 27.6 years) individuals. This difference between the age groups was enhanced after acidification of the plasmas (p<0.0001), possibly reflecting a decrease of alpha-synuclein-antibody complexes or chaperone activity in older individuals. Our results support the concept that alpha-synuclein homeostasis may be impaired early on, possibly due to disturbance of the proteostasis network, a key component of healthy aging. Thus, alpha-synuclein may be a novel biomarker of aging, a factor that should be considered when analyzing its presence in biological specimens.


Assuntos
Envelhecimento/metabolismo , alfa-Sinucleína/sangue , Adulto , Idoso , Envelhecimento/sangue , Biomarcadores/sangue , Regulação da Expressão Gênica , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
PLoS One ; 8(5): e64649, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23741358

RESUMO

Natural self-reactive antibodies in the peripheral blood may play a considerable role in the control of potentially toxic proteins that may otherwise accumulate in the aging brain. The significance of serum antibodies reactive against α-synuclein is not well known. We explored serum IgG levels to monomeric α-synuclein in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) with a novel and validated highly sensitive ELISA assay. Antibody levels revealed stark differences in patients compared to healthy subjects and were dependent on diagnosis, disease duration and age. Anti-α-synuclein IgG levels were increased in both patient groups, but in early DLB to a much greater extent than in AD. Increased antibody levels were most evident in younger patients, while with advanced age relatively low levels were observed, similar to healthy individuals, exhibiting stable antibody levels independent of age. Our data show the presence of differentially altered IgG levels against α-synuclein in DLB and AD, which may relate to a disturbed α-synuclein homeostasis triggered by the disease process. These observations may foster the development of novel, possibly preclinical biomarkers and immunotherapeutic strategies that target α-synuclein in neurodegenerative disease.


Assuntos
Doença de Alzheimer/sangue , Autoanticorpos/sangue , Imunoglobulina G/sangue , Doença por Corpos de Lewy/sangue , alfa-Sinucleína/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Autoanticorpos/imunologia , Estudos de Casos e Controles , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/imunologia , Doença por Corpos de Lewy/imunologia , Doença por Corpos de Lewy/patologia , Masculino , Índice de Gravidade de Doença , alfa-Sinucleína/imunologia
7.
Breast Cancer Res Treat ; 138(1): 99-108, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23420271

RESUMO

A comprehensive, blinded, pathology evaluation of HER2 testing in HER2-positive/negative breast cancers was performed among three central laboratories. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analyses were performed on 389 tumor blocks from three large adjuvant trials: N9831, BCIRG-006, and BCIRG-005. In 123 cases, multiple blocks were examined. HER2 status was defined according to FDA-approved guidelines and was independently re-assessed at each site. Discordant cases were adjudicated at an on-site, face-to-face meeting. Results across three independent pathologists were concordant by IHC in 351/381 (92 %) and FISH in 343/373 (92 %) blocks. Upon adjudication, consensus was reached on 16/30 and 18/30 of discordant IHC and FISH cases, respectively, resulting in overall concordance rates of 96 and 97 %. Among 155 HER2-negative blocks, HER2 status was confirmed in 153 (99 %). In the subset of 102 HER2-positive patients from N9831/BCIRG-006, primary blocks from discordant cases were selected, especially those with discordant test between local and central laboratories. HER2 status was confirmed in 73 (72 %) of these cases. Among 118 and 113 cases with IHC and FISH results and >1 block evaluable, block-to-block variability/heterogeneity in HER2 results was seen in 10 and 5 %, respectively. IHC-/FISH- was confirmed for 57/59 (97 %) primary blocks from N9831 (locally positive, but centrally negative); however, 5/22 (23 %) secondary blocks showed HER2 positivity. Among 53 N9831 patients with HER2-normal disease adjudicated as IHC-/FISH-(although locally positive), there was a non-statistically significant improvement in disease-free survival with concurrent trastuzumab compared to chemotherapy alone (adjusted hazard ratio 0.34; 95 % CI, 0.11-1.05; p = 0.06). There were similar agreements for IHC and FISH among pathologists (92 % each). Agreement was improved at adjudication (96 %). HER2 tumor heterogeneity appears to partially explain discordant results in cases initially tested as positive and subsequently called negative.


Assuntos
Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Adulto , Idoso , Biomarcadores Tumorais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
8.
Clin Cancer Res ; 19(6): 1567-76, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23349317

RESUMO

PURPOSE: GRN1005 is a peptide-drug conjugate with the ability to penetrate the blood-brain barrier (BBB) and tumor cells by targeting the low-density lipoprotein receptor-related protein-1. We conducted a first-in-human phase I trial of GRN1005 in patients with recurrent glioma. METHODS: Patients received GRN1005 by intravenous infusion every 3 weeks. Doses were escalated using a modified Fibonacci scheme. Study objectives included safety, tolerability, identification of the maximum tolerated dose (MTD), pharmacokinetics, and preliminary evidence of efficacy. Tumor extracted from patients undergoing surgery following administration of GRN1005 was analyzed to determine whether therapeutic concentrations of GRN1005 were achieved. RESULTS: Sixty-three patients received GRN1005 at doses of 30 to 700 mg/m(2) every 3 weeks. Therapy was well tolerated with neutropenia, leucopenia, and fatigue as the most frequent drug-associated grade 3/4 or higher toxicities. The MTD was 650 mg/m(2) every 3 weeks. Dose-limiting toxicities were grade 3 mucositis and grade 4 neutropenia. There was no evidence of central nervous system toxicity or antibody production. Pharmacokinetic analysis showed that exposure to GRN1005 was dose proportional. We observed one complete and two partial responses. Eight of 27 patients dosed ≥ 420 mg/m(2) had stable disease, which lasted a median of 51 days. Therapeutic concentrations of GRN1005 and free paclitaxel were shown in tumor tissue of surgical patients dosed with ≥ 200 mg/m(2). CONCLUSION: GRN1005 delivers paclitaxel across the BBB and achieves therapeutic concentrations in tumor tissue. It has similar toxicity to paclitaxel and appears to have activity in recurrent glioma. The recommended phase II dose is 650 mg/m(2) every 3 weeks.


Assuntos
Antineoplásicos/administração & dosagem , Glioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/análogos & derivados , Peptídeos/administração & dosagem , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Barreira Hematoencefálica/efeitos dos fármacos , Relação Dose-Resposta a Droga , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Glioma/patologia , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/farmacocinética , Peptídeos/efeitos adversos , Peptídeos/farmacocinética
9.
Clin Cancer Res ; 17(14): 4834-43, 2011 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-21768129

RESUMO

PURPOSE: registHER is a prospective, observational study of 1,023 newly diagnosed HER2-positive metastatic breast cancer (MBC) patients. EXPERIMENTAL DESIGN: Baseline characteristics of patients with and without central nervous system (CNS) metastases were compared; incidence, time to development, treatment, and survival after CNS metastases were assessed. Associations between treatment after CNS metastases and survival were evaluated. RESULTS: Of the 1,012 patients who had confirmed HER2-positive tumors, 377 (37.3%) had CNS metastases. Compared with patients with no CNS metastases, those with CNS metastases were younger and more likely to have hormone receptor-negative disease and higher disease burden. Median time to CNS progression among patients without CNS disease at initial MBC diagnosis (n = 302) was 13.3 months. Treatment with trastuzumab, chemotherapy, or surgery after CNS diagnosis was each associated with a statistically significant improvement in median overall survival (OS) following diagnosis of CNS disease (unadjusted analysis: trastuzumab vs. no trastuzumab, 17.5 vs. 3.8 months; chemotherapy vs. no chemotherapy, 16.4 vs. 3.7 months; and surgery vs. no surgery, 20.3 vs. 11.3 months). Although treatment with radiotherapy seemed to prolong median OS (13.9 vs. 8.4 months), the difference was not significant (P = 0.134). Results of multivariable proportional hazards analyses confirmed the independent significant effects of trastuzumab and chemotherapy (HR = 0.33, P < 0.001; HR = 0.64, P = 0.002, respectively). The effects of surgery and radiotherapy did not reach statistical significance (P = 0.062 and P = 0.898, respectively). CONCLUSIONS: For patients with HER2-positive MBC evaluated in registHER, the use of trastuzumab, chemotherapy, and surgery following CNS metastases were each associated with longer survival.


Assuntos
Neoplasias da Mama/patologia , Neoplasias do Sistema Nervoso Central/secundário , Receptor ErbB-2/metabolismo , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , Progressão da Doença , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Sistema de Registros , Fatores de Tempo
10.
Clin Colorectal Cancer ; 8(1): 49-54, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19203897

RESUMO

PURPOSE: Monoclonal antibodies against the epidermal growth factor receptor approved for treating metastatic colorectal cancer (mCRC) include cetuximab (a chimeric antibody) and panitumumab (a fully human antibody). Because these antibodies have differences in protein sequence, patients intolerant to one antibody might still tolerate the other. Four cases are presented from a US panitumumab compassionate-use program in which patients with mCRC who were intolerant to cetuximab received panitumumab. PATIENTS AND METHODS: Eligible patients had failed previous fluoropyrimidine therapy with oxaliplatin- and irinotecan-containing chemotherapy, had cetuximab intolerance (ie, experienced an infusion reaction), and were unable to participate in a panitumumab clinical trial. For each patient, individual Federal Drug Administration-approved single-patient treatment use Investigational New Drug- and Institutional Review Board-approved protocols were used, informed consent was obtained, and data were collected independently by the investigator. RESULTS: All 4 patients (2 men, 2 women) had received previous bevacizumab and premedications before cetuximab administration. In response to cetuximab, all 4 patients experienced Common Terminology Criteria for Adverse Events grade 3 or grade 4 infusion-reaction symptoms, which required acute therapy. Time from cetuximab discontinuation to panitumumab administration ranged from 8 days to 5 months. Panitumumab monotherapy was administered at approximately 6 mg/kg every 2 weeks. Two patients received premedications before panitumumab use. No physician reported any infusion reaction to panitumumab. One patient had stable disease, and 3 patients had disease progression. CONCLUSION: Though this small case series provides evidence that patients with mCRC intolerant to cetuximab can receive subsequent panitumumab monotherapy without experiencing infusion reactions, additional clinical testing is needed to definitively examine this finding.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Cetuximab , Neoplasias Colorretais/patologia , Evolução Fatal , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Panitumumabe , Resultado do Tratamento
11.
J Neurosci Res ; 86(2): 392-402, 2008 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-17893914

RESUMO

In multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE), clinical disease is associated with infiltration of the central nervous system (CNS) by immune cells. Subsequent remission with remyelination has been linked to an increased occurrence of oligodendrocyte progenitor (O2A) cells. Platelet-derived growth factor (PDGF) and fibroblast growth factor-2 (FGF-2) are key growth factors for O2A cells, yet little is known about their relevance in EAE and MS. We analyzed the expression of PDGF, FGF-2, and their receptors by peripheral-blood leukocytes (PBLs) and lymphocyte subsets during MBP-induced EAE. Strong up-regulation of PDGF, but not FGF-2, was observed in PBLs, with the highest expression after the disease maximum. T, NK, and NKT cells expressed PDGF, which is a novel observation because thus far only monocytes/macrophages have been reported to express PDGF. These results extend the idea that growth factors may contribute to improved CNS tissue repair, including PDGF, which is secreted by lesion-homing immune cells. The production of PDGF by lymphocytes may have potential therapeutic value when activating or modulating T-cell responses in demyelinating diseases.


Assuntos
Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Fator de Crescimento Derivado de Plaquetas/biossíntese , Animais , Fator 2 de Crescimento de Fibroblastos/biossíntese , Citometria de Fluxo , Imunofluorescência , Expressão Gênica , Imuno-Histoquímica , Células Matadoras Naturais/metabolismo , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos Lew , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/metabolismo , Regulação para Cima
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