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1.
CNS Neurosci Ther ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34767694

RESUMO

AIMS: This study aimed to explore the pathomechanism of a mutation on the leucine-rich glioma inactivated 1 gene (LGI1) identified in a family having autosomal dominant lateral temporal lobe epilepsy (ADLTE), using a precise knock-in mouse model. METHODS AND RESULTS: A novel LGI1 mutation, c.152A>G; p. Asp51Gly, was identified by whole exome sequencing in a Chinese family with ADLTE. The pathomechanism of the mutation was explored by generating Lgi1D51G knock-in mice that precisely phenocopied the epileptic symptoms of human patients. The Lgi1D51G / D51G mice showed spontaneous recurrent generalized seizures and premature death. The Lgi1D51G /+ mice had partial epilepsy, with half of them displaying epileptiform discharges on electroencephalography. They also showed enhanced sensitivity to the convulsant agent pentylenetetrazole. Mechanistically, the secretion of Lgi1 was impaired in the brain of the D51G knock-in mice and the protein level was drastically reduced. Moreover, the antiepileptic drugs, carbamazepine, oxcarbazepine, and sodium valproate, could prolong the survival time of Lgi1D51G / D51G mice, and oxcarbazepine appeared to be the most effective. CONCLUSIONS: We identified a novel epilepsy-causing mutation of LGI1 in humans. The Lgi1D51G /+ mouse model, precisely phenocopying epileptic symptoms of human patients, could be a useful tool in future studies on the pathogenesis and potential therapies for epilepsy.

2.
Neuroscience ; 429: 78-91, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31917345

RESUMO

Enkephalin (ENK) has been implicated in pain modulation within the spinal dorsal horn (SDH). Revealing the mechanisms underlying ENK analgesia entails the anatomical and functional knowledge of spinal ENK-ergic circuits. Herein, we combined morphological and electrophysiological studies to unravel local ENK-ergic circuitry within the SDH. First, the distribution pattern of spinal ENK-ergic neurons was observed in adult preproenkephalin (PPE)-GFP knock-in mice. Next, the retrograde tracer tetramethylrhodamine (TMR) or horseradish peroxidase (HRP) was injected into the parabrachial nucleus (PBN) in PPE-GFP mice. Immunofluorescent staining showed I-isolectin B4 (IB4) labeled non-peptidergic afferents were in close apposition to TMR-labeled PBN-projecting neurons within lamina I as well as PPE-immunoreactivity (-ir) neurons within lamina II. Some TMR-labeled neurons were simultaneously in close association with both IB4 and PPE-ir terminals. Synaptic connections of these components were further confirmed by electron microscopy. Finally, TMR was injected into the PBN in adult C57BL/6 mice. Whole-cell patch recordings showed that δ-opioid receptor (DOR) agonist, [D-Pen2,5]-enkephalin (DPDPE, 1 µM), significantly reduced the frequency of miniature excitatory postsynaptic current (mEPSC) and decreased the activity of TMR-labeled neurons. In conclusion, spinal ENKergic neurons receive direct excitatory inputs from primary afferents, which might be directly recruited to release ENK under the condition of noxious stimuli; ENK could inhibit the glutamatergic transmission towards projecting neurons via presynaptic and postsynaptic DORs. These morphological and functional evidence may explain the mechanisms underlying the analgesic effects exerted by ENK within the SDH.


Assuntos
Axônios , Nociceptividade , Animais , Camundongos , Camundongos Endogâmicos C57BL , Neurônios , Células do Corno Posterior , Corno Dorsal da Medula Espinal
3.
Mol Med Rep ; 17(2): 2803-2810, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29257262

RESUMO

Chronic pain occurs in ~85-90% of chronic pancreatitis (CP) patients. However, as the pathogenesis of CP pain remains to be fully understood, the current therapies for CP pain remain inadequate. Emerging evidence has suggested that the epigenetic modulations of genes are involved in chronic pain. In the present study, intrapancreatic trinitrobenzene sulfonic acid infusions were used to establish a CP model in rats. Mechanical allodynia was measured with von Frey filaments. Immunofluorescent staining analysis was used to observe the expression changes of histone deacetylase 2 (HDAC2) and µ­opioid receptor (MOR), and intrathecal administration of the selective HDAC2 inhibitor AR­42 was used to assess the underlying mechanisms. The expression levels of c­Jun N­terminal kinase (JNK) in the thoracic spinal cord were detected by western blotting, and the mRNA expression levels of interleukin (IL)1­ß, IL­6 and tumor necrosis factor (TNF)­α were detected by reverse transcription­quantitative polymerase chain reaction. The results demonstrated that HDAC2 expression was upregulated during the course of CP induction, while MOR activity in the thoracic spinal dorsal horn was significantly suppressed. Intrathecal infusion of AR­42 significantly attenuated CP­induced mechanical allodynia, with rescued MOR activity. Additionally, HDAC2 facilitated the release of inflammatory cytokines, including IL­1ß, IL­6 and TNF­α. These results suggested that the underlying mechanisms of HDAC2 regulating MOR activity under CP induction may occur via promoting the release of inflammatory cytokines, thus activating the JNK signaling pathway. The present study suggested that the epigenetic­regulated disturbance of MOR is dependent on the endogenous analgesia system in CP, which may a provide novel therapeutic strategy for treating pain in CP.


Assuntos
Dor Crônica/complicações , Epigênese Genética , Histona Desacetilase 2/genética , Pancreatite Crônica/complicações , Receptores Opioides mu/genética , Corno Dorsal da Medula Espinal/patologia , Animais , Dor Crônica/genética , Dor Crônica/metabolismo , Dor Crônica/patologia , Modelos Animais de Doenças , Histona Desacetilase 2/metabolismo , Hiperalgesia/complicações , Hiperalgesia/genética , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Masculino , Pancreatite Crônica/genética , Pancreatite Crônica/metabolismo , Pancreatite Crônica/patologia , Ratos , Ratos Sprague-Dawley , Receptores Opioides mu/metabolismo , Transdução de Sinais , Corno Dorsal da Medula Espinal/metabolismo , Regulação para Cima
4.
Arch Med Sci ; 11(3): 544-50, 2015 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-26170847

RESUMO

INTRODUCTION: The aim of the study was to analyze clinicopathologic characteristics and survival and to identify prognostic factors for Chinese patients with HER2-positive metastatic breast cancer. MATERIAL AND METHODS: A total of 243 patients with HER2-positive metastatic breast cancer, treated during the period 2002 to 2009, were followed up from initial disease diagnosis to death or date of last follow-up (December 2011). Cumulative survival curves were created using Kaplan-Meier analysis with the log-rank test. Prognostic factors were analyzed by univariate and multivariate Cox proportional hazards regression analysis. RESULTS: During follow-up, 205 patients died, with a median OS of 27 months (95% CI: 23.5, 30.5 months), and the 1-, 3-, and 5-year survival rates were 84.4%, 38.6%, and 18.1%, respectively. The median OS of HR+ patients was significantly higher than that of HR- patients (p < 0.001). Surgery (hazard ratio = 0.60, p = 0.002), endocrine therapy (hazard ratio = 0.53, p < 0.01), and anti-HER2 therapy (hazard ratio = 0.63, p = 0.003) were favorable independent prognostic factors for patients with HER2-positive metastatic breast cancer. CONCLUSIONS: These results indicated that surgical intervention, endocrine therapy, and anti-HER2 therapy were good for these HER2 positive patients with metastatic breast cancer, but ECOG performance status < 1 and metastasis to brain were unfavorable independent prognostic factors. HR status was not an independent prognostic factor.

5.
Chin J Cancer ; 33(10): 492-500, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25104281

RESUMO

The local recurrence rate of phyllodes tumors of the breast varies widely among different subtypes, and distant metastasis is associated with poor survival. This study aimed to identify factors that are predictive of local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with phyllodes tumors of the breast. Clinical data of all patients with a phyllodes tumor of the breast (n = 192) treated at Sun Yat-sen University Cancer Center between March 1997 and December 2012 were reviewed. The Pearson Χ² test was used to investigate the relationship between clinical features of patients and histotypes of tumors. Univariate and multivariate Cox regression analyses were performed to identify factors that are predictive of LRFS, DMFS, and OS. In total, 31 (16.1%) patients developed local recurrence, and 12 (6.3%) developed distant metastasis. For the patients who developed local recurrence, the median age at the diagnosis of primary tumor was 33 years (range, 17-56 years), and the median size of primary tumor was 6.0 cm (range, 0.8-18 cm). For patients who developed distant metastasis, the median age at the diagnosis of primary tumor was 46 years (range, 24-68 years), and the median size of primary tumor was 5.0 cm (range, 0.8-18 cm). In univariate analysis, age, size, hemorrhage, and margin status were found to be predictive factors for LRFS (P = 0.009, 0.024, 0.004, and 0.001, respectively), whereas histotype, epithelial hyperplasia, margin status, and local recurrence were predictors of DMFS (P = 0.001, 0.007, 0.007, and < 0.001, respectively). In multivariate analysis, independent prognostic factors for LRFS included age [hazard ratio (HR) = 3.045, P = 0.005], tumor size (HR = 2.668, P = 0.013), histotype (HR = 1.715, P = 0.017), and margin status (HR = 4.530, P< 0.001). Histotype (DMFS: HR = 4.409, P = 0.002; OS: HR = 4.194, P = 0.003) and margin status (DMFS: HR = 2.581, P = 0.013; OS: HR = 2.507, P = 0.020) were independent predictors of both DMFS and OS. In this cohort, younger age, a larger tumor size, a higher tumor grade, and positive margins were associated with lower rates of LRFS. Histotype and margin status were found to be independent predictors of DMFS and OS.


Assuntos
Neoplasias da Mama , Metástase Neoplásica , Recidiva Local de Neoplasia , Tumor Filoide , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Fatores de Risco
6.
Asian Pac J Cancer Prev ; 13(4): 1645-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22799382

RESUMO

PURPOSE: This study aimed to assess possible interactive effects of coping styles and psychological stress on depression and anxiety symptoms in Chinese women shortly after diagnosis of breast cancer. METHODS: Four hundred and one patients with breast cancer were face-to-face interviewed by trained research staff according to a standardized questionnaire including information on socio-demographic characteristics, psychological stress, coping styles, and anxiety and depressive symptoms. Interactive effects were assessed by hierarchical multiple regression analyses. RESULTS: There were significant associations of the four domains of psychological stress with anxiety and depressive symptoms except for the relationship between "worrying about health being harmed" and depressive symptoms. "Abreaction coping behavior" and "escaping coping behavior" significantly increased the level of both anxiety and depressive symptoms; whereas an "active coping style" resulted in significant decrease. The interaction of "active coping behavior" with "worrying about health being harmed" significantly increased the risk of the anxiety symptoms, while adopting "self-relaxing coping behavior" was associated with significant decrease. The interaction of "worry about daily life and social relationship being restricted" with "escaping coping behavior" significantly increased the risk of the depressive symptoms. CONCLUSIONS: The results of this study suggest that certain coping styles might moderate the association of psychological stress with anxiety and depressive symptoms in Chinese women with breast cancer.


Assuntos
Adaptação Psicológica , Ansiedade/etiologia , Neoplasias da Mama/psicologia , Depressão/etiologia , Estresse Psicológico/complicações , Adolescente , Adulto , China , Feminino , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Análise de Regressão , Inquéritos e Questionários , Adulto Jovem
7.
J Cancer Res Clin Oncol ; 138(4): 705-14, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22237454

RESUMO

PURPOSE: The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. We compared the characteristics and prognosis of bilateral breast cancer and unilateral breast cancer. METHODS: Our study included 4,183 patients with breast cancer who were treated at Sun Yat-sen University Cancer Center between January 1, 2000, and December 31, 2007. Bilateral breast cancer was categorized as synchronous (within 3 months) or metachronous (diagnosed after 3 months of first cancer). SPSS was used for data analysis. RESULTS: 106 (2.5%) and 31 (0.7%) patients were diagnosed with metachronous and synchronous bilateral cancer. Women with bilateral cancer had more frequent postmenopause, HER-2 negativity, and advanced disease than in patients with unilateral cancer. Young age at diagnosis, invasive lobular carcinoma, ER/PR negativity, HER-2 positivity, radiation, large tumor size (T > 5 cm), and stage III disease of the first cancer were risk factors for contralateral cancer. The 5-year disease-free survival and overall survival rates were 76 and 83% for unilateral cancer, while 32 and 72% for bilateral cancer (P = 0.000 for both). CONCLUSIONS: Bilateral cancer was associated with shorter disease-free survival and overall survival than unilateral cancer. The prognosis of metachronous bilateral cancer, especially those diagnosed within 2 years after the first cancer was significantly worse than synchronous bilateral cancer.


Assuntos
/estatística & dados numéricos , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Adulto , Neoplasias da Mama/metabolismo , China , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pós-Menopausa , Prognóstico , Receptor ErbB-2/metabolismo , Fatores de Risco , Fatores de Tempo
8.
Med Oncol ; 29(1): 39-47, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21302001

RESUMO

Trastuzumab has been the standard treatment in first-line treatment of HER-2-positive advanced breast cancer (H2ABC). This study explored whether the delayed and repeated use of trastuzumab could influence overall survival (OS). A total of 128 patients with H2ABC who had received at least one line of trastuzumab-based regimens were included. The primary endpoint was OS defined as from the date of first diagnosis of H2ABC to death. The median OS of initiating trastuzumab in first-line group (n = 56), in the second-line group (n = 32), and the third- or more-line group (n = 40) was 40.6 m, 39.5 m, and 38 m, respectively (P = 0.867). For patients who had received over one line of trastuzumab (n = 46), the median OS was 44 m, and for those receiving only one line (n = 67), it was 27.6 m (P = 0.059). The delayed use of trastuzumab has no negative effect on the OS of patients with H2ABC. There is a trend of improved OS over the repeated use of trastuzumab.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Adulto , Idoso , Neoplasias da Mama/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Razão de Chances , Receptor ErbB-2/biossíntese , Estudos Retrospectivos , Trastuzumab
9.
Asian Pac J Cancer Prev ; 12(10): 2523-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22320935

RESUMO

PURPOSE: The aim of the present study was to assess the association of psychological stress and social support with anxiety and depressive symptoms in Chinese newly diagnosed breast cancer patients. METHODS: Four hundred and one patients with breast cancer were recruited. Their demographic characteristics, psychological stress and social support were determined with a structured questionnaire, and their anxiety and depressive symptoms were assessed with the Hospital Anxiety and Depression Scale. RESULTS: Psychological stressors caused by breast cancer diagnosed originated from five major sources, as determined by factor analysis. These included "Worrying about health being harmed, " "Fear of decline of physical function, " "Fear of work being harmed, " "Worry about daily life and social relationship being restricted, " and "Fear of family being harmed. " Hierarchical linear regression analysis indicated that, after adjusting for gender, age, marital status, educational level, and duration of illness, solid social support can alleviate such symptoms. CONCLUSIONS: The results of this study suggest that there are strong associations between patients' needs and psychological distress with newly diagnosed breast cancer. Social support might affect these associations in Chinese women with breast cancer.


Assuntos
Neoplasias da Mama/psicologia , Apoio Social , Estresse Psicológico , Adaptação Psicológica , Adolescente , Adulto , Ansiedade/psicologia , China , Depressão/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
10.
Chin J Cancer ; 29(4): 413-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20346218

RESUMO

BACKGROUND AND OBJECTIVE: The brain is one of the most common metastatic sites of breast cancer. Brain metastases develop in 10%-15% of patients with breast cancer and are associated with poor prognosis. The purpose of this retrospective study was to analyze the clinical characteristics and survival of patients with brain metastases due to breast cancer of different subtypes and to identify the prognostic factors that affect clinical outcome. METHODS: A total of 89 patients with breast cancer brain metastases diagnosed between October 1997 and July 2008 at Sun Yat-sen University Cancer Center were included in this study. Among the 89 patients, the number of luminal A, luminal B, human epidermal growth factor receptor 2 (HER-2), and triple-negative (TN) subtypes were 30, 20, 16, and 14, respectively; 9 patients had an unknown subtype. The clinical characteristics, pathologic features, and prognostic factors were analyzed both at the initial diagnosis and at the diagnosis of brain metastases. Endocrine therapy for patients with luminal subtypes was further studied. RESULTS: The median age of patients was 46 years (range 28-74 years). The median survival time was 8.0 months (range, 0-80 months), the 1-year survival rate was 32% and the 5-year survival rate was 4%. The time to brain metastasis differed according to clinical stage at the initial diagnosis, and the time for patients with the luminal A subtype was the longest (P < 0.001). Multivariate analysis demonstrated that performance status score > 1, multiple brain metastases and without whole brain radiotherapy (WBRT) in combination with chemotherapy were associated with poor prognosis. Compared with the luminal A subtype, features of the HER-2 and TN subtypes included early metastases, rapid progression after first-line treatment (8.0 months vs. 11.0 months), and poor overall survival (25.0 months vs. 63.0 months). The luminal A subtype showed a tendency for good prognosis and slow growth. Tamoxifen could improve the survival of luminal A/B subtypes (median survival 24.0 months vs. 7.0 months, respectively, P = 0.002). CONCLUSIONS: The prognosis of brain metastases from breast cancer was poor, especially in patients with HER-2 and TN subtypes. Generally, WBRT in combination with chemotherapy was the standard treatment modality. Patients with the luminal subtypes could benefit from tamoxifen.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Adulto , Idoso , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/classificação , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/secundário , Quimioterapia Adjuvante , Irradiação Craniana/métodos , Feminino , Seguimentos , Humanos , Mastectomia/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Receptor ErbB-2/sangue , Receptores de Estrogênio/sangue , Receptores de Progesterona/sangue , Estudos Retrospectivos , Taxa de Sobrevida , Tamoxifeno/uso terapêutico
11.
Ai Zheng ; 27(12): 1302-6, 2008 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-19079998

RESUMO

BACKGROUND & OBJECTIVE: Retroperitoneal lymph node dissection(RPLND) is one of the main modalities for nonseminomatous germ cell tumors (NSGCTs). RPLND has achieved relatively high efficacy for stage I/II NSGCTs. Currently, the postoperative complication rate of conventional RPLND is relatively high. This study was to summarize therapeutic efficacy of modified RPLND for stageI/II NSGCTs, thus to explore the reasonable therapy strategy for those diseases. METHODS: Clinical data of 31 patients with stage I/II NSGCTs underwent RPLND from Aug.2003 to Aug.2007 in Sun Yat-sen University Cancer Center, were retrospectively analyzed. All cases received modified RPLND after radical orchidectomy. Four cases received two to three cycles of BEP (bleomycin,etoposide and cisplatin) chemotherapy prior to RPLND. Thirteen cases received one to five cycles of adjuvant cisplatin-based chemotherapy after primary RPLND. RESULTS: The mean operating time was 147 min (rang 120-200 min) and the mean blood loss was 116 ml (rang 50-300 mL) of modified RPLND. The mean number of dissected lymph nodes sent for pathological examination was 15 (rang 3-40). Retroperitoneal lymph node metastases were confirmed in 15 cases, two of which were fibrosis. According to the pathologic classification after operation, there were 16 cases at stage I, six cases at stage IIA, six cases at stage IIB, and three cases at stage IIC. There was no occurrence of perioperational and postoperational complications. The mean follow-up time was 33 months, ranged eight to 58 months. Twenty-nine patients achieved tumor-free survival, without elevation of blood alpha-fetal protein (AFP) or human chorionic gonadotropin (HCG). One patient developed postoperative recurrence in the retroperitoneum 17 months after operation. After receiving two cycles of salvage therapy, his serum AFP and beta-HCG returned to normal ranges. Another patient had metastasis in the liver and lung six months after operation, but achieved complete response after six cycles of adjuvant cisplatin-based chemotherapy. Antegrade ejaculation was preserved in 96.8% of patients. The mean operative time was 175 vs. 143 min(P=0.002), and the blood loss was 200 vs.104 mL in the group with and without preoperative chemotherapy, respectively(P<0.001). CONCLUSIONS: Modified RPLND achieves satisfactory results for stageI/II NSGCTs patients. It decreases damages to normal organs as well as causes less perioperative and postoperative complications compared to conventional PRLND.


Assuntos
Excisão de Linfonodo , Linfonodos/cirurgia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Testiculares/cirurgia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Perda Sanguínea Cirúrgica , Quimioterapia Adjuvante , Gonadotropina Coriônica/sangue , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Etoposídeo/uso terapêutico , Seguimentos , Germinoma/sangue , Germinoma/tratamento farmacológico , Germinoma/patologia , Germinoma/cirurgia , Humanos , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/sangue , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Orquiectomia , Espaço Retroperitoneal , Estudos Retrospectivos , Neoplasias Testiculares/sangue , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Adulto Jovem , alfa-Fetoproteínas/metabolismo
12.
Ai Zheng ; 27(12): 1307-9, 2008 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-19079999

RESUMO

BACKGROUND & OBJECTIVE: It has been proved that trastuzumab has clinical activity in early and advanced breast cancer with Her2-overexpression. This study was to analyze the safety of trastuzumab after adjuvant chemotherapy in 30 Chinese Her2-positive early breast cancer patients. METHODS: Trastuzumab was administrated after adjuvant chemotherapy every 21 days. The initial dose was 8 mg/kg, and the subsequent dose was 6 mg/kg, for four to 35 cycles (medium 18 cycles). The side effects of these patients, especially cardiotoxicity, were analyzed. RESULTS: Thirty patients with Her2-positive early breast cancer were entered into the study. The average treatment period was one year (range nine weeks to two years). Two patients had shivering and fever during the first infusion with trastuzumab. Left ventricular ejection fraction (LVEF) level dropped in 18 cases after treatment with trastuzumab, half of which decreased more then 10%û however, no cardiac failure was observed. CONCLUSIONS: The post-surgical treatment of trastuzumab in Chinese patients with Her2-positive early breast cancer shows a satisfactory safety profile. However, the potential cardiotoxicity of trastuzumab should be carefully monitored during therapy.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/sangue , Carcinoma Ductal de Mama/sangue , Quimioterapia Adjuvante , Feminino , Febre/induzido quimicamente , Testes de Função Cardíaca , Humanos , Mastectomia , Pessoa de Meia-Idade , Período Pós-Operatório , Receptor ErbB-2/sangue , Estudos Retrospectivos , Tremor por Sensação de Frio , Volume Sistólico , Trastuzumab
13.
Ai Zheng ; 27(9): 947-50, 2008 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-18799033

RESUMO

BACKGROUND & OBJECTIVE: HER2 is overexpressed in approximately 20.0% to 30.0% of breast cancer patients. This alteration is associated with poor prognosis, and may affect response to hormonal therapy and chemotherapy. Chemotherapy combined with trastuzumab can significantly improve the treatment efficacy and survival of Her-2/neu overexpressing breast cancer patients. Docetaxel is an effective drug used for metastatic breast cancer recently. This study was to evaluate the efficacy and toxicity of trastuzumab combined with docetaxel in the treatment for metastatic breast cancer patients with overexpressed Her-2/neu. METHODS: Twenty-two metastatic breast cancer patients with overexpressed HER2/neu were entered into the study. Trastuzumab and docetaxel (75 mg/m(2)) were administrated on day 1 and repeated every 21 days. The initial dose of trastuzumab was 8 mg/kg and subsequent doses were 6 mg/kg. RESULTS: Overall 96 cycles were administrated to the 22 patients (medium three cycles per patient, range 2-6 cycles). All cases were evaluable. The overall response rate was 63.6% (14/22). Two patients achieved complete response (CR), 12 patients achieved partial response (PR), four patients achieved stable disease (SD), and four patients had progressive disease (PD). The median time to progression was 5.4 months. One year overall survival was 59.0%. The major toxicity was myelosuppression. A few patients had fever at first infusion of trastuzumab and minor heart failure. CONCLUSION: Trastuzumab combined with docetaxel is an effective and well-tolerated therapy for Her-2/neu overexpressing metastatic breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Anemia/induzido quimicamente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/secundário , Docetaxel , Exantema/induzido quimicamente , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , Indução de Remissão , Taxa de Sobrevida , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Trombocitopenia/induzido quimicamente , Trastuzumab
14.
Nan Fang Yi Ke Da Xue Xue Bao ; 28(9): 1707-9, 2008 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-18819904

RESUMO

OBJECTIVE: To evaluate the efficacy and toxicity in patients with HER2 overexpressing metastatic breast cancer. METHODS: Twenty-one patients with HER2 overexpressing metastatic breast cancer entered into the study. Trastuzumab (8 mg/kg day 1, then 6 mg/kg every 21 days or 4 mg/kg, then 2 mg/kg every week) and vinorelbine (25 mg/m(2)) was given on days 1 and 8 every 21 days. RESULTS: Overall 56 cycles were given to the 21 patients enrolled into the study (mean 2, range 1-6). All can be evaluated. The response rate was 33.33% (7/21), one patient achieved complete response (CR), six patients achieved partial response (PR), four patients achieved stable disease (SD), ten patients achieved progressive disease (PD)]. The median time to progression was 3.5 months. One year overall survival was 33%. The major toxicity was myelosuppression and peripheral neuritis. A few patients were observed with fever and lower grade cardiac failure. CONCLUSION: The combination of trastuzumab and vinorelbine is an effective and well tolerated therapy in patients with pretreated metastatic breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Anemia/induzido quimicamente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Metástase Neoplásica , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Trastuzumab , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , Vinorelbina , Vômito/induzido quimicamente
15.
Ai Zheng ; 26(12): 1373-6, 2007 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-18076805

RESUMO

BACKGROUND & OBJECTIVE: Chemotherapy is one of major treatments of metastatic breast cancer. Anthracyclines and taxanes are usually considered as the most active agents in breast cancer and are often used as adjuvant or first-line therapy. Gemcitabine and vinorelbine are active agents in breast cancer. This study was to evaluate the efficacy of gemcitabine combined vinorelbine on the patients with metastatic breast cancer, who had previously received treatment of anthracyclines and/or taxanes. METHODS: Thirty-four patients with metastatic breast cancer, who had been previously treated with anthracyclines alone or with taxanes, were enrolled. The patients received 30-minute intravenous injection of gemcitabine (1 000 mg/m(2)) and intravenous bolus injection of vinorelbine(25 mg/m(2)) on Days 1 and 8; the regimen was repeated every 21 days. RESULTS: A total of 109 cycles were given to the 34 patients (median, 3 cycles; range, 1-6 cycles). The treatment responses were evaluable in all patients. Of the 34 patients, 9 achieved partial remission (PR), 19 had stable disease (SD), 6 had progressive disease (PD)û the response rate was 26.47%. The median time to progression was 5.4 months. The median overall survival was 17.8 months. The 1-year overall survival rate was 68% [95% confidence interval (CI): 50%-86%], the 2-year overall survival rate was 46% (95% CI: 26%-66%). The major adverse events were grade I-II myelosuppression, peripheral neurologic toxicities, nausea and vomiting. Some patients had rash and hepatic dysfunction. CONCLUSION: The combination of gemcitabine and vinorelbine is an effective and well tolerated regimen for the patients with metastatic breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Vimblastina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/secundário , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Metástase Neoplásica , Neutropenia/induzido quimicamente , Indução de Remissão , Taxa de Sobrevida , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vinorelbina , Vômito/induzido quimicamente
16.
Ai Zheng ; 23(12): 1710-3, 2004 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-15601567

RESUMO

BACKGROUND & OBJECTIVE: Hormone and Herceptin therapy for metastatic breast cancer is commonly based on expression of estrogen receptor (ER) and progestin receptor (PR), and over-expression of HER-2 in primary breast cancer, but studies comparing receptor statuses in primary and metastatic focuses of the same patient are limited. This study was designed to investigate discordance of ER, PR,and HER-2 statuses between primary and metastatic focuses of breast cancer. METHODS: Immunohistochemistry assay was used to detect expression of ER, PR, and HER-2 receptor in primary and metastatic focuses of 65 cases of breast cancer. RESULTS: Positive rate of ER in primary focuses was 56.9% (37/65), significantly higher than that in metastatic focuses (33.8%, 22/65)(P< 0.01); while positive rates of PR and HER-2 receptor have no significant difference between primary and metastatic focuses. Total discordance rates of ER, PR, and HER-2 were 35.4%, 29.2%, and 16.9%, respectively. CONCLUSION: Difference in expression level of ER between primary and metastatic focuses of breast cancer was significant, while differences of expression of PR, and HER-2 wasn't significant, but we still should think highly of the expression differences of ER,PR,and HER-2 in our clinical practices.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias Hepáticas/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/metabolismo , Neoplasias da Mama Masculina/patologia , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo
17.
Ai Zheng ; 23(11 Suppl): 1431-6, 2004 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-15566651

RESUMO

BACKGROUND & OBJECTIVE: Capxol is a Cremophor-free,protein stabilized, nanoparticle formulation of paclitaxel. This phase I study was designed to evaluate the tolerability/safety, toxicity profile, and maximum tolerated dose (MTD) of Capxol administered intravenously in Chinese patients with advanced solid tumor, and to provide the recommending dose for the phase II trial. METHOD: Capxol was administered intravenously over 30 minutes, no premedication was required. Doses of Capxol ranged from 135 to 350 mg/m(2). The treatment was repeated at 3 weeks interval. RESULTS: 22 patients were treated with Capxol and totally 94 treatments cycles were completed. No acute hypersensitivity reactions were observed during the infusion period. The treatment was tolerated well. Most of AEs (95%) were grade 1/2; >/= grade 3 AEs were only 5%. The most common toxicities were mild leucopenia and peripheral sensory neuropathy. The dose-limiting toxicities,which occurred at dose level of 350 mg/m(2),were grade 4 neutropenia (1 out of 3 patients) and grade 3 diplopia (1 out of 3 patients). The MTD was thus determined at 300 mg/m(2). Among 21 patients who were evaluable for efficacy, 1 CR, 7 PR, 9 SD, 4 PD were observed, overall response rate (CR+PR) was 38%. CONCLUSION: This phase I trial has demonstrated that Capxol has several advantages on clinical application, which include non-premedication required, shorter infusion time,higher paclitaxel MTD and safer toxicity. The results support for that a phase II clinical trial to further evaluate the antitumor activity of this drug in Chinese patients is worthy. The recommended dose for phase II clinical trial is 260 mg/m(2), I.V. over 30 minutes,and treatment repeats at every 3 weeks.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Dose Máxima Tolerável , Paclitaxel/efeitos adversos , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Diplopia/induzido quimicamente , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Nanotecnologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem
18.
Ai Zheng ; 22(8): 867-9, 2003 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-12917037

RESUMO

BACKGROUND & OBJECTIVE: Phase II clinical trails showed that paclitaxel is effective in treatment of advanced gastric cancer (AGC). The combination of paclitaxel and 5-fluorouracil (5-FU) in the treatment of advanced gastric cancer is effective and safe. This study was designed to evaluate the efficacy and the toxicity of paclitaxel combined with semimonthly 5-FU/Leucovorin for the AGC patients. METHODS: Twenty-five measurable patients with AGC proved pathologically were enrolled into this study. The chemotherapy regimen was comprised of paclitaxel,75 mg/m(2) i.v. in a 3-hour infusion followed by 2-hour infusion of leucovorin 200 mg/m(2), then 10-minute intravenous bolus of 5-FU 375 mg/m(2), then 48-hour infusion of 5-FU 2.8 g/m(2) using an ambulatory pump. The regimen was given per 14 days. One cycle consisted of twice chemotherapy regimens. All enrolled patients received at least two cycles of treatment. RESULTS: After two cycles of chemotherapy, the complete remission and the partial remission were 8% and 60%, respectively. The median duration of response was 4 months. No treatment-related death occurred. Phlebitis,feeling disorder, and alopecia were main side effects. CONCLUSION: Semimonthly 5-FU/LV combined with paclitaxel has high release rate but comparatively mild toxicity for AGC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem
19.
Ai Zheng ; 22(4): 404-6, 2003 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-12703999

RESUMO

BACKGROUND & OBJECTIVE: In most instances, advanced non-small cell lung cancer (NSCLC) is treated with primary chemotherapy. Many chemotherapy regimens can palliate cancer-related symptoms and modestly improve survival and quality of life. This clinical trial was designed to compare the efficacy and toxicity of two regimens: PG regimen [cisplatin and gemcitabine] versus PN regimen [cisplatin and vinorelbine]. METHODS: A total of 64 patients were enrolled in this study, 31 patients received PG regimen and 33 patients received PN regimen. Patients in both groups were well-matched with baseline disease characteristics (P >0.05). RESULTS: In PG group, the response rate was 32.3% [10/31, 95% confidence interval (CI):16.3%-48.7%][1 complete response (CR), 9 partial response (PR), 17 no change (NC), 4 progressive disease (PD)]; whereas in group PN, the response rate was 29.03% (9/31,95% CI:13.1%-44.9%) (0CR, 9PR, 17NC, 5PD). The difference of response rates between two groups was not statistically significant (P=0.526, Chi-square test). The median survival were 12 months for group PG (95%CI:10-14 months) and 11 months for group PN (95% CI:10-12 months). The difference of median survival between two groups was not statistically significant(P=0.5799, log-rang test). The major toxicity was myelosuppression. Leucopenia was more pronounced in group PN (P=0.009), Thrombocytopenia was more pronounced in group PG(P=0.01). CONCLUSION: PG and PN are two effective regimens for the patients with advanced NSCLC; the major toxicity was myelosuppression. Leucopenia was pronounced in group PN. Thrombocytopenia was pronounced in group PG. Neurotoxicity was observed in group PN.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vinorelbina
20.
Ai Zheng ; 21(8): 903-6, 2002 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-12478904

RESUMO

BACKGROUND & OBJECTIVE: Adriamycin, dacarbazine and ifosfamide are three effective chemotherapy drugs in treating progressive soft tissue sarcoma. However, few regimen is effective for the patients who failed in treatment with prior Adriamycin and ifosfamide at standard dose. This study was designed to observe and evaluate the efficacy and toxicity of high dose ifosfamide(HDI) regimen on pre-treated soft tissue sarcoma. METHODS: Ten patients with advanced soft tissue sarcoma and 5 patients after surgical resection were treated with HDI administered by continuous infusion at a dose of 14 g/m2 per cycle over 6 days. All patients were pretreated with anthracycline +/- standard dose ifosfamide. RESULTS: An overall response rate of 40% was observed with 2 complete and 2 partial remission. In the follow up at 4-48 month, the overall median survival time was 21 +/- 3.29 months and the median response duration was 6 +/- 1.45 months. The major toxicity was myelosuppression. 45.9% patients experienced grade 3-4 neutropenia. CONCLUSION: HDI is an active salvage regimen in anthracycline +/- standard dose ifosfamide pretreated soft tissue sarcoma.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Ifosfamida/uso terapêutico , Terapia de Salvação/métodos , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Ifosfamida/efeitos adversos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Terapia de Salvação/efeitos adversos , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
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