Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.550
Filtrar
1.
Mol Brain ; 15(1): 41, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35526002

RESUMO

Monoamine oxidase (MAO) inhibitors have been investigated for the treatment of neuropathic pain. Here, we assessed the antiallodynic effects of a novel MAO-B inhibitor, KDS2010, on paclitaxel (PTX)-induced mechanical hypersensitivity. Oral administration of KDS2010 effectively relieved PTX-induced mechanical hypersensitivity in a dose-dependent manner. KDS2010 (25 mg/Kg) significantly prevented and suppressed PTX-induced pain responses with minimal effects on the body weight, motor activity, and working memory. KDS2010 significantly reduced reactive astrocytosis and reactive oxygen species (ROS) level in the L4-L6 spinal cord of PTX-treated mice. Furthermore, KDS2010 reversed the attenuation of GABAergic spontaneous inhibitory postsynaptic current (sIPSC) frequency in spinal dorsal horn neurons, although it failed to restore the reduced tonic GABAA inhibition nor the increased GABA transporter 1 (GAT1) expression in PTX-treated mice. In addition, bath application of a reactive oxygen species (ROS) scavenger (PBN) restored the sIPSC frequency in PTX-treated mice but not in control and PTX + KDS2010-treated mice. These results indicated that the antiallodynic effect of KDS2010 is not due to a MAO-B-dependent GABA production. Finally, PBN alone also exerted a similar analgesic effect as KDS2010, but a co-treatment of PBN with KDS2010 showed no additive effect, suggesting that inhibition of MAO-B-dependent ROS production is responsible for the analgesic effect by KDS2010 on PTX-induced allodynia. Overall, KDS2010 attenuated PTX-induced pain behaviors by restoring the altered ROS level and GABAergic inhibitory signaling in the spinal cord, suggesting that KDS2010 is a promising therapeutic strategy for chemotherapy-induced peripheral neuropathy.


Assuntos
Analgésicos , Inibidores da Monoaminoxidase , Neuralgia , Analgésicos/farmacologia , Animais , Hiperalgesia/complicações , Hiperalgesia/tratamento farmacológico , Camundongos , Inibidores da Monoaminoxidase/farmacologia , Neuralgia/tratamento farmacológico , Paclitaxel/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Medula Espinal/metabolismo , Ácido gama-Aminobutírico/farmacologia
2.
Pharmacol Res Perspect ; 10(3): e00941, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35568997

RESUMO

The IMpower trials reported significant effects of atezolizumab-containing chemotherapies on Caucasian patients. Chinese patients differ from their Western counterparts in terms of driver mutations, etiologies, and regimen tolerance. In China, atezolizumab-containing chemotherapies are not cost-effective. Atezolizumab addition triggers grade >3 adverse events. Here, we evaluated the effectiveness and the safety profile of atezolizumab plus carboplatin and nab-paclitaxel compared to carboplatin and nab-paclitaxel in treatment-naïve Chinese patients with confirmed stage IV, non-squamous, non-small-cell lung cancer. All patients completed six cycles of 1200 mg of atezolizumab/3 weeks plus 6 mg/ml/min area-under-the-curve carboplatin/3 weeks plus 100 mg/m2 nab-paclitaxel/week (n = 115; ACN cohort) or 6 mg/ml/min area-under-the-curve carboplatin/3 weeks plus 100 mg/m2 nab-paclitaxel/week (n = 130; CNP cohort). The progression-free survival (12.98 ± 2.57 months vs. 10.89 ± 2.18 months, p < .0001) and overall survival (38.04 ± 19.8 months vs. 33.59 ± 87 months, p = .012) of patients in the ACN cohort were higher than those of patients in the CNP cohort after 48 weeks of follow-up. A total of 97 (84%) patients in the ACN cohort and 94 (72%) in the CNP cohort developed grade ≥3 adverse events (p = .030). A total of 84 (73%) patients from the ACN cohort and 107 (82%) from the CNP cohort died during 48 weeks of follow-up (p = .091). The addition of atezolizumab to carboplatin and nab-paclitaxel enhanced progression-free and overall survival but increased the risk of grade ≥3 adverse events in Chinese, treatment-naïve, stage IV, non-squamous, non-small-cell lung cancer patients who completed treatment (Level of Evidence: III; Technical Efficacy Stage: 4).


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Albuminas , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/efeitos adversos , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Estudos Retrospectivos
3.
Trials ; 23(1): 334, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449070

RESUMO

BACKGROUND: Peripheral arterial disease is a progressive atherosclerotic disease with symptoms ranging from an intermittent claudication to acute critical limb ischemia and amputations. Drug-coated balloons and stents were developed to prevent neo-intimal proliferation and restenosis after percutaneous transluminal angioplasty. Randomized controlled trials showed that drug-coated, notably paclitaxel-coated, devices reduce restenosis, late lumen loss, and the need for target lesion re-vascularization compared with uncoated ones. However, the size of these trials was too small to prove superiority for "hard" clinical outcomes. Moreover, available studies were characterized by too restrictive eligibility criteria. Finally, it remains unclear whether paclitaxel-coated balloons may impair long-term survival. Alternative drug-coated balloons, the so-called limus-based analogs, have been approved for clinical use in patients with peripheral arterial disease. By encapsulating sirolimus in phospholipid drug nanocarriers, they optimize adhesion properties of sirolimus and provide better bioavailability. METHODS: In this investigator-initiated all-comer open-label phase III randomized controlled trial, we will evaluate whether sirolimus-coated balloon angioplasty is non-inferior and eventually superior, according to a predefined hierarchical analysis, to uncoated balloon angioplasty in adults with infra-inguinal peripheral arterial disease requiring endovascular angioplasty. Key exclusion criteria are pregnancy or breastfeeding, known intolerance or allergy to sirolimus, and participation in a clinical trial during the previous 3 months. The primary efficacy outcome is the composite of two clinically relevant non-subjective "hard" outcomes: unplanned major amputation of the target limb and endovascular or surgical target lesion re-vascularization for critical limb ischemia occurring within 1 year of randomization. The primary safety outcome includes death from all causes. DISCUSSION: By focusing on clinically relevant outcomes, this study will provide useful information on the efficacy and safety of sirolimus-coated balloon catheters for infra-inguinal peripheral arterial disease in a representative ("all-comer") population of unselected patients. As regulatory agencies had raised safety concerns in patients exposed to paclitaxel-coated devices (versus uncoated ones), collect mortality data up to 5 years after randomization will be collected. TRIAL REGISTRATION: ClinicalTrials.gov NCT04238546.


Assuntos
Angioplastia com Balão , Paclitaxel , Doença Arterial Periférica , Sirolimo , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/métodos , Ensaios Clínicos Fase III como Assunto , Materiais Revestidos Biocompatíveis , Constrição Patológica , Artéria Femoral , Humanos , Paclitaxel/efeitos adversos , Doença Arterial Periférica/terapia , Artéria Poplítea , Ensaios Clínicos Controlados Aleatórios como Assunto , Sirolimo/efeitos adversos , Resultado do Tratamento , Grau de Desobstrução Vascular
4.
Trials ; 23(1): 261, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35382842

RESUMO

BACKGROUND: The standard initial treatment for ovarian cancer is surgery and platinum-based chemotherapy and potentially maintenance therapy with avastin or inhibitors of poly-ADP ribose polymerase (PARP). While a proportion of women are cured by this approach, the vast majority will relapse and become resistant to platinum chemotherapy either initially or on subsequent treatment. There is an unmet need to improve response to treatment and quality of life in these women. TAK228 is a novel therapy that can be added to standard treatment in the participant population and the aim of the DICE trial is to assess its effectiveness. Laboratory and clinical research has shown that these ovarian cancers may respond to the molecular target of a drug such as TAK228, and there have been studies using it in other advanced solid tumours including endometrial cancer. METHODS: One hundred twenty-four eligible women will be recruited from participating research sites in the United Kingdom (UK) and Germany. Randomised participants will receive either weekly paclitaxel alone (standard treatment, n = 62) or TAK228 plus weekly paclitaxel (n = 62) until the cancer significantly worsens; there are significant adverse events or any other protocol-defined stopping criteria. Participants will be monitored for response to treatment (using radiological imaging), adverse events and quality of life during both randomised treatment and subsequent follow-up. DISCUSSION: The primary objective/endpoint of the study is to compare the two treatments in terms of progression-free survival, or the length of time that each participant is alive without the cancer significantly worsening according to defined assessment criteria. If the addition of TAK228 to weekly paclitaxel chemotherapy is shown to significantly improve this statistically, and adverse events and quality of life are not significantly worse than standard treatment, then TAK228 plus weekly paclitaxel could potentially be taken forward within the context of a larger phase III trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03648489 . Registered on 27 August 2018.


Assuntos
Neoplasias Ovarianas , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/efeitos adversos
6.
Methods Cell Biol ; 168: 277-298, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35366987

RESUMO

While cancer patients may have chemotherapeutics to thank for being cured of their malignancy, they are often left to suffer a disabling neuropathy induced by that same cancer treatment. This neuropathy, known as chemotherapy-induced peripheral neuropathy, or CIPN, is one of the most debilitating survivorship concerns for patients, with many citing hallmark symptoms of hyperalgesia, allodynia, and numbness, and subsequently reducing their dose or even ceasing treatment altogether. Investigations into this interplay between the antineoplastic activity of chemotherapeutic agents and the preservation of peripheral nerve health are therefore crucial for the development of CIPN treatment and prevention methods. Responding to need, current literature is inundated with varying preclinical models of CIPN. This chapter thus seeks to provide a detailed and reliable methodology for the induction and assessment of CIPN in mice, using a preclinical model that is both reproducible and translatable to several aspects of the clinical phenotype. Specifically, this chapter lays out a model for intermittent low-dose paclitaxel induction of CIPN in C57BL/6J mice, and a testing of this induction via von Frey filament mechanical hypersensitivity assays, a mechanical hyposensitivity (numbness) assay, and a cold-thermal allodynia assay (acetone test). These protocols can easily be adjusted to fit the needs of individual CIPN experiments, as stated throughout the chapter.


Assuntos
Antineoplásicos , Doenças do Sistema Nervoso Periférico , Animais , Antineoplásicos/toxicidade , Humanos , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/genética , Camundongos , Camundongos Endogâmicos C57BL , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico
7.
Zhonghua Zhong Liu Za Zhi ; 44(4): 364-369, 2022 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-35448926

RESUMO

Objective: To explore the efficacy and safety of real-world eribulin in the treatment of metastatic breast cancer. Methods: From December 2019 to December 2020, patients with advanced breast cancer were selected from Beijing Chaoyang District Sanhuan Cancer Hospital, Shandong Cancer Hospital, Peking University Cancer Hospital, Baotou Cancer Hospital, Shengjing Hospital Affiliated to China Medical University, and Cancer Hospital of Chinese Academy of Medical Sciences. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: The median progression-free survival (PFS) of 77 patients was 5 months, the objective response rate (ORR) was 33.8%, and the disease control rate (DCR) was 71.4%. The ORR of patients with triple-negative breast cancer was 23.1%, and the DCR was 57.7%; the ORR of patients with Luminal breast cancer was 40.0%, and the DCR was 77.8%; the ORR of patients with HER-2 overexpression breast cancer was 33.3%, and the DCR was 83.3%. ORR of 50.0% and DCR of 66.7% for patients treated with eribulin as first to second line treatment, ORR of 29.4% and DCR of 76.5% for patients treated with third to fourth line and ORR of 28.6% and DCR of 71.4% for patients treated with five to eleven line. The ORR of patients in the eribulin monotherapy group was 40.0% and the DCR was 66.0%; the ORR of patients in the combination chemotherapy or targeted therapy group was 22.2% and the DCR was 81.5%. Patients with a history of treatment with paclitaxel, docetaxel, or albumin paclitaxel during the adjuvant phase or after recurrent metastasis had an ORR of 32.9% and a DCR of 69.9% when treated with eribulin. The treatment efficacy is an independent prognostic factor affecting patient survival (P<0.001). The main adverse reactions in the whole group of patients were Grade Ⅲ-Ⅳ neutrophil decline [29.9% (23/77)], and other adverse reactions were Grade Ⅲ-Ⅳ fatigue [5.2% (4/77)], Grade Ⅲ-Ⅳ peripheral nerve abnormality [2.6% (2/77)] and Grade Ⅲ-Ⅳ alopecia [2.6% (2/77)]. Conclusions: Eribulin still has good antitumor activity against various molecular subtypes of breast cancer and advanced breast cancer that has failed multiple lines of chemotherapy, and the adverse effects can be controlled, so it has a good clinical application value.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Neoplasias da Mama/patologia , Feminino , Furanos/efeitos adversos , Humanos , Cetonas/efeitos adversos , Paclitaxel/efeitos adversos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
8.
Biochem Biophys Res Commun ; 603: 94-101, 2022 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-35279463

RESUMO

Scalp cooling is currently the most approved treatment to prevent alopecia due to chemotherapy for cancer. Few reports can be available, and the mechanisms involved in scalp cooling were unclear. The present work tries to reveal a preliminary inhibitory mechanism of scalp cooling on paclitaxel-induced alopecia. The results found that low temperature enhanced local vasoconstriction to 0.32 (dimensionless diameter, @ 22 °C) and the vascular diameter presented an oscillating attenuation, which led to the concentration reduction of chemotherapeutic drugs transported by blood flow. Cooling significantly rescued M-HFK cells treated by paclitaxel, and the lower temperature for the better protection due to weakening the cytotoxicity in some extent. Cell cycle results showed that the G0/G1 phase was arrested at low temperature (i.e. 22 °C), which was beneficial to mitigate the effect of paclitaxel on the G2/M phase cycle and finally made the cell cycle return to normal. Also, cold stimulation significantly increased the concentration of HSP70 more than 3 times (@22 °C for 2h) compared with that of the control group, which means low temperature can protect cells from stresses. Furtherly, Cooling reduced the number of PH3+ and Caspase-3+ cells in the hair follicle, and effectively inhibited the cell apoptosis in the vitro hair follicle and alopecia in the mice experiments. The current work provides a basis for deeply understanding the chemotherapy-induced alopecia prevention with scalp cooling.


Assuntos
Antineoplásicos , Neoplasias da Mama , Hipotermia Induzida , Paclitaxel , Alopecia/induzido quimicamente , Alopecia/prevenção & controle , Animais , Antineoplásicos/efeitos adversos , Feminino , Folículo Piloso , Humanos , Hipotermia Induzida/métodos , Camundongos , Paclitaxel/efeitos adversos , Couro Cabeludo , Temperatura
9.
PLoS One ; 17(3): e0264653, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35231078

RESUMO

BACKGROUND: Pancreatic cancer is associated with a high thromboembolism risk. We investigated the significance of early venous thromboembolism (VTE) detection in patients with unresectable metastatic pancreatic cancer (UR-MPC) who received first-line chemotherapy with gemcitabine plus nab-paclitaxel (GnP). METHODS: This single-center retrospective study enrolled 174 patients with UR-MPC who underwent GnP as a first-line chemotherapy from April 2017 to March 2020. The early detection of VTE (deep venous thrombosis and pulmonary thromboembolism) was defined as diagnosis by the first follow-up CT scan after the initiation of chemotherapy. We compared the patients with early detection of VTE (VTE (+) group) with the others (VTE (-) group). We examined overall survival (OS), progress free survival (PFS), severe adverse events, and predictors associated with OS using the Cox proportional hazards model. RESULTS: Early detection of VTE was observed in 17 patients (9.8%). Thirteen patients were diagnosed with VTE at treatment initiation, and four patients were diagnosed after treatment initiation. The median time to diagnosis after treatment initiation was 55 days (range: 31-71 days). Only 3 patients were symptomatic. The VTE (+) group exhibited worse OS and PFS than the VTE (-) group (OS: 259 days vs. 400 days, P < 0.001; PFS: 120 days vs. 162 days, P = 0.008). The frequency of grade 3-4 adverse events was not significantly different. Although the performance status was poorer in the VTE (+) group, VTE was identified as a statistically significant independent predictor for OS in multivariate analyses (HR, 1.87; 95% CI, 1.02-3.44; P = 0.041). CONCLUSIONS: Early VTE detection is a predictor of a poor prognosis in UR-MPC patients who receive GnP as first-line chemotherapy, suggesting that screening VTE for patients with UR-MPC is crucial, even if patients are asymptomatic.


Assuntos
Neoplasias Pancreáticas , Tromboembolia Venosa , Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/análogos & derivados , Detecção Precoce de Câncer , Humanos , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico
10.
Int Immunopharmacol ; 107: 108693, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35303507

RESUMO

The purpose of this study was to evaluate if phytocannabinoids, synthetic cannabidiol (CBD), and tetrahydrocannabivarin (THCV), and their combination, could protect mice from Paclitaxel-induced peripheral neuropathy (PIPN). Six groups of C57BL/6J mice (n = 6) were used in this study. The mice were given paclitaxel (PTX) (8 mg/kg/day, i.p.) on days 1, 3, 5, and 7 to induce neuropathy. Mice were evaluated for behavioral parameters, and dorsal root ganglions (DRG) were collected from the animals and subjected to RNA sequencing and westernblot analysis at the end of the study. On cultured DRGs derived from adult male rats, immunocytochemistry and mitochondrial functional assays were also performed. When compared to individual treatments, the combination of CBD and THCV improved thermal and mechanical neurobehavioral symptoms in mice by twofold. Targets for CBD and THCV therapy were identified by KEGG (RNA sequencing). PTX reduced the expression of p-AMPK, SIRT1, NRF2, HO1, SOD2, and catalase while increasing the expression of PI3K, p-AKT, p-P38 MAP kinase, BAX, TGF-ß, NLRP3 inflammasome, and caspase 3 in DRG homogenates of mice. Combination therapy outperformed monotherapy in reversing these protein expressions. The addition of CBD and THCV to DRG primary cultures reduced mitochondrial superoxides while increasing mitochondrial membrane potentials. WAY100135 and rimonabant altered the neuroprotective effects of CBD and THCV respectively by blocking 5-HT1A and CB1 receptors in mice and DRG primary cultures. The entourage effect of CBD and THCV against PIPN appears to protect neurons in mice via 5HT1A and CB1 receptors respectively.


Assuntos
Canabidiol , Canabinoides , Neuralgia , Animais , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Canabinoides/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Paclitaxel/efeitos adversos , Ratos , Roedores
12.
JACC Cardiovasc Interv ; 15(7): 770-779, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35305906

RESUMO

OBJECTIVES: The aim of this randomized controlled trial was to investigate a novel sirolimus-coated balloon (SCB) compared with the best investigated paclitaxel-coated balloon (PCB). BACKGROUND: There is increasing clinical evidence for the treatment of coronary de novo disease using drug-coated balloons. However, it is unclear whether paclitaxel remains the drug of choice or if sirolimus is an alternative, in analogy to drug-eluting stents. METHODS: Seventy patients with coronary de novo lesions were enrolled in a randomized, multicenter trial to compare a novel SCB (SeQuent SCB, B. Braun Melsungen; 4 µg/mm2) with a PCB (SeQuent Please, B. Braun Melsungen; 3 µg/mm2). The primary endpoint was angiographic late lumen loss (LLL) at 6 months. Secondary endpoints included major adverse cardiovascular events and individual clinical endpoints such as cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis. RESULTS: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment LLL was 0.01 ± 0.33 mm in the PCB group versus 0.10 ± 0.32 mm in the SCB group. The mean difference between SCB and PCB was 0.08 (95% CI: -0.07 to 0.24). Noninferiority at a predefined margin of 0.35 was shown. However, negative LLL was more frequent in the PCB group (60% of lesions vs 32% in the SCB group; P = 0.019). Major adverse cardiovascular events up to 12 months also did not differ between the groups. CONCLUSIONS: This first-in-human comparison of a novel SCB with a crystalline coating showed similar angiographic outcomes in the treatment of coronary de novo disease compared with a clinically proven PCB. However, late luminal enlargement was more frequently observed after PCB treatment. (Treatment of Coronary De-Novo Stenosis by a Sirolimus Coated Balloon or a Paclitaxel Coated Balloon Catheter Malaysia [SCBDNMAL]; NCT04017364).


Assuntos
Angioplastia Coronária com Balão , Fármacos Cardiovasculares , Doença da Artéria Coronariana , Reestenose Coronária , Angioplastia Coronária com Balão/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Humanos , Paclitaxel/efeitos adversos , Estudos Prospectivos , Sirolimo/efeitos adversos , Resultado do Tratamento
14.
Pak J Pharm Sci ; 35(1(Special)): 355-359, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35236647

RESUMO

To investigate the value of cisplatin plus paclitaxel in patients with middle and advanced cervical cancer after laparoscopic nerve-sparing extensive hysterectomy and its effect on their T lymphocyte subsets. 44 patients with middle and advanced cervical cancer were randomly divided into the control group (n = 22) and the observation group (n = 22). Patients in the control group received nab-paclitaxel as chemotherapy, while patients in the observation group received cisplatin plus nab-paclitaxel as adjuvant therapy. The local recurrence and distant metastasis rates were statistically analyzed after 1 year of follow-up. The overall effective rate in the observation group was significantly higher than that in the control group (P<0.05). The serum levels of IL-4, IL-10 and TNF-α in the two groups were reduced markedly after treatment than before treatment (P<0.05) and the observation group was significantly lower than the control group (P<0.05). After treatment, the proportion of CD3+ and CD4+ cells increased, the proportion of CD8+ cells decreased more significantly than that in the control group (P<0.05). The combination of cisplatin and paclitaxel was demonstrated to have obviously synergistic and attenuated effects after middle and advanced cervical cancer surgery, optimize the efficacy, reduce adverse effects, and improve the body's immune function.


Assuntos
Cisplatino/uso terapêutico , Histerectomia/métodos , Paclitaxel/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Citocinas/genética , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Subpopulações de Linfócitos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos
15.
BMC Cancer ; 22(1): 269, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35287613

RESUMO

BACKGROUND: The de-escalation treatment in patients with low-risk HER2-positive early breast cancer (eBC) is an attractive strategy to avoid unnecessary treatment and improve the quality of life of patients. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor (TKI), has shown efficacy in patients with advanced HER2-positive breast cancer. Meanwhile, nanoparticle albumin-bound (nab)-paclitaxel reveals survival benefit over solvent-based paclitaxel and eliminates the toxicities associated with the solvent. However, the efficacy and safety of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for low-risk HER2 + eBC patients have not been evaluated. METHODS: This is a multicenter, open-label, single-arm phase II study. A sample size of 261 patients with tumor ≤ 3 cm, lymph node-negative (N0) or micrometastatic (N1mi), HER2 + breast cancer will be recruited. Eligible patients will receive nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year. The primary endpoint is invasive disease-free survival. A sub-study will be conducted to investigate different prophylactic strategies for diarrhea, which is the most common adverse event of pan-HER TKIs. One hundred and twenty patients from the main study will be randomly (1:1) allocated to receive loperamide either during the first cycle (4 mg tid on days 1-7, then 4 mg bid on days 8-21) or the first 2 cycles (4 mg tid on days 1-7, then 4 mg bid on days 8-42). The primary endpoint of the sub-study is the incidence of grade ≥ 3 diarrhea. DISCUSSION: This is the first prospective study of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for patients with low-risk HER2-positive eBC. It would probably provide robust evidence for de-escalating strategy of HER2-positive eBC and appropriate management for pyrotinib-related diarrhea. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04659499 . Registered on December 9, 2020.


Assuntos
Acrilamidas/administração & dosagem , Albuminas/administração & dosagem , Aminoquinolinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Paclitaxel/administração & dosagem , Acrilamidas/efeitos adversos , Albuminas/efeitos adversos , Aminoquinolinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Feminino , Humanos , Incidência , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Receptor ErbB-2/metabolismo , Resultado do Tratamento
16.
BMJ Open ; 12(3): e053182, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35296476

RESUMO

INTRODUCTION: Network meta-analyses have confirmed that paclitaxel plus carboplatin could improve progression-free survival (PFS) and overall survival (OS) compared with platinum alone. However, detailed implementation schedule (weekly or 3-weekly therapy) was not specified in clinical practice guidelines. Evidence from studies is also inconsistent. We will conduct a systematic review and meta-analysis to evaluate the benefits and harms of weekly therapy and 3-weekly therapy of paclitaxel combined with carboplatin in women with ovarian cancer. METHODS: We will search PubMed, EMBASE and the Cochrane Library databases to include relevant randomised controlled trials comparing weekly therapy versus 3-weekly therapy of paclitaxel combined with carboplatin for women with ovarian cancer. Random-effects model will be used to pool data for patient-reported outcomes including survival rate, OS, PFS and adverse events. Grading of Recommendation, Assessment, Development and Evaluation approach will be used to rate the quality of evidence. ETHICS AND DISSEMINATION: This systematic review and meta-analysis will be based on published data and does not therefore require specific ethical approval or consent for participation. The results will be published in a peer-reviewed journal. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/GJUMA.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ovarianas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Carcinoma Epitelial do Ovário , Feminino , Humanos , Metanálise como Assunto , Paclitaxel/efeitos adversos , Revisões Sistemáticas como Assunto
18.
G Ital Cardiol (Rome) ; 23(4): 295-298, 2022 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-35343481

RESUMO

We report the case of a 50-year-old female patient with breast cancer who, during preoperative workup, presented repeated wide QRS complex tachycardias, recorded by Holter ECG. She was immediately referred to a hub center for electrophysiological study where she was diagnosed with right ventricular outflow tract ventricular tachycardia and underwent catheter ablation. The chemotherapy with paclitaxel that the patient was receiving combined with psychological stress may have triggered the arrhythmias.


Assuntos
Ablação por Cateter , Taquicardia Ventricular , Arritmias Cardíacas/cirurgia , Eletrocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Taquicardia Ventricular/induzido quimicamente , Taquicardia Ventricular/diagnóstico
20.
J Cardiovasc Surg (Torino) ; 63(1): 8-12, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35179337

RESUMO

BACKGROUND: There appears to be an association between paclitaxel-coated devices and increased 5-year all-cause mortality. METHODS: We are conducting a prospective, randomized, controlled, single-center, noninferiority study. All consecutive patients with femoropopliteal arterial disease who fulfilled the inclusion/exclusion criteria are sequentially and consecutively assigned to either paclitaxel (Ranger, Boston Scientific) or sirolimus (MagicTouch, Concept Medical) coated balloon angioplasty treatment. The primary outcome are procedural success and primary vessel patency at index procedure. The secondary outcomes are 30-day and 12-month freedom from MAEs (amputation, death, TLR/TVR, MI, distal embolization that requires a separate intervention or hospitalization), procedural success (≤30% residual diameter stenosis or occlusion after the procedure), Rutherford category improvement (reduction ≤1 category) and ABI improvement (increase ≥0.10 from baseline). RESULTS: A total of six patients have been enrolled in the present study up to now. The mean age was 72.6 years old and five were male. All patients had angiographic evidence of isolated occlusion in the transition segment of the distal femoral superficial artery in the popliteal artery. The mean length was 109 mm. Three patients were treated by sirolimus-coated (group A) and three by paclitaxel coated balloon angioplasty (group B). The primary patency and procedural success was in two of three and three of three patients, for group A and B, respectively. CONCLUSIONS: Preliminary results show safety and feasibility of the Sirolimus-coated balloon angioplasty. Further investigation and increase of sample size will allow for more sustained conclusions regarding patency and procedural success of this type of balloons for the endovascular treatment of peripheral arterial disease.


Assuntos
Angioplastia com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Artéria Femoral , Paclitaxel/administração & dosagem , Doença Arterial Periférica/terapia , Artéria Poplítea , Sirolimo/administração & dosagem , Idoso , Amputação , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/mortalidade , Fármacos Cardiovasculares/efeitos adversos , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Humanos , Salvamento de Membro , Masculino , Paclitaxel/efeitos adversos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Placa Aterosclerótica , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Intervalo Livre de Progressão , Sirolimo/efeitos adversos , Fatores de Tempo , Grau de Desobstrução Vascular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...