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1.
Orv Hetil ; 161(11): 425-433, 2020 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-32148096

RESUMO

Introduction: Endometrial cancer is the most common invasive gynecologic malignancy in developed countries. The best survival rates are expected after surgical removal, thus the aim of a complex treatment is to achieve resecability in locally and locoregionally advanced disease. Aim: The primary purpose of this study was to evaluate if the neoadjuvant systemic treatment leads to better overall survival compared to irradiation solely. Method: From January 2015 to December 2018, we enrolled 28 patients diagnosed with irresecable, locally and locoregionally advanced high-risk endometrial carcinoma. Patients were treated by neoadjuvant paclitaxel-carboplatin, then radical hysterectomy, bilateral oophorectomy and lymphadenectomy were performed. Results: After administration of 6 cycles of carboplatin-paclitaxel, the control MR test showed tumor shrinkage in all patients. Complete resection was achieved in the case of every patient. Tumor residuum in lymph nodes was verified in 4 cases by pathological evaluation. The 2-year survival and the 2-year progression-free survival rates were 65,1% and 66,1%, respectively. The median overall survival was 16,5 months. Conclusion: Neoadjuvant treatment can be an effective approach in providing the conditions for complete tumor resection, which may result in survival advantage. Despite multimodal treatment, prognosis is poor. Orv Hetil. 2020; 161(11): 425-433.


Assuntos
Carboplatina/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/cirurgia , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino/uso terapêutico , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Excisão de Linfonodo , Estadiamento de Neoplasias , Ovariectomia , Taxa de Sobrevida , Resultado do Tratamento
2.
Bratisl Lek Listy ; 121(2): 143-150, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115968

RESUMO

OBJECTIVES: This study was aimed to explore the effects of follistatin on cisplatin-induced renal dysfunction, histopathological changes, apoptosis, inflammation and oxidative damage in rats. BACKGROUND: Follistatin plays an important role in the developmental and regeneration processes of kidney by blocking the actions of activin, which is a member of transforming growth factor-ß superfamily. METHODS: Twenty seven rats were separated into 4 equal groups: Control, Cp (cisplatin, 6 mg/kg, intrapertoneally (ip)), F1 (cisplatin + 1 µg/day follistatin ip for 4 consecutive days) and F4 (cisplatin + 4 µg/day follistatin ip single dose) groups. Renal health was monitored by blood urea nitrogen, serum creatinine and histological analysis. Apoptosis, inflammation and oxidative stress was investigated in kidney tissue. Activin A levels in serum and kidney were evaluated as well. RESULTS: Follistatin administration showed a considerable nephroprotective effect against cisplatin-induced nephrotoxicity by preventing renal functional and structural abnormalities, apoptosis and inflammation. The activin A levels in both serum and kidney were also suppressed by follistatin administration. CONCLUSION: Exogenous follistatin ameliorates acute kidney injury, by blocking activin A. The renoprotective effect of follistatin against cisplatin-induced nephrotoxicity appears to be associated with its anti-inflammatory, antiapoptotic and direct nephroprotective actions (Tab. 1, Fig. 7, Ref. 23).


Assuntos
Lesão Renal Aguda , Cisplatino , Folistatina , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Cisplatino/efeitos adversos , Folistatina/farmacologia , Folistatina/uso terapêutico , Inflamação , Rim , Estresse Oxidativo , Ratos
3.
Zhonghua Zhong Liu Za Zhi ; 42(2): 133-138, 2020 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-32135648

RESUMO

Objective: To evaluate the long-term effect and safety of chrono-chemotherapy combined with intensity modulated radiotherapy (IMRT) in locally advanced nasopharyngeal carcinoma (NPC). Methods: 160 patients with locally advanced NPC were randomly divided into a chrono group and conventional group according to random number table. In the first stage, all patients underwent two cycles of induced chemotherapy, consisting of docetaxel, cisplatin and 5-Fu every 21 days. Notably, patients received chrono-moduated chemotherapy according to circadian rhythm in the chrono group, and conventional chemotherapy in the conventional group. Then, 21 days after the completion of first stage, three cycles of concurrent cisplatin chemotherapy every 21 days were given to all patients during IMRT. The median follow-up after the completion of radiotherapy was 31 months. Long-term side effects and the survival of patients were observed. Results: Patients in the chrono group had significantly lower rates of hearing loss (22.72%), dysphagia (0) and neck fibrosis (4.54%) compared with those in the conventional group (39.13%、8.69%, 15.94%, respectively, all P<0.05). Meanwhile, the 1- year overall survival rates (97.0% vs 92.8%), 3-year overall survival rates (80.3% vs 81.2%), 1-year progression free survival rates (95.5% vs 87.0%), 3-year progression free survival rates (71.2% vs 73.9%), 1-year locoregional relapse-free survival rates (97.0% vs 95.7%), 1-year locoregional relapse-free survival rates (92.4% vs 92.8%), 1-year distant metastasis-free survival rates (97.0% vs 98.6%) and 3-year distant metastasis-free survival rates (90.9% vs 91.3%) between the chrono group and the conventional group were not statistically significant (all P>0.05). Conclusions: Compared with conventional chemotherapy, chrono-chemotherapy combined with IMRT didn't affect long-term survival, but reducing the incidence of adverse events in patients with locally advanced NPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Terapia Combinada , Docetaxel/administração & dosagem , Cronoterapia Farmacológica , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Radioterapia de Intensidade Modulada/métodos , Resultado do Tratamento
4.
Artigo em Chinês | MEDLINE | ID: mdl-32086932

RESUMO

Cisplatin is an anti-tumor drug which is widely used for the treatment of various solid tumors. Unfortunately, seriousside-effects have affected patients, such as hearing loss. Up to now, there is no clear and effective measure to protect the cisplatin-induced ototoxicity in the clinical use of cisplatin studies indicated that autophagy may be involved in the whole process of cisplatin-induced hearing loss. In this review, the relationship between cisplatin ototoxicity and autophagy was reviewed. It is hoped that this study can provide reference for further study of cisplatin ototoxicity and intervention of autophagy with autophagy activator or inhibitor.


Assuntos
Antineoplásicos/efeitos adversos , Autofagia , Cisplatino/efeitos adversos , Perda Auditiva/induzido quimicamente , Humanos
6.
Anatol J Cardiol ; 23(2): 118, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32011333
8.
Chem Commun (Camb) ; 56(18): 2695-2698, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32030397

RESUMO

A BODIPY-based fluorescent sensor PS with an NO4S2 podand ligand was studied for the selective detection of Pt2+ over 21 cations as well as selected platinum drugs in aqueous medium. The platinum sensor PS shows 28-fold, 22-fold and 14-fold fluorescence turn-on enhancements to Pt2+, cisplatin and nedaplatin, and was thereby employed to detect platinum drugs in A-549 human lung cancer cells.


Assuntos
Compostos de Boro/química , Cisplatino/análise , Corantes Fluorescentes/química , Neoplasias Pulmonares/diagnóstico por imagem , Platina/análise , Células A549 , Cisplatino/uso terapêutico , Humanos , Ligantes , Neoplasias Pulmonares/tratamento farmacológico , Estrutura Molecular , Imagem Óptica , Espectrometria de Fluorescência
9.
Chem Commun (Camb) ; 56(20): 3069-3072, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32049075

RESUMO

Niacin-ligated platinum(iv)-ruthenium(ii) chimeric complexes (PtRu 1-4) have been synthesized and evaluated for their antitumor performance. Using the optimal complex, PtRu-1, we show that this water-soluble chimeric prodrug not only potently inhibits the metastasis and proliferation of tumor cells but also has an unexpectedly higher safety margin in animals compared with the traditionally-used, clinically approved drug cisplatin.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Niacina/farmacologia , Platina/farmacologia , Rutênio/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/química , Cisplatino/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Niacina/química , Platina/química , Rutênio/química , Relação Estrutura-Atividade
10.
Life Sci ; 244: 117280, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31926239

RESUMO

AIMS: Recently, chemoresistance has been recognized as an obstacle in the treatment of gastric cancer (GC). The aim of this study was to investigate the biological functions and underlying mechanisms of propofol in GC chemoresistance. MAIN METHODS: CCK-8 assay, flow cytometry and immunofluorescent staining were performed to assess the IC50 concentration, cell apoptosis and autophagy activity of cisplatin in both GC chemosensitive cells (SGC7901) and chemoresistant cells (SGC7901/CDDP). The expression pattern of MALAT1 in GC cells was detected by qRT-PCR. The shRNAs and overexpressing plasmids were employed for the loss or gain-of-function. Dual-luciferase reporter assay was subjected to verify the binding relationship between MALAT1 and miR-30e. Besides, ATG5 mRNA and protein levels were determined using qRT-PCR and western blot analysis. Furthermore, GC xenograft mice model was established to validate the in vitro findings. KEY FINDINGS: Chemoresistant GC cells presented higher IC50 of cisplatin, increased autophagy activity and stronger expression of MALAT1. The application of propofol promoted cell apoptosis and reduced the activity of autophagy through downregulating MALAT1. Silencing of MALAT1 inhibited chemo-induced autophagy, whereas MALAT1 overexpression promoted autophagy in GC cells. Mechanistic researches demonstrated that MALAT1 could bind with miR-30e to regulate ATG5 expression, thus causing the suppression of autophagy. In vivo GC xenograft model treated with both propofol and cisplatin also showed significantly decreased tumor size and weight, which was enhanced by knockdown of MALAT1. SIGNIFICANCE: Altogether, our study revealed a novel mechanism of propofol of lncRNA MALAT1/miR-30e/ATG5 mediated autophagy-related chemoresistance in GC, casting new lights on the understanding of propofol.


Assuntos
MicroRNAs/genética , Propofol/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/genética , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , China , Cisplatino/metabolismo , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Propofol/farmacologia , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Life Sci ; 244: 117299, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31953157

RESUMO

AIMS: Notch signaling is highly implicated in several cancers and chemoresistance. Therefore, Notch-targeted therapies might be beneficial in enhancing chemotherapeutic effect and cancer regression. This study aimed to investigate implication of Notch in development and progression of solid Ehrlich carcinoma (SEC) and enhancement of anticancer effect of cisplatin (CIS) by addition of thymoquinone (TQ) and pentoxifylline (PTX) through modulation of Notch. MAIN METHODS: SEC was induced in mice as model for mammary carcinoma by s.c. injection of 1 × 106 Ehrlich cells into back of the mice. On 12th day, solid tumor was developed and mice were divided into seven groups; tumor control, early CIS (ECIS), ECIS + ETQ, ECIS + ETQ + EPTX, late CIS (LCIS), LCIS + LTQ, and LCIS + LTQ + LPTX. Early treatment was started on 12th day, whereas late treatment was begun on 19th day from tumor inoculation. At the endpoint, samples were collected for detection of Notch1, Hes1, Jagged1, ß-catenin, TNF-α, IL-6, IFN-γ, IL-2, VEGF, apoptosis, CD4, and CD8. KEY FINDINGS: Adding PTX and TQ to CIS significantly reduced Notch1, Hes1, Jagged1, ß-catenin, TNF-α, IL-6, IFN-γ, and VEGF with increment in IL-2, CD4, CD8, and apoptotic cells. Moreover, early treated groups showed remarkable attenuation in tumor growth and the relevant parameters compared to their counterpart later groups. SIGNIFICANCE: Addition of PTX with TQ to CIS showed a synergistic chemotherapeutic action and induced better oncostatic effect mainly through Notch suppression. Consequently, shutting Notch could be of great interest in promoting chemosensetivity and cancer control.


Assuntos
Benzoquinonas/farmacologia , Pentoxifilina/farmacologia , Receptores Notch/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Benzoquinonas/metabolismo , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/metabolismo , Cisplatino/metabolismo , Cisplatino/farmacologia , Feminino , Camundongos , Pentoxifilina/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Anticancer Res ; 40(1): 67-73, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892553

RESUMO

BACKGROUND/AIM: Aberrant expression of the SEI1 oncogene has been prevalently found in a variety of human cancers, including oral squamous cell carcinoma (OSCC). Recent studies have shown that cisplatin up-regulates the expression of SEI1 in breast and bladder cancer cells, thus inhibiting apoptosis and cell death in these cells. In the present study, we investigated the impact of cisplatin on the expression of SEI1 in OSCC cells. MATERIALS AND METHODS: Four OSCC cell lines, CAL27, SCC4, SCC15, and SCC22A were treated with cisplatin and 5-fluorouracil, and changes in SEI1 expression in these cells were evaluated using quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analyses. RESULTS: Cisplatin significantly induced SEI1 expression in the tested OSCC cells. Contrarily, cisplatin treatment did not affect the expression of gankyrin and BMI1, two oncogenes frequently overexpressed in a coordinate manner with SEI1 in OSCC. Additionally, 5-fluorouracil did not bring about any detectable changes in SEI1 expression in these cells. CONCLUSION: Cisplatin-induced up-regulation of SEI1 expression in OSCC is specific, and such induction could underlie the development of resistance to cisplatin in OSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Cisplatino/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Bucais/genética , Oncogenes , Fatores de Transcrição/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/farmacologia , Humanos
15.
J Cancer Res Clin Oncol ; 146(2): 343-356, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31932908

RESUMO

PURPOSE: We set out to determine whether clinically tested epigenetic drugs against class I histone deacetylases (HDACs) affect hallmarks of the metastatic process. METHODS: We treated permanent and primary renal, lung, and breast cancer cells with the class I histone deacetylase inhibitors (HDACi) entinostat (MS-275) and valproic acid (VPA), the replicative stress inducer hydroxyurea (HU), the DNA-damaging agent cis-platinum (L-OHP), and the cytokine transforming growth factor-ß (TGFß). We used proteomics, quantitative PCR, immunoblot, single cell DNA damage assays, and flow cytometry to analyze cell fate after drug exposure. RESULTS: We show that HDACi interfere with DNA repair protein expression and trigger DNA damage and apoptosis alone and in combination with established chemotherapeutics. Furthermore, HDACi disrupt the balance of cell adhesion protein expression and abrogate TGFß-induced cellular plasticity of transformed cells. CONCLUSION: HDACi suppress the epithelial-mesenchymal transition (EMT) and compromise the DNA integrity of cancer cells. These data encourage further testing of HDACi against tumor cells.


Assuntos
Reparo do DNA/fisiologia , Proteínas de Ligação a DNA/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Neoplasias/tratamento farmacológico , Animais , Benzamidas/farmacologia , Plasticidade Celular/efeitos dos fármacos , Cisplatino/farmacologia , Enzimas Reparadoras do DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos , Humanos , Hidroxiureia/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Piridinas/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Ácido Valproico/farmacologia
16.
Dis Colon Rectum ; 63(2): 242-255, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31914116

RESUMO

BACKGROUND: Peritoneal metastases arise in patients with a variety of primary cancers, and are associated with a poor prognosis. Systemic chemotherapy is the mainstay of treatment; however, the morbidity is considerable and the survival benefit is modest. Cytoreductive surgery and heated intraperitoneal chemotherapy is a potentially curative treatment available to a minority of patients; however, most develop recurrent disease. A novel palliative treatment for peritoneal metastases, pressurized intraperitoneal aerosol chemotherapy, has recently been introduced. Pressurized intraperitoneal aerosol chemotherapy utilizes an aerosol of chemotherapy in carbon dioxide gas. It is instilled into the abdomen under pressure via laparoscopic ports. No cytoreduction is performed. Pressurized intraperitoneal aerosol chemotherapy can be repeated at 6-week intervals. Oxaliplatin or cis-platinum and doxorubicin have been used to date. OBJECTIVE: This study aims to systematically review and evaluate the method, and the preclinical and early clinical results of pressurized intraperitoneal aerosol chemotherapy. DATA SOURCES: Medline and the Cochrane Library were the data sources for the study. STUDY SELECTION: Peer-reviewed series of greater than 10 patients, with sufficient patient data, through April 2019, were selected. INTERVENTION: Patients with peritoneal metastases underwent pressurized intraperitoneal aerosol chemotherapy. MAIN OUTCOME MEASURES: Patient dropout, histologic tumor response, adverse events, and 30-day mortality were the primary outcomes measured. RESULTS: A total of 921 patients with peritoneal metastases were brought to the operating room for pressurized intraperitoneal aerosol chemotherapy. The number of pressurized intraperitoneal aerosol chemotherapy treatments administered was as follows: 1 treatment, 862 (94%); 2 treatments, 645 (70%); and 3 treatments, 390 patients (42%). Initial laparoscopic access was not possible in 59 patients (6.4%). Common Terminology Criteria for Adverse Events grade 3 or higher were noted in 13.7% of the patients who, collectively, underwent a total of 2116 treatments. The 30-day mortality was 2.4% (22/921). LIMITATIONS: This study was limited by the heterogeneity of reported data and primary tumor types and by the lack of long-term survival data. CONCLUSIONS: Early clinical results are encouraging, but tumor-specific, prospective, randomized trials are needed to compare pressurized intraperitoneal aerosol chemotherapy to systemic chemotherapy. This method has yet to be introduced to the United States. It is another therapeutic option for patients with peritoneal metastases and will broaden the patient base for future clinical trials.


Assuntos
Aerossóis/administração & dosagem , Cuidados Paliativos/métodos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Aerossóis/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dióxido de Carbono/administração & dosagem , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/métodos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Humanos , Hipertermia Induzida/métodos , Instilação de Medicamentos , Laparoscopia/métodos , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Neoplasias Peritoneais/mortalidade , Pressão , Resultado do Tratamento
17.
Artigo em Alemão | MEDLINE | ID: mdl-31968390

RESUMO

Electrochemotherapy (ECT) is a symptom control method for inoperable or exulcerating cutaneous metastases or skin cancer. With the help of electroporation, an enhancement of the efficacy of the administered chemotherapeutic agent, bleomycin or cisplatin, is achieved, which leads to a local reduction of the metastases and thereby has a low impact on the systemic health.ECT can be performed under local, regional or general anaesthesia, whereby the form of anaesthesia depends on the number and extent of the metastases as well as the affected body site. For general anaesthesia, there are some special aspects to consider. To prevent lung damage from bleomycin, the patient has to be ventilated with a low FiO2 (< 0.3), or preferably with room air. To avoid drug interactions and postoperative pain, general anaesthesia is performed as TIVA in deep relaxation. The anaesthesia team should be aware of the necessary precautions when applying chemotherapeutic agents and should recognize contraindications to performing anaesthesia in ECT in advance.


Assuntos
Anestesia/métodos , Antineoplásicos , Eletroquimioterapia , Neoplasias Cutâneas , Antineoplásicos/administração & dosagem , Bleomicina , Cisplatino , Humanos , Neoplasias Cutâneas/secundário , Neoplasias Cutâneas/terapia
18.
Medicine (Baltimore) ; 99(1): e18663, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895831

RESUMO

BACKGROUND: Radiotherapy concurrent with cisplatin is the standard regimen used for treatment of locally advanced cervical carcinoma. In this meta-analysis, survival, recurrence, compliance, and acute adverse effects were compared between weekly and triweekly cisplatin-based concurrent chemoradiotherapy regimens for treatment of cervical cancer. METHODS: A systematic search for relevant studies was conducted using PubMed, Cochrane Library, EMBASE, and Medline databases. Fixed- or random-effects models were used for pooled analysis. The endpoints were overall survival, recurrence, compliance, and acute adverse effects reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Eight randomized controlled trials met the inclusion criteria. No significant differences were observed between the 2 arms with respect to recurrence, survival, and acute adverse effects (all P > .05). However, the triweekly cisplatin regimen was associated with significantly lower incidence of local recurrence (OR, 1.72; 95% CI, 1.07-2.78; P = .03), radiotherapy completion (OR, 2.08; 95% CI, 0.99-4.38; P = .05), and anemia (OR, 2.10; 95% CI, 1.01-4.37; P = .05), while a weekly cisplatin regimen was associated with a lower risk of leukopenia (OR, 0.57; 95% CI, 0.42-0.92; P = .00) and thrombocytopenia (OR, 0.55; 95% CI, 0.31-0.97; P = .04). CONCLUSIONS: Triweekly cisplatin-based chemotherapy significantly reduced local recurrence with tolerable toxicity and might be the optimal regimen in concurrent chemoradiotherapy for locally advanced cervical carcinoma.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma/terapia , Cisplatino/administração & dosagem , Neoplasias do Colo do Útero/terapia , Quimiorradioterapia , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Nat Commun ; 11(1): 567, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992692

RESUMO

Since the discovery of metal nanoparticles (NPs) in the 1960s, unknown toxicity, cost and the ethical hurdles of research in humans have hindered the translation of these NPs to clinical use. In this work, we demonstrate that Pt NPs with protein coronas are generated in vivo in human blood when a patient is treated with cisplatin. These self-assembled Pt NPs form rapidly, accumulate in tumors, and remain in the body for an extended period of time. Additionally, the Pt NPs are safe for use in humans and can act as anti-cancer agents to inhibit chemotherapy-resistant tumor growth by consuming intracellular glutathione and activating apoptosis. The tumor inhibitory activity is greatly amplified when the Pt NPs are loaded in vitro with the chemotherapeutic drug, daunorubicin, and the formulation is effective even in daunorubicin-resistant models. These in vivo-generated metal NPs represent a biocompatible drug delivery platform for chemotherapy resistant tumor treatment.


Assuntos
Antineoplásicos/sangue , Antineoplásicos/farmacologia , Nanopartículas Metálicas/química , Platina/sangue , Platina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Daunorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Tolerância a Medicamentos , Feminino , Glutationa/metabolismo , Células Hep G2 , Humanos , Células K562 , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Tamanho da Partícula , Coroa de Proteína , Fatores de Tempo , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
20.
Life Sci ; 244: 117339, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31972210

RESUMO

AIM: Despite recent advances in therapeutic strategies, cancer is still a leading cause of mortality worldwide. Mitochondrial dysfunction is implicated in cancer initiation and metastasis, and even in chemo- and radio-resistance. However, the precise role of mitochondria in cancer is crosstalk and controversial. This study is trying to find out the effect of transferring normal mitochondria into the highly aggressive and proliferative MDA-MB-231 cancer cells, and to evaluate the effect of the transfer with/without a combination therapy with cisplatin. MATERIALS AND METHODS: Normal mitochondria were isolated from human umbilical cord derived-mesenchymal stem cells. The mitochondria were transferred into the MDA-MB-231 cells, and also into cells with mitochondrial dysfunction induced by rhodamine red 6 (R6G). Cell proliferation and sensitivity of the cells to cisplatin were measured by cell counting after the mitochondria transfer. Also, apoptosis was evaluated by DAPI staining and in situ cell death detection (TdT-mediated dUTP nickend labeling; TUNEL) methods. Migration capability of the cells was studied by transwell assay. KEY FINDINGS: Transfer of normal mitochondria into MDA-MB-231 cells increased cell proliferation. However, the transfer of mitochondria enhanced cisplatin-induced apoptosis in MDA-MB-231 cells in which mitochondria were already disrupted. Introduction of normal cell-derived mitochondria into the MDA-MB-231 cells increased their invasive, but decreased the migration potency of the cells in the group with mitochondrial dysfunction (MDA + RG6 + Cisplatin). CONCLUSION: The introduction of healthy mitochondria to highly aggressive and proliferative cells would be considered as a new therapeutic modality for some types of cancer.


Assuntos
Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Células-Tronco Mesenquimais/patologia , Mitocôndrias/patologia , Cordão Umbilical/patologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Células Tumorais Cultivadas , Cordão Umbilical/efeitos dos fármacos
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