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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(8): 774-780, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31422617

RESUMO

Objective: To investigate the clinical value of laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis. Methods: From January 2019 to June 2019, the clinical data of 6 patients diagnosed as gastric cancer with peritoneal metastasis were retrospectively analyzed in the Gastrointestinal Surgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Five were male and 1 was female. The median age was 69.5 (28-77) years. The median body mass index (BMI) was 22.8 (19.6-23.5). All procedures were performed under general anesthesia with endotracheal intubation. The patient's body position and facility layout in the operating room were consistent with those of laparoscopic gastrectomy. The operator's position: the main surgeon was located on the right side of the patient, the first assistant stood on the left side of the patient, and the scopist stood between the patient's legs. Surgical procedure: (1) trocar location: three abdominal trocars was adopted, with one 12 mm umbilical port for the 30° laparoscope (point A). Location of the other two trocars was dependent on the procedure of exploration or biopsy as well as the two polyester cuff position of the peritoneal dialysis catheter: Usually one 5 mm port in the anterior midline 5 cm inferior to the umbilicus point was selected as point B to ensure that the distal end of the catheter could reach the Douglas pouch. The other 5 mm port was located in the right lower quadrant lateral to the umbilicus to establish the subcutaneous tunnel tract, and the proximal cuff was situated 2 cm away from the desired exit site (point C).(2) exploration of the abdominal cavity: a 30° laparoscope was inserted from 12 mm trocar below the umbilicus to explore the entire peritoneal cavity. The uterus and adnexa should be explored additionally for women. Once peritoneal metastasis was investigated and identified, primary laparoscopic peritoneal dialysis catheter implantation was performed so as to facilitate subsequent peritoneal chemotherapy. Ascites were collected for cytology in patients with ascites. (3) peritoneal dialysis catheter placement: the peritoneal dialysis catheter was introduced into the abdominal cavity from point A. Under the direct vision of laparoscopy, 2-0 absorbable ligature was reserved at the expected fixation point of the proximal cuff (point B) for the final knot closure. Non-traumatic graspers were used to pull the distal cuff of peritoneal dialysis catheter out of the abdominal cavity through point B. The 5-mm trocar was removed simultaneously, and the distal cuff was fixed between bilateral rectus sheaths at the anterior midline port site preperitoneally. To prevent subsequent ascites and chemotherapy fluid extravasation, the reserved crocheted wire was knotted. From point C the subcutaneous tunnel tract was created before the peritoneal steath towards the port site lateral to the umbilicus. Satisfactory catheter irrigation and outflow were then confirmed. Chemotherapy regimen after peritoneal dialysis catheterization: all patients began intraperitoneal chemotherapy on the second day after surgery. On the 1st and 8th day of each 3-weeks cycle, paclitaxel (20 mg/m(2)) was administered through peritoneal dialysis catheter, and paclitaxel (50 mg/m(2)) was injected intravenously. Meanwhile, S-1 was orally administered twice daily at a dose of 80 mg·m(-2)·d(-1) for 14 consecutive days followed by 7-days rest. To observe the patients' intraoperative and postoperative conditions. Results: All the procedures were performed successfully without intraoperative complications or conversion to laparotomy. No 30 day postoperative complications were observed. The median operative time was 33.5 (23-38) min. The median time to first flatus was 1(1-2) days, and the median postoperative hospital stay was 3 (3-4) days, without short-term complications within 30 days postoperatively. The last follow-up was up to July 10, 2019, and the patients were followed for 4(1-6) months. No ascites extravasation was observed and no death occurred in the 6 patients. There was no catheter obstruction or peritoneal fluid extravasation during and after chemotherapy. Conclusion: Laparoscopic peritoneal dialysis catheter implantation was safe and feasible for patients with peritoneal metastasis of gastric cancer. The abdominal exploration, tumor staging and the abdominal chemotherapy device implantation can be completed simultaneously, which could simplify the surgical approach, improve the quality of life for patients and further propose a new direction for the development of abdominal chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Paclitaxel/administração & dosagem , Diálise Peritoneal/instrumentação , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Cateterismo/métodos , Cateteres de Demora , China , Feminino , Humanos , Infusões Intravenosas , Infusões Parenterais , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/métodos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto Jovem
2.
Medicine (Baltimore) ; 98(26): e16249, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261590

RESUMO

The aim of this paper was to evaluate the activity and tolerability of oral vinorelbine in patients with advanced castration resistant prostate cancer (CRPC) who progressed after a minimum of three lines including: abiraterone acetate, docetaxel, cabazitaxel, and enzalutamide.Treatment consisted of weekly oral vinorelbine 60 mg/m. Chemotherapy was administered until disease progression or unacceptable toxicity.Twenty-six patients received vinorelbine: their median age was 74 years (range 58-84 years). Twenty-four (92.3%) patients had bone metastases. A decrease in PSA levels ≥50% was observed in 2 patients (7.7%). Among the subjects who were symptomatic at baseline, pain was reduced in 3 patients (13.6%) with a significant decrease in analgesic use. Median progression-free survival was 9 weeks (95% CI: 7 to 11) and median overall survival was 17 weeks (95% CI: 12 to 22). Treatment was well tolerated, and no grade 4 toxicities were observed.Our findings do not suggest the use of oral vinorelbine on a weekly schedule, in CRPC heavily pre-treated.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Vinorelbina/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias Ósseas/secundário , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias de Próstata Resistentes à Castração/patologia , Resultado do Tratamento , Vinorelbina/efeitos adversos
3.
Int J Nanomedicine ; 14: 4461-4474, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31296986

RESUMO

Background: Vincristine is a potent therapeutic agent with well-defined activity against hematologic malignancies and solid tumors. It is a cell-cycle specific drug with concentration and exposure duration dependent activity. When used by liposomal delivery, it exhibits enhanced anti-tumor activity. However, vincristine liposome formulation in the clinic is supplied as a 3-vial-kit due to lacking sufficient stability. So it has to be prepared in situ prior to use through a multi-step process. Purpose: The purpose here is to develop a more stable and ready-to-use liposomal formulation for vincritstine in one vial. Patients and methods: A series of preparations were investigated based on sphingomyelin/cholesterol/PEG2000-DSPE lipid composition, with different drug/lipid (D/L) ratios (1/10, 1/5, 1/2), using an active sucrose octasulfate triethylamine salt gradient loading method. In this work, compared to generic vincristine sulfate liposome injection (GVM), the stability both in vivo and in vitro and efficacy in vivo of novel vincristine liposomes were investigated. Results: It was shown that the degradation of vincristine during 2-8°C storage was significantly decreased from 8.2% in 1 month (GVM) to 2.9% in 12 months (D/L ratio 1/5). The half-time for sphingomyelin/cholesterol/PEG2000-DSPE liposomes in vivo could be adjusted from 17.4 h (D/L ratio 1/10) to 22.7 h (D/L ratio 1/2) in rats, while the half-time for GVM was only 11.1 h. The increase in drug retention contributed to the lower in vivo toxicity. The antitumor efficacy was evaluated using a human melanoma tumor model and showed remarkable improvement compared to GVM. Conclusion: The study demonstrates that the new formulation with the drug/lipid ratio of 1/5 owns a higher encapsulation efficiency, better stability, lower toxicity and superior antitumor efficacy, which is screened out for further development.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Lipossomos/química , Vincristina/química , Vincristina/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Colesterol/química , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Ratos Wistar , Esfingomielinas/química , Vincristina/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
4.
J Nanobiotechnology ; 17(1): 78, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269964

RESUMO

BACKGROUND: The construction of a multifunctional drug delivery system with a variety of advantageous features, including targeted delivery, controlled release and combined therapy, is highly attractive but remains a challenge. RESULTS: In this study, we developed a MoS2-based hyaluronic acid (HA)-functionalized nanoplatform capable of achieving targeted delivery of camptothecin (CPT) and dual-stimuli-responsive drug release. HA was connected to MoS2 via a disulfide linkage, forming a sheddable HA shell on the surface of MoS2. This unique design not only effectively prevented the encapsulated CPT from randomly leaking during blood circulation but also significantly accelerated the drug release in response to tumor-associated glutathione (GSH). Moreover, the MoS2-based generated heat upon near-infrared (NIR) irradiation could further increase the drug release rate as well as induce photothermal ablation of cancer cells. The results of in vitro and in vivo experiments revealed that MoS2-SS-HA-CPT effectively suppressed cell proliferation and inhibited tumor growth in lung cancer cell-bearing mice under NIR irradiation via synergetic chemo-photothermal therapy. CONCLUSIONS: The as-prepared MoS2-SS-HA-CPT with high targeting ability, dual-stimuli-responsive drug release, and synergistic chemo-photothermal therapy may provide a new strategy for cancer therapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/administração & dosagem , Dissulfetos/química , Portadores de Fármacos/química , Molibdênio/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Liberação Controlada de Fármacos , Feminino , Corantes Fluorescentes/química , Humanos , Ácido Hialurônico/química , Hipertermia Induzida , Raios Infravermelhos , Camundongos Nus , Transplante de Neoplasias , Oxirredução , Fotoquimioterapia/métodos
5.
J Cancer Res Clin Oncol ; 145(8): 1987-1998, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31214760

RESUMO

PURPOSE: Based on the poor prognosis of drug resistance in pediatric acute lymphoblastic leukemia (ALL) and adverse effects of chemotherapy, this study was aimed to evaluate the effect of several herbal extracts on leukemic cells. METHODS: Two subtypes of T- and B-ALL cell lines, followed by ALL primary cells were treated with cinnamon, ginger, and green tea extracts, alone or in combination with methotrexate (MTX). Possible apoptosis was investigated using Annexin-V/PI double staining. Real-time PCR was applied to evaluate the expression levels of related ABC transporters upon combination therapy. RESULTS: The IC50s for cinnamon, ginger and green tea extracts on ALL cell lines were 300 µg/ml, 167 µg/ml and 70 µg/ml, respectively. Surprisingly, the methotrexate (MTX)-resistant sub-line showed more sensitivity to ginger. Combined treatment with ginger and MTX showed synergistic effects on CCRF-CEM, Nalm-6 and ALL primary cells. It was shown that ginger does not impair the high expression levels of ABCA2 or ABCA3 transporter genes in the ALL malignant cells, suggesting other molecular pathways involved in its anticancer potential. CONCLUSION: To the best of our knowledge, this is the first study that reveals the antileukemic effect of ginger extract on both, pediatric ALL cell lines and primary cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Gengibre/química , Extratos Vegetais/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Cinnamomum zeylanicum/química , Terapia Combinada , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Fitoterapia , Extratos Vegetais/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Chá/química , Células Tumorais Cultivadas , Adulto Jovem
6.
AAPS PharmSciTech ; 20(6): 220, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201588

RESUMO

In this study, poly-(lactic-co-glycolic) acid (PLGA) was conjugated with aspartic acid and was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy. Docetaxel-loaded polymeric micelles were prepared, and piperine was tagged. The neuroblastoma cytotoxicity studies revealed a substantially higher cytotoxic potential of the developed system to that of plain docetaxel, which was further corroborated by cellular uptake employing confocal laser scanning microscopy. The hemocompatible system was able to enhance the pharmacokinetic profile in terms of 6.5-fold increment in bioavailability followed by a 3.5 times increase in the retention time in comparison with the plain drug. The single-point brain bioavailability of docetaxel was amplified by 3.3-folds, signifying a better uptake and distribution to brain employing these carriers. The findings are unique as the physically adsorbed piperine was released before the DTX, increasing the propensity of curbing the CYP3A4 enzyme, which plays a vital role in the degradation of docetaxel. Meanwhile, piperine might have compromised the P-gp efflux mechanism, which can be ascribed to the enhanced retention of the drug at the target site. The elevated target site concentrations and extended residence by a biocompatible nanocarrier supplemented with co-delivery of piperine inherit immense promises to deliver this BCS class IV drug more safely and effectively.


Assuntos
Alcaloides/química , Antineoplásicos Fitogênicos/administração & dosagem , Benzodioxóis/química , Docetaxel/administração & dosagem , Micelas , Piperidinas/química , Alcamidas Poli-Insaturadas/química , Animais , Antineoplásicos Fitogênicos/farmacocinética , Disponibilidade Biológica , Encéfalo/metabolismo , Linhagem Celular Tumoral , Docetaxel/farmacocinética , Humanos , Ratos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier
7.
BMC Complement Altern Med ; 19(1): 133, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31215421

RESUMO

BACKGROUND: Elemene is an effective anticancer component extracted from Zingiberaceae plants. This work was aimed to evaluate the anti-tumor effect and mechanism actions of elemene on pancreatic carcinoma in vitro and in vivo. METHODS: The anti-proliferation experiment was measured by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) method in the time of 24, 48 and 72 h in three different dosages. The cell cycle was detected by flow cytometer after 12 h treatment. Forty-eight nude mice were subcutaneously xenograft with BxPC-3 pancreatic cancer cells and divided into four groups: Control group and high, medium, low dosage of elemene (20, 40 and 60 mg/kg) treatment groups. Immunoblot and immunohistochemical methods were applied to detect the protein expression of P53 and Bcl-2 in the tumor of pancreatic cancer xenografts. H & E staining was used to detect the histopathological changes in each group. RESULTS: A significant inhibition effect was observed in the anti-proliferation of BxPC-3 and Panc-1 cells in vitro in the time course of 24, 48 and 72 h with a dose dependent manner. The cell cycle results showed that elemene could arrest pancreatic cancer cells in the S phase after 12 h treatment in BxPC-3 and Panc-1 cell line. The in vivo BxPC-3 xenografts study exhibited that elemene was significantly decreased the tumor size in the high dosage group, compared to control group. And there is no any significant change in body weight of all animals. H&E pathology section result showed that treatment with elemene significantly decreased the inflammation cells and reduced the histopathological changes with a dose-dependent manner. Meanwhile, treatment with elemene significantly up-regulates the protein expression of P53, while down-regulate the protein expression of Bcl-2 in the tumor tissues, respectively. Furthermore, the western blot result showed that treatment with elemene increased the expression of P53 and decreased the expression of Bcl-2, compared with the control group, which is similar to the results of immunohistochemical staining. CONCLUSIONS: This study suggests that elemene has a potential anti pancreatic cancer effect, down-regulation the protein expression of Bcl-2 and up-regulation the protein expression of P53 in a dose dependent manner may be is the anti-tumor mechanism.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Sesquiterpenos/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/fisiopatologia , Proteína Supressora de Tumor p53 , Ensaios Antitumorais Modelo de Xenoenxerto , Zingiberaceae/química
8.
BMC Complement Altern Med ; 19(1): 151, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242894

RESUMO

BACKGROUND: Costunolide, a sesquiterpene lactone extracted from Radix Aucklandiae, has the activity against multiple cancers. However, the effect of costunolide on gastric cancer (GC) have remained to be ambiguous. In this study, we investigated the underlying mechanisms of apoptosis induced by costunolide in human gastric adenocarcinoma BGC-823 cells in vitro and in vivo. METHODS: The viability of BGC-823 cells was detected by MTT assay. The apoptosis and mitochondrial membrane potential (ΔΨm) of BGC-823 cells induced by costunolide were analyzed by flow cytometry. The inhibiton of costunolide on human gastric adenocarcinoma was estimated in xenografts in nude mice. Apoptosis related proteins and genes were detected by Western blot and Q-PCR. RESULTS: Costunolide inhibited the viability of BGC-823 cells in a time and concentration dependent manner. Costunolide induced the apoptosis and lowered the ΔΨm of BGC-823 cells significantly. Costunolide increased the expression of Bax, cleaved caspase 9, cleaved caspase 7, cleaved caspase 3 and cleaved poly ADP ribose polymerase (PARP) proteins and decreased the expression of Bcl-2, pro-caspase 9, pro-caspase 7, pro-caspase 3 and PARP proteins. Costunolide upregulated the expression of puma, Bak1 and Bax mRNA and downregulated the expression of Bcl-2 mRNA. In addition, we demonstrated that costunolide inhibited the growth and induced apoptosis of BGC-823 cells xenografted in athymic nude mice. Costunolide increased the expression of cleaved caspase 9, cleaved caspase 3 and Bax proteins and decreased the expression of Bcl-2 protein in xenografted tumor. Costunolide upregulated the expression of puma and Bax mRNA and decreased the expression of Bcl-2 mRNA in xenografted tumor. CONCLUSIONS: Collectively, our results suggested that costunolide induced mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells and could be the candidate drug against GC in clinical practice.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Sesquiterpenos/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/fisiopatologia , Animais , Caspases/genética , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/metabolismo , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/fisiopatologia
9.
J Cancer Res Clin Oncol ; 145(7): 1665-1679, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31127362

RESUMO

PURPOSE: Phytochemicals are naturally occurring plant-derived compounds and some of them have the potential to serve as anticancer drugs. Based on recent evidence, aberrantly regulated expression of microRNAs (miRNAs) is closely associated with malignancy. MicroRNAs are characterized as small non-coding RNAs functioning as posttranscriptional regulators of gene expression. Accordingly, miRNAs regulate various target genes, some of which are involved in the process of carcinogenesis. RESULTS: This comprehensive review emphasizes the anticancer potential of phytochemicals, either isolated or in combination, mediated by miRNAs. The ability to modulate the expression of miRNAs demonstrates their importance as regulators of tumorigenesis. Phytochemicals as anticancer agents targeting miRNAs are widely studied in preclinical in vitro and in vivo research. Unfortunately, their anticancer efficacy in targeting miRNAs is less investigated in clinical research. CONCLUSIONS: Significant anticancer properties of phytochemicals as regulators of miRNA expression have been proven, but more studies investigating their clinical relevance are needed.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , MicroRNAs/biossíntese , Neoplasias/tratamento farmacológico , Neoplasias/genética , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Humanos , MicroRNAs/genética , Neoplasias/patologia
10.
Nanomedicine (Lond) ; 14(10): 1323-1341, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31124758

RESUMO

The poor solubility of paclitaxel (PTX), the most commonly used anticancer drug (Taxol®), has long hindered the development of successful formulations. In 2005, the launch of Abraxane®, a human albumin-based preparation of PTX, competed with Taxol® in the commercial market. The success of Abraxane pushed other generic preparations aside, sparking competition among the global pharmaceutical companies to develop the novel and superior PTX nanotechnology-driven formulations. Unsurprisingly, the success underlying with cancer treatment using nano PTX therapy has now entered into a new era of drug development, patentability, preclinical and clinical evaluation, leading eventually to a significant increase in the regulatory approval of the products. The present article aims to provide recent progress in the development of nano PTX formulations by various pharmaceutical companies for safe and effective drug therapies for patients benefit.


Assuntos
Paclitaxel Ligado a Albumina/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel Ligado a Albumina/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Humanos , Polímeros/química , Solubilidade
11.
Int J Oncol ; 54(6): 1995-2004, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31081045

RESUMO

Harmine (HM) is a ß­carboline alkaloid found in multiple medicinal plants. It has been used in folk medicine for anticancer therapy; however, the molecular mechanism of HM on human breast cancer remains unclear. Transcriptional co­activator with PDZ­binding motif (TAZ), also known as WW domain­containing transcription regulator 1, serves an important role in the carcinogenesis and progression of breast cancer. The aim of the present study was to elucidate the potential anticancer activity and mechanism of HM in breast cancer, in vitro and in vivo. Cell proliferation was measured using a CCK­8 assay, apoptotic activity was detected by flow cytometry and DAPI staining, and cell migration was examined using a wound healing assay. The expression of proteins, including extracellular signal­regulate kinase (Erk), phosphorylated (p­) Erk, protein kinase B (Akt), p­Akt, B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein (Bax), were determined by western blotting. The mRNA expression of TAZ was detected using reverse transcription­quantitative polymerase chain reaction analysis. The expression of proteins in mouse tumor tissues were examined by immunohistochemistry. HM significantly suppressed cellular proliferation and migration, promoted apoptosis in vitro and inhibited tumor growth in vivo. In addition, HM significantly decreased the expression of TAZ, p­Erk, p­Akt and Bcl­2, but increased that of Bax. The overexpression of TAZ in breast cancer cells inhibited the antitumor effect of HM. In conclusion, HM was found to induce apoptosis and prevent the proliferation and migration of human breast cancer cell lines, possibly via the downregulation of TAZ.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Harmina/administração & dosagem , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Harmina/farmacologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Células MCF-7 , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Int J Oncol ; 54(6): 2069-2079, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31081060

RESUMO

Advanced metastatic melanoma is a malignant tumor for which there is currently no effective treatment due to resistance development. Ginsenoside Rg3, a saponin component extracted from ginseng roots, has been shown to reduce melanoma cell proliferation by decreasing histone deacetylase 3 and increasing p53 acetylation. The availability of data on the role of Rg3 in melanoma is currently extremely limited. The aim of the present study was to further investigate the effects of Rg3 on B16 melanoma cells and the underlying molecular events. The findings demonstrated that Rg3 suppressed the proliferation and DNA synthesis of B16 cells. Rg3 exposure induced tumor cell cycle arrest at the S phase and reduced the expression of proliferating cell nuclear antigen (PCNA). Rg3 treatment also decreased metastasis of B16 cells in vitro and in vivo. The results indicated that this reduction was due to downregulation of matrix metalloproteinase (MMP)­2 and MMP­9. Moreover, Rg3 inhibited melanoma­induced angiogenesis, most likely by downregulating vascular endothelial growth factor (VEGF) in B16 cells. Rg3 exposure decreased the expression of VEGF in B16 cells and the VEGF downregulation further suppressed angiogenesis by attenuating the proliferation and migration of vascular endothelial cells. Finally, the western blotting data demonstrated that Rg3 reduced the expression of extracellular signal­regulated kinase (ERK) and protein kinase B (Akt) in vitro and in vivo. This result indicated that the antimelanoma effects of Rg3 may be mediated through suppression of ERK and Akt signaling. Further research is required to assess the value of Rg3 as a novel therapeutic strategy for melanoma in the clinical setting.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Regulação para Baixo , Ginsenosídeos/administração & dosagem , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/farmacologia , Humanos , Masculino , Melanoma/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
BMJ Case Rep ; 12(3)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30936335

RESUMO

Therapies of complementary and alternative medicine (CAM) are used increasingly in paediatric oncology. We present and discuss the influence of supportive mistletoe therapy on factors, such as quality of life, physical ability and performance, and course of disease based on the case of a female patient diagnosed at age 18 with metastasised neuroblastoma, which responded insufficiently to chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/patologia , Neuroblastoma/patologia , Extratos Vegetais/administração & dosagem , Atividades Cotidianas , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/fisiopatologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/fisiopatologia , Escolaridade , Feminino , Humanos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/fisiopatologia , Fitoterapia , Qualidade de Vida , Resultado do Tratamento
14.
BMJ Case Rep ; 12(4)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30962211

RESUMO

A woman in her mid-70s with metastatic pancreatic adenocarcinoma presented with fatigue, nausea and bilateral leg swelling, 4 days after an intravenous gemcitabine infusion. Additional examination and laboratory tests showed mild hypertension, low haemoglobin, high lactate dehydrogenase, low platelet count and high serum creatinine. The patient was subsequently diagnosed with haemolytic uraemic syndrome (HUS), and gemcitabine administration was immediately ceased. The patient received a 5-day course of methylprednisolone, with a full recovery being made 10 days after diagnosis. Clinicians should be aware of the rare but serious complication of gemcitabine-induced HUS (GiHUS), as early diagnosis and management, which includes prompt discontinuation of gemcitabine, are crucial in promptly resolving this condition. This case report describes one treatment that can be used for the treatment of GiHUS, while briefly covering some other novel treatments that have been described in other studies.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/efeitos adversos , Desoxicitidina/análogos & derivados , Síndrome Hemolítico-Urêmica/etiologia , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Síndrome Hemolítico-Urêmica/terapia , Humanos , Metilprednisolona/administração & dosagem , Paclitaxel/administração & dosagem
15.
J Agric Food Chem ; 67(17): 4709-4719, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30990036

RESUMO

Cancer is a significant disease burden worldwide. Chemotherapy is the mainstay of cancer treatment. Clinically used chemotherapeutic agents may elicit severe side effects. Remarkably, most of cancer cells develop chemoresistance after a period of treatment. Therefore, it is imperative to seek more effective agents without side effects. In recent years, increasing research efforts have attempted to identify natural agents that may be used alone or in combination with traditional therapeutics for cancer management. Resveratrol is a natural polyphenolic phytoalexin that can be found in various foods including blueberries, peanuts, and red wine. As a natural food ingredient, resveratrol possesses antioxidant, anti-inflammatory, and cardioprotective properties. Moreover, resveratrol exhibited promising effects in suppressing the initiation and progression of cancers. Noncoding RNAs (ncRNAs) have been universally accepted as vital regulators in cancer pathogenesis. The modulation of miRNAs and lncRNAs by resveratrol has been described. Thus, the mechanism involving the domination of ncRNA function is one of the keys to understand the anticancer effects of resveratrol. In this review, we focus on the antagonistic effects of resveratrol on cancer progression through regulation of miRNAs and lncRNAs. We also discuss the potential application of resveratrol in cancer management.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , MicroRNAs/genética , Neoplasias/tratamento farmacológico , RNA Longo não Codificante/genética , Resveratrol/administração & dosagem , Animais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/metabolismo , Terapia de Alvo Molecular , Neoplasias/genética , Neoplasias/metabolismo , RNA Longo não Codificante/metabolismo
16.
Drug Deliv ; 26(1): 443-458, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30929529

RESUMO

Modification of nanoparticle surfaces with PEG has been widely considered the gold standard for many years. However, PEGylation presents controversial and serious challenges including lack of functionality, hindered cellular interaction, allergic reactions, and stimulation of IgM production after repetitive dosing that accelerates blood clearance of the nanoparticles. We report the development of novel liposomal formulations surface-modified with a low molecular weight, branched polyethyleneimine (bPEI)-lipid conjugate for use as an alternative to PEG. The formulations had very good stability characteristics in ion- and protein-rich mediums. Protein adsorption onto the liposomal surface did not interfere with the cellular interaction. bPEI-modified liposomes (PEIPOS) showed enhanced association with three different cell lines by up to 75 times compared to plain or PEGylated liposomes and were without carrier toxicity. They also penetrated the deeper layers of 3D spheroids. Encapsulating paclitaxel (PTX) into PEIPOS did not change its main mechanism of action. PEIPOS complexed and intracellularly delivered siRNAs and downregulated resistance-associated proteins. Finally, tumor growth inhibition was observed in a mouse ovarian xenograft tumor model, without signs of toxicity, in animals treated with the siRNA/PTX co-loaded formulation. These complex-in-nature but simple-in-design novel liposomal formulations constitute viable and promising alternatives with added functionality to their PEGylated counterparts.


Assuntos
Nanopartículas , Paclitaxel/administração & dosagem , Polietilenoimina/química , RNA Interferente Pequeno/administração & dosagem , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Portadores de Fármacos/química , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Lipídeos/química , Lipossomos , Camundongos , Camundongos Nus , Neoplasias Ovarianas/terapia , Paclitaxel/farmacologia , Polietilenoglicóis/química , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Complement Ther Med ; 43: 295-299, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30935547

RESUMO

The natural compound amygdalin has gained high popularity among tumor patients as a complementary or alternative treatment option. However, due to metabolization of amygdalin to cyanide (HCN) following oral consumption, there could be a high risk of lactic acidosis caused by cyanide intoxication. The present retrospective study was undertaken to evaluate cyanide blood and lactate plasma levels of tumor patients (n = 55) before and after intravenous (i.v.) amygdalin infusion. All patients had also continuously ingested amygdalin tablets (3 x 500 mg/day), excepting on the days of i.v. administration. Each patient received one to five intravenous amygdalin treatments. The time period between each i.v. application ranged between 4-6 days. The initial i.v. dose was 6 mg (n = 28), 9 mg (n = 1), 15 mg (n = 1) or 18 mg (n = 25). The mean cyanide blood level before i.v. amygdalin administration was 34.74 µg/L, which increased significantly to a mean value of 66.20 µg/L after i. v. amygdalin application. In contrast, lactate decreased significantly from 1266 µmol/L pre-infusion to 868 µmol/L post-infusion. Increasing i.v. amygdalin by 1 mg was also associated with a significant increase in the cyanide level, while the lactate blood level significantly decreased. This is the first study evaluating cyanide levels under conditions employed by amygdalin administrators, i.e. after chronic oral amygdalin intake and then again after a closely subsequent intravenous amygdalin administration. Since lactate decreased, whilst cyanide increased, it is concluded that elevation of cyanide does not induce metabolic acidosis in terms of an increased lactate level.


Assuntos
Amigdalina/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Cianetos/sangue , Lactatos/sangue , Administração Intravenosa/métodos , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Estudos Retrospectivos
18.
Cancer Sci ; 110(5): 1746-1759, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30907478

RESUMO

Osteosarcoma is the most common primary malignant bone tumor. Raddeanin A (RA) is an active oleanane-type triterpenoid saponin extracted from the traditional Chinese herb Anemone raddeana Regel that exerts antitumor activity against several cancer types. However, the effect of RA on osteosarcoma remains unclear. In the present study, we showed that RA inhibited proliferation and induced apoptosis of osteosarcoma cells in a dose- and time-dependent way in vitro and in vivo. RA treatment resulted in excessive reactive oxygen species (ROS) generation and JNK and ERK1/2 activation. Apoptosis induction was evaluated by the activation of caspase-3, caspase-8, and caspase-9 and poly-ADP ribose polymerase (PARP) cleavage. RA-induced cell death was significantly restored by the ROS scavenger glutathione (GSH), the pharmacological inhibitor of JNK SP600125, or specific JNK knockdown by shRNA. Additionally, signal transducer and activator of transcription 3 (STAT3) activation was suppressed by RA in human osteosarcoma, and this suppression was restored by GSH, SP600125, and JNK-shRNA. Further investigation showed that STAT3 phosphorylation was increased after JNK knockdown. In a tibial xenograft tumor model, RA induced osteosarcoma apoptosis and notably inhibited tumor growth. Taken together, our results show that RA suppresses proliferation and induces apoptosis by modulating the JNK/c-Jun and STAT3 signaling pathways in human osteosarcoma. Therefore, RA may be a promising candidate antitumor drug for osteosarcoma intervention.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Saponinas/administração & dosagem , Animais , Antineoplásicos Fitogênicos/farmacologia , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Osteossarcoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Saponinas/farmacologia , Fatores de Tempo , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J Exp Clin Cancer Res ; 38(1): 139, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30922391

RESUMO

BACKGROUND: Nuciferine (NF), extracted from the leaves of N. nucifera Gaertn, has been shown to exhibit anti-tumor and anti-viral pharmacological properties. It can also penetrate the blood brain barrier (BBB). However, the mechanism by which NF inhibits glioblastoma (GBM) progression is not well understood. We aimed to determine the anti-tumor effect of NF on GBM cell lines and clarify the potential molecular mechanism involved. METHODS: U87MG and U251 cell lines were used in vitro to assess the anti-tumor efficacy of NF. Cytotoxicity, viability, and proliferation were evaluated by MTT and colony formation assay. After Annexin V-FITC and PI staining, flow cytometry was performed to evaluate apoptosis and cell cycle changes in NF-treated GBM cells. Wound healing and Transwell assays were used to assess migration and invasion of GBM cells. Western blot analysis, immunofluorescence staining, immunohistochemistry, and bioinformatics were used to gain insights into the molecular mechanisms. Preclinical therapeutic efficacy was mainly estimated by ultrasound and MRI in xenograft nude mouse models. RESULTS: NF inhibited the proliferation, mobility, stemness, angiogenesis, and epithelial-to-mesenchymal transition (EMT) of GBM cells. Additionally, NF induced apoptosis and G2 cell cycle arrest. Slug expression was also decreased by NF via the AKT and STAT3 signaling pathways. Interestingly, we discovered that NF affected GBM cells partly by targeting SOX2, which may be upstream of the AKT and STAT3 pathways. Finally, NF led to significant tumor control in GBM xenograft models. CONCLUSIONS: NF inhibited the progression of GBM via the SOX2-AKT/STAT3-Slug signaling pathway. SOX2-targeting with NF may offer a novel therapeutic approach for GBM treatment.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Aporfinas/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos Fitogênicos/farmacologia , Aporfinas/farmacologia , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Progressão da Doença , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glioblastoma/metabolismo , Humanos , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Fator de Transcrição STAT3/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Adv Mater ; 31(16): e1807533, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30847970

RESUMO

To stress the role of deoxyribonucleic acid (DNA) as a drug carrier, an efficient conjugation strategy in which chemotherapeutics can be grafted onto a phosphorothiolated DNA backbone through the reaction between the phosphorothioate group (PS) and a benzyl bromide group is proposed. As a proof of concept, benzyl-bromide-modified paclitaxel (PTX) is employed to graft onto the DNA backbone at the PS modification sites. Due to the easy preparation of phosphorothiolated DNA at any desired position during its solid-phase synthesis, diblock DNA strands containing both normal phosphodiester segment (PO DNA) and phosphorothiolate segment (PS DNA) are directly grafted with a multitude of PTXs without using complicated and exogenous linkers. Then, the resulting amphiphilic PO DNA-blocked-(PS DNA-grafted PTX) conjugates (PO DNA-b-(PS DNA-g-PTX)) assemble into PTX-loaded spherical nucleic acid (SNA)-like micellar nanoparticles (PTX-SNAs) with a high drug loading ratio up to ≈53%. Importantly, the PO DNA segment maintains its molecular recognition property and biological functions, which allows the as-prepared PTX-SNAs to be further functionalized with tumor-targeting aptamers, fluorescent probe strands, or antisense sequences. These multifunctional PTX-SNAs demonstrate active tumor-targeting delivery, efficient inhibition of tumor growth, and the reversal of drug resistance both in vitro and in vivo for comprehensive antitumor therapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , DNA/química , Portadores de Fármacos/química , Paclitaxel/administração & dosagem , Oligonucleotídeos Fosforotioatos/química , Animais , Aptâmeros de Nucleotídeos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos , Corantes Fluorescentes/química , Humanos , Camundongos Nus , Micelas , Nanopartículas/química
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