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1.
Acta Cir Bras ; 34(12): e201901207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049187

RESUMO

In the muscle invasive bladder cancer (MIBC) standard of care treatment only patients presenting a major pathological tumor response are more likely to show the established modest 5% absolute survival benefit at 5 years after cisplatin-based neoadjuvant chemotherapy (NAC). To overcome the drawbacks of a blind NAC (i.e. late cystectomy with unnecessary NAC adverse events) with potential to survival improvements, preclinical models of urothelial carcinoma have arisen in this generation as a way to pre-determine drug resistance even before therapy is targeted. The implantation of tumor specimens in the chorioallantoic membrane (MCA) of the chicken embryo results in a high-efficiency graft, thus allowing large-scale studies of patient-derived "tumor avatar". This article discusses a novel approach that exploits cancer multidrug resistance to provide personalized phenotype-based therapy utilizing the MIBC NAC dilemma.


Assuntos
Carcinoma/tratamento farmacológico , Membrana Corioalantoide , Neoplasias Experimentais/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Urotélio , Animais , Carcinoma/patologia , Membrana Corioalantoide/patologia , Humanos , Ilustração Médica , Terapia Neoadjuvante , Inoculação de Neoplasia , Neoplasias Experimentais/patologia , Fenótipo , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
2.
World Neurosurg ; 133: e252-e258, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31505283

RESUMO

BACKGROUND: Selection of appropriate treatment for patients with recurrent brain metastasis (BM) remains uncertain. Recent studies have demonstrated a significant response rate and acceptable toxicity using fractionated stereotactic radiosurgery (FSRS) in patients with locally recurrent large BM. The aim of this study was to evaluate efficacy and toxicity of FSRS with bevacizumab as a new salvage treatment for locally recurrent BM with previous high-dose irradiation. METHODS: Patients with recurrent BM previously irradiated were enrolled. Salvage FSRS dose was 9.5-29 Gy (2-5 fractions) with 62%-75% isodose line by CyberKnife according to the brain tumor volume, site, and previous dose. Bevacizumab was prescribed for 4 cycles (5 mg/kg, every 3 weeks). The primary objective was to identify the overall survival after salvage treatment. Secondary objectives included clinical response (Karnofsky performance scale), imaging response (magnetic resonance imaging) and treatment-related adverse events. RESULTS: From December 2009 to October 2016, 24 patients were enrolled. The 1-year overall survival after salvage stereotactic radiosurgery was 87.5%. Twenty-three (96%) patients had a positive imaging response with a T2 volume reduction range of 6-22 cm3 (median 14 cm3, P = 0.032, paired t test). Significant clinical improvement was achieved (best Karnofsky performance scale score, P < 0.05, paired t test). Grade 1/2 fatigue was observed in 8 (33%) patients. Grade 3 fatigue and headache occurred in 1 patient. CONCLUSIONS: FSRS with adjuvant bevacizumab treatment showed favorable clinical and radiologic control as a salvage treatment regimen. The diagnoses of radiation necrosis and local recurrence after salvage FSRS warrant further study.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/secundário , Carcinoma/secundário , Recidiva Local de Neoplasia/cirurgia , Radiocirurgia/métodos , Terapia de Salvação/métodos , Adulto , Idoso , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Carcinoma/tratamento farmacológico , Carcinoma/radioterapia , Carcinoma/cirurgia , Terapia Combinada , Irradiação Craniana , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Prospectivos
3.
Lancet ; 394(10214): 2084-2095, 2019 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-31791688

RESUMO

BACKGROUND: Carboplatin and paclitaxel administered every 3 weeks is standard-of-care first-line chemotherapy for epithelial ovarian cancer. The Japanese JGOG3016 trial showed a significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly carboplatin. In this study, we aimed to compare efficacy and safety of two dose-dense weekly regimens to standard 3-weekly chemotherapy in a predominantly European population with epithelial ovarian cancer. METHODS: In this phase 3 trial, women with newly diagnosed International Federation of Gynecology and Obstetrics stage IC-IV epithelial ovarian cancer were randomly assigned to group 1 (carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m2 paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m2 paclitaxel weekly), or group 3 (carboplatin AUC2 and 80 mg/m2 paclitaxel weekly). Written informed consent was provided by all women who entered the trial. The protocol had the appropriate national research ethics committee approval for the countries where the study was conducted. Patients entered the trial after immediate primary surgery, or before neoadjuvant chemotherapy with subsequent planned delayed primary surgery. The trial coprimary outcomes were progression-free survival and overall survival. Data analyses were done on an intention-to-treat basis, and were powered to detect a hazard ratio of 0·75 in progression-free survival. The main comparisons were between the control group (group 1) and each of the weekly research groups (groups 2 and 3). FINDINGS: Between June 6, 2011, and Nov 28, 2014, 1566 women were randomly assigned to treatment. 72% (365), completed six protocol-defined treatment cycles in group 1, 60% (305) in group 2, and 63% (322) in group 3, although 90% (454), 89% (454), and 85% (437) completed six platinum-based chemotherapy cycles, respectively. Paclitaxel dose intensification was achieved with weekly treatment (median total paclitaxel dose 1010 mg/m2 in group 1; 1233 mg/m2 in group 2; 1274 mg/m2 in group 3). By February, 2017, 1018 (65%) patients had experienced disease progression. No significant progression-free survival increase was observed with either weekly regimen (restricted mean survival time 24·4 months [97·5% CI 23·0-26·0] in group 1, 24·9 months [24·0-25·9] in group 2, 25·3 months [23·9-26·9] in group 3; median progression-free survival 17·7 months [IQR 10·6-not reached] in group 1, 20·8 months [11·9-59·0] in group 2, 21·0 months [12·0-54·0] in group 3; log-rank p=0·35 for group 2 vs group 1; group 3 vs 1 p=0·51). Although grade 3 or 4 toxic effects increased with weekly treatment, these effects were predominantly uncomplicated. Febrile neutropenia and sensory neuropathy incidences were similar across groups. INTERPRETATION: Weekly dose-dense chemotherapy can be delivered successfully as first-line treatment for epithelial ovarian cancer but does not significantly improve progression-free survival compared with standard 3-weekly chemotherapy in predominantly European populations. FUNDING: Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, Cancer Australia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Idoso , Grupo com Ancestrais do Continente Asiático , Carboplatina/administração & dosagem , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Procedimentos Cirúrgicos de Citorredução , Grupo com Ancestrais do Continente Europeu , Neoplasias das Tubas Uterinas/patologia , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologia , Neoplasias Peritoneais/patologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais
4.
Acta Cir Bras ; 34(10): e201901001, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31826147

RESUMO

PURPOSE: To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats. METHODS: We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500µg/kg injected i.p; DMBA+ACE+Vincristine 250µg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, hematology and histopathology were used to validate the treatments. RESULTS: All animals survived. A gradual weight gain in all groups was observed, with no significant difference (p>0.05). The oral administration of ACE and ACE+vincristine 50% significantly reduced breast tumors incidence examined with PET-18FDG and fluorescence (p<0.001). Significant reduction of serum transaminases, oxidative stress and hematological toxicity were observed in these groups. Antioxidant enzyme levels in breast tissue were significantly higher compared to the DMBA and DMBA+vincristine groups. CONCLUSION: These results demonstrate for the first time that ACE positively influences the treatment of DMBA-induced breast cancer in animal model, inducing a reduction in oxidative stress and chemotherapy toxicity, meaning that ACE may have clinical implication in further studies.


Assuntos
Antineoplásicos/farmacologia , Bignoniaceae/química , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Neoplasias Experimentais/tratamento farmacológico , Extratos Vegetais/farmacologia , 9,10-Dimetil-1,2-benzantraceno , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinógenos , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Catalase/análise , Feminino , Fluordesoxiglucose F18 , Glutationa Peroxidase/análise , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/patologia , Imagem Óptica/métodos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Ratos Wistar , Reprodutibilidade dos Testes , Superóxido Dismutase/análise , Fatores de Tempo , Resultado do Tratamento , Vincristina/farmacologia , Vincristina/uso terapêutico
5.
BMC Complement Altern Med ; 19(1): 312, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729992

RESUMO

BACKGROUND: Cervical cancer is the second-leading cause of cancer-related mortality in females. Coix lacryma-jobi L. var. ma-yuen (Rom.Caill.) Stapf ex Hook. f. is the most widely recognized medicinal herb for its remedial effects against inflammation, endocrine system dysfunctions, warts, chapped skin, rheumatism, and neuralgia and is also a nourishing food. METHODS: To investigate the activity of Coix lacryma-jobi sprout extract (CLSE) on cell proliferation in human cervical cancer HeLa cells, we conducted a Cell Counting Kit-8 (CCK-8) assay. Flow-cytometric analysis and western blot analysis were performed to verify the effect of CLSE on the regulation of the cell cycle and apoptosis in HeLa cells. RESULTS: We observed that CLSE significantly inhibited cell proliferation. Furthermore, CLSE dose-dependently promoted cell cycle arrest at the sub-G1/ S phase in HeLa cells, as detected by bromodeoxyuridine (BrdU) staining. The cell-cycle-arrest effects of CLSE in HeLa cells were associated with downregulation of cyclin D1 and cyclin-dependent kinases (CDKs) 2, 4, and 6. Moreover, CLSE induced apoptosis, as determined by flow-cytometric analysis and nuclear DNA fragmentation with Annexin V/propidium iodide (PI) and 4'6'-diamidino-2-phenylindole (DAPI) staining. Induction of apoptosis by CLSE was involved in inhibition of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) and upregulation of the apoptotic proteins p53, cleaved poly (ADP-ribose) polymerase (PARP), cleaved caspase-3, and cleaved caspase-8. Finally, we observed that CLSE inactivated the phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) pathways. CONCLUSIONS: CLSE causes cell cycle arrest and apoptotic cell death through inactivation of the PI3K/AKT pathway in HeLa cells, suggesting it is a viable therapeutic agent for cervical cancer owing to its anticancer effects.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma/fisiopatologia , Coix/química , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero/fisiopatologia , Carcinoma/tratamento farmacológico , Carcinoma/genética , Carcinoma/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Coix/crescimento & desenvolvimento , Feminino , Humanos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo
6.
Int J Mol Sci ; 20(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370215

RESUMO

Dedifferentiated endometrial carcinoma (DDEC) is defined as an undifferentiated carcinoma admixed with differentiated endometrioid carcinoma (Grade 1 or 2). It has poor prognosis compared with Grade 3 endometrioid adenocarcinoma and is often associated with the loss of mismatch repair (MMR) proteins, which is seen in microsatellite instability (MSI)-type endometrial cancer. Recent studies have shown that the effectiveness of immune checkpoint inhibitor therapy is related to MMR deficiency; therefore, we analyzed the immunophenotype (MMR deficient and expression of PD-L1) of 17 DDEC cases. In the undifferentiated component, nine cases (53%) were deficient in MMR proteins and nine cases (53%) expressed PD-L1. PD-L1 expression was significantly associated with MMR deficiency (p = 0.026). In addition, the presence of tumor-infiltrating lymphocytes (CD8+) was significantly associated with MMR deficiency (p = 0.026). In contrast, none of the cases showed PD-L1 expression in the well-differentiated component. Our results show that DDEC could be a target for immune checkpoint inhibitors (anti PD-L1/PD-1 antibodies), especially in the undifferentiated component. As a treatment strategy for DDEC, conventional paclitaxel plus carboplatin and cisplatin plus doxorubicin therapies are effective for those with the well-differentiated component. However, by using immune checkpoint inhibitors in combination with other conventional treatments, it may be possible to control the undifferentiated component and improve prognosis.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Idoso , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Carboplatina/uso terapêutico , Carcinoma/genética , Carcinoma/imunologia , Carcinoma/patologia , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/imunologia , Carcinoma Endometrioide/patologia , Cisplatino/uso terapêutico , Reparo de Erro de Pareamento de DNA/efeitos dos fármacos , Doxorrubicina/uso terapêutico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/patologia , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Linfócitos do Interstício Tumoral , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/uso terapêutico , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia
8.
Mar Drugs ; 17(8)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426405

RESUMO

Chemical analysis of a cultivation of an Australian Mugil mullet gastrointestinal tract (GIT) derived fungus, Scopulariopsis sp. CMB-F458, yielded the known lipodepsipeptides scopularides A (1) and B (2). A comparative global natural product social (GNPS) molecular networking analysis of ×63 co-isolated fungi, detected two additional fungi producing new scopularides, with Beauveria sp. CMB-F585 yielding scopularides C-G (3-7) and Scopulariopsis sp. CMB-F115 yielding scopularide H (8). Structures inclusive of absolute configurations were assigned by detailed spectroscopic and C3 Marfey's analysis, together with X-ray analyses of 3 and 8, and biosynthetic considerations. Scopularides A-H (1-8) did not exhibit significant growth inhibitory activity against a selection of Gram positive (+ve) and negative (-ve) bacteria, a fungus, or a panel of three human carcinoma cell lines.


Assuntos
Depsipeptídeos/química , Peixes/microbiologia , Trato Gastrointestinal/microbiologia , Scopulariopsis/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Austrália , Bactérias/efeitos dos fármacos , Produtos Biológicos/química , Carcinoma/tratamento farmacológico , Linhagem Celular Tumoral , Células Hep G2 , Humanos
9.
Acta Otolaryngol ; 139(10): 918-925, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31460818

RESUMO

Background: No large-scale retrospective studies have examined the efficacy and safety of nivolumab. Objective: This retrospective study aimed to investigate the efficacy and safety of nivolumab administered to patients in multiple facilities. Material and methods: The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS) and overall survival (OS). For safety, adverse event occurrence rates by grade, deaths and severe adverse events were investigated. OS and PFS were also examined according to whether immune-related adverse events (irAEs) appeared. Statistical analysis was conducted using log-rank testing, with values of p < .05 considered significant. Results: Nivolumab was administered to 100 patients with a history of receiving platinum-based drugs. ORR was 13.5% and disease control rate was 49.0%. Median PFS was 3.7 months. Median OS was 9.6 months. For all grades, irAEs occurred in 30 patients. The 1-year survival rate in the subgroup without irAEs was 34.0%, compared to 52.6% with irAEs (p = .041). Conclusions and significance: The 1-year survival rate was better in patients who developed irAEs. This is a new finding for head and neck cancer. Appearance of irAEs could also be used as an indicator of expected therapeutic effect in head and neck cancer.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/patologia , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
10.
Medicine (Baltimore) ; 98(33): e16834, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415404

RESUMO

RATIONALE: Pembrolizumab, an immune-checkpoint inhibitor (ICI), has been shown to be effective for treatment-naive patients with non-small cell lung cancer (NSCLC) and high expression of programmed death-ligand 1 (PD-L1). Therefore, treatment regimens containing pembrolizumab have become a standard therapy for these patients. However, the use of pembrolizumab is limited owing to the side effects of ICIs. PATIENT CONCERNS AND DIAGNOSES: The patient was a 65-year-old man with a left lung mass surrounded by interstitial shadow. The tumor was diagnosed as adenocarcinoma, cT4N3M0, stage IIIC, and the tumor cells showed high PD-L1 expression. It was unclear whether the interstitial shadow was interstitial lung disease (ILD) or lymphangitis carcinomatosa. INTERVENTIONS AND OUTCOMES: The patient received carboplatin and nab-paclitaxel, a less risky regimen for ILD, as the first-line therapy. Administration of 2 cycles of this regimen markedly improved both the tumor diameter and interstitial shadow. The interstitial shadow was clinically diagnosed as lymphangitis carcinomatosa and not ILD. Subsequently, the patient was treated with pembrolizumab, and the tumor showed much further shrinkage with no deterioration of the interstitial shadow. To date, the patient is alive with no complaints and no disease progression, and has continued pembrolizumab treatment for a total of 12 months. LESSONS: In patients at a high risk of ICI-related side effects, platinum-doublet chemotherapy may be permitted as the first-line therapy for NSCLC with high PD-L1 expression. However, if the risk associated with ICIs is resolved, early switching from chemotherapy to pembrolizumab might be desirable, even if the chemotherapy is effective.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Neoplasias Pulmonares/diagnóstico , Linfangite/diagnóstico , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Linfangite/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Compostos de Platina/uso terapêutico
11.
Drug Deliv ; 26(1): 661-672, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31257941

RESUMO

The biodegradability and clearance of metal-based nanomaterials have been questioned worldwide, which have greatly limited their clinical translation. Herein, ultrathin manganese dioxide (MnO2) nanosheets with broad near-infrared (NIR) absorption and pH-dependent degradation properties were prepared. After being modified with polyethylene glycol-cyclic arginine-glycineaspartic acid tripeptide (PEG-cRGD), the MnO2 nanosheets were then used as photothermal agent and nanocarrier to encapsulate chlorin e6 (Ce6) for targeted photothermal (PTT) and photodynamic (PDT) of cancer. As expected, the MnO2-PEG-cRGD nanosheets show high Ce6 loading capacity (351 mg/g), superb photothermal conversion performance (37.2%) and excellent colloidal stability. These nanosheets also exhibit pH-dependent and NIR-induced Ce6 release. Furthermore, the MnO2 nanosheets can be degraded by reacting with hydrogen peroxide in the acidic microenvironment, which are able to elevate the oxygen concentration in situ and thus reverses the tumor hypoxia. Thanks to these favorable properties and the cRGD-mediated tumor-targeted ability, the fabricated MnO2-PEG-cRGD/Ce6 nanocomposites can be effectively up taken by alpha-v beta-3 (αvß3) integrin over-expressed prostatic carcinoma PC3 cells and achieve favorable therapeutic outcomes under a single 660 nm NIR laser, which is also verified by in vitro studies. The biodegradable MnO2-PEG-cRGD/Ce6 nanosheets developed in this work can be a promising nanoplatform for synergetic PTT/PDT cancer therapy.


Assuntos
Plásticos Biodegradáveis/química , Carcinoma/tratamento farmacológico , Compostos de Manganês/química , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Óxidos/química , Neoplasias da Próstata/tratamento farmacológico , Linhagem Celular Tumoral , Células HeLa , Humanos , Masculino , Células PC-3 , Peptídeos Cíclicos/química , Fotoquimioterapia/métodos , Polietilenoglicóis/química , Porfirinas/química
12.
BMC Complement Altern Med ; 19(1): 161, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277622

RESUMO

BACKGROUND: Cervical cancer is the second most prevalent cancer worldwide. Portulaca oleracea L. polysaccharide (POL-P3b) has been found to have enhancing immune and anti-cervical cancer activity by oral administration. Dendritic cells (DC) play a key roles in regulating intestinal immune homeostasis. In this study, we analyzed the inhibition apoptosis effects of POL-P3b on intestinal DC and relevant mechanisms. METHODS: Intestinal DC was isolated from U14-bearing mice treated with POL-P3b (50 mg/kg, 100 mg/kg and 200 mg/kg, respectively). The effects of POL-P3b on proliferation and inhibiting apoptosis in intestinal DC were evaluated by MTT assay, Hoechst 33342 and Annexin V-FITC/PI staining. Mitochondrial Ca2+ was analyzed using flow cytometry instrument. The potential mechanisms underlying POL-P3b-induced protection of intestinal DC from cervical cancer-induced apoptosis were detected with Western blotting evaluation of expression levels of TLR4 and relevant proteins for apoptotic signaling pathway. RESULTS: We found that a large number of intestinal DC were apoptosis in U14-bearing mice. Treatment with POL-P3b in U14-bearing mice at different doses for 12 d resulted in a significant increase in intestinal DC survival, and the mechanisms were related to inhibiting DC apoptosis. CONCLUSION: Our results suggested that POL-P3b-induced protection against tumor-induced intestinal DC apoptosis through stimulating the TLR4-PI3K/AKT-NF-κB signaling pathway. This study enhanced understanding of the oral administration with POL-P3b exerted on anti-tumor activity and its action mechanism.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Células Dendríticas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Portulaca/química , Administração Oral , Animais , Antineoplásicos Fitogênicos/análise , Antineoplásicos Fitogênicos/uso terapêutico , Cálcio/metabolismo , Carcinoma/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Intestinos/imunologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Transdução de Sinais , Neoplasias do Colo do Útero/tratamento farmacológico
13.
Tumori ; 105(4_suppl): 3-12, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31264522

RESUMO

In the past two decades, the treatment landscape for patients with metastatic renal cell carcinoma has significantly changed thanks to the approval of several targeted molecular therapies (VEGF and mTOR inhibitors) and recently immune-checkpoint inhibitors. The Italian Association of Medical Oncology (AIOM) Renal Cell Cancer (RCC) Guidelines Panel has developed clinical guidelines to provide evidence-based information and recommendations to oncologists, urologists and all professionals involved in the management of patients with renal cell cancer.


Assuntos
Neoplasias Renais/tratamento farmacológico , Oncologia/normas , Carcinoma/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Itália
14.
Int J Mol Sci ; 20(13)2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31262032

RESUMO

Cisplatin-based chemotherapy is the primary treatment for metastatic bladder urothelial carcinoma (UC). Most patients inevitably encounter drug resistance and resultant disease relapse. Reduced apoptosis plays a critical role in chemoresistance. Trifluoperazine (TFP), an antipsychotic agent, has demonstrated antitumor effects on various cancers. This study investigated the efficacy of TFP in inhibiting cisplatin-resistant bladder UC and explored the underlying mechanism. Our results revealed that cisplatin-resistant UC cells (T24/R) upregulated the antiapoptotic factor, B-cell lymphoma-extra large (Bcl-xL). Knockdown of Bcl-xL by siRNA resensitized cisplatin-resistant cells to the cisplatin cytotoxic effect. TFP (10-45 µM) alone elicited dose-dependent cytotoxicity, apoptosis, and G0/G1 arrest on T24/R cells. Co-treatment of TFP potentiated cisplatin-induced cytotoxicity in T24/R cells. The phenomenon that TFP alleviated cisplatin resistance to T24/R was accompanied with concurrent suppression of Bcl-xL. In vivo models confirmed that TFP alone effectively suppressed the T24/R xenograft in nude mice. TFP co-treatment enhanced the antitumor effect of cisplatin on the T24/R xenograft. Our results demonstrated that TFP effectively inhibited cisplatin-resistant UCs and circumvented cisplatin resistance with concurrent Bcl-xL downregulation. These findings provide a promising insight to develop a therapeutic strategy for chemoresistant UCs.


Assuntos
Antipsicóticos/farmacologia , Carcinoma/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Trifluoperazina/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Proteína bcl-X/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antipsicóticos/uso terapêutico , Apoptose , Carcinoma/metabolismo , Linhagem Celular , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Regulação para Baixo , Humanos , Camundongos , Trifluoperazina/uso terapêutico , Neoplasias da Bexiga Urinária/metabolismo , Urotélio/efeitos dos fármacos , Urotélio/metabolismo , Urotélio/patologia , Proteína bcl-X/genética
15.
BMJ Case Rep ; 12(7)2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31331929

RESUMO

Recognition of new cutaneous side effects of combination chemotherapy can help prevent unnecessary cessation or reduction of cancer therapy. Periorbital rash has not been found with docetaxel alone, but here, we report it as a result of combination chemotherapy. A series of three patients who received docetaxel in combination with other chemotherapies developed clinically near-identical, distinctive periorbital rashes. Rashes resolved by resolving underlying docetaxel-induced epiphora in conjunction with ophthalmological consultation, topical skin-directed care, and in some cases, chemotherapy dose reduction. It is important for dermatologists and oncologists to recognise the increased severity of cutaneous reactions when docetaxel is used in combination chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/efeitos adversos , Erupção por Droga/etiologia , Dermatoses Faciais/induzido quimicamente , Adulto , Idoso , Carcinoma/tratamento farmacológico , Cetuximab/administração & dosagem , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Nivolumabe/administração & dosagem , Neoplasias Parotídeas/tratamento farmacológico , Neoplasias da Base do Crânio/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico
16.
Int J Mol Sci ; 20(13)2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31252615

RESUMO

Interleukin (IL)-6 plays a crucial role in the progression, invasion, and metastasis of breast cancer. Triple-negative breast cancer (TNBC) cell line MDA-MB-231 is known for its aggressive metastasis. Epithelial to mesenchymal transition (EMT) is a critical process in cancer metastasis. The positive correlation between IL-6 and EMT in tumor microenvironment is reported. We found significantly upregulated IL-6 expression in MDA-MB-231 cells. A blockade of IL-6 expression decreased levels of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), phosphorylated protein kinase B (pAkt), and cell cycle-related molecules, including cyclin-dependent kinases (CDKs) and cyclins in MDA-MB-231 cells. A short-hairpin RNA (shRNA)-mediated blockade of IL-6 expression inhibited migration and N-cadherin expression and induced E-cadherin expression in MDA-MB-231 cells. Growth rate was slower for the tumors derived from IL-6 shRNA-treated MDA-MB-231 cells than for those derived from control shRNA-treated MDA-MB-231 cells. The expression of pSTAT3, phosphorylated extracellular signal-regulated kinase (pERK), PI3K, pAkt, snail, vimentin, and N-cadherin was significantly lower in tumors from IL-6 shRNA-treated MDA-MB cells. In addition, apigenin treatment significantly inhibited the growth of MDA-MB-231-derived xenograft tumors along with the protein expressions of pSTAT3, pERK, IL-6, PI3K, pAkt, and N-cadherin. Our results demonstrate that the anti-invasive effect of apigenin in MDA-MB-231-derived xenograft tumors is mediated by the inhibition of IL-6-linked downstream signaling pathway.


Assuntos
Antineoplásicos/uso terapêutico , Apigenina/uso terapêutico , Carcinoma/tratamento farmacológico , Interleucina-6/metabolismo , Neoplasias Mamárias Experimentais/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apigenina/farmacologia , Ciclinas/genética , Ciclinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Interleucina-6/genética , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Zhongguo Fei Ai Za Zhi ; 22(6): 329-335, 2019 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-31196365

RESUMO

BACKGROUND: Pneumonic-type lung carcinoma is a special type of lung cancer both clinically and radiologically. Here we present our experience on pneumonic-type lung carcinoma in an attempt to investigate the clinical, radiological and pathological features, diagnostic procedures, treatment, and prognosis of this type of tumor. METHODS: Pathologically confirmed lung cancer with a chest CT characterized by ground glass opacity or consolidation was defined as pneumonic-type lung carcinoma. Cases with advanced pneumonic-type lung carcinoma admitted to Peking Union Medical College Hospital (PUMCH) from January 1, 2013 to August 30, 2018 were enrolled. Retrospective analysis of clinical data and survival follow-up of these patients was conducted. RESULTS: A total of 46 cases were enrolled, all of which were adenocarcinoma. Cough (41/46, 89.1%) and expectoration (35/46, 76.1%) were the most prominent symptoms. The most frequent chest CT findings were ground glass attenuation (87.0%), patchy consolidation (84.8%), and multiple ground-glass nodules (84.8%). Multiple cystic changes (40%) and cavitation (13%) were also quite frequent. Ipsilateral and contralateral intrapulmonary metastasis were noted in 95.3% and 84.8% of cases respectively. The median duration from symptom onset to diagnosis was 214 days (95%CI: 129-298). Both surgical lung biopsy and CT-guided percutaneous lung biopsy had a diagnostic yield of 100%. Transbronchial lung biopsy (TBLB) combined with bronchoalveolar lavage (BAL) had a diagnostic yield of 80.9% (17/21). Sputum cytology had a diagnostic yield of 45% (9/20). Twenty-six cases were invasive mucinous adenocarcinoma (26/46, 56.5%) and the remainder were unable to identify pathological subtypes due to lack of adequate biopsy sample size. EGFR mutation was detected in 15.8% (6/38) of patients and ALK rearrangement was detected in 3.0% (1/33) of patients. The median overall survival for these patients was 522 d (95%CI: 424-619). In patients without EGFR mutation or ALK rearrangement, chemotherapy significantly improved survival (HR=0.155, P=0.002,2). The median overall survival was 547 d (95%CI: 492-602 d) with chemotherapy and 331 d (95%CI: 22-919) without chemotherapy. CONCLUSIONS: Diagnosis of pneumonic-type carcinoma is usually delayed due to clinical and radiological features mimicking pulmonary infection. TBLB combined with BAL has a quite high diagnostic yield. The most frequent histological type is invasive mucinous adenocarcinoma. The incidence of EGFR mutation or ALK rearrangement is low in pneumonic-type carcinoma. For patients without cancer driver genes, chemotherapy is recommended to improve overall survival.


Assuntos
Carcinoma/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Idoso , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/genética , Carcinoma/patologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X
19.
Medicine (Baltimore) ; 98(23): e15999, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169742

RESUMO

BACKGROUND: We performed the present systematic review and meta-analysis to evaluate the efficacy and safety for S-1-based regimens comparing to intravenous fluorouracil-based ones in Asian patients with metastatic colorectal carcinoma (mCRC). METHODS: Eligible prospective and controlled randomized clinical trials (RCT) were included, of which data were extracted by inclusion criteria and exclusion ones. Odds ratio (OR) and Hazard ratio (HR) of outcomes including objective response rate (ORR), disease control rate (DCR), progressive-free survival (PFS), overall survival (OS), and adverse events (AEs) were explored for the final analysis between the 2 groups. RESULTS: A total of 23 eligible prospective, controlled RCTs including 2269 patients were enrolled for the pooled analysis. With the meta-analysis of available data, the results of the present research showed that there was no statistical difference on short-term efficacy including ORR (HR = 0.85, 95% CI: 0.71-1.01; P = .07) or DCR (HR = 0.88, 95% CI: 0.69-1.11; P = .27), as well as long-term efficacy including PFS (HR = 1.00, 95% CI: 0.90-1.11; P = .98) or OS (HR = 0.95, 95% CI: 0.82-1.10; P = .50). In addition, the incidences of AEs including leucopenia, neutropenia, and vomiting were statistically lower in S-1-based regimens comparing to intravenous fluorouracil-based ones, regardless of all grade or high grade (all P <.05). However, there were no significant differences detected among other AEs including anemia, thrombocytopenia, increased alanine aminotransferase concentration, stomatitis, anorexia, diarrhea, hand-foot syndrome (HFS), or sensory neuropathy among the 2 groups (all P >.05). CONCLUSIONS: The present meta-analysis revealed that S-1-based regimens might be associated with comparable efficacy, as well as lower risk of leucopenia, neutropenia, and vomiting at all/high grade comparing to intravenous fluorouracil-based ones in Asian patients with mCRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/administração & dosagem , Pirimidinas/administração & dosagem , Administração Intravenosa , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Carcinoma/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
20.
Zhonghua Zhong Liu Za Zhi ; 41(6): 415-420, 2019 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-31216826

RESUMO

Objective: To evaluate the tolerability and short-term efficacy of chemo-radiotherapy in 125 patients with stage ⅡB-ⅣA esophageal carcinoma after radical resection. Methods: We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo-radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results: 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo-radiotherapy (41.6%), while 73 patients underwent only 1-4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up (6.4%). The 1-year and 3-year overall survival rate were 91.6% and 57.0%, respectively, with a median survival time of 64.4 months. The 1-year and 3-year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo-radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1-2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P=0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P=0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor (P=0.010). Conclusions: Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB-ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.


Assuntos
Carcinoma/tratamento farmacológico , Carcinoma/radioterapia , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Radioterapia Adjuvante/efeitos adversos , Carcinoma/cirurgia , Quimioterapia Adjuvante/métodos , Terapia Combinada/efeitos adversos , Neoplasias Esofágicas/cirurgia , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento
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