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1.
Anticancer Res ; 39(10): 5417-5425, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570436

RESUMO

BACKGROUND/AIM: Chemotherapy with docetaxel (DTX) is used for castration-resistant prostate cancer (CRPC), but it is inadequate. MATERIALS AND METHODS: We evaluated the effect of the combination treatment DTX and the mTOR inhibitor temsirolimus (TEM) in the PC3 prostate cancer cell line, by focusing on the induction of autophagy and apoptosis. RESULTS: TEM induced autophagy but not apoptosis even at a high dose, whereas DTX induced apoptosis. The combination of low-dose DTX and TEM caused a 34% suppression in cell proliferation compared to monotherapy with a higher dose of DTX. The induction of apoptosis was increased by their combination. The combination with DTX overcame the induction of autophagy by TEM. The combination treatment suppressed tumor growth 72% less than the control group after 14 days of treatment in vivo. CONCLUSION: The combination of TEM and DTX induced apoptosis by overcoming autophagy and enhanced the anticancer effect compared to monotherapy.


Assuntos
Antineoplásicos/administração & dosagem , Autofagia/efeitos dos fármacos , Docetaxel/administração & dosagem , Próstata/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Sirolimo/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Terapia Combinada/métodos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células PC-3 , Inibidores de Proteínas Quinases/administração & dosagem , Sirolimo/administração & dosagem
2.
Medicine (Baltimore) ; 98(38): e16988, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567935

RESUMO

RATIONALE: Peripherally inserted central catheters (PICC), normally located at the lower 1/3rd of the superior vena cava (SVC) and cavo-atrial junction, are commonly used in cancer patients. Persistent left superior vena cava (PLSVC) is a vascular anomaly, in patients with which seldom research was reported about PICC implanted. After obtaining written informed consent, we present a case where two successful insertions of PICC were performed in a 50-year-old female patient with PLSVC and right SVC. PATIENTS CONCERNS: The patient had ovarian cancer and was admitted for chemotherapy using PICC. DIAGNOSES: Ovarian cancer and PLSVC. INTERVENTIONS AND OUTCOMES: Following insertion of PICC in PLSVC, thrombosis developed. PICC was removed after routine anticoagulation therapy. Owing to tumor recurrence, a second PICC was inserted in the right SVC without any complications. LESSONS: PICC insertion in PLSVC for chemotherapy may be associated with an increased risk of deep venous thrombosis of the upper extremity. A right catheter insertion in patient with PLSVC was preferred.


Assuntos
Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Malformações Vasculares/complicações , Veia Cava Superior/anormalidades , Trombose Venosa/diagnóstico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Braço , Cateterismo Periférico/efeitos adversos , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/complicações , Neoplasias Ovarianas/complicações , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia
3.
Bull Cancer ; 106(10): 847-859, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31521255

RESUMO

INTRODUCTION: The Cancer Observatory, from the OMEDITs (Observatory for Medicines and Medical Devices and Treatment Innovations) of Bretagne and Pays de la Loire areas has conducted a survey aiming to know and map the current practices of management of patients by Oral Anti-cancer Drug (OAD) in inter-region. METHODS: Forty eight cancer centers received by e-mail in July and October 2016 a questionnaire concerning the management of OADs : from prescription by the specialist of oncology, to the intervention of the pharmacist (analysis and pharmaceutical consulting), to follow-up by nurse, as well as the financing of this activity and the feelings of the actors about this organizational set up. RESULTS: Fifty-seven professionals from 31 centers, including the most important ones, responded to the survey. As a result, half of the establishments carry out a pharmaceutical analysis for some or all of the OAD prescriptions and only 30% carry out a pharmaceutical consulting. The nurse consultation is, on the other hand, more largely implanted (74% of the centers) as well as the telephone follow-up (6%). More than 90% of professionals believe that the organizational set up could be improved and more secure by, at least, the stronger involvement of pharmacists, the development of tools for nurse (for monitoring, therapeutic education…) and by improving the city-hospital link. CONCLUSION: This survey shows the variability in the management of patients under OAD because of the lack of resources to ensure the fairness and sustainability of the organizational set up. The hospital/city link could still be optimized to secure patient care.


Assuntos
Antineoplásicos/administração & dosagem , Pesquisas sobre Serviços de Saúde/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Administração Oral , Institutos de Câncer/estatística & dados numéricos , Continuidade da Assistência ao Paciente/estatística & dados numéricos , Prescrições de Medicamentos , França , Humanos , Papel do Profissional de Enfermagem , Objetivos Organizacionais , Satisfação do Paciente , Farmacêuticos , Padrões de Prática em Enfermagem/estatística & dados numéricos , Telefone
4.
Cancer Radiother ; 23(6-7): 662-665, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473087

RESUMO

Chemoradiotherapy is now considered the standard of care for many locally advanced diseases. Cytotoxic drugs have been largely evaluated in this setting, with cisplatin and 5FU the most often used drugs. A large amount of pre-clinical studies has demonstrated the synergy between both modalities. Concomitant administration seems the more beneficial in many diseases. Emergence of new approaches, combining targeted therapies and radiotherapy (RT) is now a reality. The main example is the association of cetuximab and RT in head and neck carcinomas, even if, 14 years after the initial publication, the best way to use it is still unknown. New compounds as inhibitors of DNA-repair or immune checkpoints are under investigation and showed early promising results.


Assuntos
Antineoplásicos/administração & dosagem , Quimiorradioterapia/tendências , Neoplasias/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/administração & dosagem , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Reparo do DNA/efeitos dos fármacos , Docetaxel/administração & dosagem , Esquema de Medicação , Fluoruracila/administração & dosagem , Humanos , Terapia de Alvo Molecular/métodos , Órgãos em Risco/efeitos da radiação , Lesões por Radiação/prevenção & controle , Fatores de Tempo
5.
Medicina (B Aires) ; 79(4): 280-283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487248

RESUMO

The purpose of the study was to evaluate the outcome of patients under 18 months diagnosed with neuroblastoma. Between April 2006 and December 2013, 45 consecutive patients followed in Hospital de Pediatría Garrahan, were retrospectively reviewed. With a median age of 9.3 months (1-18 months) N-myc amplification was detected in 5 out of 38 patients, 1p deletion (del1p) in 4 patients, and 11q aberration in one patient. With a median follow-up of 53 (range: 6-109 months), at 24 months the event free survival (EFS) of all patients was 83% (SE 6%) and overall survival (OS) of 88% (SE 5%). Significant difference was found in OS and EFS between patients with stages L1, L2 and Ms vs. stage M (p = 0.01 and p = 0.01 respectively). EFS for each stage: L1 85% (SE 7%), L2 100%, MS 100%, vs. M 55% (SE 16%). OS: L1 90% (SE 6%), L2 100%, MS 100%, vs. M 66% (SE 15%). OS and EFS results are similar to those reported in international studies. However, better identification of biological prognostic factors will warr ant accurate staging and consequently an appropriate treatment.


Assuntos
Antineoplásicos/administração & dosagem , Neuroblastoma/diagnóstico , Neuroblastoma/tratamento farmacológico , Protocolos Antineoplásicos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Neuroblastoma/mortalidade , Prognóstico , Estudos Retrospectivos
6.
Khirurgiia (Mosk) ; (9): 93-98, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31532174

RESUMO

Objective - to improve short- and long-term outcomes of locally advanced pancreatic body-tail cancer followed by major vessels invasion. MATERIAL AND METHODS: A case report of pure laparoscopic DP-CAR procedure with portal vein resection for locally advanced pancreatic body-tail cancer followed by severe abdominal pain in a 49-year-old patient is presented. RESULTS: Liver or stomach ischemia was not observed. Portal wall resection wasn't associated with any complication and resulted R0-resection. Postoperative period was complicated by Grade B pancreatic fistula. Preoperative abdominal pain completely disappeared after surgery. Surgery time was 330 min, intraoperative blood loss - 300 ml. The patient is currently undergoing FOLFIRINOX adjuvant chemotherapy. CT in 90 days after surgery confirmed no progression of disease or liver/stomach blood supply congestion. CONCLUSION: Modern technologies provide the opportunity to perform pure laparoscopic advanced surgical procedures with major vessels resection. Pure laparoscopic DP-CAR procedure with portal vein resection is effective and safe procedure that can be performed with all principles of open surgery and is associated with acceptable short- and long-term results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Artéria Celíaca/cirurgia , Laparoscopia/métodos , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Veia Porta/cirurgia , Antineoplásicos/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Pessoa de Meia-Idade , Invasividade Neoplásica , Oxaliplatina/administração & dosagem , Pancreatectomia/efeitos adversos , Fístula Pancreática/etiologia , Neoplasias Pancreáticas/patologia , Veia Porta/patologia
7.
Pan Afr Med J ; 33: 134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31558933

RESUMO

Primary angiosarcoma of the breast is an extremely rare tumour with a difficult diagnosis and poor prognosis. We report a case of primary breast angiosarcoma diagnosed in the pathology department of the University Hospital of Oujda. An analysis of the epidemiological, diagnostic and therapeutic aspects of this type of tumour is made in this manuscript. Mastectomy is the standard treatment; the place of radiotherapy and chemotherapy is not well established. We report a case of a 18- year-old woman having an infectious symptomatology of the right breast for which she received an anti-infectious therapy inducing regression of inflammatory symptoms presented with a quick growing mass. Initial core needle biopsy showed a malignant vascular proliferation. The patient underwent a mastectomy. The tumor histology showed papillary formations and vascular structures lined by atypical cells with hyperchromatic nucleus and eosinophilic cytoplasm. The tumor cells expressed CD34 and CD31 but were negative for cytokeratin. The diagnosis of angiosarcoma grade I was made. The patient is now receiving chemotherapy. She is still alive.


Assuntos
Neoplasias da Mama/diagnóstico , Hemangiossarcoma/diagnóstico , Mastectomia/métodos , Adolescente , Antígenos CD34/metabolismo , Antineoplásicos/administração & dosagem , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , Humanos , Gradação de Tumores , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo
8.
Medicine (Baltimore) ; 98(36): e16967, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490378

RESUMO

No standard methods are recommended for patients with advanced metastatic non-small-cell lung cancer (NSCLC) experiencing progression after 2 or more lines treatment now. The aim of this retrospective study was to assess the efficacy and safety of apatinib in metastatic NSCLC patients after second-line or more treatments failure in a real-world setting.A total of 52 advanced NSCLC patients who experienced progression after second-line and more treatments and received apatinib from March 2016 to February 2018 were retrospectively reviewed. Patients were treated with oral apatinib 500 mg QD (take the medicine once a day), every 4 weeks for a cycle. Responding and stable patients continued the treatment until progression or intolerable toxicity. The overall survival (OS), progression-free survival (PFS), objective remission rate (ORR) and disease control rate (DCR), and side effects of the drug were collected and reviewed.The ORR and the DCR were 6.9% and 67.4%. The median PFS and median OS of all patients were 3.8 months and 5.8 months, respectively. The Eastern Cooperative Oncology Group score was the independent influencing factor of PFS and OS for the advanced NSCLC patients who were treated with apatinib after second-line and above standard regimens (PFS: hazard ratio [HR] = 4.446, 95% confidence interval [CI]: 1.185-16.678, P = .027 and OS: HR = 8.149, 95% CI: 1.173-56.596, P = .034). The most common adverse events apatinib-related included hypertension (19.2%), hand-foot syndrome (11.5%), and mucous membrane reaction (17.3%). And treatment-related grade 3/4 toxicities were low.Apatinib showed favorable efficacy and safety and could be a treatment option in patients with advanced NSCLC experiencing progression after second-line and more treatment.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Piridinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Estudos Retrospectivos
9.
Anticancer Res ; 39(9): 5003-5007, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519607

RESUMO

Incorporating bortezomib and/or lenalidomide in the management of plasmablastic lymphoma is an attractive option due to the reported high response rates. However, concerns about overlapping toxicities can deter clinicians from incorporating these novel agents into chemotherapy. In this case report we describe a patient with plasmablastic lymphoma, who received both lenalidomide and bortezomib as part of upfront treatment for a high-risk plasmablastic lymphoma. After completing intensive chemotherapy, the patient was transitioned to a regimen of daily lenalidomide and biweekly bortezomib to decrease the chance of relapse. This maintenance phase was given for 6 months and was well tolerated. Despite having multiple adverse risk factors, the patient remains in remission, 18 months following diagnosis.


Assuntos
Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Linfoma Plasmablástico/tratamento farmacológico , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Bortezomib/administração & dosagem , Gerenciamento Clínico , Feminino , Humanos , Quimioterapia de Indução , Imagem por Ressonância Magnética , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Linfoma Plasmablástico/diagnóstico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X
10.
Anticancer Res ; 39(9): 5149-5156, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519627

RESUMO

BACKGROUND: Factors associated with response to lenvatinib have not been clarified in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This study retrospectively analyzed 50 patients treated with lenvatinib as first-line therapy between March 2018 and March 2019. Patients were divided into two groups by the Modified Response Evaluation Criteria in Solid Tumours (mRECIST) (responders and non-responders, whose best overall responses were complete (CR)/partial response (PR) and stable (SD)/progressive disease (PD), respectively). Factors associated with response were assessed, including the relative dose intensity 8 weeks after lenvatinib induction (8W-RDI). RESULTS: The best overall responses were 0/22/14/14 of CR/PR/SD/PD. Multivariate analysis revealed that only 8W-RDI was significantly associated with response. The receiver operating characteristic curve for 8W-RDI in differentiating responders from non-responders revealed a cut-off value of 75%. Patients with 8W-RDI ≥75% experienced a higher response rate and longer progression-free survival than patients with 8W-RDI <75%. CONCLUSION: Our results suggest that maintaining an RDI ≥75% during the initial 8 weeks of lenvatinib treatment has a favorable impact on response.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento
11.
Anticancer Res ; 39(9): 5165-5170, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519629

RESUMO

BACKGROUND/AIM: Daratumumab is a promising novel agent for relapsed/refractory multiple myeloma (RRMM). However, there are limited data on its efficacy and toxicity profiles in real-world patients, especially in the Asian population. PATIENTS AND METHODS: This was a multicenter, retrospective, longitudinal cohort study set between January 2017 and April 2019. We collected and analyzed clinical and survival data of 21 patients treated with daratumumab monotherapy. All patients were previously exposed to proteasome inhibitors and immunomodulatory drugs. RESULTS: The overall response rate was 42.1%, including one complete remission (4.8%) and three very good partial responses (14.3%). The cycles of daratumumab delivered were three (range=1-10 cycles) and the median progression-free survival was 6 months, while the overall survival was not reached. Infusion reaction was observed in nine patients (42.9%), and one discontinued permanently. Fatigue was the most common adverse event (52.4%), and there were five cases of documented infection during daratumumab treatment, two of them leading to the death of the patient. CONCLUSION: Daratumumab monotherapy showed fairly promising activity with modest tolerance in heavily treated Asian RRMM patients.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Mieloma Múltiplo/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Ásia , Linhagem Celular Tumoral , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Medicine (Baltimore) ; 98(37): e16986, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517817

RESUMO

RATIONALE: Cavernous hemangiomas referred to as venous malformations (VMs), are not true vascular tumors. The treatment of cavernous hemangiomas is controversial. PATIENT CONCERNS: A five-year-old girl with a cavernous hemangioma on her right buttock had undergone surgery but recurred 1 month after the operation. DIAGNOSES: Cavernous hemangioma was diagnosed on the basis of physical examination, magnetic resonance imaging (MRI) and postoperative pathologic examination. INTERVENTIONS: We treated her with intralesional injection of triamcinolone acetonide (TCA) for 8 times. OUTCOMES: She was cured and had no recurrence during the 3-month follow-up. LESSONS: This prompts that TCA may provide a more effective and safer choice for the treatment of cavernous hemangiomas.


Assuntos
Antineoplásicos/administração & dosagem , Hemangioma Cavernoso/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Triancinolona Acetonida/administração & dosagem , Nádegas , Pré-Escolar , Feminino , Hemangioma Cavernoso/diagnóstico por imagem , Hemangioma Cavernoso/patologia , Hemangioma Cavernoso/cirurgia , Humanos , Injeções Intralesionais , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia
14.
Pharm Res ; 36(10): 140, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31367876

RESUMO

PURPOSE: In order to overcome the obstacles and side effects of classical chemotherapy, numerous studies have been performed to develop the treatment based on targeted transport of active compounds directly to the site of action. Since tumor cells are featured with intensified glucose metabolism, we set out to develop innovative, glucose-modified PAMAM dendrimer for the delivery of doxorubicin to breast cancer cells. METHODS: PAMAM-dox-glc conjugate was synthesized and characterized by 1H NMR, FT-IR, size and zeta potential measurements. The drug release rate from conjugate was evaluated by dialysis under different pH conditions. The expression level of GLUT family receptors in cells cultured in full and glucose-deprived medium was evaluated by quantitative real-time RT-PCR and flow cytometry. The cytotoxicity of conjugate in presence or absence of GLUT1 inhibitors was determined by MTT assay. RESULTS: We showed that PAMAM-dox-glc conjugate exhibits pH-dependent drug release and increased cytotoxic activity compared to free drug in cells cultured in medium without glucose. Further, we proved that these cells overexpress transporters of GLUT family. The toxic effect of conjugate was eliminated by the application of specific GLUT1 inhibitors. CONCLUSION: Our findings revealed that the glucose moiety plays a crucial role in the recognition of cells with high expression of GLUT receptors. By selectively blocking GLUT1 transporter we showed its importance for the cytotoxic activity of PAMAM-dox-glc conjugate. These results suggest that PAMAM-glucose formulations may constitute an efficient platform for the specific delivery of anticancer drugs to tumor cells overexpressing transporters of GLUT family.


Assuntos
Antineoplásicos/farmacologia , Dendrímeros/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Transportador de Glucose Tipo 1/metabolismo , Glucose/efeitos adversos , Antineoplásicos/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Liberação Controlada de Fármacos , Regulação da Expressão Gênica , Glucose/química , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Tamanho da Partícula
15.
Anticancer Res ; 39(8): 4031-4041, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366485

RESUMO

BACKGROUND/AIM: Eribulin is currently used to treat advanced and metastatic breast cancer in the clinical setting; however, its efficacy is inhibited by resistance acquisition in many cases. Thus, the present study established two eribulin-resistant breast-cancer cell lines, and used these to investigate the mechanisms that underly eribulin-resistance acquisition. MATERIALS AND METHODS: Eribulin-resistant breast-cancer cell lines were generated by culturing MDA-MB-231 and MCF-7 cells with increasing concentrations of eribulin. RESULTS: The eribulin-resistant cells acquired resistance to eribulin, as well as several other anticancer drugs. After eribulin treatment, the eribulin-resistant cell lines showed no morphological change, no increased expression of epithelial-cadherin, nor any significant alteration in cell-cycle distribution. In contrast, the expression levels of programmed death-ligand 1 were increased in the MCF-7/eribulin-resistant compared to MCF-7 cells. CONCLUSION: The herein developed eribulin-resistant cell lines acquired cross-resistance to various anticancer agents, and displayed resistance to eribulin-induced effects on microtubule function and epithelial-mesenchymal transition (EMT).


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Furanos/administração & dosagem , Cetonas/administração & dosagem , Animais , Antineoplásicos/efeitos adversos , Mama/efeitos dos fármacos , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Furanos/efeitos adversos , Humanos , Cetonas/efeitos adversos , Células MCF-7 , Camundongos , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Pharm Res ; 36(10): 149, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420752

RESUMO

PURPOSE: Combinatorial approach can be beneficial for cancer treatment with better patient recovery. Co-delivery of natural and synthetic anticancer drug not only valuable to achieve better anticancer effectivity but also to ascertain toxicity. This study was aimed to co-deliver berberine (natural origin) and doxorubicin (synthetic origin) utilizing conjugation/encapsulation strategy through poly (lactic-co-glycolic acid) (PLGA) nanoparticles. METHODS: Doxorubicin was efficiently conjugated to PLGA via carbodiimide chemistry and the PLGA-doxorubicin conjugate (PDC) was used for encapsulation of berberine (PDBNP). RESULTS: Significant anti-proliferative against MDA-MB-231 and T47D breast cancer cell lines were observed with IC50 of 1.94 ± 0.22 and 1.02 ± 0.36 µM, which was significantly better than both the bio-actives (p < 0.05). The ROS study revealed that the PDBNP portrayed the slight increase in the reactive oxygen species (ROS) pattern in MDA-MB-231 cell line in a dose-dependent manner, while in T47D cells, no significant change in ROS was seen. PDBNP exhibits significant alteration (depolarization) in mitochondrial membrane permeability and arrest of cell cycle progression at sub G1 phase while the Annexin V/PI assay followed by confocal microscopy resulted into cell death mode to be because of necrosis against MDA-MB-231 cells. In vivo studies in Sprague Dawley rats revealed almost 14-fold increase in half life and a significant increase in plasma drug concentration. CONCLUSION: The overall approach of PLGA based co-delivery of doxorubicin and berberine witnessed synergetic effect and reduced toxicity as evidenced by preliminary toxicity studies.


Assuntos
Antineoplásicos/administração & dosagem , Berberina/administração & dosagem , Doxorrubicina/administração & dosagem , Nanocápsulas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Berberina/farmacocinética , Berberina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Interações de Medicamentos , Liberação Controlada de Fármacos , Humanos , Masculino , Ratos Sprague-Dawley
17.
Expert Rev Pharmacoecon Outcomes Res ; 19(5): 505-508, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31379219

RESUMO

Introduction: The analysis was conducted to assess a cost-efficacy analysis of new antiemetic drugs (netupitant plus palonosetron (NEPA)) for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in highly and moderately emetogenic chemotherapy for cancer treatment. Areas covered:The present evaluation was restricted to pivotal phase III randomized controlled trials (RCTs) of NEPA versus (vs.) palonosetron for the prophylaxis of CINV. We calculated the pharmacological costs necessary to get the benefit in complete response (CR), for each trial. Our analysis evaluated 2 RCTs, including 1720 patients. Referring to both highly and moderately emetogenic chemotherapy, NEPA plus DEX was economic superior to palonosetron (PALO) plus DEX, with 13 312 € and 7885 € gain in medical costs every 100 patients treated, respectively. The cost-effectiveness ratios (CERs) (€/CR) in highly emetoge nic risk were 1.24 and 13.23 for the NEPA and PALO group, respectively and 1.49 and 15.20 for the same groups in moderately emetogenic risk. The incremental cost-effectiveness ratio (ICER) between the groups was 1016.18 €/CR and 1024.03 €/CR in highly and moderately emetogenic risk, respectively. Expert opinion:The combination of NEPA plus DEX is cost-effective for preventing CINV in highly and moderately (AC-based) emetogenic cancer treatment.


Assuntos
Antieméticos/administração & dosagem , Palonossetrom/administração & dosagem , Piridinas/administração & dosagem , Antieméticos/economia , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Análise Custo-Benefício , Dexametasona/administração & dosagem , Dexametasona/economia , Humanos , Náusea/induzido quimicamente , Náusea/economia , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Palonossetrom/economia , Piridinas/economia , Ensaios Clínicos Controlados Aleatórios como Assunto , Vômito/induzido quimicamente , Vômito/economia , Vômito/prevenção & controle
18.
Expert Rev Clin Pharmacol ; 12(9): 841-849, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31454267

RESUMO

Introduction: The receptor tyrosine kinase FLT3 is the most commonly mutated gene in acute myeloid leukemia (AML). FLT3-internal tandem duplication mutations are associated with an increased risk of relapse, and a number of small molecule inhibitors of FLT3 have been developed. The highly potent and selective FLT3 kinase inhibitor gilteritinib is the first tyrosine kinase inhibitor approved as monotherapy for the treatment of relapsed and/or refractory FLT3-mutated AML. Areas covered: We review the biology and prognostic significance of FLT3 mutations in AML and discuss the pharmacology, clinical efficacy, and toxicity profile of gilteritinib. We also summarize important differences among the various FLT3 inhibitors that are currently approved or under development and highlight areas of ongoing research. Expert opinion: Gilteritinib has been shown to improve survival compared to salvage chemotherapy in relapsed and/or refractory FLT3-mutated AML. Gilteritinib is orally available with a favorable toxicity profile and as such is quickly becoming the standard of care for this patient population. Ongoing clinical trials are evaluating gilteritinib in combination with frontline chemotherapy, in combination with other agents such as venetoclax and azacitidine for patients who are ineligible for standard induction therapy, and as a maintenance agent.


Assuntos
Compostos de Anilina/administração & dosagem , Antineoplásicos/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Pirazinas/administração & dosagem , Compostos de Anilina/efeitos adversos , Compostos de Anilina/farmacologia , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Humanos , Leucemia Mieloide Aguda/genética , Mutação , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacologia , Pirazinas/efeitos adversos , Pirazinas/farmacologia , Recidiva , Sobrevida , Tirosina Quinase 3 Semelhante a fms/genética
19.
J Cancer Res Clin Oncol ; 145(10): 2613-2624, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31463717

RESUMO

PURPOSE: To determine the frequency of co-occurring genes in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation and the predictive effect of co-mutations on the efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs). METHODS: 54 patients with advanced NSCLC were tested for 422 clinically relevant genes by next-generation sequencing (NGS) before treatment. Among them, patients with EGFR mutation received first-line treatment of EGFR-TKIs. Progression-free survival (PFS) and objective response rate (ORR) were evaluated using Kaplan-Meier methods and compared between two groups using log-rank test. RESULTS: Among 24 EGFR mutant and 30 EGFR wild-type patients, co-mutation rate was lower in patients with EGFR mutation (62.5% [15/24] vs 93.3% [28/30], p = 0.005). There was lower frequency for co-alterations in BRAF (0% [0/24] vs 20% [7/30], p = 0.033), NF1 (4.2% [1/24] vs 30% [9/30], p = 0.038) and RAS-RAF-MAPK pathway genes (16.6% [4/24] vs 56.7% [17/30], p = 0.003) in EGFR mutation group. 24 patients with EGFR mutation received first-line treatment of gefitinib or erlotinib, with an ORR of 83.3% and a median PFS of 12.3 months (95% CI 10.00-14.60). Co-mutation was associated with shorter median PFS (10.2 months [95% CI 5.20-15.20] vs 15.3 months [95% CI 12.09-15.81]; HR 0.29 [95% CI 0.10-0.82]; p = 0.014) in EGFR mutation cohort. Among patients with EGFR mutation and distant metastasis, median PFS was decreased in those with co-mutations (6.3 months [95% CI 3.25-9.35] vs 22.0 months[95% CI 12.10-31.90]; HR 0.12 [95% CI 0.00-5.87]; p = 0.007) and frequency of PIK3CA (0% [0/12] vs 41.7% [5/12], p = 0.037) and PI3K/AKT/mTOR pathway genes (0% [0/12] vs 50% [6/12], p = 0.014) was lower. CONCLUSION: The presence of co-mutations was lower in the EGFR mutation patients and reduces the efficacy of EGFR-TKI, especially in patients with distant metastases. Lower frequency of co-mutation in PIK3CA and PI3K/AKT/mTOR pathway genes may be responsible for promoting metastasis and limiting the efficacy of EGFR-TKIs.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Mutação , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do Tratamento
20.
Hautarzt ; 70(9): 684-690, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31468071

RESUMO

BACKGROUND: Merkel cell carcinoma (MCC) is a rare but aggressive form of skin cancer in which Merkel cell polyomavirus infection and chronic exposure to ultraviolet radiation are key risk factors. Immune checkpoint inhibition has revolutionized the treatment of locally advanced, inoperable and metastatic MCC. AIM: To outline the modern management of MCC based on advances in our understanding of MCC tumour biology and the development of immune checkpoint inhibitors, namely inhibitors of programmed cell death protein (PD)-1- and PD­1 ligand 1 (PD-L1). METHODS: A review of the scientific literature listed in PubMed. RESULTS: First line therapy with the PD-L1 blocking antibody avelumab is associated with a response rate of 62%. In the second line setting, for example after chemotherapy, the response rate only reaches 33%. However, in patients who responded in the second line setting, 69% remained relapse free after 2 years. Treatment responses occurred on average after 6.1 weeks of therapy. First line treatment with pembrolizumab (anti-PD­1 antibody) is associated with a 2-year survival rate of 69% and the median survival rate has not been reached. Whilst the various chemotherapy regimens are associated with similar response rates, these are typically short lived. DISCUSSION: Checkpoint inhibition offers an effective treatment option for patients with MCC. Avelumab is currently licensed as a treatment for metastatic disease. Chemotherapy remains an option to reduce tumor load, or in the context of resistance and/or contraindications to immune checkpoint therapy. Adjuvant and neoadjuvant use of checkpoint inhibition in MCC may represent a future treatment strategy pending the results of on-going clinical trials.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Carcinoma de Célula de Merkel/tratamento farmacológico , Carcinoma de Célula de Merkel/imunologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/imunologia , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Carcinoma de Célula de Merkel/patologia , Humanos , Recidiva Local de Neoplasia , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Raios Ultravioleta
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