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1.
Acta Gastroenterol Belg ; 84(1): 65-72, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33639695

RESUMEN

Aim: The aim of this retrospective multicenter study was to evaluate the differences in the timing for starting systemic therapies as the first-line treatment for hepatocellular carcinoma (HCC). Methods: A total of 375 patients with HCC treated with sorafenib from May 2009 to March 2018 and 56 patients treated with lenvatinib from March 2018 to November 2018 at our affiliated hospitals were included in this study. Results: The median ages of the sorafenib and lenvatinib groups were 71.0 (interquartile range [IQR]: 64.0-77.0) and 73.5 (IQR: 68.0 -80.0) years old, and 300 (80.0%) and 42 (75.0%) patients were men, respectively. The Barcelona Clinic Liver Cancer stage was early, intermediate and advanced in 39 patients (10.4%), 133 patients (35.5%) and 203 patients (54.1%) in the sorafenib group and 1 patient (1.8%), 17 patients (30.4%) and 38 patients (67.9%) in the lenvatinib group, respectively. In the analysis of intermediate HCC, patients who satisfied the criteria of TACE failure/refractoriness (P=0.017), those with ALBI grade 1 (P=0.040), and those with a serum AFP level < 200 ng/ml (P=0.027) were found more frequently in the lenvatinib group than in the sorafenib group, with statistical significance. The objective response rate (ORR) of lenvatinib was 34.8% in the overall patients and 46.7% in the intermediate-stage HCC patients, which was significantly higher than sorafenib (P=0.001, P=0.017). Conclusions: The emergence of lenvatinib has encouraged physicians to start systemic chemotherapy earlier in intermediatestage HCC patients.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Anciano , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Compuestos de Fenilurea/uso terapéutico , Quinolinas , Estudios Retrospectivos , Sorafenib/uso terapéutico
2.
Medicine (Baltimore) ; 100(3): e23802, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33545943

RESUMEN

BACKGROUND: Thymic carcinoma is a rare malignancy, and platinum-based chemotherapy has not previously been established as a standard treatment for advanced or metastatic thymic carcinoma. With the breakthrough and progress of immunotherapy, the possibility of curing thymic carcinoma has greatly increased. Some clinical trials have reported that compared with traditional platinum-based chemotherapy, the use of programmed death 1 and programmed death ligand 1 inhibitors alone can benefit patients and effectively prolong their overall survival. We compare the efficacy of single immunotherapy with traditional platinum-based chemotherapy in a systematic review and meta-analysis to provide a reliable basis for clinicians. METHODS: Pubmed (Medline), Web of Science, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar will be searched for relevant randomised controlled trials, quasi- randomised controlled trials, and Hi-Q(high quality) prospective cohort trials published or unpublished in any language before March 1, 2021. Subgroup analysis will be performed in tumor pathological stage and ethnicity. INPLASY registration number: INPLASY2020110060. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: The results of this systematic review and meta-analysis will provide a basis for clinicians to formulate the best chemotherapy regimen for patients, as well as a research clue for clinical researchers in this field. The results of this study will expand the treatment options for thymic carcinoma, but due to the nature of the disease and intervention, large sample clinical trials are not abundant, so we will include some high-quality small sample trials, which may cause high heterogeneity. INPLASY REGISTRATION NUMBER: INPLASY2020110060.


Asunto(s)
Antineoplásicos/uso terapéutico , Inmunoterapia , Platino (Metal)/uso terapéutico , Timoma/terapia , Neoplasias del Timo/terapia , Humanos , Metaanálisis como Asunto , Metástasis de la Neoplasia , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como Asunto , Timoma/secundario , Neoplasias del Timo/patología
3.
Nat Commun ; 12(1): 801, 2021 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-33547324

RESUMEN

Most trials do not release interim summaries on efficacy and toxicity of the experimental treatments being tested, with this information only released to the public after the trial has ended. While early release of clinical trial data to physicians and patients can inform enrollment decision making, it may also affect key operating characteristics of the trial, statistical validity and trial duration. We investigate the public release of early efficacy and toxicity results, during ongoing clinical studies, to better inform patients about their enrollment options. We use simulation models of phase II glioblastoma (GBM) clinical trials in which early efficacy and toxicity estimates are periodically released accordingly to a pre-specified protocol. Patients can use the reported interim efficacy and toxicity information, with the support of physicians, to decide which trial to enroll in. We describe potential effects on various operating characteristics, including the study duration, selection bias and power.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/psicología , Drogas en Investigación/uso terapéutico , Glioblastoma/psicología , Difusión de la Información/métodos , Modelación Específica para el Paciente , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Ensayos Clínicos como Asunto , Toma de Decisiones , Glioblastoma/tratamiento farmacológico , Glioblastoma/mortalidad , Glioblastoma/patología , Humanos , Difusión de la Información/ética , Seguridad del Paciente , Selección de Paciente/ética , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
4.
Int J Nanomedicine ; 16: 683-700, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33536754

RESUMEN

Purpose: To develop an externally triggered rapid-release targeted system for treating ovarian cancer, gemcitabine (GMC) was entrapped into sonosensitive (SoS) folate (Fo)-modified liposomes (LPs). Methods: GMC-loaded LPs (GMC LPs), GMC-loaded Fo-targeted LPs (GMC-Fo LPs), and GMC-loaded Fo-targeted SoS LPs (GMC-SoS Fo LPs) were prepared utilizing a film-hydration technique and evaluated based on particle size, ζ-potential, and percentage entrapped drug. Cellular uptake of the fluorescent delivery systems in Fo-expressing ovarian cancer cells was quantified using flow cytometry. Finally, tumor-targeting ability, in vivo evaluation, and pharmacokinetic studies were performed. Results: GMC LPs, GMC-Fo LPs, and GMC-SoS Fo LPs were successfully prepared, with sizes of <120.3±2.4 nm, 39.7 mV ζ-potential, and 86.3%±1.84% entrapped drug. Cellular uptake of GMC-SoS Fo LPs improved 6.51-fold over GMC LPs (under ultrasonic irradiation - p<0.05). However, cellular uptake of GMC-Fo LPs improved just 1.24-fold over GMC LPs (p>0.05). Biodistribution study showed that of GMC concentration in tumors treated with GMC-SoS-Fo LPs (with ultrasound) improved 2.89-fold that of free GMC (p<0.05). In vivo, GMC-SoS Fo LPs showed the highest antiproliferative and antitumor action on ovarian cancer. Conclusion: These findings showed that externally triggered rapid-release SoS Fo-modified LPs are a promising system for delivering rapid-release drugs into tumors.


Asunto(s)
Desoxicitidina/análogos & derivados , Ácido Fólico/química , Ultrasonido , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Desoxicitidina/administración & dosificación , Desoxicitidina/sangre , Desoxicitidina/farmacocinética , Desoxicitidina/farmacología , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Endocitosis/efectos de los fármacos , Femenino , Humanos , Liposomas , Neoplasias Ováricas/sangre , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Tamaño de la Partícula , Ratas Sprague-Dawley , Distribución Tisular/efectos de los fármacos
5.
Medicine (Baltimore) ; 100(6): e24703, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33578607

RESUMEN

RATIONALE: The abnormal expression of B-cell lymphoma-2 (Bcl-2) family members is often associated with the progression of the disease. Bcl-2 inhibitors (eg, venetoclax) were first reported to inhibit the proliferation of malignant lymphocytes and have a significant effect on patients with chronic lymphoblastic leukemia, but research on myeloid tumors is relatively delayed. Venetoclax was approved in 2018 for the treatment of acute myeloid leukemia (AML) patients who were not suitable for high-dose chemotherapy. The approval of venetoclax is an advance in the treatment of hematological tumors. PATIENT CONCERNS: Here we report a 64-year-old male with an increased white blood cell (WBC) count (39.0 × 109/L) and lymphocyte count (30.6 × 109/L) on physical examination in July 2014. The patients were diagnosed with chronic lymphocytic leukemia (CLL) through bone marrow (BM) smears and immunophenotyping without any cytogenetic or molecular abnormalities. Chlorambucil was prescribed, WBC was stable between 15 × 109/L and 25 × 109/L in the past 6 years. He came to the hospital again in May 2020 and complained of fatigue for 2 weeks. WBC (16.7 × 109/L) and lymphocyte (14.76 × 109/L) counts were increased, hemoglobin (HGB) and platelet (PLT) were decreased in peripheral blood, which indicated the progression of the disease. DIAGNOSES: The patient was diagnosed as secondary AML after CLL based on the clinical and laboratory findings. INTERVENTIONS: He achieved a morphological complete remission in both AML and CLL without any adverse reactions after one course of venetoclax monotherapy. OUTCOMES: He received standard daunorubicin and cytarabine combined with venetoclax as consolidation therapy and is now ready for allogeneic-hematopoietic stem cell transplantation. LESSONS: Our case presents a challenge to traditional treatment. New drugs such as venetoclax have shown outstanding effects in this respect. High expression of Bcl-2 can identify the responders of venetoclax. These findings should be validated in future clinical trials. We fully believe that in the near future, the comprehensive use of targeted drugs with different mechanisms will not only improve the quality of life of patients, but also completely change the prognosis of patients with recurrent and refractory hematological malignancies.


Asunto(s)
Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/etiología , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/uso terapéutico , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Daunorrubicina/administración & dosificación , Daunorrubicina/uso terapéutico , Progresión de la Enfermedad , Trasplante de Células Madre Hematopoyéticas/normas , Humanos , Inmunofenotipificación/métodos , Leucemia Linfocítica Crónica de Células B/patología , Leucemia Mieloide Aguda/patología , Recuento de Leucocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Resultado del Tratamiento
6.
Gan To Kagaku Ryoho ; 48(2): 269-272, 2021 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-33597378

RESUMEN

A 67-year-old woman was admitted with melena. A colonoscopy detected a 50 mm submucosal tumor close to the dentate line. We diagnosed the rectal gastrointestinal stromal tumor by EUS-FNA. With the expectation of tumor shrinkage and strong hope of the patient, we started imatinib mesylate as neoadjuvant chemotherapy. A CT scan after 3 months after administration of imatinib mesylate showed the reduction of the size to 35 mm. We operated transanal endoscopic surgery considering the localization of the tumor. From histopathological findings, the tumor was low risk in the modified-Fletcher classification, and low risk in the Miettinen classification. Eight months after the operation, no recurrence was observed without further adjuvant chemotherapy. In this case, we were able to resect the tumor without injuring the film of tumor by operating transanal endoscopic surgery, because of tumor shrinkage with imatinib mesylate as neoadjuvant chemotherapy. I considered that using imatinib mesylate preoperatively was contributed to minimally invasive surgery.


Asunto(s)
Antineoplásicos , Tumores del Estroma Gastrointestinal , Neoplasias del Recto , Anciano , Antineoplásicos/uso terapéutico , Femenino , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Mesilato de Imatinib/uso terapéutico , Procedimientos Quirúrgicos Mínimamente Invasivos , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/cirugía , Recto
8.
Cells ; 10(2)2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33540625

RESUMEN

Since the beginning of the SARS-CoV-2(severe acute respiratory syndrome-coronavirus-2) pandemic, arace to develop a vaccine has been initiated, considering the massive and rather significant economic and healthcare hits that this virus has caused. The pathophysiology occurring following COVID-19(coronavirus disease-2019) infection has givenhints regarding the supportive and symptomatic treatments to establish for patients, as no specific anti-SARS-CoV-2 is available yet. Patient symptoms vary greatly and range from mild symptoms to severe fatal complications. Supportive treatments include antipyretics, antiviral therapies, different combinations of broad-spectrum antibiotics, hydroxychloroquine and plasma transfusion. Unfortunately, cancer patients are at higher risk of viral infection and more likely to develop serious complications due to their immunocompromised state, the fact that they are already administering multiple medications, as well as combined comorbidity compared to the general population. It may seem impossible to find a drug that possesses both potent antiviral and anticancer effects specifically against COVID-19 infection and its complications and the existing malignancy, respectively. Thymoquinone (TQ) is the most pharmacologically active ingredient in Nigella sativa seeds (black seeds); it is reported to have anticancer, anti-inflammatory and antioxidant effects in various settings. In this review, we will discuss the multiple effects of TQ specifically against COVID-19, its beneficial effects against COVID-19 pathophysiology and multiple-organ complications, its use as an adjuvant for supportive COVID-19 therapy and cancer therapy, and finally, its anticancer effects.


Asunto(s)
Antineoplásicos , Antivirales , Benzoquinonas , Reposicionamiento de Medicamentos , Neoplasias , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Benzoquinonas/farmacología , Benzoquinonas/uso terapéutico , /tratamiento farmacológico , Línea Celular Tumoral , Humanos , Ratones , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Ratas
9.
Adv Exp Med Biol ; 1295: 29-48, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33543454

RESUMEN

Tumor-homing peptides are widely used for improving tumor selectivity of anticancer drugs and imaging agents. The goal is to increase tumor uptake and reduce accumulation at nontarget sites. Here, we describe current approaches for tumor-homing peptide identification and validation, and provide comprehensive overview of classes of tumor-homing peptides undergoing preclinical and clinical development. We focus on unique mechanistic features and applications of a recently discovered class of tumor-homing peptides, tumor-penetrating C-end Rule (CendR) peptides, that can be used for tissue penetrative targeting of extravascular tumor tissue. Finally, we discuss unanswered questions and future directions in the field of development of peptide-guided smart drugs and imaging agents.


Asunto(s)
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Humanos , Neoplasias/tratamiento farmacológico , Péptidos/uso terapéutico
10.
Medicine (Baltimore) ; 100(3): e23956, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33545974

RESUMEN

BACKGROUND: The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of adjuvant targeted therapy by sunitinib combined with surgery in the treatment of advanced or metastatic renal cell carcinoma. METHODS: PubMed/Medline, Web of Science, Cochrane Library, ClinicalTrials.gov (http://www.ClinicalTrials.gov), China National Knowledge Infrastructure (CNKI) will be searched for clinical research articles related to the efficacy and safety of adjuvant therapy combined with surgery in the treatment of advanced and metastatic RCC. The identification, inclusion and exclusion flow charts will be conducted according to the PRISMA guidelines. The quality assessment will be done by Quadas-2 evaluation tool. Key parameters including OS in 10, 20, 30, and 40 months, PFS in 10, 20, and 30 months, objective response rate (ORR), stable disease (SD) rate, progressive disease (PD) rate, median OS and PFS, types of AEs and their occurrence rates, etc will be extracted. The evaluation of the efficacy and safety will be pooled by CMA. RESULTS: This systematic review will provide evidence on the efficacy and safety of adjuvant therapy by sunitinib combined with surgery in treating advanced and metastatic RCC. CONCLUSION: The study aims to generalize data concerning the response rate, OS, PFS and rates of adverse effects of the perioperative use of sunitinib in advanced and metastatic RCC patients. The evidence provided by this systematic review and meta-analysis will help guide the clinical decision making and enlighten the future management of advanced or metastatic RCC. REGISTRATION: This protocol has been registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY registration number: INPLASY2020110093; INPLASY DOI number: 10.37766/inplasy2020.11.0093 Available at: https://inplasy.com).


Asunto(s)
Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/cirugía , Quimioterapia Adyuvante/normas , Protocolos Clínicos , Antineoplásicos/uso terapéutico , Quimioterapia Adyuvante/métodos , Humanos , Metaanálisis como Asunto , Sunitinib/uso terapéutico , Revisiones Sistemáticas como Asunto
11.
Medicine (Baltimore) ; 100(3): e24068, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33546009

RESUMEN

ABSTRACT: Currently, the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is the standard therapy for metastatic pancreatic cancer. In recent years, FOLFIRINOX-based neoadjuvant therapy for locally advanced pancreatic cancer (LAPC) has been gaining an increasing amount of attention, owing to its ability to reduce disease stage and transform LAPC to borderline resectable or even resectable pancreatic cancer. Accordingly, we aimed to evaluate the efficacy of first-line FOLFIRINOX chemotherapy in patients with LAPC.We searched PubMed, Embase, and Cochrane Library from the time of establishment till January 1, 2020 and included studies focusing on LAPC patients who received FOLFIRINOX as first-line neoadjuvant treatment. The primary outcomes were: resection rate and radical (R0) resection rate while the secondary outcomes were: objective response rate, overall survival, progression-free survival, and rate of grade 3 to 4 adverse events. The meta package for R 3.6.2 was used for heterogeneity and publication bias testing.Twenty-one studies, including 653 patients with LAPC, were selected. After treatment with FOLFIRINOX, the resection rate was 26% (95% confidence interval [CI] = 20%-32%, I2 = 61%) and R0 resection rate was 88% (95% CI = 78%-95%, I2 = 62%). The response rate was 34% (95% CI = 25%-43%, I2 = 56%). The median overall survival and progression-free survival durations ranged from 10.0 to 32.7 months and 3.0 to 25.3 months, respectively. The observed grade 3 to 4 adverse events were neutropenia (20.0 per 100 patients, 95% CI = 14%-27%, I2 = 75%), febrile neutropenia (7.0 per 100 patients, 95% CI = 5%-9%, I2 = 42%), thrombocytopenia (6.0 per 100 patients, 95% CI = 5%-8%, I2 = 27%), nausea/vomiting (7.0 per 100 patients, 95% CI = 7%-12%, I2 = 76%), diarrhea (10.0 per 100 patients, 95% CI = 8%-12%, I2 = 38%), and fatigue (9.0 per 100 patients, 95% CI = 7%-11%, I2 = 43%).FOLFIRINOX-based neoadjuvant chemotherapy has the potential to improve the rates of resection, R0 resection, and median OS in LAPC. Our results require further validation in large, high-quality randomized controlled trials.


Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Neoadyuvante , Neoplasias Pancreáticas/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Humanos , Irinotecán/uso terapéutico , Leucovorina/uso terapéutico , Oxaliplatino/uso terapéutico , Neoplasias Pancreáticas/cirugía
12.
Medicine (Baltimore) ; 100(3): e24135, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33546025

RESUMEN

ABSTRACT: Proteins in S100 family exhibit different expressions patterns and perform different cytological functions, playing substantial roles in certain cancers, carcinogenesis, and disease progression. However, the expression and role of S100 family members in the prognosis of hepatocellular carcinoma (HCC) remains unclear. To investigate the effect of S100 family members for the prognosis of liver cancer, we assessed overall survival (OS) using a Kaplan-Meier plotter (KM plotter) in liver cancer patients with different situation. Our results showed that 15 members of the S100 family exhibited high levels of expression and these levels were correlated with OS in liver cancer patients. The higher expression of S100A5, S100A7, S100A7A, S100A12, S100Z, and S100G was reflected with better survival in liver cancer patients. However, worse prognosis was related to higher levels of expression of S100A2, S100A6, S100A8, S100A9, S100A10, S100A11, S10013, S100A14, and S100P. We then evaluated the prognostic values of S100 family members expression for evaluating different stages of AJCC-T, vascular invasion, alcohol consumption, and the presence of hepatitis virus in liver cancer patients. Lastly, we studied the prognostic values of S100 family members expression for patients after sorafenib treatment. In conclusion, our findings show that the proteins of S100 family members exhibit differential expression and may be useful as targets for liver cancer, facilitating novel diagnostic and therapeutic strategies in cancer.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Terapia Molecular Dirigida , Proteínas S100/metabolismo , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Sorafenib/uso terapéutico
13.
Adv Exp Med Biol ; 1295: 77-95, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33543456

RESUMEN

Nanomedicine has been a hot topic in the field of tumor therapy in the past few decades. Because of the enhanced permeability and retention effect (EPR effect), nanomedicine can passively yet selectively accumulate at tumor tissues. As a result, it can improve drug concentration in tumor tissues and reduce drug distribution in normal tissues, thereby contributing to enhanced antitumor effect and reduced adverse effects. However, the therapeutic efficacy of anticancer nanomedicine is not satisfactory in clinical settings. Therefore, how to improve the clinical therapeutic effect of nanomedicine has become an urgent problem. The grand challenges of nanomedicine lie in how to overcome various pathophysiological barriers and simultaneously kill cancer cells effectively in hypoxic tumor microenvironment (TME). To this end, the development of novel stimuli-responsive nanomedicine has become a new research hotspot. While a great deal of progress has been made in this direction and preclinical results report many different kinds of promising multifunctional smart nanomedicine, the design of these intelligent nanomedicines is often too complicated, the requirements for the preparation processes are strict, the cost is high, and the clinical translation is difficult. Thus, it is more practical to find solutions to promote the therapeutic efficacy of commercialized nanomedicines, for example, Doxil®, Oncaspar®, DaunoXome®, Abraxane®, to name a few. Increasing attention has been paid to the combination of modern advanced medical technology and nanomedicine for the treatment of various malignancies. Recently, we found that hyperbaric oxygen (HBO) therapy could enhance Doxil® antitumor efficacy. Inspired by this study, we further carried out researches on the combination of HBO therapy with other nanomedicines for various cancer therapies, and revealed that HBO therapy could significantly boost antitumor efficacy of nanomedicine-mediated photodynamic therapy and photothermal therapy in different kinds of tumors, including hepatocellular carcinoma, breast cancer, and gliomas. Our results implicate that HBO therapy might be a universal strategy to boost therapeutic efficacy of nanomedicine against hypoxic solid malignancies.


Asunto(s)
Antineoplásicos , Oxigenación Hiperbárica , Neoplasias , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Nanomedicina , Neoplasias/tratamiento farmacológico , Microambiente Tumoral
14.
Adv Exp Med Biol ; 1295: 271-299, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33543464

RESUMEN

Multiple studies about tumor biology have revealed the determinant role of the tumor microenvironment in cancer progression, resulting from the dynamic interactions between tumor cells and surrounding stromal cells within the extracellular matrix. This malignant microenvironment highly impacts the efficacy of anticancer nanoparticles by displaying drug resistance mechanisms, as well as intrinsic physical and biochemical barriers, which hamper their intratumoral accumulation and biological activity.Currently, two-dimensional cell cultures are used as the initial screening method in vitro for testing cytotoxic nanocarriers. However, this fails to mimic the tumor heterogeneity, as well as the three-dimensional tumor architecture and pathophysiological barriers, leading to an inaccurate pharmacological evaluation.Biomimetic 3D in vitro tumor models, on the other hand, are emerging as promising tools for more accurately assessing nanoparticle activity, owing to their ability to recapitulate certain features of the tumor microenvironment and thus provide mechanistic insights into nanocarrier intratumoral penetration and diffusion rates.Notwithstanding, in vivo validation of nanomedicines remains irreplaceable at the preclinical stage, and a vast variety of more advanced in vivo tumor models is currently available. Such complex animal models (e.g., genetically engineered mice and patient-derived xenografts) are capable of better predicting nanocarrier clinical efficiency, as they closely resemble the heterogeneity of the human tumor microenvironment.Herein, the development of physiologically more relevant in vitro and in vivo tumor models for the preclinical evaluation of anticancer nanoparticles will be discussed, as well as the current limitations and future challenges in clinical translation.


Asunto(s)
Antineoplásicos , Nanopartículas , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Nanomedicina , Esferoides Celulares , Microambiente Tumoral
15.
Nat Commun ; 12(1): 898, 2021 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-33563973

RESUMEN

Radiation sensitivity varies greatly between tissues. The transcription factor p53 mediates the response to radiation; however, the abundance of p53 protein does not correlate well with the extent of radiosensitivity across tissues. Given recent studies showing that the temporal dynamics of p53 influence the fate of cultured cells in response to irradiation, we set out to determine the dynamic behavior of p53 and its impact on radiation sensitivity in vivo. We find that radiosensitive tissues show prolonged p53 signaling after radiation, while more resistant tissues show transient p53 activation. Sustaining p53 using a small molecule (NMI801) that inhibits Mdm2, a negative regulator of p53, reduced viability in cell culture and suppressed tumor growth. Our work proposes a mechanism for the control of radiation sensitivity and suggests tools to alter the dynamics of p53 to enhance tumor clearance. Similar approaches can be used to enhance killing of cancer cells or reduce toxicity in normal tissues following genotoxic therapies.


Asunto(s)
Tolerancia a Radiación , Proteína p53 Supresora de Tumor/metabolismo , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Humanos , Ratones , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Unión Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-mdm2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Tolerancia a Radiación/efectos de los fármacos , Distribución Tisular/efectos de los fármacos , Carga Tumoral/efectos de los fármacos , Proteína p53 Supresora de Tumor/efectos de la radiación , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Medicine (Baltimore) ; 100(6): e24590, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33578558

RESUMEN

BACKGROUND: Lung cancer (LC), with the high incidence in malignant tumors in the world, and seriously affects people's lives and brings a great economic burden. Previous clinical studies on Shen-Ling-Bai-Zhu-San (SLBZS) combined with chemotherapy for the treatment of lung cancer have been increasing, but there are no systematic reviews. This study aims to systematically study the efficacy and safety of SLBZS combined with chemotherapy in the treatment of LC. METHODS: The Chinese and English databases will be searched by us for related documents, and the search time limit is January 2021. Databases including PubMed, Embase, Web of Science, the Cochrane Library, Chinese databases include China National Knowledge Infrastructure, Wanfang Data, ChongqingVIP Information Resource Integration Service Platform, China Biomedical Literature. The international clinical trial registration platform and the Chinese clinical trial registration platform will be searched by us to find ongoing or unpublished trials. After screening the literature based on inclusion and exclusion criteria, 2 researchers independently extracted data. The primary outcomes were the treatment efficiency. RevMan 5.3.5 software will be used for statistical analysis. The Recommendation, Assessment, Development, and Evaluation (GRADE) system will be used to evaluate the quality evidence of each result. RESULTS: This study will provide the latest evidence for the SLBZS combined with chemotherapy for LC. CONCLUSION: The efficacy and safety of SLBZS combined with chemotherapy for LC will be evaluated. UNIQUE INPLASY NUMBER: INPLASY202110025.


Asunto(s)
Carcinoma Broncogénico/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Humanos , Medicina China Tradicional , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto
17.
JAMA ; 325(7): 669-685, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33591350

RESUMEN

Importance: Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide with more than 1.85 million cases and 850 000 deaths annually. Of new colorectal cancer diagnoses, 20% of patients have metastatic disease at presentation and another 25% who present with localized disease will later develop metastases. Observations: Colorectal cancer is the third most common cause of cancer mortality for men and women in the United States, with 53 200 deaths projected in 2020. Among people diagnosed with metastatic colorectal cancer, approximately 70% to 75% of patients survive beyond 1 year, 30% to 35% beyond 3 years, and fewer than 20% beyond 5 years from diagnosis. The primary treatment for unresectable metastatic CRC is systemic therapy (cytotoxic chemotherapy, biologic therapy such as antibodies to cellular growth factors, immunotherapy, and their combinations.) Clinical trials completed in the past 5 years have demonstrated that tailoring treatment to the molecular and pathologic features of the tumor improves overall survival. Genomic profiling to detect somatic variants is important because it identifies the treatments that may be effective. For the 50% of patients with metastatic CRC with KRAS/NRAS/BRAF wild-type tumors, cetuximab and panitumumab (monoclonal antibodies to the epithelial growth factor receptor [EGFR]), in combination with chemotherapy, can extend median survival by 2 to 4 months compared with chemotherapy alone. However, for the 35% to 40% of patients with KRAS or NRAS sequence variations (formerly termed mutations), effective targeted therapies are not yet available. For the 5% to 10% with BRAF V600E sequence variations, targeted combination therapy with BRAF and EGFR inhibitors extended overall survival to 9.3 months, compared to 5.9 months for those receiving standard chemotherapy. For the 5% with microsatellite instability (the presence of numerous insertions or deletions at repetitive DNA units) or mismatch repair deficiency, immunotherapy may be used in the first or subsequent line and has improved treatment outcomes with a median overall survival of 31.4 months in previously treated patients. Conclusions and Relevance: Advances in molecular profiling of metastatic CRC facilitate the ability to direct treatments to the biologic features of the tumor for specific patient subsets. Although cures remain uncommon, more patients can anticipate extended survival. Genomic profiling allows treatment selection so that more patients derive benefit and fewer are exposed to toxicity from ineffective therapies.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/secundario , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Femenino , Perfil Genético , Humanos , Quimioterapia de Mantención , Masculino , Técnicas de Diagnóstico Molecular , Pronóstico , Tasa de Supervivencia
18.
Zhonghua Zhong Liu Za Zhi ; 43(2): 218-223, 2021 Feb 23.
Artículo en Chino | MEDLINE | ID: mdl-33601488

RESUMEN

Objective: To explore the latest progress of oncology drug clinical trials in China under COVID-19, as well as to provide decision-making evidence for related stakeholders. Research progress of oncology drug trials and approved cancer drugs in China in 2020 were systematically summarized and compared with 2019. Methods: Information Disclosure Platform for Drug Clinical Studies and China Food and Drug Administration Query System for Domestic and Imported Drug were searched for registered clinical trials and approved oncology drugs, respectively. The trial scope, stage, drug type, effect and mechanism of domestic and global pharmaceutical enterprises were compared between 2019 and 2020. Results: A total of 722 cancer drug trials registered in China in 2020, with an annual growth rate of 52.3%, accounting for 28.3% of all registered trials. Among them, 603 (83.5%) trials were initiated by domestic pharmaceutical enterprises, and 105 (14.5%) were international multicenter trials, phase I trials accounted for 44.5%. For all those trials, there were 458 cancer drug varieties, with an annual growth rate of 36.7%, and 361 (85.8%) were developed by domestic enterprises. Most of the investigational products were therapeutic innovative drugs (77.1%), major in tumor treatment (92.8%). In terms of mechanism, targeted drugs were the most popular, accounting for 76.6%, and programmed cell death-1 (PD-1) and epithelial growth factor receptor (EGFR) were the most common targets. In addition, there were 19 anticancer drugs from 17 companies approved in China in 2019, with 10 drugs from domestic companies. Lung cancer and breast cancer are the most common indications for both registered trials and marketed drugs. No statistically significant differences were found between 2020 and 2019 in terms of the distribution of trial sponsor, scope and stage, as well as the distribution of drug type, effect and mechanism (P>0.05). Conclusions: During the Covid-19 epidemic period, clinical trials of oncology drugs in China progress smoothly and maintain a high growth rate. Series of innovative products obtained by domestic enterprises in 2020 is the main driving force of development of oncology drug clinical trials in China.


Asunto(s)
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapéutico , China , Ensayos Clínicos como Asunto , Humanos , Oncología Médica , Neoplasias/tratamiento farmacológico , Estados Unidos
19.
BMJ Case Rep ; 14(2)2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33526533

RESUMEN

Implantable venous access devices are routinely used, but they are not without complications. A 4-year-old male child with B cell acute lymphoblastic leukaemia was planned for chemotherapy. Chemo port was accessed through the right internal jugular vein. Check X-ray was done, which showed the correct placement of the catheter. Two months after chemo port insertion when the patient underwent chemotherapy, he developed a fever and he was started on intravenous antibiotics. On the next two admissions, the patient had a fever with chamber site oedema for which culture was done, which revealed Pseudomonas and Candida, which responded to antibiotic and antifungal therapies. In the successive admission, the patient had immediate local oedema on injecting chemotherapy. Exploration was done, which revealed chamber base perforation. It is an infrequent complication and has been reported in only three studies.


Asunto(s)
Infecciones Relacionadas con Catéteres , Falla de Equipo , Extravasación de Materiales Terapéuticos y Diagnósticos , Dispositivos de Acceso Vascular , Antineoplásicos/uso terapéutico , Preescolar , Remoción de Dispositivos , Humanos , Quimioterapia de Mantención , Masculino , Metotrexato/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico
20.
Medicine (Baltimore) ; 100(7): e24758, 2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33607823

RESUMEN

BACKGROUND: Malignant pleural effusion (MPE) is one of the commonest causes of an exudative pleural effusion. Breathlessness, dyspnea and other symptoms often seriously distress and affect the quality of life. The external application of mirabilite and rhubarb (EAMR) combined with intrathoracic infusion of cisplatin, as an alternative treatment for MPE, is popular in China. The study aims to assess its effectiveness and safety combined with intrathoracic chemotherapy. METHODS: This study is a prospective, randomized controlled clinical trial. Patient visits were performed at baseline and days 14 and 28 after treatment. Clinical outcomes were measured after chest drain placement using the criterion of efficacy refer to WHO standard, and QLQ-C30 questionnaire. RESULTS: Database records of patients treated in our institution for MPE between October, 2016 and March, 2019. The study included 84 eligible patients. They were categorized with a randomization schedule into treatment group (N = 42) and control group (N = 42). There is statistical significance in the comparison of the total effective rate between these 2 groups (66.67% vs 54.76%, P < .05). Furthermore, there is statistical significance in the comparison of items of Physical (1.95 ±â€Š0.50 vs 2.19 ±â€Š0.58%, P < .05), Pain (1.98 ±â€Š0.42 vs 2.07 ±â€Š0.32, P < .05), and Global Health (1.23 ±â€Š0.64 vs 1.13 ±â€Š0.23%, P < .05) between these 2 groups. None of the patients had adverse reactions such as skin allergy and chest tightness. CONCLUSIONS: The total effective rate of treatment group using extra external application of mirabilite rhubarb powder is significantly higher than that of control group. The improvement of patients' clinical symptoms is greater in treatment group and no adverse reactions is found. Therefore, external application of mirabilite and rhubarb combined with intrathoracic infusion of cisplatin is an effective method for the treatment of MPE, which is worth popularizing.


Asunto(s)
Catárticos/administración & dosificación , Derrame Pleural Maligno/tratamiento farmacológico , Rheum/efectos adversos , Sulfatos/administración & dosificación , Administración Cutánea , Adulto , Anciano , Antineoplásicos/uso terapéutico , Cisplatino/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
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