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1.
Int J Hyperthermia ; 38(1): 1013-1022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34192990

RESUMO

PURPOSE: We aimed to determine the effects and possible mechanisms of hyperthermic intraperitoneal chemotherapy (HIPEC) in targeting ovarian cancer stem-like cells (CSCs). METHODS: Murine ovarian cancer cell lines presenting CSC surface markers were grown intraperitoneally in both immunocompetent and immunodeficient mice, which were then treated by intraperitoneal hyperthermia with the chemotherapeutic agents: paclitaxel and cisplatin. Tumor growth was measured by non-invasive luminescent imaging. Intraperitoneal immune cells, such as CD4+, CD8+ T cells, macrophages, and dendritic cells, were evaluated through flow cytometry analysis. RESULTS: Combined hyperthermia and chemotherapy exhibited an efficient therapeutic effect in the immunocompetent mice. However, a similar effect was not observed in the immunodeficient mice. Intraperitoneal hyperthermia increased the number of Intraperitoneal macrophages and dendritic cells that were lost due to chemotherapy. Compared with ovarian cancer bulk cells, CSCs were more susceptible to phagocytosis by macrophages. CONCLUSION: We demonstrated that the superior therapeutic efficacy and reduced proportion of CSCs associated with intraperitoneal hyperthermic chemotherapy were immune-related. Hyperthermia recruits the phagocytes that target surviving CSCs after chemotherapy. These results provide a novel mechanism for the efficacy of HIPEC in treating ovarian cancer.


Assuntos
Hipertermia Induzida , Neoplasias Ovarianas , Animais , Linfócitos T CD8-Positivos , Terapia Combinada , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Camundongos , Células-Tronco Neoplásicas , Neoplasias Ovarianas/tratamento farmacológico
2.
Int J Nanomedicine ; 16: 4351-4369, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234430

RESUMO

Purpose: Multifunctional nanoparticles with targeted therapeutic function and diagnostic-imaging are of great interest in the domain of precision therapy. NIR laser responsive nanoparticles (PLGA-PEG-FA encapsulating Bi2S3, PFP, and Dox (designed as FBPD NPs)) are synthesized for ovarian cancer targeted combination therapy with CT/PA dual-modal imaging guidance (PA: photoacoustic; CT: X-ray computed tomography). Methods and Results: The FBPD NPS prepared by the double emulsification method revealed excellent dispersity, great stability, outstanding optical properties. The temperature of FBPD NPs increased rapidly after laser irradiation, inducing liquid-to-gas conversion of perfluoropentane (PFP), and promoting the release of Dox up to 86.7%. These FBPD NPs demonstrated their outstanding imaging capability for both PA and CT imaging both in vitro and in vivo, providing the potential for therapeutic guidance and monitoring. Assisted by folic acid, these nanoparticles could highly enrich in ovarian tumor tissue and the accumulation peaked at 3 h after intravenous administration. The desirable photothermal-conversion efficiency of the nanoparticles combined with chemotherapy achieved highly efficient therapy, which was demonstrated both in vitro and in vivo. Conclusion: We successfully constructed multifunctional theranostic FBPD NPs for highly efficient PTT/chemotherapy combined therapy with dual CT/PA imaging guidance/monitoring. The unique nanoparticles with multiple abilities pave an emerging way toward precise treatment of ovarian cancer.


Assuntos
Raios Infravermelhos , Lasers , Nanopartículas/uso terapêutico , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Técnicas Fotoacústicas , Tomografia Computadorizada por Raios X , Animais , Terapia Combinada , Feminino , Ácido Fólico/química , Humanos , Nanopartículas/química , Poliésteres/química , Polietilenoglicóis/química
3.
Int J Mol Sci ; 22(12)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34202978

RESUMO

Niemann-Pick type C (NPC) disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol in the late endo-lysosomal system of cells. Progressive neurological deterioration and the onset of symptoms, such as ataxia, seizures, cognitive decline, and severe dementia, are pathognomonic features of the disease. In addition, different pathological similarities, including degeneration of hippocampal and cortical neurons, hyperphosphorylated tau, and neurofibrillary tangle formation, have been identified between NPC disease and other neurodegenerative pathologies. However, the underlying pathophysiological mechanisms are not yet well understood, and even a real cure to counteract neurodegeneration has not been identified. Therefore, the combination of current pharmacological therapies, represented by miglustat and cyclodextrin, and non-pharmacological approaches, such as physical exercise and appropriate diet, could represent a strategy to improve the quality of life of NPC patients. Based on this evidence, in our review we focused on the neurodegenerative aspects of NPC disease, summarizing the current knowledge on the molecular and biochemical mechanisms responsible for cognitive impairment, and suggesting physical exercise and nutritional treatments as additional non-pharmacologic approaches to reduce the progression and neurodegenerative course of NPC disease.


Assuntos
Suscetibilidade a Doenças , Degeneração Neural/etiologia , Doença de Niemann-Pick Tipo C/etiologia , Doença de Niemann-Pick Tipo C/terapia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Tomada de Decisão Clínica , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Humanos , Degeneração Neural/diagnóstico , Doença de Niemann-Pick Tipo C/diagnóstico , Doença de Niemann-Pick Tipo C/tratamento farmacológico , Resultado do Tratamento
4.
JSLS ; 25(2)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248343

RESUMO

Introduction: Simultaneous robot assisted colon and liver resections are being performed more frequently at present due to the expanded adoption of the robotic platform for surgical management of metastatic colon cancer. However, this approach has not been studied in detail with only case series available in the literature. The aim of this systematic review was to evaluate the current body of evidence on the feasibility of performing simultaneous robotic colon and liver resections. Methods: A systematic review was performed through PubMed to identify relevant articles describing simultaneous colon and liver resections for metastatic colon cancer. Results: A total of 28 patients underwent simultaneous resections robotically with an average operative time of 420.3 minutes and average blood loss of 275.6 ml. Postoperative stay was 8.6 days on average with all cases achieving negative surgical margins. Conclusions: Robotic simultaneous resection of colorectal cancer with liver metastases is technically feasible and seems oncologically equivalent to open or laparoscopic surgery. Further studies are urgently needed to assess benefits of robotic surgery in the patient population.


Assuntos
Colectomia/métodos , Neoplasias do Colo/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Neoplasias do Colo/patologia , Terapia Combinada , Humanos , Laparoscopia/métodos , Neoplasias Hepáticas/secundário , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Duração da Cirurgia
5.
BMC Infect Dis ; 21(1): 636, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215207

RESUMO

BACKGROUND: This study aimed to investigate the epidemiology, microbiology, and risk factors associated with mortality and multi-drug resistance bacterial bloodstream infections (BSIs) among adult cancer patients in Shiraz, Iran. We also report a four-year trend of antimicrobial resistance patterns of BSIs. METHODS: We conducted a retrospective study at a referral oncology hospital from July 2015 to August 2019, which included all adults with confirmed BSI. RESULTS: 2393 blood cultures tested during the four-year study period; 414 positive cultures were included. The mean age of our patients was 47.57 ± 17.46 years old. Central Line-Associated BSI (CLABSI) was more common in solid tumors than patients with hematological malignancies. Gram-negative (GN) bacteria were more detected (63.3%, 262) than gram-positive bacteria (36.7%, 152). Escherichia coli was the most common gram-negative organism (123/262, 47%), followed by Pseudomonas spp. (82/262, 31%) and Klebsiella pneumoniae (38/262, 14.5%). Coagulase-negative staphylococci (CoNS) was the most frequently isolated pathogen among gram-positive bacteria (83/152, 54.6%). Acinetobacter spp., Pseudomonas spp., E. coli, and K. pneumoniae were the most common Extended-Spectrum Beta-Lactamase (ESBL) producers (100, 96.2, 66.7%, and 60.7, respectively). Acinetobacter spp., Pseudomonas spp., Enterobacter spp., E. coli, and K. pneumoniae were the most common carbapenem-resistant (CR) isolates (77.8, 70.7, 33.3, 24.4, and 13.2%, respectively). Out of 257 Enterobacterales and non-fermenter gram-negative BSIs, 39.3% (101/257) were carbapenem-resistant. Although the incidence of multi-drug resistance (MDR) gram-negative BSI increased annually during 2015-2018, the mortality rate of gram-negative BSI remains unchanged at about 20% (p-value = 0.55); however, the mortality rate was significantly greater (35.4%) in those with resistant gram-positive BSI (p-value = 0.001). The overall mortality rate was 21.5%. Early (7-day mortality) and late mortality rate (30-day mortality) were 10 and 3.4%, respectively. CONCLUSIONS: The emergence of MDR gram-negative BSI is a significant healthcare problem in oncology centers. The high proportion of the most frequently isolated pathogens were CR and ESBL-producing Enterobacterales and Pseudomonas spp. We have few effective choices against MDRGN BSI, especially in high-risk cancer patients, which necessitate newer treatment options.


Assuntos
Bacteriemia/complicações , Bactérias/patogenicidade , Farmacorresistência Bacteriana , Resistência a Múltiplos Medicamentos , Neoplasias/mortalidade , Sepse/complicações , Bacteriemia/microbiologia , Bactérias/isolamento & purificação , Terapia Combinada , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/etiologia , Neoplasias/patologia , Estudos Retrospectivos , Fatores de Risco , Sepse/microbiologia
6.
World J Gastroenterol ; 27(24): 3630-3642, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34239274

RESUMO

BACKGROUND: Liver transplantation (LT) presents a curative treatment option in patients with early stage hepatocellular carcinoma (HCC) who are not eligible for resection or ablation therapy. Due to a risk of up 30% for waitlist drop-out upon tumor progression, bridging therapies are used to halt tumor growth. Transarterial chemoembolization (TACE) and less commonly stereotactic body radiation therapy (SBRT) or a combination of TACE and SBRT, are used as bridging therapies in LT. However, it remains unclear if one of those treatment options is superior. The analysis of explant livers after transplantation provides the unique opportunity to investigate treatment response by histopathology. AIM: To analyze histopathological response to a combination of TACE and SBRT in HCC in comparison to TACE or SBRT alone. METHODS: In this multicenter retrospective study, 27 patients who received liver transplantation for HCC were analyzed. Patients received either TACE or SBRT alone, or a combination of TACE and SBRT as bridging therapy to liver transplantation. Liver explants of all patients who received at least one TACE and/or SBRT were analyzed for the presence of residual vital tumor tissue by histopathology to assess differences in treatment response to bridging therapies. Statistical analysis was performed using Fisher-Freeman-Halton exact test, Kruskal-Wallis and Mann-Whitney-U tests. RESULTS: Fourteen patients received TACE only, four patients SBRT only, and nine patients a combination therapy of TACE and SBRT. There were no significant differences between groups regarding age, sex, etiology of underlying liver disease or number and size of tumor lesions. Strikingly, analysis of liver explants revealed that almost all patients in the TACE and SBRT combination group (8/9, 89%) showed no residual vital tumor tissue by histopathology, whereas TACE or SBRT alone resulted in significantly lower rates of complete histopathological response (0/14, 0% and 1/4, 25%, respectively, P value < 0.001). CONCLUSION: Our data suggests that a combination of TACE and SBRT increases the rate of complete histopathological response compared to TACE or SBRT alone in bridging to liver transplantation.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Radiocirurgia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Humanos , Neoplasias Hepáticas/terapia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
7.
Drug Deliv ; 28(1): 1496-1500, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34259091

RESUMO

COVID-19 can cause serious respiratory complications resulting in the need for invasive ventilatory support and concurrent aerosol therapy. Aerosol therapy is considered a high risk procedure for the transmission of patient derived infectious aerosol droplets. Critical-care workers are considered to be at a high risk of inhaling such infectious droplets. The objective of this work was to use noninvasive optical methods to visualize the potential release of aerosol droplets during aerosol therapy in a model of an invasively ventilated adult patient. The noninvasive Schlieren imaging technique was used to visualize the movement of air and aerosol. Three different aerosol delivery devices: (i) a pressurized metered dose inhaler (pMDI), (ii) a compressed air driven jet nebulizer (JN), and (iii) a vibrating mesh nebulizer (VMN), were used to deliver an aerosolized therapeutic at two different positions: (i) on the inspiratory limb at the wye and (ii) on the patient side of the wye, between the wye and endotracheal tube, to a simulated intubated adult patient. Irrespective of position, there was a significant release of air and aerosol from the ventilator circuit during aerosol delivery with the pMDI and the compressed air driven JN. There was no such release when aerosol therapy was delivered with a closed-circuit VMN. Selection of aerosol delivery device is a major determining factor in the release of infectious patient derived bioaerosol from an invasively mechanically ventilated patient receiving aerosol therapy.


Assuntos
Aerossóis , COVID-19 , Transmissão de Doença Infecciosa/prevenção & controle , Inaladores Dosimetrados , Nebulizadores e Vaporizadores , Respiração Artificial/métodos , Terapia Respiratória , Aerossóis/administração & dosagem , Aerossóis/efeitos adversos , COVID-19/fisiopatologia , COVID-19/terapia , COVID-19/transmissão , Terapia Combinada , Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/normas , Humanos , Exposição Ocupacional/prevenção & controle , Projetos de Pesquisa , Terapia Respiratória/efeitos adversos , Terapia Respiratória/instrumentação , Terapia Respiratória/métodos , Gestão de Riscos , SARS-CoV-2
8.
J Coll Physicians Surg Pak ; 30(7): 858-860, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34271793

RESUMO

Radical surgery to achieve optimal cytoreduction in locally advanced caecal cancer may dictate femoral or sciatic nerve resection, especially in cases with pelvic side-wall involvement. In such a situation, gait disturbance is inevitable. A 61-year male with a new-onset right leg limping due to locally advanced right colon carcinoma underwent cytoreductive surgery (CRS) with partial resection of right pelvic side- wall, and hyperthermic intraperitoneal chemotherapy (HIPEC). During the operation, we aimed to preserve both the sciatic and femoral nerves to prevent further deterioration of his right leg limping postoperatively. However, we did not compromise the principles of radical surgery and all tumoral implants around femoral vessels and nerves were removed. Completeness of cytoreduction score was zero (CC0). The resection of all macroscopic disease is the main goal of CRS, but as seen in our case with tumor-related walking difficulty, nerve-sparing CRS and HIPEC may prevent further deterioration of the situation. Key Words: Cytoreductive surgery, Hyperthermic intraperitoneal chemotherapy, Sciatic nerve, Femoral nerve, Caecal cancer.


Assuntos
Neoplasias do Ceco , Hipertermia Induzida , Neoplasias Peritoneais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Marcha , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Perna (Membro) , Masculino , Neoplasias Peritoneais/terapia , Taxa de Sobrevida
9.
Nat Commun ; 12(1): 4299, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262038

RESUMO

Radiofrequency ablation (RFA) is clinically adopted to destruct solid tumors, but is often incapable of completely ablating large tumors and those with multiple metastatic sites. Here we develop a CaCO3-assisted double emulsion method to encapsulate lipoxidase and hemin with poly(lactic-co-glycolic acid) (PLGA) to enhance RFA. We show the HLCaP nanoreactors (NRs) with pH-dependent catalytic capacity can continuously produce cytotoxic lipid radicals via the lipid peroxidation chain reaction using cancer cell debris as the fuel. Upon being fixed inside the residual tumors post RFA, HLCaP NRs exhibit a suppression effect on residual tumors in mice and rabbits by triggering ferroptosis. Moreover, treatment with HLCaP NRs post RFA can prime antitumor immunity to effectively suppress the growth of both residual and metastatic tumors, also in combination with immune checkpoint blockade. This work highlights that tumor-debris-fueled nanoreactors can benefit RFA by inhibiting tumor recurrence and preventing tumor metastasis.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Nanomedicina/métodos , Neoplasias/terapia , Ablação por Radiofrequência , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Animais , Carbonato de Cálcio/química , Carbonato de Cálcio/uso terapêutico , Catálise , Linhagem Celular Tumoral , Terapia Combinada , Ferroptose/efeitos dos fármacos , Hemina/química , Hemina/uso terapêutico , Humanos , Concentração de Íons de Hidrogênio , Inibidores de Checkpoint Imunológico/uso terapêutico , Morte Celular Imunogênica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoxigenase/química , Lipoxigenase/uso terapêutico , Camundongos , Metástase Neoplásica , Neoplasia Residual , Neoplasias/imunologia , Neoplasias/patologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/uso terapêutico , Coelhos
11.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202537

RESUMO

The liver is an organ with impressive regenerative potential and has been shown to heal sizable portions after their removal. However, certain diseases can overstimulate its potential to self-heal and cause excessive cellular matrix and collagen buildup. Decompensation of liver fibrosis leads to cirrhosis, a buildup of fibrotic ECM that impedes the liver's ability to efficiently exchange fluid. This review summarizes the complex immunological activities in different liver diseases, and how failure to maintain liver homeostasis leads to progressive fibrotic tissue development. We also discuss a variety of pathologies that lead to liver cirrhosis, such as alcoholic liver disease and chronic hepatitis B virus (HBV). Mesenchymal stem cells are widely studied for their potential in tissue replacement and engineering. Herein, we discuss the potential of MSCs to regulate immune response and alter the disease state. Substantial efforts have been performed in preclinical animal testing, showing promising results following inhibition of host immunity. Finally, we outline the current state of clinical trials with mesenchymal stem cells and other cellular and non-cellular therapies as they relate to the detection and treatment of liver cirrhosis.


Assuntos
Suscetibilidade a Doenças , Hepatopatias/etiologia , Hepatopatias/metabolismo , Animais , Biomarcadores , Terapia Combinada , Gerenciamento Clínico , Progressão da Doença , Suscetibilidade a Doenças/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Hepatopatias/diagnóstico , Hepatopatias/terapia , Pesquisa Médica Translacional
12.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202897

RESUMO

Osteonecrosis of the femoral head (ONFH) is a debilitating disease with major social and economic impacts. It frequently affects relatively young adults and has a predilection for rapid progression to femoral head collapse and end-stage hip arthritis. If not diagnosed and treated properly in the early stages, ONFH has devastating consequences and leads to mandatory total hip arthroplasty. The pathophysiology of non-traumatic ONFH is very complex and not fully understood. While multiple risk factors have been associated with secondary ONFH, there are still many cases in which a clear etiology cannot be established. Recognition of the prothrombotic state as part of the etiopathogeny of primary ONFH provides an opportunity for early medical intervention, with implications for both prophylaxis and therapy aimed at slowing or stopping the progression of the disease. Hereditary thrombophilia and hypofibrinolysis are associated with thrombotic occlusion of bone vessels. Anticoagulant treatment can change the natural course of the disease and improve patients' quality of life. The present work focused on highlighting the association between hereditary thrombophilia/hypofibrinolysis states and ONFH, emphasizing the importance of identifying this condition. We have also provided strong arguments to support the efficiency and safety of anticoagulant treatment in the early stages of the disease, encouraging etiological diagnosis and prompt therapeutic intervention. In the era of direct oral anticoagulants, new therapeutic options have become available, enabling better long-term compliance.


Assuntos
Suscetibilidade a Doenças , Necrose da Cabeça do Fêmur/etiologia , Trombofilia/sangue , Trombofilia/complicações , Animais , Biomarcadores , Transtornos Herdados da Coagulação Sanguínea/sangue , Transtornos Herdados da Coagulação Sanguínea/complicações , Transtornos Herdados da Coagulação Sanguínea/etiologia , Terapia Combinada , Gerenciamento Clínico , Necrose da Cabeça do Fêmur/terapia , Predisposição Genética para Doença , Humanos , Trombofilia/etiologia , Resultado do Tratamento
13.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209535

RESUMO

Epilepsy can be both a primary pathology and a secondary effect of many neurological conditions. Many papers show that neuroinflammation is a product of epilepsy, and that in pathological conditions characterized by neuroinflammation, there is a higher probability to develop epilepsy. However, the bidirectional mechanism of the reciprocal interaction between epilepsy and neuroinflammation remains to be fully understood. Here, we attempt to explore and discuss the relationship between epilepsy and inflammation in some paradigmatic neurological and systemic disorders associated with epilepsy. In particular, we have chosen one representative form of epilepsy for each one of its actual known etiologies. A better understanding of the mechanistic link between neuroinflammation and epilepsy would be important to improve subject-based therapies, both for prophylaxis and for the treatment of epilepsy.


Assuntos
Suscetibilidade a Doenças , Epilepsia/etiologia , Inflamação/complicações , Animais , Biomarcadores , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/patologia , Terapia Combinada , Gerenciamento Clínico , Epilepsia/diagnóstico , Epilepsia/metabolismo , Epilepsia/terapia , Predisposição Genética para Doença , Humanos , Inflamação/etiologia , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/patologia , Avaliação de Sintomas , Resultado do Tratamento
14.
J Clin Neurosci ; 90: 39-47, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34275579

RESUMO

The optimal timing of adjuvant radiochemotherapy (RCT) in glioblastoma (GBM) patients remains unknown and the paradigm of 'the sooner, the better' has been challenged by many recent publications. In this study, we present unique data on the outcomes of patients with significant treatment delays. The study group consisted of 346 GBM patients (median age 56.8 years) who received surgical treatment (total or subtotal resection) and then underwent adjuvant concurrent RCT at one institution. The main endpoint was overall survival (OS). The Univariate and multivariate Cox Proportional-Hazard Model, log-rank test, and Kaplan-Meier method were used for the analysis. The median OS was 18.7 months and the 5-year overall survival was 8.5%. The median time interval from surgery to RCT was 9.8 weeks. The Cox regression showed that the time interval had no statistically significant impact on OS both in uni- and multivariate analysis. The explorative analysis suggested a positive trend for improved survival for patients in the 1st quartile of the time interval, especially for patients with residual disease or local recurrence prior to RCT, However, considering the 6.9 weeks median interval in the 1st quartile, this subgroup should still be regarded as 'moderate delay' compared with other literature data. The results indicate that the time interval is not a clear prognostic factor in the treatment of GBM. Prospective trials are highly warranted, as data suggest that moderate delays in the initiation of adjuvant treatment might be associated with survival benefit.


Assuntos
Neoplasias Encefálicas/terapia , Quimiorradioterapia Adjuvante/métodos , Glioblastoma/terapia , Procedimentos Neurocirúrgicos/métodos , Tempo para o Tratamento , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Terapia Combinada/métodos , Feminino , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Modelos de Riscos Proporcionais
15.
Med Sci Monit ; 27: e933973, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34276042

RESUMO

Vaccinated, non-vaccinated, and immunosuppressed individuals will continue to be infected with SARS-CoV-2. Therefore, there is a priority to develop treatments that reduce the severity of COVID-19 in patients who require hospital admission. Interleukin-6 (IL-6) is a proinflammatory cytokine. In 2011, a humanized monoclonal antibody to the IL-6 receptor (IL-6R), tocilizumab, was approved by the US Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis, and Castleman's disease. In 2017, tocilizumab was approved to treat chimeric antigen receptor (CAR) T-cell therapy-induced cytokine release syndrome (CRS). In 2021, the results of the REMAP-CAP clinical trial (NCT02735707) and the COVID-19 Therapy (RECOVERY) clinical trial (NCT04381936) supported FDA Emergency Use Authorization (EUA) for tocilizumab to treat hospitalized patients with moderate and severe COVID-19. Monoclonal antibodies are currently in clinical development or undergoing clinical trials to treat COVID-19. Further clinical trials will provide safety and efficacy data on targeting IL-6 and IL-6R and provide rationales for more personalized combination treatments to control the systemic effects of SARS-CoV-2 infection in hospitalized patients with moderate and severe COVID-19. This Editorial aims to present the background to the recent authorization of tocilizumab, a humanized therapeutic monoclonal antibody to the IL-6 receptor (IL-6R), for hospitalized patients with moderate and severe COVID-19 and future combination therapies.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/terapia , Interleucina-6/imunologia , Terapia Combinada , Humanos
16.
Int J Nanomedicine ; 16: 4597-4614, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267515

RESUMO

Malignant gliomas (MGs) are the most common and devastating primary brain tumor. At present, surgical interventions, radiotherapy, and chemotherapy are only marginally effective in prolonging the life expectancy of patients with MGs. Inherent heterogeneity, aggressive invasion and infiltration, intact physical barriers, and the numerous mechanisms underlying chemotherapy and radiotherapy resistance contribute to the poor prognosis for patients with MGs. Various studies have investigated methods to overcome these obstacles in MG treatment. In this review, we address difficulties in MG treatment and focus on promising polymeric local drug delivery systems. In contrast to most local delivery systems, which are directly implanted into the residual cavity after intratumoral injection or the surgical removal of a tumor, some rapidly developing and promising nanotechnological methods-including surface-decorated nanoparticles, magnetic nanoparticles, and focused ultrasound assist transport-are administered through (systemic) intravascular injection. We also discuss further synergistic and multimodal strategies for heightening therapeutic efficacy. Finally, we outline the challenges and therapeutic potential of these polymeric drug delivery systems.


Assuntos
Portadores de Fármacos , Glioma/tratamento farmacológico , Polímeros , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Terapia Combinada , Portadores de Fármacos/química , Humanos , Polímeros/química
17.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208592

RESUMO

Mitochondrial DNA depletion and multiple deletions syndromes (MDDS) constitute a group of mitochondrial diseases defined by dysfunctional mitochondrial DNA (mtDNA) replication and maintenance. As is the case for many other mitochondrial diseases, the options for the treatment of these disorders are rather limited today. Some aggressive treatments such as liver transplantation or allogeneic stem cell transplantation are among the few available options for patients with some forms of MDDS. However, in recent years, significant advances in our knowledge of the biochemical pathomechanisms accounting for dysfunctional mtDNA replication have been achieved, which has opened new prospects for the treatment of these often fatal diseases. Current strategies under investigation to treat MDDS range from small molecule substrate enhancement approaches to more complex treatments, such as lentiviral or adenoassociated vector-mediated gene therapy. Some of these experimental therapies have already reached the clinical phase with very promising results, however, they are hampered by the fact that these are all rare disorders and so the patient recruitment potential for clinical trials is very limited.


Assuntos
DNA Mitocondrial , Mitocôndrias/genética , Doenças Mitocondriais/etiologia , Doenças Mitocondriais/terapia , Animais , Terapia Combinada , Replicação do DNA , Gerenciamento Clínico , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Humanos , Mitocôndrias/metabolismo , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Mutação
18.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208697

RESUMO

Traditional antimicrobial therapies for periodontitis (PD) have long focused on non-selective and direct approaches. Professional cleaning of the subgingival biofilm by instrumentation of dental root surfaces, known as scaling and root planning (SRP), is the mainstay of periodontal therapy and is indisputably effective. Non-physical approaches used as adjuncts to SRP, such as chemical and biological agents, will be the focus of this review. In this regard, traditional agents such as oral antiseptics and antibiotics, delivered either locally or systemically, were briefly reviewed as a backdrop. While generally effective in winning the "battle" against PD in the short term, by reducing its signs and symptoms, patients receiving such therapies are more susceptible to recurrence of PD. Moreover, the long-term consequences of such therapies are still in question. In particular, concern about chronic use of systemic antibiotics and their influence on the oral and gut microbiota is warranted, considering antibiotic resistance plasmids, and potential transfer between oral and non-oral microbes. In the interest of winning the "battle and the war", new more selective and targeted antimicrobials and biologics for PD are being studied. These are principally indirect, blocking pathways involved in bacterial colonization, nutrient acquisition, inflammation or cellular invasion without directly killing the pathogens. This review will focus on current and prospective antimicrobial therapies for PD, emphasizing therapies that act indirectly on the microbiota, with clearly defined cellular and molecular targets.


Assuntos
Antibacterianos/uso terapêutico , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Terapia Combinada , Gerenciamento Clínico , Suscetibilidade a Doenças , Vias de Administração de Medicamentos , Humanos , Periodontite/metabolismo , Resultado do Tratamento
20.
Medicine (Baltimore) ; 100(27): e26557, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232198

RESUMO

ABSTRACT: Radiomics transforms the medical images into high-dimensional quantitative features and provides potential information about tumor phenotypes and heterogeneity. We conducted a retrospective analysis to explore and validate radiomics model based on contrast-enhanced computed tomography (CECT) to predict recurrence of locally advanced oesophageal squamous cell cancer (SCC) within 2 years after trimodal therapy. This study collected CECT and clinical data of consecutive 220 patients with pathology-confirmed locally advanced oesophageal SCC (154 in the training cohort and 66 in the validation cohort). Univariate statistical test and the least absolute shrinkage and selection operator method were performed to select the optimal radiomics features. Logistic regression was conducted to build radiomics model, clinical model, and combined model of both the radiomics and clinical features. Predictive performance was judged by the area under receiver operating characteristics curve (AUC), accuracy, and F1-score in the training and validation cohorts. Ten optimal radiomics features and/or 7 clinical features were selected to build radiomics model, clinical model, and the combined model. The integrated model of radiomics and clinical features was superior to radiomics model or clinical model in predicting recurrence of locally advanced oesophageal SCC within 2 years in the training (AUC: 0.879 vs 0.815 or 0.763; accuracy: 0.844 vs 0.773 or 0.740; and F1-score: 0.886 vs 0.839 or 0.815, respectively) and validation (AUC: 0.857 vs 0.720 or 0.750; accuracy: 0.788 vs 0.700 or 0.697; and F1-score: 0.851 vs 0.800 or 0.787, respectively) cohorts. The combined model of radiomics and clinical features shows better performance than the radiomics or clinical model to predict the recurrence of locally advanced oesophageal SCC within 2 years after trimodal therapy.


Assuntos
Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X/métodos , Terapia Combinada , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Fatores de Tempo
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