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1.
Anticancer Res ; 41(4): 2193-2195, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813433

RESUMEN

BACKGROUND/AIM: Since January 2020, coronavirus disease (COVID-19) cases have been confirmed in Japan, and the number of patients with COVID-19 has been increasing. Two emergency declarations have been made previously and one is currently in effect. Based on our experience of a situation that could affect cancer treatment, this study retrospectively examined the correlation between perioperative anticancer therapy and COVID-19 incidence in patients with breast cancer. PATIENTS AND METHODS: Patients who underwent perioperative anticancer therapy for breast cancer at our hospital from February 2020 to February 2021 were included in this study. The presence or absence of COVID-19, timing of anticancer drug initiation, and clinical data were collected. RESULTS: No cases of COVID-19 were diagnosed in patients receiving perioperative anticancer therapy at our hospital. CONCLUSION: Regimen modification, active use of supportive care, and patient lifestyle were factors reducing the incidence of COVID-19.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama , Atención Perioperativa/métodos , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante/estadística & datos numéricos , Terapia Combinada , Femenino , Humanos , Huésped Inmunocomprometido , Incidencia , Japón/epidemiología , Persona de Mediana Edad , Terapia Neoadyuvante/estadística & datos numéricos , Atención Perioperativa/efectos adversos , Atención Perioperativa/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , /fisiología
2.
Anticancer Res ; 41(4): 2093-2100, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813419

RESUMEN

BACKGROUND/AIM: The Renin-Angiotensin system (RAS) induces immunosuppression in the tumor microenvironment, and RAS inhibitors (RASi) improve the tumor immune microenvironment. We evaluated the impact of RASi on the efficacy anti-programmed cell death-1/Ligand-1 (anti-PD-1/PD-L1) antibodies. PATIENTS AND METHODS: This retrospective study analyzed non-small cell lung cancer (NSCLC) patients who received anti-PD-1/PD-L1 antibodies monotherapy as second- or later-line treatment. We classified patients into those with or without use of RASi. RESULTS: A total of 256 NSCLC patients were included and 37 patients used RASi. The median PFS of patients treated with RASi was significantly longer than that of patients treated without (HR=0.59, 95%CI=0.40-0.88). The median OS of patients treated with RASi tended to be longer than that of patients treated without (HR=0.71, 95%CI=0.45-1.11). CONCLUSION: The use of RASi was associated with a significantly longer PFS in NSCLC patients treated with anti-PD-1/PD-L1 antibodies. RASi use may enhance the efficacy of anti-PD-1/PD-L1 antibodies.


Asunto(s)
Antagonistas de Receptores de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antihipertensivos/uso terapéutico , Antineoplásicos Inmunológicos/administración & dosificación , Antígeno B7-H1/inmunología , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Sinergismo Farmacológico , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Japón/epidemiología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Nivolumab/uso terapéutico , Sistema Renina-Angiotensina/efectos de los fármacos , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
3.
Anticancer Res ; 41(4): 2101-2110, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813420

RESUMEN

BACKGROUND/AIM: To evaluate if topical support therapy during static-intensity modulated radiotherapy (sIMRT) course is able to equal the characteristic minimum risk for radiation proctitis of Image-guided volumetric modulated arc therapy (IG-VMAT) treatment among localized prostate cancer patients. PATIENTS AND METHODS: Rectal toxicity data of the above patients were retrospectively collected throughout three different clinical periods at our Radiotherapy Deparment: from October 2011 to December 2012, prostate cancer patients were treated with sIMRT and in advance supported by means of daily topical corticosteroids; from January 2013 to November 2016, topical corticosteroids were replaced by daily hyaluronic acid enemas; from December 2016 to May 2018 eligible patients were treated with newly introduced IG-VMAT supported by only on-demand topical corticosteroids. RESULTS: Among 359 eligible patients, IG-VMAT was proven generally more effective than sIMRT supported by topical medications in terms of proctitis reduction, although without clinical and practical relevance. CONCLUSION: Topical medications might have a role in radiation proctitis prevention.


Asunto(s)
Antiinflamatorios/administración & dosificación , Proctitis/prevención & control , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Radioterapia de Intensidad Modulada , Administración Tópica , Anciano , Anciano de 80 o más Años , Beclometasona/administración & dosificación , Enema/métodos , Humanos , Ácido Hialurónico/administración & dosificación , Italia , Masculino , Persona de Mediana Edad , Tratamientos Conservadores del Órgano/métodos , Proctitis/etiología , Neoplasias de la Próstata/patología , Hipofraccionamiento de la Dosis de Radiación , Traumatismos por Radiación/prevención & control , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/efectos adversos , Radioterapia Guiada por Imagen/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos
4.
Anticancer Res ; 41(4): 2111-2115, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813421

RESUMEN

BACKGROUND/AIM: It has been hypothesized that many, or even most cancers, utilize a unique immunomodulatory protein, called the progesterone induced blocking factor (PIBF) to allow spread of the cancer. Support for this concept has been provided by cancer cell line studies showing that PIBF is produced by these cancer cells and mifepristone suppresses this protein and inhibits proliferation of these cells. Furthermore, controlled murine studies with several spontaneous different types of cancer showed a clear beneficial effect of mifepristone over placebo control. Finally, there have been a variety of anecdotal reports showing efficacy of mifepristone in providing increased length and quality of life in patients with different types of advanced cancers. CASE REPORT: Single agent mifepristone was found to provide significant palliative benefit for a 51-year-old male whose metastatic advanced fibroblastic osteosarcoma progressed despite surgery, radiotherapy, multiagent chemotherapy, and targeted therapy. CONCLUSION: Thus, osteosarcoma can be added to the list of cancers, not necessarily associated with the classic nuclear progesterone receptor, that seem to respond to progesterone receptor antagonist therapy.


Asunto(s)
Neoplasias Óseas/tratamiento farmacológico , Mifepristona/administración & dosificación , Osteosarcoma/tratamiento farmacológico , Cuidados Paliativos/métodos , Administración Oral , Neoplasias Óseas/patología , Dolor en Cáncer/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Osteosarcoma/patología , Calidad de Vida , Tibia , Resultado del Tratamiento
5.
Anticancer Res ; 41(4): 2141-2145, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813425

RESUMEN

BACKGROUND/AIM: We compared the outcome of docetaxel, cisplatin, and 5-fluorouracil as combination chemoradiotherapy (DCF-RT) for unresectable locally advanced thoracic esophageal cancer (EC) with that of cisplatin (CDDP) and 5-fluorouracil (5-FU) as combination chemoradiotherapy (CF-RT) in clinical settings. PATIENTS AND METHODS: Seventy-three patients with unresectable locally advanced thoracic EC were included in this study. CF (n=38) consisted of intravenous CDDP at 70 mg/m2 (day 1) and 5-FU at 700 mg/m2 (days 1 to 4), repeated every four weeks for two cycles. DCF (n=35) consisted of intravenous docetaxel at 50 mg/m2 (day 1), CDDP at 60 mg/m2 (day 1), and 5-FU at 600 mg/m2 (days 1 to 4), repeated every four weeks for two cycles. Patients were irradiated with 60 Gy in 30 fractions. RESULTS: The overall complete response (CR) rate of DCF-RT was significantly higher than that of CF-RT (36.7% vs. 3.7%, p=0.003). The 3-year overall survival (OS) rate of DCF-RT was significantly higher than that of CF-RT (32.8% vs. 8.5%, p<0.001). CONCLUSION: DCF-RT demonstrated a higher CR rate and OS for unresectable locally advanced thoracic EC than CF-RT.


Asunto(s)
Quimioradioterapia , Cisplatino/administración & dosificación , Docetaxel/administración & dosificación , Neoplasias Esofágicas/terapia , Fluorouracilo/administración & dosificación , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Cisplatino/efectos adversos , Progresión de la Enfermedad , Docetaxel/efectos adversos , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Femenino , Fluorouracilo/efectos adversos , Humanos , Japón/epidemiología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
6.
Anticancer Res ; 41(4): 2157-2163, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813427

RESUMEN

BACKGROUND: This study assessed the efficacy and safety of biweekly trifluridine and tipiracil hydrochloride (TAS-102) with bevacizumab combination therapy for patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: We included 19 patients with mCRC who received TAS-102 and bevacizumab combination therapy biweekly as third-line chemotherapy. The primary endpoint was progression-free survival. RESULTS: Patients had a median age of 73 years and most (73.4%) were men. The median progression-free and overall survival were 5.6 and 11.5 months, respectively. Five (26.3%) patients achieved a response and the disease control rate was 12/19 (63.1%). One patient (5.2%) experienced neutropenia grade 3 or more. The median time from baseline performance status 0/1 to worsening to 2 or more was 10.3 months. CONCLUSION: Biweekly TAS-102 plus bevacizumab facilitates tumor shrinkage by reducing the incidence of grade 3 or more neutropenia, improving survival, and maintaining performance status. This combination may represent a treatment option for patients with late-stage mCRC receiving third- or later-line therapy.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Pirrolidinas/administración & dosificación , Timina/administración & dosificación , Trifluridina/administración & dosificación , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Neutropenia Febril Inducida por Quimioterapia/etiología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pirrolidinas/efectos adversos , Análisis de Supervivencia , Timina/efectos adversos , Resultado del Tratamiento , Trifluridina/efectos adversos
7.
Rev Bras Epidemiol ; 24: e210014, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33825774

RESUMEN

OBJECTIVE: To investigate sociodemographic factors associated with the willingness to take the pandemic influenza vaccine. METHODS: This is a cross-sectional study of Brazilian civil servants participating in the fourth wave (2012-2013) of the longitudinal Pró-Saúde Study. Associations were expressed as odds ratios (OR) and 95% confidence intervals (95%CI), estimated by multivariate logistic regression models. RESULTS: Among 2,828 participants, 15.9% would not be willing to vaccinate in the future if the Brazilian Ministry of Health promoted a new vaccination campaign against pandemic influenza. Not willing to vaccinate in the future was strongly associated with not taking the pandemic influenza vaccine in 2010 (OR = 9.0, 95%CI 6.9 - 11.6). Among the unvaccinated, females, those aged > 60 years, and non-health care workers were less willing to vaccinate in the future. Again, in the vaccinated group, females were less willing to vaccinate. CONCLUSION: Multidisciplinary efforts should be encouraged in order to identify reasons for refusing vaccination, focusing on the individual and group perceptions of susceptibility, severity, benefits, and barriers to vaccination. Such information is needed to identify target groups for the delivery of customized interventions towards preventing emerging pandemics, such as avian influenza and COVID-19.


Asunto(s)
Empleados de Gobierno , Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Aceptación de la Atención de Salud , Vacunación , Brasil/epidemiología , Estudios Transversales , Femenino , Empleados de Gobierno/psicología , Empleados de Gobierno/estadística & datos numéricos , Humanos , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud/estadística & datos numéricos , Vacunación/psicología
8.
Cardiovasc Diabetol ; 20(1): 75, 2021 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-33789663

RESUMEN

The 6th Cardiovascular Outcome Trial (CVOT) Summit "Cardiovascular and Renal Outcomes 2020" was the first to be held virtually on October 29-30, 2020. As in previous years, this summit served as reference meeting for in-depth discussions on the topic of recently completed and presented major outcome trials. This year, focus was placed on the outcomes of VERTIS-CV, EMPEROR-Reduced, DAPA-CKD, and FIDELIO-DKD. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussion evolved from major outcome trials using SGLT-2 inhibitors for treatment and prevention of heart failure and chronic kidney disease in people with and without diabetes, to additional therapy options for chronic kidney disease with a novel mineralocorticoid receptor antagonist. Furthermore, challenges in diabetes management like COVID-19 and obesity, as well as novel treatment strategies and guidelines, were discussed.The 7th Cardiovascular Outcome Trial Summit will be held virtually on November, 18-19, 2021 ( http://www.cvot.org ).


Asunto(s)
/epidemiología , Enfermedades Cardiovasculares/epidemiología , Ensayos Clínicos como Asunto/métodos , Congresos como Asunto/tendencias , Insuficiencia Renal Crónica/epidemiología , Informe de Investigación/tendencias , /terapia , Enfermedades Cardiovasculares/terapia , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Humanos , Riñón/efectos de los fármacos , Riñón/fisiología , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Insuficiencia Renal Crónica/terapia , Inhibidores del Cotransportador de Sodio-Glucosa 2/administración & dosificación , Resultado del Tratamiento
9.
Anticancer Res ; 41(4): 1745-1751, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813378

RESUMEN

BACKGROUND/AIM: Osteosarcoma is the most frequent malignant bone tumor. Failure of first-line therapy results in poor prognosis of osteosarcoma. In the present report, we examined the efficacy of the combination of oral recombinant methioninase (o-rMETase) and docetaxel (DOC) on an osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model. MATERIALS AND METHODS: Osteosarcoma-PDOX models were established by tumor insertion within the tibia of nude mice. The osteosarcoma PDOX models were randomized into four groups (4-5 mice per group): control; o-rMETae alone; DOC alone; o- rMETase combined with DOC. The treatment period was 3 weeks. RESULTS: The combination of o-rMETase and DOC showed significant efficacy compared to the control group (p=0.03). In contrast, there was no significant efficacy of o-rMETase alone or DOC alone (p=0.65, 0.60, respectively). CONCLUSION: o-rMETase converted an osteosarcoma PDOX from DOC-resistant to -sensitive. This combination therapy may be effective against recalcitrant osteosarcoma and other recalcitrant cancers.


Asunto(s)
Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Óseas/tratamiento farmacológico , Liasas de Carbono-Azufre/administración & dosificación , Docetaxel/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Osteosarcoma/tratamiento farmacológico , Tibia/efectos de los fármacos , Administración Oral , Adolescente , Animales , Neoplasias Óseas/patología , Humanos , Masculino , Ratones Desnudos , Osteosarcoma/patología , Proteínas Recombinantes/administración & dosificación , Tibia/patología , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Acta Med Indones ; 53(1): 105-107, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33818413

RESUMEN

Acute bacterial skin and skin-structure infections (ABSSSI) is defined in 2013 by the US Food and Drug Administration as a bacterial cellulitis/erysipelas, major skin abscesses, and wound infections. The Infectious Diseases Society of America (IDSA) in 2014 classifies skin and soft-tissue infection (SSTI) as either non-purulent (which includes cellulitis, erysipelas, and necrotizing infection) or purulent (including furuncle, carbuncle, and abscess). Among hospitalized patients with SSTI, healthcare-associated infections account for 73.5% of all cases. Notably, skin and skin-structure infections caused by Pseudomonas aeruginosa, a common hospital pathogen, was reported to cause higher total cost and longer hospital length of stay compared to non-P. aeruginosa cases, despite causing only approximately 5.7% of all healthcare-associated SSTIs. Infection with P. aeruginosa should always be considered in non-healing skin infections in patients with prolonged hospitalization and antibiotic exposure. Tissue culture, preferably taken by surgical debridement, should be promptly performed; and when hospital-infection is suspected, appropriate antibiotics should be started along with removal of all devitalized tissue and to promote skin and soft tissue healing. Expedited discharge should be considered when possible, with adequate antibiotic treatment and follow up for definitive wound treatment.


Asunto(s)
/complicaciones , Desbridamiento/métodos , Enfermedad Iatrogénica , Linezolid/administración & dosificación , Enfermedades Cutáneas Infecciosas , Antibacterianos/administración & dosificación , /fisiopatología , Femenino , Hospitalización , Humanos , Persona de Mediana Edad , Piel/microbiología , Piel/patología , Enfermedades Cutáneas Infecciosas/diagnóstico , Enfermedades Cutáneas Infecciosas/etiología , Enfermedades Cutáneas Infecciosas/fisiopatología , Enfermedades Cutáneas Infecciosas/terapia , Resultado del Tratamiento
14.
Int J Nanomedicine ; 16: 2357-2372, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790554

RESUMEN

Purpose: Non-small cell lung cancer (NSCLC) is an aggressive tumor with high mortality and poor prognosis. In this study, we designed a liposome encapsulating polymeric micelles (PMs) loaded with vinorelbine (NVB) and cis-diamminedichloroplatinum (II) (cisplatin or CDDP) for the treatment of NSCLC. Materials and Methods: Sodium poly(α-l-glutamic acid)-graft-methoxy-polyethylene glycol (PLG-G-PEG5K) was used to prepare NVB-loaded NVB-PMs and CDDP-loaded CDDP-PMs that were co-encapsulated into liposomes by a reverse evaporation method, yielding NVB and CDDP co-delivery liposomes (CoNP-lips) composed of egg phosphatidyl lipid-80/cholesterol/DPPG/DSPE-mPEG2000 at a molar ratio of 52:32:14:2. The CoNP-lips were characterized in terms of particle size, zeta potential, drug content, encapsulation efficiency, and structural properties. Drug release by the CoNP-lips as well as their stability and cytotoxicity was evaluated in vitro, and their antitumor efficacy was assessed in a mouse xenograft model of Lewis lung carcinoma cell-derived tumors. Results: CoNP-lips had a spherical shape with uniform size distribution; the average particle size was 162.97±9.06 nm, and the average zeta potential was -13.02±0.22 mV. In vitro cytotoxicity analysis and the combination index demonstrated that the CoNP-lips achieved a synergistic cytotoxic effect at an NVB:CDDP weight ratio of 2:1 in an NSCLC cell line. There was sustained release of both drugs from CoNP-lips. The pharmacokinetic analysis showed that CoNP-lips had a higher plasma half-life than NP solution, with 6.52- and 8.03-fold larger areas under the receiver operating characteristic curves of NVB and CDDP. CoNP-lips showed antitumor efficacy in tumor-bearing C57BL/6 mice and drug accumulation in tumors via the enhanced permeability and retention effect. Conclusion: CoNP-lips are a promising formulation for targeted therapy in NSCLC.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/uso terapéutico , Sistemas de Liberación de Medicamentos , Neoplasias Pulmonares/tratamiento farmacológico , Micelas , Polímeros/química , Vinorelbina/uso terapéutico , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cisplatino/administración & dosificación , Cisplatino/farmacocinética , Cisplatino/farmacología , Liberación de Fármacos , Humanos , Liposomas , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos C57BL , Nanopartículas/ultraestructura , Tamaño de la Partícula , Polietilenglicoles/química , Ratas Sprague-Dawley , Distribución Tisular , Vinorelbina/farmacocinética , Vinorelbina/farmacología
15.
Int J Nanomedicine ; 16: 2373-2388, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790555

RESUMEN

Aim: The metastasis of breast cancer is an important cause of tumor recurrence. This study highlights that tyrosine kinase inhibitors dasatinib (DAS) and rosiglitazone (ROZ) inhibit tumor growth and reduce the occurrence of tumor cell metastasis. Due to the poor water solubility, short half-time in the body of DAS and ROZ, which increases the difficulty of tumor treatment, as well as the demand for nano-drug delivery systems for organ-specific therapies. Methods: Hyaluronic acid (HA) and DAS are bonded by a pH-sensitive ester bond to form an HA-DAS polymer. Then, ROZ was added as the core, D-A-tocopherol polydiethylene glycol isosuccinate (TPGS) and HA-DAS were used as carriers to form HA-DAS and TPGS mixed micelle system loaded with ROZ (THDR-NPs). The size and structure of THDR-NPs were characterized, the drug release, stability and biosafety of THDR-NPs were studied. In vitro, the cytotoxicity, targeting effect and tumor metastasis inhibition of THDR-NPs were evaluated in human breast cancer cell lines. In addition, the selective potency of designed THDR-NPs in depleting was further verified in vivo in the tumor-bearing nude mice model. Results: The designed THDR-NPs have a particle size of less than 100 nm, good stability, biological safety and sustained release, and showed strong therapeutic effects on breast cancer models in vitro and in vivo. Moreover, it has been proved that THDR-NPs have the ability to inhibit tumor metastasis. Conclusion: DAS and ROZ were designed into micelles, the efficacy of THDR-NPs was higher than that of free drugs. These results indicate that nanoparticles have a good application prospect in the treatment of tumor metastasis.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Animales , Peso Corporal/efectos de los fármacos , Neoplasias de la Mama/patología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Dasatinib/administración & dosificación , Dasatinib/farmacocinética , Dasatinib/farmacología , Dasatinib/uso terapéutico , Portadores de Fármacos/química , Liberación de Fármacos , Endocitosis/efectos de los fármacos , Femenino , Hemólisis/efectos de los fármacos , Humanos , Ácido Hialurónico/química , Ratones Endogámicos BALB C , Ratones Desnudos , Micelas , Nanopartículas/química , Nanopartículas/ultraestructura , Tamaño de la Partícula , Espectroscopía de Protones por Resonancia Magnética , Ratas Sprague-Dawley , Rosiglitazona/farmacocinética , Rosiglitazona/farmacología , Rosiglitazona/uso terapéutico , Electricidad Estática , Distribución Tisular/efectos de los fármacos , Carga Tumoral/efectos de los fármacos
16.
Int J Nanomedicine ; 16: 2389-2404, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790556

RESUMEN

Recently, there has been an incredible increase in research about the abnormal growth of cells (neoplasm), focusing on the management, treatment and preventing reoccurrence. It has been understood that the natural defense system, composed of a variety of immune defensive cells, does not just limit its function in eliminating neoplastic cells, but also controls the growth and spread of tumor cells of different kinds to other parts of the body. Cancer immunotherapy, is a cancer treatment plan that educates the body's defensive system to forestall, control, and eliminate tumor cells. The effectiveness of immunotherapy is achieved, to its highest efficacy, by the use of nanoparticles (NPs) for precise and timely delivery of immunotherapies to specific targeted neoplasms, with less or no harm to the healthy cells. Immunotherapies have been affirmed in clinical trials as a cancer regimen for various types of cancers, the side effects resulting from imprecise and non-targeted conveyance is well managed with the use of nanoparticles. Nonetheless, we will concentrate on enhancing cancer immunotherapy approaches by the use of nanoparticles for the productivity of antitumor immunity. Nanoparticles will be presented and utilized as an objective immunotherapy delivery system for high exactness and are thus a promising methodology for cancer treatment.


Asunto(s)
Sistemas de Liberación de Medicamentos , Objetivos , Inmunoterapia , Nanopartículas/química , Neoplasias/inmunología , Neoplasias/terapia , Animales , Humanos , Nanopartículas/administración & dosificación
17.
Lancet Oncol ; 22(4): 450-462, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33794205

RESUMEN

BACKGROUND: Chemoradiotherapy is the standard of care for unresected locally advanced squamous cell carcinoma of the head and neck. We aimed to assess if addition of avelumab (anti-PD-L1) to chemoradiotherapy could improve treatment outcomes for this patient population. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 study, patients were recruited from 196 hospitals and cancer treatment centres in 22 countries. Patients aged 18 years or older, with histologically confirmed, previously untreated, locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity (unselected for PD-L1 status), an Eastern Cooperative Oncology Group performance status score of 0 or 1, and who could receive chemoradiotherapy were eligible. Patients were randomly assigned (1:1) centrally by means of stratified block randomisation with block size four (stratified by human papillomavirus status, tumour stage, and nodal stage, and done by an interactive response technology system) to receive 10 mg/kg avelumab intravenously every 2 weeks plus chemoradiotherapy (100 mg/m2 cisplatin every 3 weeks plus intensity-modulated radiotherapy with standard fractionation of 70 Gy [35 fractions during 7 weeks]; avelumab group) or placebo plus chemoradiotherapy (placebo group). This was preceded by a single 10 mg/kg avelumab or placebo lead-in dose given 7 days previously and followed by 10 mg/kg avelumab or placebo every 2 weeks maintenance therapy for up to 12 months. The primary endpoint was progression-free survival by investigator assessment per modified Response Evaluation Criteria in Solid Tumors, version 1.1, in all randomly assigned patients. Adverse events were assessed in patients who received at least one dose of avelumab or placebo. This trial is registered with ClinicalTrials.gov, NCT02952586. Enrolment is no longer ongoing, and the trial has been discontinued. FINDINGS: Between Dec 12, 2016, and Jan 29, 2019, from 907 patients screened, 697 patients were randomly assigned to the avelumab group (n=350) or the placebo group (n=347). Median follow-up for progression-free survival was 14·6 months (IQR 8·5-19·6) in the avelumab group and 14·8 months (11·6-18·8) in the placebo group. Median progression-free survival was not reached (95% CI 16·9 months-not estimable) in the avelumab group and not reached (23·0 months-not estimable) in the placebo group (stratified hazard ratio 1·21 [95% CI 0·93-1·57] favouring the placebo group; one-sided p=0·92). The most common grade 3 or worse treatment-related adverse events were neutropenia (57 [16%] of 348 patients in the avelumab group vs 52 [15%] of 344 patients in the placebo group), mucosal inflammation (50 [14%] vs 45 [13%]), dysphagia (49 [14%] vs 47 [14%]), and anaemia (41 [12%] vs 44 [13%]). Serious treatment-related adverse events occurred in 124 (36%) patients in the avelumab group and in 109 (32%) patients in the placebo group. Treatment-related deaths occurred in two (1%) patients in the avelumab group (due to general disorders and site conditions, and vascular rupture) and one (<1%) in the placebo group (due to acute respiratory failure). INTERPRETATION: The primary objective of prolonging progression-free survival with avelumab plus chemoradiotherapy followed by avelumab maintenance in patients with locally advanced squamous cell carcinoma of the head and neck was not met. These findings may help inform the design of future trials investigating the combination of immune checkpoint inhibitors plus CRT. FUNDING: Pfizer and Merck KGaA, Darmstadt, Germany.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Quimioradioterapia , Cisplatino/administración & dosificación , Método Doble Ciego , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Placebos/administración & dosificación , Supervivencia sin Progresión , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Nivel de Atención
18.
Lancet Oncol ; 22(4): 489-498, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33794206

RESUMEN

BACKGROUND: Alpelisib, a PI3Kα-selective inhibitor and degrader, plus fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in SOLAR-1; limited data are available in the post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess alpelisib plus endocrine therapy in this setting in three cohorts defined by immediate previous treatment; here, we report results from cohort A. METHODS: This ongoing, phase 2, multicentre, open-label, non-comparative study enrolled patients with hormone receptor-positive, HER2-negative, advanced breast cancer with tumour PIK3CA mutation, following progression on or after previous therapy, including CDK4/6 inhibitors, from 114 study locations (cancer centres, medical centres, university hospitals, and hospitals) in 18 countries worldwide. Participants aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 2 or less, with no more than two previous anticancer treatments and no more than one previous chemotherapy regimen, were enrolled in three cohorts. In cohort A, patients must have had progression on or after a CDK4/6 inhibitor plus an aromatase inhibitor as the immediate previous treatment. Patients received oral alpelisib 300 mg/day (continuously) plus fulvestrant 500 mg intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1. The primary endpoint was the proportion of patients alive without disease progression at 6 months per local assessment using Response Evaluation Criteria in Solid Tumors, version 1.1, in patients with a centrally confirmed PIK3CA mutation. This trial is registered with ClinicalTrials.gov, NCT03056755. FINDINGS: Between Aug 14, 2017, and Dec 17, 2019 (data cutoff), 127 patients with at least 6 months' follow-up were enrolled into cohort A. 121 patients had a centrally confirmed PIK3CA mutation. At data cutoff, median follow-up was 11·7 months (IQR 8·5-15·9). 61 (50·4%; 95% CI 41·2-59·6) of 121 patients were alive without disease progression at 6 months. The most frequent grade 3 or worse adverse events were hyperglycaemia (36 [28%] of 127 patients), rash (12 [9%]), and rash maculopapular (12 [9%]). Serious adverse events occurred in 33 (26%) of 127 patients. No treatment-related deaths were reported. INTERPRETATION: BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor. FUNDING: Novartis Pharmaceuticals.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Fosfatidilinositol 3-Quinasa Clase I/genética , Quinasa 4 Dependiente de la Ciclina/genética , Quinasa 6 Dependiente de la Ciclina/genética , Tiazoles/administración & dosificación , Adolescente , Adulto , Anciano , Inhibidores de la Aromatasa/administración & dosificación , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Antagonistas del Receptor de Estrógeno/administración & dosificación , Femenino , Fulvestrant/administración & dosificación , Humanos , Persona de Mediana Edad , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/genética , Receptores Estrogénicos/genética , Receptores de Progesterona/antagonistas & inhibidores , Receptores de Progesterona/genética
19.
Lancet Oncol ; 22(4): 538-547, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33794207

RESUMEN

BACKGROUND: The concept of the use of MRI for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer was introduced 20 years ago. Here, we report on EMBRACE-I, which aimed to evaluate local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT. METHODS: EMBRACE-I was a prospective, observational, multicentre cohort study. Data from patients from 24 centres in Europe, Asia, and North America were prospectively collected. The inclusion criteria were patients older than 18 years, with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, The International Federation of Gynecology and Obstetrics (FIGO) stage IB-IVA disease or FIGO stage IVB disease restricted to paraaortic lymph metastasis below the L1-L2 interspace, suitable for curative treatment. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m2, 5-6 cycles, 1 day per cycle, plus 45-50 Gy external-beam radiotherapy delivered in 1·8-2 Gy fractions) followed by MRI-based IGABT. The MRI-based IGABT target volume definition and dose reporting was according to Groupe Européen de Curiethérapie European Society for Radiation Oncology recommendations. IGABT dose prescription was open according to institutional practice. Local control and late morbidity were selected as primary endpoints in all patients available for analysis. The study was registered with ClinicalTrials.gov, NCT00920920. FINDINGS: Patient accrual began on July 30, 2008, and closed on Dec 29, 2015. A total of 1416 patients were registered in the database. After exclusion for not meeting patient selection criteria before treatment, being registered but not entered in the database, meeting the exclusion criteria, and being falsely excluded, data from 1341 patients were available for analysis of disease and data from 1251 patients were available for assessment of morbidity outcome. MRI-based IGABT including dose optimisation was done in 1317 (98·2%) of 1341 patients. Median high-risk clinical target volume was 28 cm3 (IQR 20-40) and median minimal dose to 90% of the clinical target volume (D90%) was 90 Gy (IQR 85-94) equi-effective dose in 2 Gy per fraction. At a median follow-up of 51 months (IQR 20-64), actuarial overall 5-year local control was 92% (95% CI 90-93). Actuarial cumulative 5-year incidence of grade 3-5 morbidity was 6·8% (95% CI 5·4-8·6) for genitourinary events, 8·5% (6·9-10·6) for gastrointestinal events, 5·7% (4·3-7·6) for vaginal events, and 3·2% (2·2-4·5) for fistulae. INTERPRETATION: Chemoradiotherapy and MRI-based IGABT result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies. FUNDING: Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems.


Asunto(s)
Braquiterapia/métodos , Imagen por Resonancia Magnética/métodos , Radioterapia Guiada por Imagen/métodos , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Quimioradioterapia/métodos , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Calidad de Vida , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología
20.
Int J Nanomedicine ; 16: 2405-2417, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33814907

RESUMEN

Purpose: Ciprofloxacin (CIP) has poor lung targeting after oral inhalation. This study developed optimized inhalable nanostructured lipid carriers (NLCs) for CIP to enhance deposition and accumulation in deeper parts of the lungs for treatment of noncystic fibrosis bronchiectasis (NCFB). Methods: NLC formulations based on stearic acid and oleic acid were successfully prepared by hot homogenization and in vitro-characterized. CIP-NLCs were formulated into nanocomposite micro particles (NCMPs) for administration in dry powder inhalation (DPI) formulations by spray-drying (SD) using different ratios of chitosan (CH) as a carrier. DPI formulations were evaluated for drug content and in vitro deposition, and their mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD), and emitted dose (ED) were determined. Results: The CIP-NLCs were in the nanometric size range (102.3 ± 4.6 nm), had a low polydispersity index (0.267 ± 0.12), and efficient CIP encapsulation (98.75% ± 0.048%), in addition to a spherical and smooth shape with superior antibacterial activity. The in vitro drug release profile of CIP from CIP-NLCs showed 80% release in 10 h. SD of CIP-NLCs with different ratios of CH generated NCMPs with good yield (>65%). The NCMPs had a corrugated surface, but with increasing lipid:CH ratios, more spherical, smooth, and homogenous NCMPs were obtained. In addition, there was a significant change in the FPF with increasing lipid:CH ratios (P ˂ 0.05). NCMP-1 (lipid:CH = 1:0.5) had the highest FPD (45.0 µg) and FPF (49.2%), while NCMP-3 (lipid:CH = 1:1.5) had the lowest FPF (37.4%). All NCMP powders had an MMAD in the optimum size range of 3.9-5.1 µm. Conclusion: Novel inhalable CIP NCMP powders are a potential new approach to improved target ability and delivery of CIP for NCFB treatment.


Asunto(s)
Bronquiectasia/tratamiento farmacológico , Ciprofloxacino/uso terapéutico , Portadores de Fármacos/química , Lípidos/química , Nanoestructuras/química , Administración por Inhalación , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Quitosano/química , Ciprofloxacino/administración & dosificación , Portadores de Fármacos/administración & dosificación , Liberación de Fármacos , Inhaladores de Polvo Seco , Fibrosis , Cinética , Liposomas , Pulmón , Pruebas de Sensibilidad Microbiana , Nanoestructuras/ultraestructura , Tamaño de la Partícula , Electricidad Estática
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