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1.
Chem Biol Interact ; 335: 109367, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33412154

RESUMEN

Metastasis is the leading cause of death in retinoblastoma (Rb) patients. Tubeimoside II (TBMS II) is a compound enriched in the Traditional Chinese Medicine (TCM) Tu Bei Mu. It has been shown to induce cytotoxicity of several types of tumors; however, littler is known about its effect on Rb. This study investigated the influence of TBMS II on TGF-ß1-induced metastasis of human retinoblastoma Y-79 and WERI-Rb-1 cells. The data showed that TBMS II significantly inhibited epithelial-mesenchymal transition (EMT), cell adhesion, migration and invasion via reducing TGF-ß1-induced oxidative stress in Rb cells. Further findings revealed that TBMS II exerted its inhibitory effect against TGF-ß1-induced metastatic progression of Rb cells via suppressing redoxosome-dependent EGFR activation including EGFR phosphorylation and oxidation, and the activation of such signaling attenuated TBMS II's effect. Our study reveals that TBMS II impacts on TGF-ß1-induced metastatic progression of Rb cells, and this information may contribute to better understanding the therapeutic potentials of TBMS II on metastatic Rb.


Asunto(s)
Antineoplásicos/farmacología , Metástasis de la Neoplasia/tratamiento farmacológico , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/tratamiento farmacológico , Saponinas/farmacología , Triterpenos/farmacología , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Transición Epitelial-Mesenquimal/efectos de los fármacos , Receptores ErbB/metabolismo , Humanos , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fosforilación/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
2.
Medicine (Baltimore) ; 100(1): e24018, 2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33429766

RESUMEN

INTRODUCTION: Pembrolizumab, a monoclonal antibody targeting programmed cell death-1 (PD-1), is approved as a therapy for unresectable or metastatic melanoma. Immunotherapy-associated pneumonitis is an uncommon event. PATIENT CONCERNS: A 73-year-old man was admitted to our hospital with a history of melanoma on the left side of the face (resected in December 2012) and metastasis to the left lung upper lobe (resected in November 2016). Recurrence of metastasis to the bilateral lungs and left pleura was detected in April 2018. A complete response was achieved following treatment with pembrolizumab, with lower limb rashes the only adverse events occurring during therapy. The patient was readmitted in March 2019 with a productive cough, shortness of breath, and mild fever, and sputum culture identified Escherichia coli. DIAGNOSIS: A diagnosis of pneumonia was made, and although cough and shortness of breath responded to ceftazidime and levofloxacin, but fever and poor appetite persisted. Computed tomography showed no improvement in the bilateral lower lobe lesions. Prednisone was initiated based on a clinical diagnosis of immunotherapy-related pneumonitis. The response to prednisone confirmed the diagnosis. INTERVENTIONS: The patient first received ceftazidime and levofloxacin, but the symptoms persisted. Prednisone was initiated based on a clinical diagnosis of immunotherapy-related pneumonitis. OUTCOME: Complete resolution of the bilateral lung lesions occurred after 45 days of prednisone therapy. CONCLUSION: This case report highlights that both pneumonitis and bacterial pneumonia can occur as complications of anti-PD-1 immunotherapy.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Inmunoterapia/efectos adversos , Melanoma/tratamiento farmacológico , Neumonía Bacteriana/etiología , Neumonía/etiología , Anciano , Tos/etiología , Disnea/etiología , Fiebre/etiología , Humanos , Inmunoterapia/métodos , Inmunoterapia/normas , Masculino , Melanoma/complicaciones , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/fisiopatología , Neumonía/fisiopatología , Neumonía Bacteriana/fisiopatología
3.
Chem Biol Interact ; 335: 109362, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33358999

RESUMEN

Saringosterol acetate (SSA) was isolated from an edible brown alga Hizikia fusiforme. In this study, we developed an adult zebrafish human hepatocellular carcinoma (HCC) xenograft model to confirm that SSA inhibits tumor growth and metastasis. Established Hep3B cells labeled with the fluorescent tracker CM-Dil were xenografted into the abdominal cavity of zebrafish once every three days for one month. Compared with the control group, the fish injected with Hep3B showed a significant increase in α-fetoprotein (AFP) and factors related to tumor growth and metastasis (IL-6, TNF-α, TGFß, MMP2, and MMP9). Using the model, it was proven that SSA affected survival rate, AFP production, and the levels of factors related to tumor growth and metastasis via the PI3K/AKT/mTOR and TGFß/Smad pathways. In conclusion, this HCC model can be used for in vivo experiments to investigate the inhibition of cancer, and SSA may be useful for the treatment of cancer.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Sargassum/química , Estigmasterol/análogos & derivados , Estigmasterol/uso terapéutico , Animales , Línea Celular Tumoral , Femenino , Humanos , Masculino , Metástasis de la Neoplasia/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Pez Cebra
4.
Medicine (Baltimore) ; 99(36): e22060, 2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32899071

RESUMEN

The phase III West Japan Oncology Group (WJOG) 4407G study showed noninferiority of folinic acid, bolus/continuous fluorouracil, and irinotecan plus bevacizumab to modified folinic acid, bolus/continuous fluorouracil, and oxaliplatin 6 plus bevacizumab in progression-free survival (PFS) as first-line chemotherapy for patients with metastatic colorectal cancer. The aim of this study was to evaluate the predictive and prognostic value of morphologic response in patients with colorectal liver metastases (CLM) as a post hoc analysis of the WJOG4407G study.Morphologic response was assessed by comparing contrast-enhanced computed tomography (CT) images at baseline and week 8. Three blinded radiologists evaluated CT images and classified their response as optimal, incomplete, or no response according to the morphologic criteria. Response evaluation criteria in solid tumors (RECIST) response, early tumor shrinkage (ETS), and depth of response (DpR) were also evaluated.Among 395 patients who were eligible for efficacy analysis in the WJOG4407G study, 70 patients had liver-limited disease. We finally evaluated 55 of these patients. Optimal morphologic response was identified in 19 of 55 patients (34.5%). The median PFS was 10.7 months for patients with optimal response and 10.1 months in those with incomplete/no response (log-rank, P = .96). The median overall survival (OS) was 26.2 and 35.5 months, respectively (log-rank, P = .062). According to univariate analysis, morphologic response was not associated with PFS or OS, whereas RECIST response was significantly associated with both PFS and OS, with ETS and DpR being associated with significantly longer PFS.Morphologic response might be neither a predictive nor a prognostic factor in patients with CLM undergoing chemotherapy containing bevacizumab, whereas RECIST response was significantly associated with both PFS and OS.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Adulto , Anciano , Antimetabolitos Antineoplásicos , Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/administración & dosificación , Femenino , Fluorouracilo/uso terapéutico , Humanos , Infusiones Intravenosas/métodos , Irinotecán/uso terapéutico , Japón/epidemiología , Leucovorina/administración & dosificación , Leucovorina/uso terapéutico , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/patología , Oxaliplatino/uso terapéutico , Valor Predictivo de las Pruebas , Pronóstico , Supervivencia sin Progresión , Criterios de Evaluación de Respuesta en Tumores Sólidos , Tomografía Computarizada por Rayos X/métodos , Inhibidores de Topoisomerasa I/uso terapéutico , Resultado del Tratamiento , Complejo Vitamínico B/administración & dosificación , Complejo Vitamínico B/uso terapéutico
6.
Lancet Glob Health ; 8(9): e1213-e1222, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32827483

RESUMEN

BACKGROUND: Regimens for palliation in patients with head and neck cancer recommended by the US National Comprehensive Cancer Network (NCCN) have low applicability (less than 1-3%) in low-income and middle-income countries (LMICs) because of their cost. In a previous phase 2 study, patients with head and neck cancer who received metronomic chemotherapy had better outcomes when compared with those who received intravenous cisplatin, which is commonly used as the standard of care in LMICs. We aimed to do a phase 3 study to substantiate these findings. METHODS: We did an open-label, parallel-group, non-inferiority, randomised, phase 3 trial at the Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India. We enrolled adult patients (aged 18-70 years) who planned to receive palliative systemic treatment for relapsed, recurrent, or newly diagnosed squamous cell carcinoma of the head and neck, and who had an Eastern Cooperative Oncology Group performance status score of 0-1 and measurable disease, as defined by the Response Evaluation Criteria In Solid Tumors. We randomly assigned (1:1) participants to receive either oral metronomic chemotherapy, consisting of 15 mg/m2 methotrexate once per week plus 200 mg celecoxib twice per day until disease progression or until the development of intolerable side-effects, or 75 mg/m2 intravenous cisplatin once every 3 weeks for six cycles. Randomisation was done by use of a computer-generated randomisation sequence, with a block size of four, and patients were stratified by primary tumour site and previous cancer-directed treatment. The primary endpoint was median overall survival. Assuming that 6-month overall survival in the intravenous cisplatin group would be 40%, a non-inferiority margin of 13% was defined. Both intention-to-treat and per-protocol analyses were done. All patients who completed at least one cycle of the assigned treatment were included in the safety analysis. This trial is registered with the Clinical Trials Registry-India, CTRI/2015/11/006388, and is completed. FINDINGS: Between May 16, 2016, and Jan 17, 2020, 422 patients were randomly assigned: 213 to the oral metronomic chemotherapy group and 209 to the intravenous cisplatin group. All 422 patients were included in the intention-to-treat analysis, and 418 patients (211 in the oral metronomic chemotherapy group and 207 in the intravenous cisplatin group) were included in the per-protocol analysis. At a median follow-up of 15·73 months, median overall survival in the intention-to-treat analysis population was 7·5 months (IQR 4·6-12·6) in the oral metronomic chemotherapy group compared with 6·1 months (3·2-9·6) in the intravenous cisplatin group (unadjusted HR for death 0·773 [95% CI 0·615-0·97, p=0·026]). In the per-protocol analysis population, median overall survival was 7·5 months (4·7-12·8) in the oral metronomic chemotherapy group and 6·1 months (3·4-9·6) in the intravenous cisplatin group (unadjusted HR for death 0·775 [95% CI 0·616-0·974, p=0·029]). Grade 3 or higher adverse events were observed in 37 (19%) of 196 patients in the oral metronomic chemotherapy group versus 61 (30%) of 202 patients in the intravenous cisplatin group (p=0·01). INTERPRETATION: Oral metronomic chemotherapy is non-inferior to intravenous cisplatin with respect to overall survival in head and neck cancer in the palliative setting, and is associated with fewer adverse events. It therefore represents a new alternative standard of care if current NCCN-approved options for palliative therapy are not feasible. FUNDING: Tata Memorial Center Research Administration Council. TRANSLATIONS: For the Hindi, Marathi, Gujarati, Kannada, Malayalam, Telugu, Oriya, Bengali, and Punjabi translations of the abstract see Supplementary Materials section.


Asunto(s)
Cisplatino/administración & dosificación , Cisplatino/economía , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Metástasis de la Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Administración Intravenosa , Administración Metronómica , Administración Oral , Adolescente , Adulto , Anciano , Costos y Análisis de Costo , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
7.
Nature ; 585(7823): 113-118, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32814895

RESUMEN

Cancer cells, including melanoma cells, often metastasize regionally through the lymphatic system before metastasizing systemically through the blood1-4; however, the reason for this is unclear. Here we show that melanoma cells in lymph experience less oxidative stress and form more metastases than melanoma cells in blood. Immunocompromised mice with melanomas derived from patients, and immunocompetent mice with mouse melanomas, had more melanoma cells per microlitre in tumour-draining lymph than in tumour-draining blood. Cells that metastasized through blood, but not those that metastasized through lymph, became dependent on the ferroptosis inhibitor GPX4. Cells that were pretreated with chemical ferroptosis inhibitors formed more metastases than untreated cells after intravenous, but not intralymphatic, injection. We observed multiple differences between lymph fluid and blood plasma that may contribute to decreased oxidative stress and ferroptosis in lymph, including higher levels of glutathione and oleic acid and less free iron in lymph. Oleic acid protected melanoma cells from ferroptosis in an Acsl3-dependent manner and increased their capacity to form metastatic tumours. Melanoma cells from lymph nodes were more resistant to ferroptosis and formed more metastases after intravenous injection than did melanoma cells from subcutaneous tumours. Exposure to the lymphatic environment thus protects melanoma cells from ferroptosis and increases their ability to survive during subsequent metastasis through the blood.


Asunto(s)
Ferroptosis , Linfa/metabolismo , Melanoma/patología , Metástasis de la Neoplasia/patología , Animales , Supervivencia Celular , Coenzima A Ligasas/metabolismo , Femenino , Ferroptosis/efectos de los fármacos , Glutatión/metabolismo , Humanos , Hierro/metabolismo , Masculino , Melanoma/sangre , Melanoma/metabolismo , Ratones , Metástasis de la Neoplasia/tratamiento farmacológico , Ácido Oléico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Análisis de Componente Principal
8.
Adv Exp Med Biol ; 1252: 115-124, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32816270

RESUMEN

Available data on systemic treatments in pregnancy-associated breast cancer (PABC) is reviewed in this section. These treatments include chemotherapy, endocrine therapy (ET), small molecule inhibitors, monoclonal antibodies against human epidermal growth factor receptor 2 (EGFR-2) also known as HER2; and human epidermal growth factor receptor 3 (EGFR-3), also known as HER3.In local disease, systemic treatment can be delivered as neoadjuvant (before surgery) or adjuvant (after surgery) treatment. In metastatic disease, systemic therapy is the main modality of treatment.Approach to PABC is based on available data in the general population, limited only by safety issues for use of medications during gestation and lactation. Therefore, treatments are similar to non-PABC patients while trying to minimize the risk to the fetus. Available data on different chemotherapies, anti-HER2 monoclonal antibodies, ET and small molecule inhibitors are discussed in detail.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Neoplasias de la Mama/patología , Femenino , Humanos , Terapia Neoadyuvante , Metástasis de la Neoplasia/tratamiento farmacológico , Embarazo , Complicaciones Neoplásicas del Embarazo/patología , Receptor ErbB-2/antagonistas & inhibidores , Trastuzumab/farmacología , Trastuzumab/uso terapéutico
9.
Life Sci ; 259: 118150, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32726663

RESUMEN

Conventional therapeutic methods against cancer, including chemotherapy, radiotherapy, surgery, and combination therapy, have exhibited different toxicity levels due to their unspecific mechanism of action. To overcome the challenges facing conventional cancer therapies, newly developed methods are being investigated. Significant levels of specificity, remarkable accumulation at the tumor site, limited side effects, and minimal off-target effects enable the newly synthesized nanoparticles (NPs) to become the preferred drug delivery method in anticancer therapeutic approaches. According to the literature, CD73 has a pivotal role in cancer progression and resistance to chemotherapy and radiotherapy. Therefore, CD73 has attracted considerable attention among scientists to target this molecule. Accordingly, FDA approved CDK inhibitors such as Dinaciclib that blocks CDK1, 2, 5, and 9, and exhibits significant anticancer activity. So in this study, we intended to simultaneously suppress CD73 and CDKs in cancer cells by using the folic acid (FA)-conjugated chitosan-lactate (CL) NPs loaded with anti-CD73 siRNA and Dinaciclib to control tumor progression and metastasis. The results showed that NPs could effectively transfect cancer cells in a FA receptor-dependent manner leading to suppression of proliferation, survival, migration, and metastatic potential. Moreover, the treatment of tumor-bearing mice with this combination strategy robustly inhibited tumor growth and enhanced survival time in mice. These findings imply the high potential of FA-CL NPs loaded with anti-CD73 siRNA and Dinaciclib for use in cancer treatment shortly.


Asunto(s)
5'-Nucleotidasa/efectos de los fármacos , Antineoplásicos/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Ácido Fólico , Nanopartículas , Compuestos de Piridinio/farmacología , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/farmacología , 5'-Nucleotidasa/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Terapia Combinada , Quinasas Ciclina-Dependientes/efectos de los fármacos , Progresión de la Enfermedad , Sistemas de Liberación de Medicamentos , Sinergismo Farmacológico , Humanos , Ratones , Metástasis de la Neoplasia/tratamiento farmacológico , Neoplasias Experimentales/tratamiento farmacológico , Ensayo de Tumor de Célula Madre
10.
Medicine (Baltimore) ; 99(29): e20821, 2020 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-32702824

RESUMEN

This study was to investigate the efficacy and safety of fulvestrant 500 mg for the treatment of hormone receptor positive advanced postmenopausal women, including ovarian ablation and investigated factors associated with prolonged time-to-treatment failure.Data from 60 women with metastatic breast cancer who were treated at Zhejiang Cancer Hospital. Patients received 500 mg (n = 60) between December 2011 and November 2012 were followed until November 2017. Main outcomes were clinical responses to fulvestrant, including best response, progressive disease, partial response, and stable disease lasting 12 months or more. Time to progression and time to progression-free-survival were also analyzed.Among the included 60 patients (mean age 47.18 years), 51 (85.0%) had received prior adjuvant therapy. During follow-up after fulvestrant treatment, the median PFS for the best response was derived as 7.0 months (inter-quartile = 4, 13.8 months). The observed median progression-free-survival time for best response was represented longer when fulvestrant was first-line treatment than when patients received prior endocrine and/or chemotherapy. Univariate analysis revealed that receiving either endocrine therapy only or endocrine therapy plus chemotherapy prior to fulvestrant treatment may be associated with median progression-free survival time to best response (P = .002, .026, .007, respectively).Fulvestrant treatment is safe and well-tolerated in women with hormone-sensitive advanced breast cancer, and first-line fulvestrant therapy increases progression-free-survival time, especially in patients without prior adjuvant treatment.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Antagonistas del Receptor de Estrógeno/uso terapéutico , Fulvestrant/uso terapéutico , Metástasis de la Neoplasia/tratamiento farmacológico , Posmenopausia/efectos de los fármacos , Adulto , Antineoplásicos Hormonales/uso terapéutico , Grupo de Ascendencia Continental Asiática/etnología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/métodos , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Supervivencia sin Progresión , Estudios Retrospectivos , Seguridad , Tiempo de Tratamiento , Resultado del Tratamiento
11.
Medicine (Baltimore) ; 99(26): e20896, 2020 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-32590800

RESUMEN

INTRODUCTION: Metastatic neuroblastoma (NB) is an aggressive malignancy with a poor prognosis. Many patients present with relapsed high-risk NB after undergoing first-line treatment, and there is no standard therapy available in this setting. PATIENT CONCERNS: The present study aimed to present the cases of 2 patients with recurrent high-risk NB. DIAGNOSIS: Two children with International Neuroblastoma Stage System stage 4 high-risk NB chemotherapy. The disease recurrent after finishing the treatment. INTERVENTIONS: Both patients (34 months old and 41 months old) experienced recurrence, received second-line treatment, and then received maintenance treatment using apatinib plus retinoic acid. The apatinib (10 mg/kg per day) and retinoic acid (160 mg/m per day) were administered on alternating 2-week cycles, which was continued for 1 year. OUTCOMES: The 2 patients had achieved complete response by the 1-year follow-up after starting apatinib plus retinoic acid, and did not experience any adverse drug reactions. CONCLUSION: The outcomes from these cases suggest that apatinib plus isotretinoin might be an option for maintenance therapy in patients with recurrent high-risk NB.


Asunto(s)
Neuroblastoma/complicaciones , Neuroblastoma/tratamiento farmacológico , Piridinas/uso terapéutico , Tretinoina/uso terapéutico , Dolor Abdominal/etiología , Antineoplásicos/uso terapéutico , Preescolar , Quimioterapia/métodos , Quimioterapia/normas , Humanos , Masculino , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/fisiopatología , Neuroblastoma/fisiopatología , Recurrencia
12.
Rev. cuba. cir ; 59(2): e935, abr.-jun. 2020. tab, graf
Artículo en Español | LILACS, CUMED | ID: biblio-1126414

RESUMEN

RESUMEN Introducción: El cáncer avanzado es aquel que crece fuera del órgano en el cual se originó. La resección quirúrgica es el método más eficaz para lograr la curación de cáncer colorrectal en 50 por ciento de los casos. Objetivo: Evaluar los resultados del tratamiento multidisciplinar, realizado a pacientes con diagnóstico de cáncer colorrectal avanzado. Método: Se realizó un estudio observacional, descriptivo, ambispectivo y de corte transversal en el Hospital Clínico Quirúrgico "Hermanos Ameijeiras" entre enero de 2013 y diciembre de 2018. La muestra fue de 219 casos. Resultados: El 34,2 por ciento de los pacientes tenían entre 70 y 79 años. Hubo predominio de localización en colon ascendente (37,4 por ciento), en 57,1 por ciento fue moderadamente diferenciado y en 34,2 por ciento en estadio IIIA. El 7,8 por ciento de los pacientes tuvo recaída con metástasis, de ellos, 70,5 por ciento en hígado. En 72,6 por ciento la vía de acceso fue laparoscópica. En 50,7 por ciento se realizó hemicolectomía derecha. Las complicaciones se observaron en 25 pacientes (35,2 por ciento). El 91,3 por ciento de los casos recibió terapia adyuvante. En 27,4 por ciento hubo recurrencia. En el análisis del tiempo libre de enfermedad y de la supervivencia se obtuvieron buenos resultados. Conclusiones: El tratamiento combinado, secuencial y multidisciplinario en enfermedad maligna colorrectal avanzada ha demostrado beneficios clínicos y mayor supervivencia. Con una morbilidad y mortalidad relacionada con el proceder quirúrgico aceptable independientemente la vía de acceso empleada(AU)


ABSTRACT Introduction: advanced cancer is cancer that has grown outside the organ in which it originated. Surgical resection is the most effective method to achieve colorectal cancer cure in 50 % of cases. Objectives: the objective was to evaluate the results of the multidisciplinary treatment, carried out on patients diagnosed with advanced colorectal cancer. Method: it is an observational, descriptive, ambispective and cross-sectional study at the "Hermanos Ameijeiras" Surgical Clinical Hospital between January 2013 and December 2018. The sample was 219 cases. Results: 34.2 percent of the patients were between 70 and 79 years old. 56.2 percent were women. There was a predominance of localization in the ascending colon (37.4 percent), in 57.1 percent it was moderately differentiated and in 34.2 percent in stage IIIA. 7.8 percent of the patients had a metastatic relapse, 70.5 percent of them in the liver. In 72.6 percent, the access route was laparoscopic. Right hemicolectomy was performed in 50.7 percent. Complications were observed in 25 patients (35.2 percent). 91.3 percent of the cases received adjuvant therapy. In 27.4 percent there was recurrence. Good results were obtained in the analysis of disease-free time and survival. Conclusion: we conclude that combined, sequential, and multidisciplinary treatment in advanced colorectal malignancy has demonstrated clinical benefits and increased survival. With an acceptable morbidity and mortality related to the surgical procedure regardless of the access route used. Multivisceral and / or en bloc resections and maximum resection manage to increase the free interval of disease progression and alleviate symptoms(AU)


Asunto(s)
Humanos , Masculino , Femenino , Anciano , Neoplasias Colorrectales/diagnóstico , Colectomía/métodos , Colon Ascendente/lesiones , Metástasis de la Neoplasia/tratamiento farmacológico , Epidemiología Descriptiva , Estudios Transversales , Estudios Observacionales como Asunto
13.
Eur J Med Chem ; 200: 112332, 2020 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-32473523

RESUMEN

Cancer invasion and metastasis are the leading causes of death. The process of metastasis or tumor cell dissemination is still much of a mystery. Emerging evidence has shown that epithelial-mesenchymal transition (EMT) plays a vital role in the progression of malignant tumor including the inducing cell invasion and metastasis as well as promoting drug resistance. Vinorelbine is a traditional chemotherapeutic agent for treatment of lung cancer and breast cancer by the selectivity to mitotic microtubules. The aim of this study was to investigate the effect of vinorelbine on three metastatic cancer cells including lung cancer (H1975), liver cancer (HepG2), and colon cancer (HCT116) cells through inhibition of metastatic abilities and EMT program. Vinorelbine inhibited the cancer cell proliferation by MTT and colony formation assays and inducing G2/M arrest and cell apoptosis via regulation of Bax, Bcl-2, and Bcl-xL. Vinorelbine decrease the migration and invasion ability of the cancer cells by wound healing assay and Tran swell test. The molecular mechanisms of vinorelbine suppressing the metastatic phenotypes of cancer cells through modulation of E-cadherin, N-cadherin, vimentin and transcription factors Snail, MMP-2 and MMP-9. Our results demonstrated that vinorelbine inhibited the cancer cell metastasis through a reduction in metastatic mobility, such as migration, invasion, and the EMT. It provided the evidence that vinorelbine can be used alone or with other agents for treatment of metastatic lung cancer, liver cancer and colon cancer.


Asunto(s)
Transición Epitelial-Mesenquimal/efectos de los fármacos , Neoplasias/patología , Moduladores de Tubulina/farmacología , Vinorelbina/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/patología , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/patología , Invasividad Neoplásica/prevención & control , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/prevención & control , Neoplasias/tratamiento farmacológico , Vinorelbina/uso terapéutico
14.
Hum Cell ; 33(3): 652-662, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32350750

RESUMEN

The tumor microenvironment (TM) is an essential factor of tumor progression. Mesenchymal stem cells (MSCs) are important components of the TM and play critical roles in cancer metastasis. Resveratrol (RES) is a potential antitumor drug that has attracted extensive attention. However, it remains unclear whether RES can exert its antitumor activity by targeting MSCs located in the TM. In this study, we demonstrated that the conditioned medium of gastric-cancer-derived MSCs (GC-MSCs) promoted gastric cancer (GC) metastasis and facilitated the progression of epithelialmesenchymal transition (EMT) of GC cells. However, after pretreatment with RES, the prometastatic effect of GC-MSCs on GC cells was reversed. Furthermore, RES reduced GC-MSC (IL-6, IL-8, MCP-1, VEGF) gene expression and protein secretion, and counteracted the activation of the GC-MSC-induced Wnt/ß-catenin signaling of GC cells, with less ß-catenin nuclear transport and declined expression of ß-catenin, CD44, and CyclinD3 in GC cells. Re-expression of ß-catenin impaired the inhibitory effect of RES on GC cells. In conclusion, RES restricted the mobility increase of GC cells and reversed the progress of EMT induced by GC-MSCs by inactivating the Wnt/ß-catenin signaling. GC-MSCs are promising target for RES in the inhibition of GC metastasis.


Asunto(s)
Células Madre Mesenquimatosas/fisiología , Metástasis de la Neoplasia/tratamiento farmacológico , Resveratrol/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Antineoplásicos Fitogénicos , Línea Celular Tumoral , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Expresión Génica/efectos de los fármacos , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Células Madre Mesenquimatosas/patología , Terapia Molecular Dirigida , Fitoterapia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Microambiente Tumoral , Proteínas Wnt/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
15.
Oncogene ; 39(23): 4567-4580, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32388539

RESUMEN

Despite the continual discovery of promising new cancer targets, drug discovery is often hampered by the poor druggability of these targets. As such, repurposing FDA-approved drugs based on cancer signatures is a useful alternative to cancer precision medicine. Here, we adopted an in silico approach based on large-scale gene expression signatures to identify drug candidates for lung cancer metastasis. Our clinicogenomic analysis identified GALNT14 as a putative driver of lung cancer metastasis, leading to poor survival. To overcome the poor druggability of GALNT14 in the control of metastasis, we utilized the Connectivity Map and identified bortezomib (BTZ) as a potent metastatic inhibitor, bypassing the direct inhibition of the enzymatic activity of GALNT14. The antimetastatic effect of BTZ was verified both in vitro and in vivo. Notably, both BTZ treatment and GALNT14 knockdown attenuated TGFß-mediated gene expression and suppressed TGFß-dependent metastatic genes. These results demonstrate that our in silico approach is a viable strategy for the use of undruggable targets in cancer therapies and for revealing the underlying mechanisms of these targets.


Asunto(s)
Antineoplásicos/farmacología , Bortezomib/farmacología , Transformación Celular Neoplásica/genética , Neoplasias Pulmonares/tratamiento farmacológico , N-Acetilgalactosaminiltransferasas/genética , Células A549 , Línea Celular Tumoral , Reposicionamiento de Medicamentos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/patología , Metástasis de la Neoplasia/tratamiento farmacológico , Medicina de Precisión/métodos , Interferencia de ARN , ARN Interferente Pequeño/genética
16.
N Engl J Med ; 382(22): 2091-2102, 2020 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-32343890

RESUMEN

BACKGROUND: Multiple loss-of-function alterations in genes that are involved in DNA repair, including homologous recombination repair, are associated with response to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition in patients with prostate and other cancers. METHODS: We conducted a randomized, open-label, phase 3 trial evaluating the PARP inhibitor olaparib in men with metastatic castration-resistant prostate cancer who had disease progression while receiving a new hormonal agent (e.g., enzalutamide or abiraterone). All the men had a qualifying alteration in prespecified genes with a direct or indirect role in homologous recombination repair. Cohort A (245 patients) had at least one alteration in BRCA1, BRCA2, or ATM; cohort B (142 patients) had alterations in any of 12 other prespecified genes, prospectively and centrally determined from tumor tissue. Patients were randomly assigned (in a 2:1 ratio) to receive olaparib or the physician's choice of enzalutamide or abiraterone (control). The primary end point was imaging-based progression-free survival in cohort A according to blinded independent central review. RESULTS: In cohort A, imaging-based progression-free survival was significantly longer in the olaparib group than in the control group (median, 7.4 months vs. 3.6 months; hazard ratio for progression or death, 0.34; 95% confidence interval, 0.25 to 0.47; P<0.001); a significant benefit was also observed with respect to the confirmed objective response rate and the time to pain progression. The median overall survival in cohort A was 18.5 months in the olaparib group and 15.1 months in the control group; 81% of the patients in the control group who had progression crossed over to receive olaparib. A significant benefit for olaparib was also seen for imaging-based progression-free survival in the overall population (cohorts A and B). Anemia and nausea were the main toxic effects in patients who received olaparib. CONCLUSIONS: In men with metastatic castration-resistant prostate cancer who had disease progression while receiving enzalutamide or abiraterone and who had alterations in genes with a role in homologous recombination repair, olaparib was associated with longer progression-free survival and better measures of response and patient-reported end points than either enzalutamide or abiraterone. (Funded by AstraZeneca and Merck Sharp & Dohme; PROfound ClinicalTrials.gov number, NCT02987543.).


Asunto(s)
Antineoplásicos/uso terapéutico , Mutación con Pérdida de Función , Ftalazinas/uso terapéutico , Piperazinas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Androstenos/efectos adversos , Androstenos/uso terapéutico , Antineoplásicos/efectos adversos , Proteínas de la Ataxia Telangiectasia Mutada/genética , Genes BRCA1 , Genes BRCA2 , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Feniltiohidantoína/efectos adversos , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/uso terapéutico , Ftalazinas/efectos adversos , Piperazinas/efectos adversos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Supervivencia sin Progresión , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología
17.
Cancer Immunol Immunother ; 69(9): 1725-1735, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32328672

RESUMEN

Surface exposed phosphatidylserine (PS) of cancer aids it to evade immune surveillance and thereby results in tumor progression. Earlier, we reported that PS targeting cationic liposomes, phosphatidylcholine-stearylamine (PC-SA), alone and in combination with doxorubicin can result in complete remission of B16F10 melanoma in C57BL/6 mice without signs of toxicity. Inducing an immunogenic response is highly crucial for any cancer therapy as it is essential in improving the tumor microenvironment for any drug to act. Herein, we demonstrate that PC-SA, besides having tumor reducing ability, elicits a strong immune response. The combination therapy (PC-SA-DOX) is superior to free DOX in enhancing the anti-tumor immune effect on CD4-positive and CD8-positive T cells for IFN-γ, IL-2 and TNF-α production in sera and splenic culture supernatants of B16F10 tumor-induced mice. An upregulation of IL-12 and NO production is evidenced in spleen cultures of these mice, thereby showing a promising role of both Th1 type and innate immune response for host anti-tumor activity. Complete elimination of cancer is sometimes accomplished by surgery, but its effectiveness is often limited due to the propensity of cancers to spread to distant organs by metastasis. In our present study, we show that in PC-SA-DOX treated mice, the elevated Th1 cytokine levels create an immuno-protective environment which thereby facilitates in curing lung metastasis. Our results, therefore, warrant the need of effective immune stimulation by anticancer formulations for inhibition of solid tumors and metastasis, demonstrated by the liposomal DOX formulation.


Asunto(s)
Aminas/farmacología , Citocinas/metabolismo , Doxorrubicina/farmacología , Liposomas/farmacología , Metástasis de la Neoplasia/tratamiento farmacológico , Células TH1/efectos de los fármacos , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Melanoma/patología , Ratones , Ratones Endogámicos C57BL , Bazo/efectos de los fármacos , Bazo/metabolismo , Células TH1/metabolismo , Microambiente Tumoral/efectos de los fármacos
18.
Adv Exp Med Biol ; 1220: 11-34, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32304077

RESUMEN

Circulating tumor cells offer an unprecedented window into the metastatic cascade, and to some extent can be considered as intermediates in the process of metastasis. They exhibit dynamic oscillations in epithelial to mesenchymal plasticity and provide important opportunities for prognosis, therapy response monitoring, and targeting of metastatic disease. In this manuscript, we review the involvement of epithelial-mesenchymal plasticity in the early steps of metastasis and what we have learned about its contribution to genomic instability and genetic diversity, tumor progression and therapeutic responses using cell culture, mouse models and circulating tumor cells enriched from patients.


Asunto(s)
Transición Epitelial-Mesenquimal , Metástasis de la Neoplasia/patología , Células Neoplásicas Circulantes/patología , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/genética
19.
Intern Med ; 59(14): 1739-1740, 2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-32296006

RESUMEN

The central nervous system efficacy of dacomitinib, a key agent used in the treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC), is unclear. We herein present our experience in the use of dacomitinib for the treatment of multiple brain metastatic lesions from EGFR-mutation-positive NSCLC in an elderly patient. This case report demonstrates that dacomitinib can be an essential treatment option for patients with brain metastases.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Metástasis de la Neoplasia/tratamiento farmacológico , Quinazolinonas/efectos adversos , Quinazolinonas/uso terapéutico , Anciano , Receptores ErbB/genética , Femenino , Humanos , Mutación
20.
Urologe A ; 59(6): 673-679, 2020 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-32274540

RESUMEN

BACKGROUND: For many decades metastatic, castration-resistant prostate cancer (mCRPC) was thought to be treatment inaccessible. However, today, five drugs with significant life-prolonging effects are available in Germany, namely abiraterone, enzalutamide, docetaxel, cabazitaxel and radium-223. OBJECTIVE: The different treatment strategies in mCRPC are reviewed. MATERIALS AND METHODS: Landmark trials with supplementary information from Medline and abstracts of international congresses (ASCO; ASCO GU, ESMO) are summarized. RESULTS: The androgen receptor (AR)-targeting agents abiraterone and enzalutamide significantly prolong overall survival before and after docetaxel therapy. In addition, cabazitaxel can be applied secondary to docetaxel. Due to the low affinity of cabazitaxel to p­glycoprotein it remains active even if docetaxel has failed. The α­emitter radium-223 can be considered in third line therapy for symptomatic patients with bone limited disease only. In patients with castration resistance, a short prostate-specific antigen (PSA) doubling time but without metastases in conventional imaging apalutamide, darolutamide and enzalutamide significantly prolong metastasis-free survival. DISCUSSION: Prostate-specific membrane antigen (PSMA)-ligand therapy and novel targeting agents such as PARP inhibitors are promising new therapeutic modalities for mCRPC. Combination treatment strategies with immunotherapy are currently being evaluated in clinical trials. Based on the results of molecular analyses of tumor tissue as well as of circulating tumor cells and DNA, treatment of prostate cancer will be increasingly personalized in the future.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos/uso terapéutico , Docetaxel/uso terapéutico , Metástasis de la Neoplasia/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Alemania , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/patología , Resultado del Tratamiento
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