Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
J Transl Med ; 22(1): 378, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649894

RESUMEN

BACKGROUND: Bacteria-based cancer therapy have demonstrated innovative strategies to combat tumors. Recent studies have focused on gram-negative bacterial outer membrane vesicles (OMVs) as a novel cancer immunotherapy strategy due to its intrinsic properties as a versatile carrier. METHOD: Here, we developed an Human Papillomavirus (HPV)-associated E7 antigen displaying Salmonella-derived OMV vaccine, utilizing a Poly(L-arginine) cell penetrating peptide (CPP) to enhance HPV16 E7 (aa49-67) H-2 Db and OMV affinity, termed SOMV-9RE7. RESULTS: Due to OMV's intrinsic immunogenic properties, SOMV-9RE7 effectively activates adaptive immunity through antigen-presenting cell uptake and antigen cross-presentation. Vaccination of engineered OMVs shows immediate tumor suppression and recruitment of infiltrating tumor-reactive immune cells. CONCLUSION: The simplicity of the arginine coating strategy boasts the versatility of immuno-stimulating OMVs that can be broadly implemented to personalized bacterial immunotherapeutic applications.


Asunto(s)
Arginina , Vacunas contra el Cáncer , Proteínas E7 de Papillomavirus , Proteínas E7 de Papillomavirus/inmunología , Vacunas contra el Cáncer/inmunología , Humanos , Animales , Membrana Externa Bacteriana/inmunología , Ratones Endogámicos C57BL , Femenino
2.
J Biomed Sci ; 31(1): 19, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38287325

RESUMEN

BACKGROUND: Previous research in FMS-like tyrosine kinase 3 ligands (FLT3L) has primarily focused on their potential to generate dendritic cells (DCs) from bone marrow progenitors, with a limited understanding of how these cells affect CD8 T cell function. In this study, we further investigated the in vivo role of FLT3L for the immunomodulatory capabilities of CD8 T cells. METHODS: Albumin-conjugated FLT3L (Alb-FLT3L) was generated and applied for translational medicine purposes; here it was used to treat naïve C57BL/6 and OT1 mice for CD8 T cell response analysis. Syngeneic B16ova and E.G7ova mouse models were employed for adoptive cell transfer to evaluate the effects of Alb-FLT3L preconditioning of CD8 T cells on tumor progression. To uncover the underlying mechanisms of Alb-FLT3L modulation, we conducted bulk RNA-seq analysis of the CD44high CD8 T cells. STAT1-deficient mice were used to elucidate the functional roles of Alb-FLT3L in the modulation of T cells. Finally, antibody blockade of type one interferon signaling and in vitro coculture of plasmacytoid DCs (pDCs) with naive CD8 T cells was performed to determine the role of pDCs in mediating regulation of CD44high CD8 T cells. RESULTS: CD44high CD8 T cells were enhanced in C57BL/6 mice administrated with Alb-FLT3L. These CD8 T cells exhibited virtual memory features and had greater proliferative and effective functions. Notably, the adoptive transfer of CD44high naïve CD8 T cells into C57BL/6 mice with B16ova tumors led to significant tumor regression. RNA-seq analysis of the CD44high naïve CD8 T cells revealed FLT3L to induce CD44high CD8 T cells in a JAK-STAT1 signaling pathway-dependent manner, as supported by results indicating a decreased ability of FLT3L to enhance CD8 T cell proliferation in STAT1-deficient mice as compared to wild-type control mice. Moreover, antibody blockade of type one interferon signaling restricted the generation of FLT3L-induced CD44high CD8 T cells, while CD44 expression was able to be induced in naïve CD8 T cells cocultured with pDCs derived from FLT3L-treated mice. This suggests the crucial role of pDCs in mediating FLT3L regulation of CD44high CD8 T cells. CONCLUSIONS: These findings provide critical insight and support the therapeutic potential of Alb-FLT3L as an immune modulator in preconditioning of naïve CD8 T cells for cancer immunotherapy.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias , Animales , Ratones , Células Dendríticas , Interferones , Ratones Endogámicos C57BL , Neoplasias/metabolismo
3.
Mar Drugs ; 18(8)2020 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-32751169

RESUMEN

Non-small cell lung cancer (NSCLC)-carrying specific epidermal growth factor receptor (EGFR) mutations can be effectively treated by a tyrosine kinase inhibitor such as gefitinib. However, the inevitable development of acquired resistance leads to the eventual failure of therapy. In this study, we show the combination effect of omega-3 fatty acid-enriched fish oil (FO) and selenium (Se) on reversing the acquired gefitinib-resistance of HCC827 NSCLC cells. The gefitinib-resistant subline HCC827GR possesses lowered proapoptotic CHOP (CCAAT/enhancer-binding protein homologous protein) and elevated cytoprotective GRP78 (glucose regulated protein of a 78 kDa molecular weight) endoplasmic reticulum (ER) stress response elements, and it has elevated ß-catenin and cyclooxygenase-2 (COX-2) levels. Combining FO and Se counteracts the above features of HCC827GR cells, accompanied by the suppression of their raised epithelial-to-mesenchymal transition (EMT) and cancer stem markers, such as vimentin, AXL, N-cadherin, CD133, CD44, and ABCG2. Accordingly, an FO and Se combination augments the gefitinib-mediated growth inhibition and apoptosis of HCC827GR cells, along with the enhanced activation of caspase -3, -9, and ER stress-related caspase-4. Intriguingly, gefitinib further increases the elevated ABCG2 and cancer stem-like side population in HCC827GR cells, which can also be diminished by the FO and Se combination. The results suggest the potential of combining FO and Se in relieving the acquired resistance of NSCLC patients to targeted therapy.


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ácidos Grasos Omega-3/farmacología , Gefitinib/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Selenio/farmacología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Combinación de Medicamentos , Chaperón BiP del Retículo Endoplásmico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología
4.
Breast Cancer Res Treat ; 170(3): 583-591, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29623575

RESUMEN

PURPOSE: The aim of this study was to confirm the therapeutic role of eribulin on Taiwanese women with metastatic breast cancer. METHODS: This retrospective study examined 449 females who received eribulin between March 2014 and June 2017 at 14 hospitals in Taiwan for treatment of locally advanced or metastatic breast cancer. RESULTS: The survival rate at 24 months was 57.2% (95% CI 51.0-62.9%) and the median time to treatment failure (TTF) was 3.91 months (95% CI 3.45-3.94). A total of 175 patients (40.1%) received eribulin for fewer than 90 days and the others received it for 90 days or more. Eight patients (1.83%) had complete remission, 82 (18.8%) had partial remission, 202 (46.3%) had stable disease, and 144 (33.0%) had progressive disease (PD). Patients' tumors with the luminal A subtype had a significantly better objective response rate. Kaplan-Meier analysis indicated that hormone receptor positivity, luminal A subtype, receipt of eribulin as the 1st to 3rd line therapy, and metastasis to fewer than 4 organs were significantly associated with longer TTF. Stepwise multivariate analysis showed that only receipt of eribulin as the 1st to 3rd line therapy was significantly associated with TTF (HR 1.49, p < 0.001). All toxicities were manageable and only 18 patients (4.1%) discontinued treatment due to adverse events. CONCLUSIONS: Eribulin appears to have better efficacy and cause fewer adverse events, especially neutropenia, in Taiwanese women than Western women.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Furanos/uso terapéutico , Cetonas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Biomarcadores de Tumor , Neoplasias de la Mama/metabolismo , Esquema de Medicación , Femenino , Furanos/administración & dosificación , Furanos/efectos adversos , Humanos , Estimación de Kaplan-Meier , Cetonas/administración & dosificación , Cetonas/efectos adversos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Taiwán , Resultado del Tratamiento , Adulto Joven
5.
Liver Int ; 38(12): 2248-2259, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29797403

RESUMEN

BACKGROUND & AIMS: Few molecules are currently verified to be actionable drug targets in cholangiocarcinoma (CCA). Serine/threonine protein phosphatase 5 (PP5) dysregulation is related to several malignancies. However, the role of PP5 in CCA is poorly defined. METHODS: Colony and tumorsphere formation assays were conducted to establish the role of PP5 in CCA tumorigenesis. Cantharidin (CTD) and norcantharidin (NCTD), both potent PP5 inhibitors, were used in in vitro and in vivo experiments to validate the potential therapeutic role of PP5. RESULTS: Increased cell growth, colony formation and tumorsphere formation were observed in PP5-overexpressing CCA cells, whereas PP5 knockdown by shRNA decreased cell growth and colony formation. Tumours from HuCCT1 xenograft-bearing mice treated with PP5-shRNA showed decreased growth and increased AMP-activated protein kinase (AMPK) phosphorylation. Furthermore, CTD treatment decreased cell viability, reduced PP5 activity and enhanced AMPK phosphorylation in CCA cell lines. Overexpressing PP5 or enhancing PP5 activity suppressed AMPK phosphorylation and decreased CTD-induced cell death. Suppressing p-AMPK with siRNA or inhibitors also decreased CTD-induced cell death, suggesting a pivotal role for PP5-AMPK cascades in CCA. Immunoprecipitation revealed that PP5 interacted with AMPK. Importantly, treatment of HuCCT1 xenograft-bearing mice with NCTD, a CTD analogue with a lower systemic toxicity in vivo, suppressed PP5 activity, increased p-AMPK and reduced tumour volume. CONCLUSIONS: Protein phosphatase 5 negatively regulates AMPK phosphorylation and contributes to CCA aggressiveness; thus, PP5 may be a potential therapeutic target in CCA.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Neoplasias de los Conductos Biliares/metabolismo , Colangiocarcinoma/metabolismo , Proteínas Nucleares/antagonistas & inhibidores , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Animales , Antineoplásicos/farmacología , Apoptosis , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Cantaridina/farmacología , Carcinogénesis , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Inhibidores Enzimáticos/farmacología , Humanos , Masculino , Ratones , Ratones Noqueados , Ratones Desnudos , Proteínas Nucleares/genética , Fosfoproteínas Fosfatasas/genética , Ensayos Antitumor por Modelo de Xenoinjerto
6.
Br J Haematol ; 169(5): 737-45, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25818840

RESUMEN

Pericardial effusion (PE) is a rare but potentially life-threatening complication for allogeneic haematopoietic stem cell transplantation (HSCT) recipients. The risk factors, aetiology, incidence and therapy are largely unclear. To investigate this issue, we reviewed 391 adult patients undergoing allogeneic HSCT between January 2003 and December 2013. Twelve out of 391 patients (3·1%) developed PE of moderate to large amounts, including 9 out of 12 patients (75%) identified as late-onset PE. Two out of the nine patients with late-onset PE experienced recurrent effusion. The median age at HSCT was 44·5 years (range: 22-63 years) among the 12 patients with PE and 47 years in the late-onset patients. Multivariate analysis revealed that multiple transplant procedures was a significant risk factor for PE (P = 0·036) and a trend as risk factor in patients aged>50 years (P = 0·066). For late-onset PE, pre-transplant age>50 years (P = 0·032) and extensive chronic graft-versus-host disease (cGVHD) (P = 0·006) remained statistically significant on multivariate analysis. Currently, there are no published data exploring the risk factors for post-transplant PE in adult patients of allogeneic HSCT. Our study determined the risk factors and incidence for the post-transplant PE, especially in the late-onset group.


Asunto(s)
Derrame Pericárdico/epidemiología , Derrame Pericárdico/etiología , Adolescente , Adulto , Anciano , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Derrame Pericárdico/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Homólogo , Adulto Joven
7.
Ann Hematol ; 93(6): 1023-9, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24441917

RESUMEN

Patients with immune thrombocytopenia (ITP) may be at increased risk of infection because of the steroids and other immunosuppressive agents used in its treatment. This study aimed to identify events that are associated with infection within 6 months of diagnosis and the impact that infection has on survival. We retrospectively evaluated 239 patients (107 men, 132 women; median age 61 years) diagnosed between January 1997 and August 2011. Every patient received steroid treatment according to the platelet count and the extent of bleeding. Logistic regression analysis was used to identify risk factors associated with the development of infection within 6 months of ITP being diagnosed. Sixty-two patients (25.9 %) developed an infection within 6 months of diagnosis. Multivariate analysis revealed that a lower absolute lymphocyte count (ALC) at diagnosis (<1 × 10(9)/l) was an independent risk factor for infection (P = 0.039; 95 % confidence interval, 1.033-3.599; odds ratio, 1.928). The time to infection event is significant shorter in those of low ALC, compared with those of higher ALC (P = 0.032). Furthermore, the 1-year mortality rate after ITP diagnosis was significantly higher in those patients who developed an infection (P = 0.001). ITP patients with a low absolute lymphocyte count at diagnosis have an increased risk of infection, and those who develop infections have lower 1-year survival.


Asunto(s)
Infecciones/etiología , Recuento de Linfocitos , Púrpura Trombocitopénica Idiopática/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Susceptibilidad a Enfermedades , Femenino , Humanos , Huésped Inmunocomprometido , Estimación de Kaplan-Meier , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/mortalidad , Púrpura Trombocitopénica Idiopática/terapia , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Terapia Recuperativa , Esplenectomía , Resultado del Tratamiento , Adulto Joven
8.
Vaccines (Basel) ; 12(4)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38675812

RESUMEN

Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins with an HPV infection, which is linked to the activation of the Janus protein tyrosine kinase (JAK)/STAT signaling pathway. Various STAT signaling pathways, such as STAT3 activation, have been well documented for their tumorigenic role, yet the role of STAT1 in tumor formation remains unclear. In the current study, STAT1-/- mice were used to investigate the role of STAT1 in the tumorigenesis of a spontaneous HPV E6/E7-expressing oral tumor model. Subsequently, our candidate HPV DNA vaccine CRT/E7 was administered to determine whether the STAT1-/- host preserves a therapeutic-responsive tumor microenvironment. The results indicated that STAT1-/- induces robust tumorigenesis, yet a controlled tumor response was attained upon CRT/E7 vaccination. Characterizing this treatment effect, immunological analysis found a higher percentage of circulating CD4+ and CD8+ T cells and tumor-specific cytotoxic T cells. In addition, a reduction in exhaustive lymphocyte activity was observed. Further analysis of a whole-cell tumor challenge affirmed these findings, as spontaneous tumor growth was more rapid in STAT1-/- mice. In conclusion, STAT1 deletion accelerates tumorigenesis, but STAT1-/- mice maintains immunocompetency in CRT/E7 treatments.

9.
Ann Hematol ; 92(11): 1495-501, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23712292

RESUMEN

Rituximab reforms the treatment of diffuse large B-cell lymphoma (DLBCL) and the prognostic significance of baseline patient features should be reevaluated. Few population-based studies have investigated the association of diabetes mellitus (DM) and outcomes of lymphoma; however, the results remain inconclusive. From January 1, 2000 to December 31, 2009, a total of 468 consecutive newly diagnosed DLBCL patients receiving first-line chemotherapy with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) or rituximab plus CHOP (R-CHOP) were enrolled. Pre-existing DM was defined according to medical history, use of antidiabetic medications, or any record of an abnormal hemoglobin A1c test. Progression-free survival (PFS) and overall survival (OS) were estimated and compared using the Kaplan-Meier method with a log-rank test. CHOP was administered in 194 patients, and 274 patients received R-CHOP. DM was identified in 16.2 % (76/468) of patients. Diabetic patients were older and more performance restricted, compared to the non-DM patients in both the CHOP and R-CHOP groups. In the CHOP group, 5-year PFS and OS were inferior in DM patients (PFS, 32.4 vs. 50.0 % (P = 0.039); OS, 38.2 vs. 62.5 % (P = 0.002)). However, outcomes were similar for both DM and non-DM patients in the context of R-CHOP treatment (PFS, 69.0 vs. 57.3 % (P = 0.179); OS, 76.2 vs. 69.8 % (P = 0.586)). The response rate of chemotherapy in DM patients was also improved to a level similar to non-DM patients with rituximab use. In conclusion, the prognostic significance of preexisting DM in DLBCL patients is changing in the rituximab era. The potentially additional benefit of rituximab in DM patients merits further investigation.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Antineoplásicos/administración & dosificación , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Diabetes Mellitus/mortalidad , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Pronóstico , Estudios Retrospectivos , Rituximab , Terapia Recuperativa/métodos , Vincristina/administración & dosificación , Adulto Joven
10.
Nutrients ; 15(21)2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37960146

RESUMEN

Prostate cancer (PC) is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related death in males worldwide. Early-stage PC patients can benefit from surgical, radiation, and hormonal therapies; however, once the tumor transitions to an androgen-refractory state, the efficacy of treatments diminishes considerably. Recently, the exploration of natural products, particularly dietary phytochemicals, has intensified in response to addressing this prevailing medical challenge. In this study, we uncovered a synergistic effect from combinatorial treatment with lovastatin (an active component in red yeast rice) and Antrodia camphorata (AC, a folk mushroom) extract against PC3 human androgen-refractory PC cells. This combinatorial modality resulted in cell cycle arrest at the G0/G1 phase and induced apoptosis, accompanied by a marked reduction in molecules responsible for cellular proliferation (p-Rb/Rb, Cyclin A, Cyclin D1, and CDK1), aggressiveness (AXL, p-AKT, and survivin), and stemness (SIRT1, Notch1, and c-Myc). In contrast, treatment with either AC or lovastatin alone only exerted limited impacts on the cell cycle, apoptosis, and the aforementioned signaling molecules. Notably, significant reductions in canonical PC stemness markers (CD44 and CD133) were observed in lovastatin/AC-treated PC3 cells. Furthermore, lovastatin and AC have been individually examined for their anti-PC properties. Our findings elucidate a pioneering discovery in the synergistic combinatorial efficacy of AC and clinically viable concentrations of lovastatin on PC3 PC cells, offering novel insights into improving the therapeutic effects of dietary natural products for future strategic design of therapeutics against androgen-refractory prostate cancer.


Asunto(s)
Productos Biológicos , Neoplasias de la Próstata , Masculino , Humanos , Andrógenos/metabolismo , Células PC-3 , Lovastatina/farmacología , Proliferación Celular , Apoptosis , Neoplasias de la Próstata/patología , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Línea Celular Tumoral
11.
mBio ; 14(5): e0212123, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37791765

RESUMEN

IMPORTANCE: Respectively, HPV16 and HPV18 cause 50% and 20% of cervical cancer cases globally. Viral proteins E6 and E7 are obligate drivers of oncogenic transformation. We recently developed a candidate therapeutic DNA vaccine, pBI-11, that targets HPV16 and HPV18 E6 and E7. Single-site intramuscular delivery of pBI-11 via a needle elicited therapeutic anti-tumor effects in mice and is now being tested in high-risk human papillomavirus+ head and neck cancer patients (NCT05799144). Needle-free biojectors such as the Tropis device show promise due to ease of administration, high patient acceptability, and the possibility of improved delivery. For example, vaccination of patients with the ZyCoV-D DNA vaccine using the Tropis device is effective against COVID19, well tolerated, and licensed. Here we show that split-dose, multi-site administration and intradermal delivery via the Tropis biojector increase the delivery of pBI-11 DNA vaccine, enhance HPV antigen-specific CD8+ T-cell responses, and improve anti-tumor therapeutic effects, suggesting its translational potential to treat HPV16/18 infection and disease.


Asunto(s)
Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Vacunas de ADN , Femenino , Humanos , Animales , Ratones , Papillomavirus Humano 16/genética , Vacunas de ADN/genética , Vacunas de ADN/uso terapéutico , Papillomavirus Humano 18/genética , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Neoplasias del Cuello Uterino/prevención & control , Infecciones por Papillomavirus/prevención & control , Vacunación , Inmunidad
12.
Nutrients ; 14(15)2022 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-35956408

RESUMEN

Cisplatin is a prevalent chemotherapeutic agent used for non-small cell lung cancer (NSCLC) that is difficult to treat by targeted therapy, but the emergence of resistance severely limits its efficacy. Thus, an effective strategy to combat cisplatin resistance is required. This study demonstrated that, at clinically achievable concentrations, the combination of selenium yeast (Se-Y) and fish oil (FO) could synergistically induce the apoptosis of cancer stem cell (CSC)-like A549 NSCLC sphere cells, accompanied by a reversal of their resistance to cisplatin. Compared to parental A549 cells, sphere cells have higher cisplatin resistance and possess elevated CSC markers (CD133 and ABCG2), epithelial-mesenchymal transition markers (anexelekto (AXL), vimentin, and N-cadherin), and cytoprotective endoplasmic reticulum (ER) stress marker (glucose-regulated protein 78) and increased oncogenic drivers, such as yes-associated protein, transcriptional coactivator with PDZ-binding motif, ß-catenin, and cyclooxygenase-2. In contrast, the proapoptotic ER stress marker CCAAT/enhancer-binding protein homologous protein and AMP-activated protein kinase (AMPK) activity were reduced in sphere cells. The Se-Y and FO combination synergistically counteracted the above molecular features of A549 sphere cells and diminished their elevated CSC-like side population. AMPK inhibition by compound C restored the side population proportion diminished by this nutrient combination. The results suggest that the Se-Y and FO combination can potentially improve the outcome of cisplatin-treated NSCLC with phenotypes such as A549 cells.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Cisplatino , Resistencia a Antineoplásicos , Neoplasias Pulmonares , Células A549/efectos de los fármacos , Células A549/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Antineoplásicos/efectos adversos , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Aceites de Pescado/metabolismo , Aceites de Pescado/farmacología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Células Madre Neoplásicas , Fenotipo , Saccharomyces cerevisiae/metabolismo , Selenio/metabolismo , Selenio/farmacología
13.
Medicine (Baltimore) ; 99(35): e21922, 2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32871929

RESUMEN

RATIONALE: Cancer-related stroke has been regarded as an emerging subtype of ischemic event. Acute treatment for this subtype may include the antiplatelet agents, anticoagulants, or endovascular intervention. PATIENT CONCERNS: A 63-year-old woman with sudden-onset right hemiparesis and conscious change was sent to our emergency department. The patient had underlying sigmoid adenocarcinoma and received chemotherapy FOLFIRI (FOL, folinic acid; F, fluorouracil; and IRI, irinotecan) with targeted therapy cetuximab following lower anterior resection since the diagnosis was made. DIAGNOSES: Brain magnetic resonance angiography revealed a filling defect in left carotid bulb, and neurosonography showed a thick atherosclerotic plaque (size 4.9 mm) in the left internal carotid artery on day 5 after the onset of stroke. INTERVENTIONS: During the first three hours after onset, administration of IV tissue plasminogen activator did not resolve the thrombus. Dabigatran (110 mg bid) started on day 7. OUTCOMES: The atherosclerotic plaque dissolved on day 24. The patient recovered her muscle strength but still had nonfluent speech in mild extent. LESSONS: Thrombolytic and anticoagulant medications in this patient suggested the thrombus formation with fibrin-rich content which may be attributable to both cancer and chemotherapy. Dabigatran, an oral anticoagulant, had a benefit for this subtype of ischemic stroke among patients with cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antitrombinas/uso terapéutico , Trombosis de las Arterias Carótidas/terapia , Arteria Carótida Interna , Infarto de la Arteria Cerebral Media/inducido químicamente , Terapia Trombolítica , Adenocarcinoma/complicaciones , Adenocarcinoma/tratamiento farmacológico , Administración Oral , Trombosis de las Arterias Carótidas/diagnóstico por imagen , Arteria Carótida Interna/diagnóstico por imagen , Dabigatrán/uso terapéutico , Femenino , Humanos , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Angiografía por Resonancia Magnética , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/terapia , Neoplasias del Colon Sigmoide/complicaciones , Neoplasias del Colon Sigmoide/tratamiento farmacológico , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/uso terapéutico
14.
Medicine (Baltimore) ; 97(30): e11593, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30045291

RESUMEN

BACKGROUND: The management of breakthrough pain (BTP) in cancer patients is a challenge. It is clinically useful to evaluate the effectiveness of rapid-onset opioid at a starting dose in proportional to the background opioid regimen. This open-label, multicenter, noncomparative study aimed to assess the efficacy and safety of proportional doses of fentanyl buccal soluble film (FBSF) in patients with breakthrough cancer pain. METHODS: Thirty patients aged 20 to 70, experiencing 1 to 3 BTP per day, receiving regimens equivalent to 60 to 360 mg/day of oral morphine or 25 to 150 µg/h of transdermal fentanyl ≥1 week, were prospectively recruited. FBSF was administered proportionally based on their current opioid regimen for baseline pain. The percentage of patients requiring dose titration was evaluated. For each BTP episode, changes in pain intensity at 30 minutes (PID30) after dosing, patient's satisfaction, the percentage of episodes requiring rescue medication, and adverse events (AEs) were recorded. RESULTS: The percentage of patients who required dose titration was 21.4% (6/28) and 12.0% (3/25) in the full analysis set and per-protocol populations, respectively. The average PID30 was 3.9, and a pain score ≤3 was achieved in 95.1% of the events. Eight out of 367 (2.2%) BTP episodes needed rescue medication. The majority of subjects (75.8%) rated their experience of pain management as good to excellent. A total of 6 drug-related AEs were reported by 3 (10.7%) patients in the safety population. CONCLUSIONS: FBSF dose in proportional to the regimen of opioid for baseline pain management is efficacious and well tolerated for the treatment of cancer patients with BTP.


Asunto(s)
Analgésicos Opioides/administración & dosificación , Dolor Irruptivo/tratamiento farmacológico , Dolor en Cáncer/tratamiento farmacológico , Fentanilo/administración & dosificación , Manejo del Dolor/métodos , Administración Bucal , Adulto , Anciano , Dolor Irruptivo/etiología , Dolor en Cáncer/etiología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Satisfacción del Paciente , Resultado del Tratamiento , Adulto Joven
15.
Oncotarget ; 8(39): 65077-65089, 2017 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-29029413

RESUMEN

Sorafenib is a multiple kinase inhibitor which targets Raf kinases, VEGFR, and PDGFR and is approved for the treatment of hepatocellular carcinoma (HCC). Previously, we found that p-STAT3 is a major target of SC-43, a sorafenib derivative. In this study, we report that SC-43-induced apoptosis in cholangiocarcinoma (CCA) via a novel mechanism. Three CCA cell lines (HuCCT-1, KKU-100 and CGCCA) were treated with SC-43 to determine their sensitivity to SC-43-induced cell death and apoptosis. We found that SC-43 activated SH2 domain-containing phosphatase 1 (SHP-1) activity, leading to p-STAT3 and downstream cyclin B1 and Cdc2 downregulation, which induced G2-M arrest and apoptotic cell death. Importantly, SC-43 augmented SHP-1 activity by direct binding to N-SH2 and relief of its autoinhibition. Deletion of the N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 counteracted the effect of SC-43-induced SHP-1 phosphatase activation and antiproliferation ability in CCA cells. In vivo assay revealed that SC-43 exhibited xenograft tumor growth inhibition, p-STAT3 reduction and SHP-1 activity elevation. In conclusion, SC-43 induced apoptosis in CCA cells through the SHP-1/STAT3 signaling pathway.

16.
Eur J Cancer ; 72: 112-123, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28027514

RESUMEN

OBJECTIVES: Cancerous inhibitor of protein phosphatase 2A (CIP2A) has emerged as a therapeutic determinant mediating the anti-cancer effects of several new agents. We investigated the efficacy and mechanism of TD52, an erlotinib derivative with minimal p-EGFR inhibition but significant CIP2A downregulation, in triple-negative breast cancer (TNBC) cells. METHODS: TNBC lines were used for in vitro studies. Cell apoptosis was examined by flow cytometry and Western blot. Signal transduction pathways in cells were assessed by Western blot. In vivo efficacy of TD52 was tested in xenograft nude mice. RESULTS: We explored the CIP2A mRNA expression in a publically available database and found that higher levels of CIP2A mRNA is associated with worse recurrence-free survival in patients with TNBC. TD52-enhanced apoptosis accompanied with CIP2A downregulation and CIP2A overexpression protected cells from TD52-mediated apoptosis. The activity of protein phosphatase 2A (PP2A) was also increased in TD52-treated cells. TD52-induced apoptosis and p-Akt downregulation was attenuated by PP2A antagonist okadaic acid. Furthermore, TD52 indirectly downregulated CIP2A transcription via disturbing the binding of Elk1 to the CIP2A promoter. Importantly, TD52 showed anti-tumour activity in mice bearing TNBC xenograft tumours and downregulated CIP2A and p-Akt in these xenografted tumours. Interestingly, higher Elk1 mRNA expression was also associated with worse recurrence-free survival in TNBC patients by Kaplan-Meier survival analysis. CONCLUSION: Our findings indicated that EGFR-independent pharmacological modulation on Elk1/CIP2A signalling mediates the apoptotic effect of TD52 in TNBC cells, suggesting the potential therapeutic strategy.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Autoantígenos/metabolismo , Receptores ErbB/metabolismo , Clorhidrato de Erlotinib/farmacología , Proteínas de la Membrana/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Proteína Elk-1 con Dominio ets/metabolismo , Animales , Autoantígenos/genética , Modelos Animales de Enfermedad , Xenoinjertos , Humanos , Péptidos y Proteínas de Señalización Intracelular , Proteínas de la Membrana/genética , Ratones , Ratones Desnudos , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/metabolismo , Células Tumorales Cultivadas , Proteína Elk-1 con Dominio ets/genética
17.
Stem Cells Int ; 2016: 5143071, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27123006

RESUMEN

The cure of hematologic disorders by allogeneic hematopoietic stem cell transplantation (HSCT) is often associated with major complications resulting in poor outcome, including graft-versus-host disease (GVHD), relapse, and death. A novel composite endpoint of GVHD-free/relapse-free survival (GRFS) in which events include grades 3-4 acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death is censored to completely characterize the survival without mortality or ongoing morbidity. In this regard, studies attempting to identify the prognostic factors of GRFS are quite scarce. Thus, we reviewed 377 adult patients undergoing allogeneic HSCT between 2003 and 2013. The 1- and 2-year GRFS were 40.8% and 36.5%, respectively, significantly worse than overall survival and disease-free survival (log-rank p < 0.001). European Group for Blood and Marrow Transplantation (EBMT) risk score > 2 (p < 0.001) and hematologic malignancy (p = 0.033) were poor prognostic factors for 1-year GRFS. For 2-year GRFS, EBMT risk score > 2 (p < 0.001), being male (p = 0.028), and hematologic malignancy (p = 0.010) were significant for poor outcome. The events between 1-year GRFS and 2-year GRFS predominantly increased in relapsed patients. With prognostic factors of GRFS, we could evaluate the probability of real recovery following HSCT without ongoing morbidity.

18.
Oncotarget ; 7(8): 9135-49, 2016 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-26824320

RESUMEN

We tested the efficacy of lapatinib, a dual tyrosine kinase inhibitor which interrupts the HER2 and epidermal growth factor receptor (EGFR) pathways, in a panel of triple-negative breast cancer (TNBC) cells, and examined the drug mechanism. Lapatinib showed an anti-proliferative effect in HCC 1937, MDA-MB-468, and MDA-MB-231 cell lines. Lapatinib induced significant apoptosis and inhibited CIP2A and p-Akt in a dose and time-dependent manner in the three TNBC cell lines. Overexpression of CIP2A reduced lapatinib-induced apoptosis in MDA-MB-468 cells. In addition, lapatinib increased PP2A activity (in relation to CIP2A inhibition). Moreover, lapatinib-induced apoptosis and p-Akt downregulation was attenuated by PP2A antagonist okadaic acid. Furthermore, lapatinib indirectly decreased CIP2A transcription by disturbing the binding of Elk1 to the CIP2A promoter. Importantly, lapatinib showed anti-tumor activity in mice bearing MDA-MB-468 xenograft tumors, and suppressed CIP2A as well as p-Akt in these xenografted tumors. In summary, inhibition of CIP2A determines the effects of lapatinib-induced apoptosis in TNBC cells. In addition to being a dual tyrosine kinase inhibitor of HER2 and EGFR, lapatinib also inhibits CIP2A/PP2A/p-Akt signaling in TNBC cells.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proteínas de la Membrana/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Proteína Fosfatasa 2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Quinazolinas/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Animales , Autoantígenos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Receptores ErbB/antagonistas & inhibidores , Humanos , Lapatinib , Células MCF-7 , Ratones , Ratones Desnudos , Regiones Promotoras Genéticas/efectos de los fármacos , Receptor ErbB-2/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/patología , Ensayos Antitumor por Modelo de Xenoinjerto
19.
J Microbiol Immunol Infect ; 49(4): 567-74, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25735797

RESUMEN

BACKGROUND: To investigate the incidence and risk factors for the occurrence of proven or probable invasive fungal infection (IFI) in adult patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We retrospectively analyzed 421 patients undergoing HSCT between 2002 and 2013 in our hospital. The risk factors for the occurrence of IFI were analyzed using Cox regression models. RESULTS: Thirty-one patients with the median age of 42 years (range, 19-60 years) developed IFI after HSCT. The post-HSCT IFI incidence was 7.4% and median time from HSCT to the diagnosis of IFI was 139 days (range, 2-1809 days). Of the pretransplant factors, European Group for Blood and Marrow Transplantation (EBMT) risk score > 2 (p = 0.001) and prior history of IFI (p = 0.006) or type 2 diabetes mellitus (DM; p = 0.042) were the significant predictors for post-HSCT IFI in univariate analyses. In multivariate analysis, EBMT risk score > 2 (p = 0.015) and prior history of IFI (p = 0.006) retained significance. Of the post-transplant factors, acute graft-versus-disease (GVHD) overall Grade III-IV (p < 0.001), extensive chronic GVHD (p = 0.002), development of post-transplant lymphoproliferative disorders (p = 0.005), and the use of high-dose steroids (p < 0.001) were statistically significant in univariate analyses. After multivariate analysis, high-dose steroids (p < 0.001) and acute GVHD overall Grade III-IV (p = 0.045) retained significance. CONCLUSION: These results suggest that risk group stratification prior to HSCT and monitoring of IFI in patients with severe GVHD receiving high-dose steroids is mandatory to reduce the mortality and morbidity of post-HSCT IFI, especially in those with prior history of IFI.


Asunto(s)
Aspergilosis/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Huésped Inmunocomprometido , Infecciones Fúngicas Invasoras/epidemiología , Adulto , Anciano , Aspergilosis/microbiología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Infecciones Fúngicas Invasoras/microbiología , Masculino , Metilprednisolona/efectos adversos , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento , Adulto Joven
20.
Biomed Res Int ; 2014: 904341, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25110705

RESUMEN

BACKGROUND AND PURPOSE: This study aimed to analyze survival, clinical responses, compliance, and adverse effects in locally advanced head and neck cancer (LAHNC) patients treated with split-dose cisplatin-based concurrent chemoradiation therapy (SD-CCRT) or cetuximab with concurrent radiation therapy (BioRT). MATERIALS AND METHODS: We retrospectively evaluated 170 LAHNC patients diagnosed between January 1, 2009, and July 31, 2012: 116 received CCRT and 54 received BioRT. RESULTS: Complete response rates were similar in the SD-CCRT and BioRT groups (63.8% versus 59.3%; P = 0.807), and locoregional relapse rates were 18.1% and 13.0%, respectively (P = 0.400). The 3-year relapse-free survival rate was 65.8% in the SD-CCRT group and 65.5% in the BioRT group, respectively (P = 0.647). The 3-year overall survival rate was 78.5% in the SD-CCRT group and 70.9% in the BioRT group, respectively (P = 0.879). Hematologic side effects were significantly more frequent in the SD-CCRT than in the BioRT group. Mucositis frequency was similar. CONCLUSIONS: Primary SD-CCRT and BioRT both showed good clinical response and survival. Hematologic toxicities were more frequent, but tolerable, in the SD-CCRT group. Both groups showed good compliance.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos/administración & dosificación , Quimioradioterapia/métodos , Cisplatino/administración & dosificación , Neoplasias de Cabeza y Cuello , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/efectos adversos , Cetuximab , Quimioradioterapia/efectos adversos , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Humanos , Masculino , Persona de Mediana Edad , Mucositis/etiología , Mucositis/mortalidad , Fármacos Sensibilizantes a Radiaciones/efectos adversos , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA