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1.
Oncologist ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39236068

RESUMEN

BACKGROUND: Smoldering multiple myeloma (SMM), an asymptomatic precursor of multiple myeloma (MM), carries a variable risk of progression to MM. There is little consensus on the efficacy or optimal timing of treatment in SMM. We systematically reviewed the landscape of all clinical trials in SMM. We compared the efficacy of treatment regimens studied in SMM to results from these regimens when used in newly diagnosed multiple myeloma (NDMM), to determine whether the data suggest deeper responses in SMM versus NDMM. METHODS: All prospective interventional clinical trials for SMM, including published studies, meeting abstracts, and unpublished trials listed on ClinicalTrials.gov up to April 1, 2023, were identified. Trial-related variables were captured, including treatment strategy and efficacy results. Relevant clinical endpoints were defined as overall survival (OS) and quality of life. RESULTS: Among 45 SMM trials identified, 38 (84.4%) assessed active myeloma drugs, while 7 (15.6%) studied bone-modifying agents alone. Of 18 randomized trials in SMM, only one (5.6%) had a primary endpoint of OS; the most common primary endpoint was progression-free survival (n = 7, 38.9%). Among 32 SMM trials with available results, 9 (28.1%) met their prespecified primary endpoint, of which 5 were single-arm studies. Six treatment regimens were tested in both SMM and NDMM; 5 regimens yielded a lower rate of very good partial response rate or better (≥VGPR) in SMM compared to the corresponding NDMM trial (32% vs 63%, 43% vs 53%, 40% vs 63%, 86% vs 89%, 92% vs 95%, and 94% vs 87%, respectively). CONCLUSION: In this systematic review of all prospective interventional clinical trials in SMM, we found significant variability in trial design, including randomization status, primary endpoints, and types of intervention used. Despite the statistical limitations, comparison of treatment regimens revealed no compelling evidence that the treatment is more effective when introduced early in SMM compared to NDMM.

2.
Ther Adv Med Oncol ; 16: 17588359241273053, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220298

RESUMEN

Background: The prognostic implications of tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are poorly studied in hematologic malignancies. Objectives: This study aimed to better understand the characteristics and prognostic value of TMB and PD-1/PD-L1 in hematologic malignancies. Design: This real-world study was conducted among patients with hematologic malignancies who had next-generation sequencing (NGS) (Foundation Medicine) at the University of California San Diego Moores Cancer Center (2014-2018). Methods: TMB was measured by NGS. PD-L1 expression (tumor proportion score, TPS) was measured by immunohistochemistry (classified as high (⩾50%), low (1-49%), and negative (<1%)). Data was curated from the electronic medical records. Results: In 388 evaluable patients, the most common diagnoses were B-cell non-Hodgkin lymphoma (NHL) (35%) and Philadelphia chromosome-negative myeloproliferative disorders (16%). Median TMB was 1.6 mutations/Mb (range, 0-46.83). Forty-eight patients (12%) had TMB ⩾10 mutations/Mb, 90% of which were B-cell or T-cell NHL. In 85 samples with available PD-L1 scores, 11 were high; 26, low; and 48, no tumor cell expression. PD-L1 TPS positive (⩾1%) was most common in T-cell NHL (7/9 (77%) cases) followed by B-cell NHL (21/51 (41%) cases). TMB ⩾4 mutations/Mb and PD-L1 score ⩾1% were significantly associated with shorter overall survival (OS) from diagnosis, with hazard ratio (HR) = 1.46 (p = 0.02, 95% confidence interval (CI) 1.05-2.03) and HR = 2.11 (p = 0.04, 95% CI 1.04-4.30), respectively; the relationship was more pronounced when PD-L1 ⩾50% versus <50% was used (HR = 2.80, p = 0.02, 95% CI 1.19-6.59). Higher TMB and higher PD-L1 positivity correlation were significant but weak (Pearson correlation coefficient R 2 = 0.04, p = 0.04). Conclusion: TMB ⩾4 mutations/Mb and positive PD-L1 TPS are poor prognostic factors, correlating with shorter OS across hematologic malignancies. Trial registration: ClinicalTrials.gov NCT02478931.

4.
Cancers (Basel) ; 15(18)2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37760639

RESUMEN

Chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We describe the real-world baseline characteristics, efficacy, safety, and post-relapse outcomes of adult patients with R/R LBCL who received CAR T-cell therapy at the University of California San Diego. A total of 66 patients with LBCL were treated with tisagenlecleucel or axicabtagene ciloleucel. The median age was 59.5, and 21% were over 70 years old. Additionally, 20% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance score of ≥2. Cytokine release syndrome incidence was 88%; immune effector cell-associated neurotoxicity syndrome incidence was 56%. All-grade infection occurred in 48% of patients and in 79% of patients > 70 years old. Complete response (CR) was achieved in 53% and partial response in 14%. Median progression-free survival (PFS) was 10.3 months; median overall survival (OS) was 28.4 months. Patients who relapsed post-CAR T-cell therapy had poor outcomes, with a median OS2 of 4.8 months. Upon multivariate analysis, both ECOG (HR 2.65, 95% CI: 1.30-5.41; p = 0.007) and ≥2 sites of extranodal involvement (HR 2.22, 95% CI: 1.15-4.31; p = 0.018) were significant predictors of PFS. Twenty-six patients were R/R to CAR T-cell therapy; six patients were in remission at the time of data cut off, one of whom received allogeneic transplant. Overall, older patients can safely undergo CAR T-cell therapy, despite the increased risk of all-grade infection. In our cohort, ECOG performance score and ≥2 sites of extranodal disease are significant predictors of PFS.

5.
Endocrinol Metab (Seoul) ; 37(1): 96-111, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35255604

RESUMEN

BACKGROUND: Diabetic nephropathy (DN) is characterized by albuminuria and accumulation of extracellular matrix (ECM) in kidney. Transforming growth factor-ß (TGF-ß) plays a central role in promoting ECM accumulation. We aimed to examine the effects of EW-7197, an inhibitor of TGF-ß type 1 receptor kinase (ALK5), in retarding the progression of DN, both in vivo, using a diabetic mouse model (db/db mice), and in vitro, in podocytes and mesangial cells. METHODS: In vivo study: 8-week-old db/db mice were orally administered EW-7197 at a dose of 5 or 20 mg/kg/day for 10 weeks. Metabolic parameters and renal function were monitored. Glomerular histomorphology and renal protein expression were evaluated by histochemical staining and Western blot analyses, respectively. In vitro study: DN was induced by high glucose (30 mM) in podocytes and TGF-ß (2 ng/mL) in mesangial cells. Cells were treated with EW-7197 (500 nM) for 24 hours and the mechanism associated with the attenuation of DN was investigated. RESULTS: Enhanced albuminuria and glomerular morphohistological changes were observed in db/db compared to that of the nondiabetic (db/m) mice. These alterations were associated with the activation of the TGF-ß signaling pathway. Treatment with EW-7197 significantly inhibited TGF-ß signaling, inflammation, apoptosis, reactive oxygen species, and endoplasmic reticulum stress in diabetic mice and renal cells. CONCLUSION: EW-7197 exhibits renoprotective effect in DN. EW-7197 alleviates renal fibrosis and inflammation in diabetes by inhibiting downstream TGF-ß signaling, thereby retarding the progression of DN. Our study supports EW-7197 as a therapeutically beneficial compound to treat DN.


Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Compuestos de Anilina , Animales , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Inflamación/complicaciones , Ratones , Triazoles/uso terapéutico
6.
J Otolaryngol Head Neck Surg ; 51(1): 5, 2022 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-35123577

RESUMEN

BACKGROUND: Germline CDKN2A mutations are a well-known cause of familial atypical multiple mole melanoma (OMIM #155601) and melanoma-pancreatic cancer syndrome (OMIM #606719). Increased risk of head and neck squamous cell carcinoma (HNSCC), particularly oral squamous cell carcinoma (OSCC) in those with germline CDKN2A mutations, has been described. However, screening for HNSCC is not a routine practice in patients with CDKN2A germline mutations and these mutations are not a conventional test for HNSCC patients without obvious risk factors. CASE PRESENTATION: We describe a female with no smoking history who developed oral squamous cell carcinoma at age 39 and had a complex clinical course of recurrent multifocal squamous cell carcinoma (SCC) and carcinoma in situ of the oral cavity and oropharynx. Detailed family history demonstrated that her mother was diagnosed with OSCC and melanoma in her 40 s, and her maternal grandfather was diagnosed with metastatic melanoma in his 40 s. Genetic testing of the patient and her mother revealed CDKN2A c.301G>T mutation. She was referred to genetic counseling as well as to dermatology, gastroenterology, and neurology for cancer surveillance. She was treated with resections and has no evidence of disease 3 years after diagnosis. CONCLUSIONS: We report a family with a CDKN2A c.301 G>T mutation who also have significant history of OSCC, adding to the growing body of literature suggesting increased risk of HNSCC, particularly OSCC, in CDKN2A germline mutation carriers. It is important to consider CDKN2A mutation testing in familial HNSCC and young patients without obvious risk factors. Moreover, surveillance for HNSCC should be routine practice in those with a CDKN2A germline mutation.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Neoplasias Cutáneas , Adulto , Carcinoma de Células Escamosas/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Femenino , Mutación de Línea Germinal , Humanos , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/genética , Mutación , Recurrencia Local de Neoplasia , Carcinoma de Células Escamosas de Cabeza y Cuello
7.
Transplant Cell Ther ; 28(1): 30.e1-30.e7, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34655803

RESUMEN

Methods that enable monitoring of therapeutic efficacy of autologous chimeric antigen receptor (CAR) T-cell therapy will be clinically useful. The aim of this study is to demonstrate the feasibility of blood-derived cell-free DNA (cfDNA) to predict CAR T-cell therapy response in patients with refractory B-cell lymphomas. Whole blood was collected before and throughout CAR T-cell therapy until day 154. Low-coverage (∼0.4×), genome-wide cfDNA sequencing, similar to that established for noninvasive prenatal testing, was performed. The genomic instability number (GIN) was used to quantify plasma copy number alteration level. Twelve patients were enrolled. Seven (58%) patients achieved a complete response (CR); 2 (25%), a partial response. Median progression-free survival was 99 days; median overall survival was not reached (median follow-up, 247 days). Altogether, 127 blood samples were analyzed (median, 10 samples/patient [range 8-13]). All 5 patients who remained in CR at the time of last measurement had GIN <170 (threshold). Two patients who attained CR, but later relapsed, and all but one patient who had best response other than CR had last GIN measurement of >170. In 5 of 6 patients with relapsed or progressive disease, increasing GIN was observed before the diagnosis by imaging. The abundance of CAR T-cell construct (absolute number of construct copies relative to the number of human genome equivalents) also showed a trend to correlate with outcome (day 10, P = .052). These data describe a proof-of-concept for the use of multiple liquid biopsy technologies to monitor therapeutic response in B-cell lymphoma patients receiving CAR T-cell therapy.


Asunto(s)
Ácidos Nucleicos Libres de Células , Linfoma de Células B , Receptores Quiméricos de Antígenos , Antígenos CD19/genética , Humanos , Inmunoterapia Adoptiva , Linfoma de Células B/genética , Receptores Quiméricos de Antígenos/genética
8.
Eur J Haematol ; 107(6): 642-649, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34431136

RESUMEN

OBJECTIVES: Castleman disease (CD) is a heterogeneous group of disorders involving systemic inflammation and lymphoproliferation. Recently, clonal mutations have been identified in unicentric CD (UCD) and idiopathic multicentric CD (iMCD), suggesting a potential underlying neoplastic process. METHODS: Patients with UCD or iMCD with next generation sequencing (NGS) data on tissue DNA and/or circulating tumor DNA (ctDNA) were included. RESULTS: Five patients were included, 4 with iMCD and 1 with UCD. Four patients (80%) were women; median age was 40 years. Three of five patients (60%) had ≥1 clonal mutation detected on biopsy among the genes included in the panel. One patient with iMCD had a 14q32-1p35 rearrangement and a der(1)dup(1)(q42q21)del(1)(q42) (1q21 being IL-6R locus) on karyotype. This patient also had a NF1 K2459fs alteration on ctDNA (0.3%). Another patient with iMCD had a KDM5C Q836* mutation, and one patient with UCD had a TNS3-ALK fusion but no ALK expression by immunohistochemistry. CONCLUSIONS: We report 4 novel somatic alterations found in patients with UCD or iMCD. The 1q21 locus contains IL-6R, and duplication of this locus may increase IL-6 expression. These findings suggest that a clonal process may be responsible for the inflammatory phenotype in some patients with UCD and iMCD.


Asunto(s)
Enfermedad de Castleman/patología , Mutación , Adulto , Enfermedad de Castleman/genética , Aberraciones Cromosómicas , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad
9.
PLoS One ; 16(4): e0250666, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33891667

RESUMEN

The anti-aging gene, klotho, has been identified as a multi-functional humoral factor and is implicated in multiple biological processes. However, the effects of klotho on podocyte injury in diabetic nephropathy are poorly understood. Thus, the current study aims to investigate the renoprotective effects of klotho against podocyte injury in diabetic nephropathy. We examined lipid accumulation and klotho expression in the kidneys of diabetic patients and animals. We stimulated cultured mouse podocytes with palmitate to induce lipotoxicity-mediated podocyte injury with or without recombinant klotho. Klotho level was decreased in podocytes of lipid-accumulated obese diabetic kidneys and palmitate-treated mouse podocytes. Palmitate-treated podocytes showed increased apoptosis, intracellular ROS, ER stress, inflammation, and fibrosis, and these were significantly attenuated by klotho administration. Klotho treatment restored palmitate-induced downregulation of the antioxidant molecules, Nrf2, Keap1, and SOD1. Klotho inhibited the phosphorylation of FOXO3a, promoted its nuclear translocation, and then upregulated MnSOD expression. In addition, klotho administration attenuated palmitate-induced cytoskeleton changes, decreased nephrin expression, and increased TRPC6 expression, eventually improving podocyte albumin permeability. These results suggest that klotho administration prevents palmitate-induced functional and morphological podocyte injuries, and this may indicate that klotho is a potential therapeutic agent for the treatment of podocyte injury in obese diabetic nephropathy.


Asunto(s)
Apoptosis/efectos de los fármacos , Nefropatías Diabéticas/patología , Glucuronidasa/farmacología , Palmitatos/farmacología , Animales , Citocinas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Proteína Forkhead Box O3/metabolismo , Glucuronidasa/genética , Glucuronidasa/metabolismo , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Proteínas Klotho , Ratones , Ratones Obesos , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Podocitos/citología , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/farmacología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Canal Catiónico TRPC6/genética , Canal Catiónico TRPC6/metabolismo , Regulación hacia Arriba/efectos de los fármacos
10.
ACS Nano ; 15(4): 6540-6550, 2021 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-33784072

RESUMEN

Silver-based nanomaterials have been versatile building blocks of various photoassisted energy applications; however, they have demonstrated poor electrochemical catalytic performance and stability, in particular, in acidic environments. Here we report a stable and high-performance electrochemical catalyst of silver telluride (AgTe) for the hydrogen evolution reaction (HER), which was synthesized with a nanoporous structure by an electrochemical synthesis method. X-ray spectroscopy techniques on the nanometer scale and high-resolution transmission electron microscopy revealed an orthorhombic structure of nanoporous AgTe with precise lattice constants. First-principles calculations show that the AgTe surface possesses highly active catalytic sites for the HER with an optimized Gibbs free energy change of hydrogen adsorption (-0.005 eV). Our nanoporous AgTe demonstrates exceptional stability and performance for the HER, an overpotential of 27 mV, and a Tafel slope of 33 mV/dec. As a stable catalyst for hydrogen production, AgTe is comparable to platinum-based catalysts and provides a breakthrough for high-performance electrochemical catalysts.

11.
Clin Chest Med ; 41(2): 223-235, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32402358

RESUMEN

The treatment of metastatic non-small cell lung cancer (NSCLC) is constantly evolving. Although the advent of immunotherapy has played an important role in the treatment of patients with NSCLC, the identification of driver mutations and the subsequent specific treatment of these targets often lead to durable responses while maintaining quality of life. This review delves into targeted therapies available for epidermal growth factor receptor, anaplastic lymphoma kinase, ROS1, neurotrophic tropomyosin receptor kinase, and BRAF- mutated NSCLC patients, as well as other mutations with promising novel drugs under clinical investigation.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/patología , Metástasis de la Neoplasia
12.
Fish Shellfish Immunol ; 102: 20-27, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32272258

RESUMEN

The aquaculture industry in Korea has grown rapidly since the 1960s, and it is a major food source. However, the expansion of aquaculture systems has increased the chances of infectious disease outbreaks, and vaccination plays an important role in commercial fish farming. This is the first comprehensive review of commercial fish vaccines in Korea. It not only provides an overview of commercially available fish vaccines and their associated approval processes and laws, but also some perspectives on research advances regarding fish vaccines in Korea. In Korea, fish vaccines are approved only after their safety and effectiveness have been verified according to the Pharmaceutical Affairs Act, and after approval, each vaccine lot must pass the national evaluation criteria. As of the end of 2019, 29 vaccines were approved for 10 fish pathogens, including both single and combination vaccines containing more than two inactivated pathogens. The approved fish vaccines consist of 2 immersion vaccines, as well as 1 intramuscular and 26 intraperitoneal vaccines, which require syringe injection. All the 29 vaccines are manufactured as formalin-inactivated vaccines; 1 is an adjuvant vaccine and 28 are non-adjuvant vaccines; 25 are bacterial vaccines, 2 are viral vaccines, 1 is a parasite vaccine, and 1 is a parasite and bacterial vaccine. In terms of the target fish species, 27 vaccines are used in the olive flounder (Paralichthys olivaceus), 1 in the starry flounder (Platichthys stellatus), and 1 in the red seabream (Pagrus major), striped beakfish (Oplegnathus fasciatus), and amberjack (Seriola quinqueradiata). This imbalance exists mostly because the olive flounder is the main farmed fish species in Korea. In 2018, 67.71 million vaccine doses were distributed following satisfactory performance in the national evaluation. They were used to vaccinate approximately 80.6% of farmed olive flounders.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Vacunas Bacterianas/uso terapéutico , Enfermedades de los Peces/prevención & control , Vacunas Antiprotozoos/uso terapéutico , Vacunación/veterinaria , Vacunas Virales/uso terapéutico , Adyuvantes Inmunológicos/administración & dosificación , Animales , Vacunas Bacterianas/administración & dosificación , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/parasitología , Enfermedades de los Peces/virología , Formaldehído/química , Vacunas Antiprotozoos/administración & dosificación , República de Corea , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/uso terapéutico , Vacunas Virales/administración & dosificación
13.
Clin Med Insights Oncol ; 14: 1179554920976366, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33447123

RESUMEN

Treatment of cancer has transformed with the introduction of checkpoint inhibitors. However, the majority of solid tumor patients do not respond to checkpoint blockade. In contrast, the response rate to programmed cell death 1 (PD-1) blockade in relapsed/refractory classical Hodgkin lymphoma (cHL) is 65% to 84% which is the highest among all cancers. Currently, checkpoint inhibitors are only approved for cHL and primary mediastinal B-cell lymphoma as the responses to single-agent checkpoint blockade in other hematologic malignancies is disappointingly low. Various established biomarkers such as programmed cell death 1 ligand 1 (PD-L1) protein surface expression, mismatch repair (MMR) status, and tumor mutational burden (TMB) are routinely used in clinical decision-making in solid tumors. In this review, we will explore these biomarkers in the context of hematologic malignancies. We review characteristic 9p24.1 structural alteration in cHL and primary mediastinal B-cell lymphoma (PMBCL) as a basis for response to PD-1 inhibition, as well as the role of antigen presentation pathways. We also explore the reported frequencies of MMR deficiency in various hematologic malignancies and investigate TMB as a predictive marker.

14.
ACS Omega ; 4(6): 10985-10990, 2019 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-31460196

RESUMEN

The chemical and electronic structure of MoO3 thin films is monitored by synchrotron-based hard X-ray photoelectron spectroscopy while annealing from room temperature to 310 °C. Color-coded 2D intensity maps of the Mo 3d and O 1s and valence band maximum (VBM) spectra show the evolution of the annealing-induced changes. Broadening of the Mo 3d and O 1s spectra indicate the reduction of MoO3. At moderate temperatures (120-200 °C), we find spectral evidence for the formation of Mo5+ and at higher temperatures (>165 °C) also of Mo4+ states. These states can be related to the spectral intensity above the VBM attributed to O vacancy induced gap states caused by partial filling of initially unoccupied Mo 4d-derived states. A clear relation between annealing temperature and the induced changes in the chemical and electronic structure suggests this approach as a route for deliberate tuning of MoO3 thin-film properties.

15.
Cancer Med ; 8(6): 2832-2839, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31016870

RESUMEN

BACKGROUND: The Philadelphia chromosome is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). While hematopoietic stem cell transplantation (HSCT) has been regarded as a favorable treatment option in adult Philadelphia-positive (Ph+) ALL, its benefit is less clear in the era of newer generation tyrosine kinase inhibitors (TKIs) like dasatinib. METHODS: This was a retrospective study that analyzed the outcomes of adult patients with Ph+ ALL treated with either combination chemotherapy plus dasatinib or combination chemotherapy plus dasatinib followed by allogeneic HSCT. RESULTS: A total of 70 patients were included; 30 (42.9%) underwent allogeneic HSCT while 40 (57.1%) received only chemotherapy plus dasatinib. In comparing overall survival (OS) rates, results between the 2 groups were similar with a 1-year OS of 93.3% versus 100% (P = 0.20), 2-year OS of 89.8% versus 86.2% (P = 0.72), and 3-year OS of 76% versus 71.3% (P = 0.56) in the transplant versus nontransplant groups, respectively. The 3-year relapse-free survival (RFS) rates were also similar at 70.5% in the transplant group and 80.1% in the nontransplant group (P = 0.94). Subgroup analyses were performed for patients with specific poor prognostic factors (higher white blood count, older age, positive minimal residual disease status), but results again showed no significant survival difference between transplant and nontransplant patients. CONCLUSIONS: While HSCT has historically led to a survival advantage in Ph+ ALL, the results of our study demonstrate that it may have a less beneficial role in the era of newer generation TKIs such as dasatinib.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Dasatinib/administración & dosificación , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Neoplasia Residual/diagnóstico , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pronóstico , Estudios Retrospectivos , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven
16.
J Glaucoma ; 28(2): 154-160, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30394980

RESUMEN

PURPOSE: To evaluate circulatory melatonin levels by assessing nocturnal urinary excretion of 6-sulfatoxymelatonin (aMT6s) in patients with primary open-angle glaucoma (POAG) and to compare the high-tension group and the low-tension group. METHODS: This study included 80 eyes of 41 POAG patients and 87 eyes of 44 control subjects. POAG group was further classified into high-tension group and low-tension group according to the pretreatment intraocular pressure (IOP). The first urine in the morning was collected and aMT6s were measured using a commercial ELISA kit. Urinary aMT6s levels were expressed as ng aMT6s/mg creatinine. Differences in melatonin levels among the control and POAG subgroups were evaluated by generalized estimating equation adjusting age, sex, sleep duration, and intereye correlation. RESULTS: Urinary aMT6s/creatinine ratio did not differ between POAG and control group (P=0.097). The difference in the aMT6s/creatinine ratio between the 3 groups-high-tension group with baseline IOP≥21 mm Hg (19.74±3.12 ng/mg), low-tension glaucoma group with baseline IOP<21 mm Hg (26.71±3.47 ng/mg), and control group (30.35±3.05 ng/mg)-was statistically significant (P=0.046). Post hoc analysis revealed that the difference between the control and high-tension glaucoma groups was significant (P=0.014), whereas the difference between the control and low-tension glaucoma groups was not (P=0.436). CONCLUSIONS: This study found low melatonin levels in high-tension glaucoma compared with the control.


Asunto(s)
Glaucoma de Ángulo Abierto/orina , Presión Intraocular/fisiología , Melatonina/análogos & derivados , Anciano , Creatinina/orina , Ensayo de Inmunoadsorción Enzimática , Femenino , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Masculino , Melatonina/orina , Persona de Mediana Edad , Hipotensión Ocular , Tonometría Ocular
17.
Sci Rep ; 7(1): 15723, 2017 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-29146956

RESUMEN

A monolithic tandem solar cell consisting of crystalline Si (c-Si)/indium tin oxide (ITO)/CuGaSe2 (CGSe) was demonstrated by stacking a CGSe solar cell on a c-Si/ITO solar cell to obtain a photovoltaic conversion efficiency of about 10%. Electrical analyses based on cell-selective light absorption were applied to individually characterize the photovoltaic performances of the top and bottom subcells. Illumination at a frequency that could be absorbed only by a targeted top or bottom subcell permitted measurement of the open-circuit voltage of the target subcell and the shunt resistance of the non-target subcell. The cell parameters measured from each subcell were very similar to those of the corresponding single cell, confirming the validity of the suggested method. In addition, separating the light absorption intensities at the top and bottom subcells made us measure the bias-dependent photocurrent for each subcell. The series resistance of a c-Si/ITO/CGSe cell subjected to bottom-cell limiting conditions was slightly large, implying that the tunnel junction was a little resistive or slightly beyond ohmic. This analysis demonstrated that aside from producing a slightly resistive tunnel junction, our fabrication processes were successful in monolithically integrating a CGSe cell onto a c-Si/ITO cell without degrading the performances of both cells.


Asunto(s)
Absorción de Radiación , Electricidad , Selenio/química , Silicio/química , Energía Solar , Luz Solar
18.
Sci Rep ; 7(1): 7336, 2017 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-28779077

RESUMEN

We demonstrated fabrication of a parabola shaped Si nanostructures of various periods by combined approach of nanosphere lithography and a single step CF4/O2 reactive ion etch (RIE) process. Silica nanosphere monolayers in a hexagonal array were well deposited by a solvent controlled spin coating technique based on binary organic solvents. We showed numerically that a parabolic Si nanostructure of an optimal period among various-shaped nanostructures overcoated with a dielectric layer of a 70 nm thickness provide the most effective antireflection. As the simulation results as a design guide, we fabricated the parabolic Si nanostructures of a 520 nm period and a 300 nm height exhibiting the lowest weighted reflectance of 2.75%. With incorporation of such parabolic Si nanostructures, a damage removal process for 20 sec and SiNx antireflection coating of a 70 nm thickness, the efficiency of solar cells increased to 17.2% while that of the planar cells without the nanostructures exhibited 16.2%. The efficiency enhancement of the cell with the Si nanostructures was attributed to the improved photocurrents arising from the broad spectral antireflection which was confirmed by the external quantum efficiency (EQE) measurements.

19.
J Nerv Ment Dis ; 204(3): 217-20, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26919300

RESUMEN

Glaucoma is a group of optic neuropathies that is more prevalent among the elderly population and commonly associates with comorbidities, including mental disorders in that population. This article reviews the relationship between glaucoma and mental disorders. In it, we discuss the coexistence of glaucoma and mental illnesses, including Alzheimer's disease, depression, and personality disorder. We also focus on the proper treatment approaches for glaucoma patients with mental comorbidity and poor treatment adherence. We summarize some cautiously recommended psychotherapeutic medications, while also discussing the psychologically adverse effects of antiglaucoma medications.


Asunto(s)
Comorbilidad , Glaucoma/psicología , Trastornos Mentales/psicología , Glaucoma/tratamiento farmacológico , Glaucoma/epidemiología , Humanos , Trastornos Mentales/inducido químicamente , Trastornos Mentales/epidemiología
20.
J Neuroophthalmol ; 36(2): 152-5, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26714238

RESUMEN

BACKGROUND: Analysis of retinal nerve fiber layer thickness and macular ganglion cell layer loss provides a noninvasive method to assess optic chiasmal compression. These techniques may provide valuable data for patient evaluation and management when combined with findings on clinical examination and neuroimaging results. METHODS: Data from 20 eyes of 10 patients with pituitary tumor treated at Inha University Hospital from 2011 to 2013 were collected. This included results of ophthalmologic examination, fundus photography, spectral domain optical coherence tomography (SD-OCT), automated visual field testing, and brain magnetic resonance imaging (MRI). Abnormal color patterns on thickness and deviation maps obtained by macular ganglion cell analysis (GCA) were evaluated and compared with visual field defects. RESULTS: Patients with pituitary tumor showed preferential ganglion cell loss in the nasal hemiretina and characteristic vertical midline-respecting perimacular ganglion cell-inner plexiform layer defects, which anatomically matched the visual field defects. CONCLUSIONS: Macular GCA using SD-OCT can be used to complement visual field assessment and brain MRI findings during evaluation of patients with pituitary tumor.


Asunto(s)
Fibras Nerviosas/patología , Neoplasias Hipofisarias/complicaciones , Enfermedades de la Retina/etiología , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Campos Visuales , Femenino , Humanos , Mácula Lútea/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Disco Óptico/patología , Neoplasias Hipofisarias/diagnóstico , Enfermedades de la Retina/diagnóstico
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