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Background: Gaucher disease (GD) is an autosomal recessive disorder characterized by excessive accumulation of glucosylceramide in multiple organs. This study was performed to determine the detection rate of GD in a selected patient population with unexplained splenomegaly in Korea. Methods: This was a multicenter, observational study conducted at 18 sites in Korea between December 2016 and February 2020. Adult patients with unexplained splenomegaly were enrolled and tested for ß-glucosidase enzyme activity on dried blood spots (DBS) and in peripheral blood leukocytes. Mutation analysis was performed if the test was positive or indeterminate for the enzyme assay. The primary endpoint was the percentage of patients with GD in patients with unexplained splenomegaly. Results: A total of 352 patients were enrolled in this study (male patients, 199; mean age, 48.42 yr). Amongst them, 14.77% of patients had concomitant hepatomegaly. The most common sign related to GD was splenomegaly (100%), followed by thrombocytopenia (44.32%) and, anemia (40.91%). The ß-glucosidase activity assay on DBS and peripheral leukocytes showed abnormal results in sixteen and six patients, respectively. Eight patients were tested for the mutation, seven of whom were negative and one patient showed a positive mutation analysis result. One female patient who presented with splenomegaly and thrombocytopenia was diagnosed with type 1 GD. The detection rate of GD was 0.2841% (exact 95% CI, 0.0072â1.5726). Conclusion: The detection rate of GD in probable high-risk patients in Korea was lower than expected. However, the role of hemato-oncologists is still important in the diagnosis of GD.
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PURPOSE: Pegfilgrastim is widely used to prevent chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) in patients with diffuse large B-cell lymphoma (DLBCL). We investigated the predictive factors affecting CIN and FN incidence in patients with DLBCL receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy with pegfilgrastim and conducted experiments to find reason for the occurrence of CIN even when pegfilgrastim was used. MATERIALS AND METHODS: We reviewed the CIN and FN events of 200 patients with DLBCL. Based on these data, we investigate the association with predictive factor and the levels of granulocyte-colony stimulating factor (G-CSF) receptor signaling pathway markers (pSTAT3, pAKT, pERK1/2, pBAD, and CXCR4) in bone marrow (BM) samples isolated from patients with DLBCL. RESULTS: FN was significantly associated with stage III/IV (hazard ratio [HR], 12.74) and low serum albumin levels (HR, 3.87). Additionally, patients with FN had lower progression-free survival (PFS; 2-year PFS, 51.1 % vs. 74.0%) and overall survival (OS; 2-year OS, 58.2% vs. 85.0%) compared to those without FN. The occurrence of CIN was associated with overexpression of G-CSF receptor signaling pathway markers, and expression levels of these markers were upregulated in BM cells co-cultured with DLBCL cells. The rate of neutrophil apoptosis was also higher in neutrophils co-cultured with DLBCL cells and was further promoted by treatment with doxorubicin. CONCLUSION: Our findings suggest that high DLBCL burden may alter the BM environment and G-CSF receptor signaling pathway, even in chemotherapy-naïve state, which may increase CIN frequency during R-CHOP chemotherapy.
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Antineoplásicos , Neutropenia Febril , Linfoma de Células B Grandes Difuso , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida , Doxorrubicina , Neutropenia Febril/inducido químicamente , Neutropenia Febril/tratamiento farmacológico , Filgrastim , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/complicaciones , Polietilenglicoles , Prednisona/efectos adversos , Receptores de Factor Estimulante de Colonias de Granulocito/uso terapéutico , Estudios Retrospectivos , Rituximab/uso terapéutico , Albúmina Sérica/uso terapéutico , Transducción de Señal , VincristinaRESUMEN
Anterior gradient protein 2 homolog (AGR2), an endoplasmic reticulum protein, is secreted in the tumor microenvironment. AGR2 is a member of the disulfide isomerase family, is highly expressed in multiple cancers, and promotes cancer metastasis. In this study, we found that etravirine, which is a non-nucleoside reverse transcriptase inhibitor, could induce AGR2 degradation via autophagy. Moreover, etravirine diminished proliferation, migration, and invasion in vitro. Moreover, in an orthotopic xenograft mouse model, the combination of etravirine and paclitaxel significantly suppressed cancer progression and metastasis. This drug may be a promising therapeutic agent for the treatment of ovarian cancer.
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Mucoproteínas/metabolismo , Nitrilos/administración & dosificación , Proteínas Oncogénicas/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/administración & dosificación , Pirimidinas/administración & dosificación , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Mucoproteínas/genética , Metástasis de la Neoplasia , Nitrilos/farmacología , Proteínas Oncogénicas/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Paclitaxel/farmacología , Proteolisis , Pirimidinas/farmacología , Inhibidores de la Transcriptasa Inversa/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
PURPOSE: There are unmet needs associated with the current treatment strategies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) due to the poor treatment outcomes of these strategies. Roflumilast, a selective phosphodiesterase-4 inhibitor used for treating chronic obstructive pulmonary disease, is effective against B-cell malignancy via phosphoinositide 3-kinase (PI3K)-activity suppression. We analyzed the effects of roflumilast combined with ESHAP (etoposide, cisplatin, methylprednisolone, and cytarabine) chemotherapy in experimental and clinical settings. MATERIALS AND METHODS: An in vitro study using lymphoma cell lines and a pilot study on relapsed/refractory DLBCL patients were conducted to investigate the effects and mechanism of the combination of roflumilast and chemotherapy. The complete response (CR), overall response rate (ORR), and 1-year progression-free survival (PFS) were analyzed. RESULTS: We found that roflumilast is efficient when combined with other chemotherapy drugs, especially cytarabine. Synergistic effects between these two drugs influence the translation of mammalian target of rapamycin and myeloid cell leukemia 1, resulting in apoptosis and inhibition of B-cell lymphoma proliferation. In clinical setting, the roflumilast group showed better rates of CR (46.2% vs. 34.6%), ORR (76.9% vs. 53.8%), and 1-year PFS (50.0% vs. 25.9%) compared with the control group, though not statistically significant. The roflumilast group showed a higher incidence of asthenia and gastrointestinal adverse events. However, grade 3 or 4 adverse events were similar in both groups. CONCLUSION: We found that roflumilast, when combined with ESHAP chemotherapy, for relapsed/refractory DLBCL was clinically active and well tolerated. This combined treatment was able to suppress PI3K activity, which is correlated with the degree of clinical response.
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Aminopiridinas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Benzamidas/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Anciano , Cisplatino/administración & dosificación , Ciclopropanos/administración & dosificación , Citarabina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas/efectos de los fármacos , Proyectos PilotoRESUMEN
Women and men share similar diseases; however, women have unique issues, including gynecologic diseases and diseases related to menstruation, menopause, and post menopause. In recent decades, scientists paid more attention to natural products and their derivatives because of their good tolerability and effectiveness in disease prevention and treatment. Olive oil is an essential component in the Mediterranean diet, a diet well known for its protective impact on human well-being. Investigation of the active components in olive oil, such as oleuropein and hydroxytyrosol, showed positive effects in various diseases. Their effects have been clarified in many suggested mechanisms and have shown promising results in animal and human studies, especially in breast cancer, ovarian cancer, postmenopausal osteoporosis, and other disorders. This review summarizes the current evidence of the role of olives and olive polyphenols in women's health issues and their potential implications in the treatment and prevention of health problems in women.
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Dieta Saludable/métodos , Olea/química , Aceite de Oliva/farmacología , Sustancias Protectoras/farmacología , Salud de la Mujer , Animales , Dieta Mediterránea , Femenino , Humanos , Glucósidos Iridoides/farmacología , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/farmacología , Aceites de Plantas/farmacología , Polifenoles/farmacologíaRESUMEN
BACKGROUND: To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. METHODS: Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. RESULTS: A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). CONCLUSION: Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.
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BACKGROUND: We investigated whether distancemax, that is, the degree of distance between the upper aerodigestive tract (UAT) mass and the farthest pathologic lymph node, was significantly associated with survival in patients with limited-stage UAT natural killer/T cell lymphoma (NKTCL). METHODS: A total of 157 patients who received chemotherapy (CTx) with/without radiotherapy (RTx) were enrolled. RESULTS: In the survival analysis, an elevated lactate dehydrogenase level [progression-free survival (PFS): hazard ratio (HR), 2.948; 95% confidence interval (CI), 1.606â5.404; P <0.001; overall survival (OS): HR, 2.619; 95% CI, 1.594â4.822; P =0.003], short distancemax (PFS: HR, 0.170; 95% CI, 0.071â0.410; P <0.001; OS: HR, 0.142; 95% CI, 0.050â0.402; P < 0.001), and CTx combined with RTx (HR, 0.168; 95%CI, 0.079â0.380; P <0.001; OS: HR, 0.193; 95% CI, 0.087â0.429; P <0.001) had an independent predictive value for PFS and OS. CONCLUSION: The evaluation of the degree of lymphatic spread and local control by CTx combined with RTx is essential in patients with limited-stage UAT NKTCL.
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The present study is to investigate whether extranodal (EN) metabolic tumor volume (MTV) would have a specific clinical meaning for survival in EN diffuse large B cell lymphoma (DLBCL) patients. Two hundred forty DLBCL patients with EN involvement received 18F-fluorodeoxygenase (FDG) positron emission tomography/computed tomography (PET/CT) were enrolled. Survival analysis revealed that low EN MTV (PFS [progression-free survival], HR = 0.278, 95% CI = 0.127-0.807, p = 0.001; OS [overall survival], HR = 0.320, 95% CI = 0.145-0.703, p = 0.003), low total MTV (PFS, HR = 0.194, 95% CI = 0.085-0.445, p < 0.001; OS, HR = 0.213, 95% CI = 0.092-0.491, p < 0.007), and high National Cancer Center Network-International Prognostic Index score (PFS, HR = 3.152, 95% CI = 1.732-5.734, p < 0.001; OS, HR = 2.457, 95% CI = 1.363-4.430, p = 0.003) were independently associated with survivals in the patients. Our data showed that EN MTV is a useful and novel prognostic parameter for predicting survival in DLBCL patients with EN involvement.
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Extensión Extranodal/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Carga Tumoral , Adulto , Anciano , Femenino , Humanos , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
In the phase 3 study RERISE, patients with newly diagnosed chronic myeloid leukaemia in chronic phase demonstrated significantly faster and higher rates of major molecular response (MMR) with twice-daily radotinib 300 mg (n = 79) or 400 mg (n = 81) than with once-daily imatinib 400 mg (n = 81) after 12 months. With ≥48 months' follow-up, MMR was higher with radotinib 300 mg (86%) or 400 mg (83%) than with imatinib (75%). Among patients with BCR-ABL1 ≤ 10% at three months, MMR and molecular response 4·5 (MR4·5 ) were achieved within 48 months by more radotinib-treated patients (300 mg: 84% and 52%, respectively; 400 mg: 74% and 44%, respectively) than imatinib-treated patients (71% and 44%, respectively). Estimated overall and progression-free survival rates at 48 months were not significantly different between imatinib (94% and 94%, respectively) and radotinib 300 mg (99% and 97%, respectively) or 400 mg (95% and 93%, respectively). The treatment failure rate was significantly higher with imatinib (19%) than with radotinib 300 mg (6%; P = 0·0197) or 400 mg (5%; P = 0·0072). Safety profiles were consistent with previous reports; most adverse events occurred within 12 months. Radotinib continues to demonstrate robust, deep molecular responses, suggesting that treatment-free remission may be attainable.
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Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Mesilato de Imatinib/uso terapéutico , Leucemia Mieloide de Fase Crónica/complicaciones , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Pirazinas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Benzamidas/farmacología , Femenino , Humanos , Mesilato de Imatinib/farmacología , Masculino , Persona de Mediana Edad , Pirazinas/farmacología , Resultado del Tratamiento , Adulto JovenRESUMEN
Autologous stem cell transplant (ASCT) is an effective treatment for non-Hodgkin lymphoma (NHL). However, recent supply issues and toxicity of carmustine have necessitated a new conditioning regimen. We conducted a multicenter, phase II study of BEB (busulfan, etoposide, and bendamustine) conditioning regimen for ASCT in patients with NHL. Thirty-one patients were enrolled and underwent ASCT with the BEB conditioning regimen. The most common subtype was diffuse large B-cell lymphoma (n = 23, 74.2%). Nine patients (29.0%) had a history of relapse, and 18 patients (58.1%) received more than 2 lines of chemotherapy before ASCT. A median number of 6.05 × 106/kg CD34 cells were infused, and all patients engrafted after a median period of 11 days. Thirteen patients (41.9%) experienced neutropenic fever, and 16 patients (51.6%) had grade 3 or 4 toxicities during ASCT. No one had a documented infection, veno-occlusive disease, or treatment-related death. Three-month complete remission rate was 81.8%. Median follow-up period of 15 months showed 6 patients (19.4%) relapsed or progressed and 3 patients died. The estimated 2-year progression-free survival and overall survival rate were 73.0% and 89.8%, respectively. Our results show that BEB conditioning regimens for ASCT are feasible with tolerable toxicity in patients with NHL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/tratamiento farmacológico , Acondicionamiento Pretrasplante/métodos , Adulto , Antifúngicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina/administración & dosificación , Clorhidrato de Bendamustina/efectos adversos , Busulfano/administración & dosificación , Busulfano/efectos adversos , Terapia Combinada , Etopósido/administración & dosificación , Etopósido/efectos adversos , Neutropenia Febril/inducido químicamente , Femenino , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Estimación de Kaplan-Meier , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Premedicación , Supervivencia sin Progresión , Estudios Prospectivos , Inducción de Remisión , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Autólogo , Adulto JovenRESUMEN
Neutropenic enterocolitis is a fatal enterocolitis occurring in neutropenic patients with immunocompromised diseases including hematologic malignancies. Gastrointestinal (GI) mucormycosis in hematologic malignancies has been rarely reported. Especially, in myelodysplastic syndrome (MDS), GI mucormycosis has never been reported. We report a case of GI mucormocysis manifesting as neutropenic enterocolitis in a patient with MDS.
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INTRODUCTION: The clinical significance of tumor burden reduction following administration of hypomethylating agents (HMAs) for transplant-eligible patients with higher risk myelodysplastic syndrome (MDS) was evaluated. PATIENTS AND METHODS: Data of 79 transplant-eligible patients (< 65 years) diagnosed with higher-risk MDS between July 2002 and March 2013 were retrospectively analyzed. Among 79 patients, 30 (38%) underwent allogeneic hematopoietic cell transplantation (HCT group), and 49 (62%) were treated with HMA alone (non-HCT group). RESULTS: The median follow-up duration was 732 days (range, 28-1952 days), and the 3-year overall survival (OS) rate of all patients was 30.6%. In the HCT group, early HCT showed a better 3-year OS rate than late HCT (67.1% vs. 25.7%; P = .035). In multivariate analysis, time/performance of allogenic transplant (no HCT vs. early HCT, hazard ratio, 0.18; 95% confidence interval, 0.04-0.81; P = .026) and follow-up higher risk International Prognostic Scoring System (hazard ratio, 6.22; 95% confidence interval, 2.09-18.51; P = .001) were significantly correlated with OS. CONCLUSION: To predict the clinical outcomes of patients with higher risk MDS, the optimal time for tumor burden evaluation is prior to follow-up rather than at the time of initial diagnosis. Patients with lower International Prognostic Scoring System risk groups after HMA treatment or early HCT had favorable OS.
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Antineoplásicos/uso terapéutico , Metilación de ADN/efectos de los fármacos , Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos/patología , Síndromes Mielodisplásicos/terapia , Adolescente , Adulto , Antineoplásicos/farmacología , Azacitidina/farmacología , Azacitidina/uso terapéutico , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/mortalidad , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
There are many preclinical and epidemiological reports suggesting a correlation between 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) or HMG-CoAR inhibitor (statin) treatment and prognosis in breast cancer. This study aimed to investigate the expression of HMG-CoAR in Korean patients with breast cancer.The expression of HMG-CoAR on tissue microarrays from 191 patients who underwent resection from 2005 to 2006 in the Pusan National University Hospital was assessed by immunohistochemistry (IHC). The IHC assessment by a board-certified pathologist included areas of both carcinoma and peritumoral tissue of the breast. The scores of cancer-specific staining were adjusted by the scores of peritumoral staining.The patients were followed for a median 9.1 years. Disease-free survival (DFS) was shorter in patients with a positive adjusted HMG-CoAR score by log-rank test (not reached vs 11.6 years, Pâ=â.011). After adjusting for age, T stage, N stage, pathological grade, perioperational chemotherapy, adjuvant radiotherapy, estrogen receptor positivity, progesterone receptor positivity, human epidermal growth factor receptor-2 positivity, and high Ki-67 (>10%), a positive adjusted HMG-CoAR IHC score was also associated with shorter DFS (hazard ratioâ=â2.638, 95% confidence interval [CI] 1.112-6.262, Pâ=â.028).The expression of HMG-CoAR might be an independent prognostic factor in breast cancer. There are established drugs targeting HMG-CoAR, and further studies on its potential as a predictive marker are needed.
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Neoplasias de la Mama/fisiopatología , Hidroximetilglutaril-CoA Reductasas/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores Socioeconómicos , Análisis de Matrices TisularesRESUMEN
LESSONS LEARNED: Irinotecan could not be proven noninferior to paclitaxel as a second-line treatment for patients with metastatic or recurrent gastric cancer.The failure to demonstrate noninferiority may have been a result of insufficient patient enrollment.Both agents were tolerable but showed different toxicity profiles. BACKGROUND: This phase III study compared the efficacy and safety of paclitaxel versus irinotecan in patients with metastatic or recurrent gastric cancer (MRGC) who had experienced disease progression following first-line chemotherapy. METHODS: Patients were randomized to receive either paclitaxel (70 mg/m2; days 1, 8, 15, every 4 weeks) or irinotecan (150 mg/m2 every other week). The primary endpoint was progression-free survival (PFS). RESULTS: This study was stopped early due to low accrual rate. A total of 112 patients were enrolled; 54 were allocated to paclitaxel and 58 to irinotecan. Median PFS for the paclitaxel and irinotecan groups was 3.5 and 2.1 months, respectively (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.86-1.88; p = .234). Noninferiority of irinotecan to paclitaxel was not proved because the upper boundary of the 95% CI (1.88) exceeded the predefined upper margin of noninferiority (1.32). Median overall survival (OS) was 8.6 months in the paclitaxel group and 7.0 months in the irinotecan group (HR, 1.39; 95% CI, 0.91-2.11; p = .126). Among toxicities greater than or equal to grade 3, neutropenia (11.5%) was the most common, followed by peripheral neuropathy (7.7%) in the paclitaxel group, and neutropenia (34.5%) followed by nausea, vomiting, and anemia (8.6%, respectively) in the irinotecan group. CONCLUSION: Although paclitaxel showed numerically longer PFS and OS compared with irinotecan, this was statistically insignificant. Both irinotecan and paclitaxel are valid second-line treatment options in MRGC.
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Antineoplásicos Fitogénicos/uso terapéutico , Irinotecán/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Fitogénicos/farmacología , Femenino , Humanos , Irinotecán/farmacología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Paclitaxel/farmacología , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: Systemic inflammatory response can be associated with the prognosis of diffuse large B cell lymphoma (DLBCL). We investigated the systemic factors significantly related to clinical outcome in relapsed/refractory DLBCL. METHODS: In 242 patients with DLBCL, several factors, including inflammatory markers were analyzed. We assessed for the correlation between the survivals [progression-free survival (PFS) and overall survival (OS)] and prognostic factors. RESULTS: In these patients, a high derived neutrophil/lymphocyte ratio (dNLR) (PFS, HR=2.452, P=0.002; OS, HR=2.542, P=0.005), high Glasgow Prognostic Score (GPS) (PFS, HR=2.435, P=0.002; OS, HR=2.621, P=0.002), and high NCCN-IPI (PFS, HR=2.836, P=0.003; OS, HR=2.928, P=0.003) were significantly associated with survival in multivariate analysis. Moreover, we proposed a risk stratification model based on dNLR, GPS, and NCCN-IPI, thereby distributing patients into 4 risk groups. There were significant differences in survival among the 4 risk groups (PFS, P<0.001; OS, P<0.001). CONCLUSION: In conclusion, dNLR, GPS, and NCCN-IPI appear to be excellent prognostic parameters for survival in relapsed/refractory DLBCL.
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OBJECTIVES: The choice of doctor is an important issue for patients with cancer, and the reputation of the doctor is the single most important factor for patients to choose a doctor. Media are providing information about the 'best cancer doctor', but they vary widely in their selection methodology. We investigated cancer physicians' attitudes towards the selection of the 'best cancer doctor' by the media, by comparing two different selection methodologies: selection by media personnel or selection through peer-review system. DESIGN: Nationwide, cross-sectional survey. SETTING: National Cancer Center and 12 Regional Cancer Centers across Korea. PARTICIPANTS: A total of 680 cancer care physicians participated in the survey (75.5% participation rate), and two were excluded due to incomplete response. MAIN OUTCOME MEASURES: Physicians' opinions on the credibility, fairness, validity, helpfulness to patients, their intention to use the information and helpfulness to improve the quality of cancer care of the two different methods. RESULTS: Only a few physicians believed that the selection method of the 'best cancer doctor' by the media personnel was credible (9.1%), fair (6.1%) or valid (10.0%). In contrast, the majority agreed that the peer-selection method of the 'best doctor' is credible (74.7%), fair (64.7%) and valid (67.4%). More physicians believed the latter methods would be useful for patients when selecting their doctor (38.5% vs 82.2%) and may lead to improvement of the quality of cancer care from the perspective of the healthcare system (12.6% vs 59.8%). The need for ensuring objectiveness and transparency was also raised. CONCLUSION: Physicians showed different attitudes towards two different selection methods. Regulations or guidelines for selecting the 'best cancer doctor' and for disclosing the information should be considered in order to control the quality of the information and to protect the customers.
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Actitud del Personal de Salud , Distinciones y Premios , Revisión por Pares/métodos , Médicos/estadística & datos numéricos , Adulto , Medios de Comunicación , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , República de Corea , Encuestas y CuestionariosRESUMEN
Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.
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BACKGROUND/AIMS: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. METHODS: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. RESULTS: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. CONCLUSION: For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.
Asunto(s)
Azacitidina/administración & dosificación , Metilación de ADN/efectos de los fármacos , Metilasas de Modificación del ADN/antagonistas & inhibidores , Decitabina/administración & dosificación , Inhibidores Enzimáticos/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos/terapia , Cuidados Paliativos/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Azacitidina/efectos adversos , Bases de Datos Factuales , Decitabina/efectos adversos , Progresión de la Enfermedad , Inhibidores Enzimáticos/efectos adversos , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/mortalidad , República de Corea , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Tumor necrosis (TN) is associated with worse prognosis in several solid cancers. Whether TN predicts poor outcome in natural killer cell / T cell lymphoma (NKTCL) is unclear. We investigated the clinical impact of TN on survival and other novel prognostic parameters in upper aero-digestive tract (UAT) NKTCL of 100 patients with limited stage. TN was significantly associated with poor performance status (p = 0.049), high Korean Prognostic Index score (p = 0.024), high C-reactive protein/albumin ratio (p = 0.003), higher maximum standard uptake value on positron emission tomography/computed tomography (PET/CT) (p = 0.008) and higher metabolic tumor volume (MTV) on PET/CT (p < 0.001). In univariate and multivariate analyses, progression-free survival and overall survival were independently associated with High MTV status (p = 0.001, p = 0.032), TN (p = 0.018, p = 0.009), local tumor invasiveness (p = 0.007, p = 0.035), complete resection (p = 0.020, p = 0.028) and regional lymph node involvement (p < 0.001, p < 0.001). TN and complete resection are concluded to be novel independent prognostic factors in patients with UAT NKTCL.
RESUMEN
BACKGROUND: Patients with paroxysmal nocturnal hemoglobinuria (PNH) often have concurrent aplastic anemia (AA). This study aimed to determine whether eculizumab-treated patients show clinical benefit regardless of concurrent AA. METHODS: We analyzed 46 PNH patients ≥18 years of age who were diagnosed by flow cytometry and treated with eculizumab for more than 6 months in the prospective Korean PNH registry. Patients were categorized into two groups: PNH patients with concurrent AA (PNH/AA, N=27) and without AA (classic PNH, N=19). Biochemical indicators of intravascular hemolysis, hematological laboratory values, transfusion requirement, and PNH-associated complications were assessed at baseline and every 6 months after initiation of eculizumab treatment. RESULTS: The median patient age was 46 years and median duration of eculizumab treatment was 34 months. Treatment with eculizumab induced rapid inhibition of hemolysis. At 6-month follow-up, LDH decreased to near normal levels in all patients; this effect was maintained until the 36-month follow-up regardless of concurrent AA. Transfusion independence was achieved by 53.3% of patients within the first 6 months of treatment and by 90.9% after 36 months of treatment. The mean number of RBC units transfused was significantly reduced, from 8.5 units during the 6 months prior to initiation of eculizumab to 1.6 units in the first 6 months of treatment, for the total study population; this effect was similar in both PNH/AA and classic PNH. CONCLUSION: This study demonstrated that eculizumab is beneficial in the management of patients with PNH/AA, similar to classic PNH.