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1.
Cytotherapy ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38795116

RESUMO

Autologous peripheral blood stem cell (PBSC) transplantation is crucial in pediatric cancer treatment, and tandem transplantation is beneficial in certain malignancies. Collecting PBSCs in small children with low body weight is challenging. We retrospectively analyzed data of pediatric cancer patients weighing <15 kg who underwent autologous PBSC harvesting in our hospital. Collections were performed in the pediatric intensive care unit over 2 or 3 consecutive days, to harvest sufficient stem cells (goal ≥2 × 106 CD34+ cells/kg per apheresate). From April 2006 to August 2021, we performed 129 collections after 50 mobilizations in 40 patients, with a median age of 1.9 (range, 0.6-5.6) years and a body weight of 11.0 (range, 6.6-14.7) kg. The median CD34+ cells in each apheresate were 4.2 (range, 0.01-40.13) × 106/kg. 78% and 56% of mobilizations achieved sufficient cell dose for single or tandem transplantation, respectively, without additional aliquoting. The preapheresis hematopoietic progenitor cell (HPC) count was highly correlated with the CD34+ cell yield in the apheresate (r = 0.555, P < 0.001). Granulocyte colony-stimulating factor alone was not effective for mobilization in children ≥2 years of age, even without radiation exposure. By combining the preapheresis HPC count ≥20/µL and the 3 significant host factors, including age <2 years, no radiation exposure and use of chemotherapy, the prediction rate of goal achievement was increased (area under the curve 0.787).

2.
Clin Nucl Med ; 49(5): e219-e221, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38409762

RESUMO

ABSTRACT: The Epstein-Barr virus-associated smooth muscle tumor (SMT) is an uncommon neoplasm. It arises mainly in 3 immunosuppression settings: HIV-associated SMT; drug-related immunosuppression in transplant recipients; and congenital immunodeficiency disorder-associated SMT. We present 18 F-FDG PET/CT findings of an adrenal Epstein-Barr virus-associated SMT in a 65-year-old woman with a history of follicular lymphoma after chemotherapy.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Folicular , Tumor de Músculo Liso , Feminino , Humanos , Idoso , Herpesvirus Humano 4 , Tumor de Músculo Liso/diagnóstico por imagem , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/complicações
3.
Int J Med Sci ; 21(1): 107-122, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164360

RESUMO

NF-κB activation is pivotal for the excess inflammation causing the critical condition and mortality of respiratory viral infection patients. This study was aimed to evaluate the effect of a banana plant extract (BPE) on suppressing NF-κB activity and acute lung inflammatory responses in mice induced by a synthetic double-stranded RNA viral mimetic, polyinosinic-polycytidylic acid (poly (I:C)). The inflammatory responses were analyzed by immunohistochemistry and HE stains and ELISA. The NF-κB activities were detected by immunohistochemistry in vivo and immunofluorescence and Western blot in vitro. Results showed that BPE significantly decreased influx of immune cells (neutrophils, lymphocytes, and total WBC), markedly suppressed the elevation of pro-inflammatory cytokines and chemokines (IL-6, RANTES, IFN-γ, MCP-1, keratinocyte-derived chemokine, and IL-17), and restored the diminished anti-inflammatory IL-10 in the bronchoalveolar lavage fluid (BALF) of poly (I:C)-stimulated mice. Accordingly, HE staining revealed that BPE treatment alleviated poly (I:C)-induced inflammatory cell infiltration and histopathologic changes in mice lungs. Moreover, immunohistochemical analysis showed that BPE reduced the pulmonary IL-6, CD11b (macrophage marker), and nuclear NF-κB p65 staining intensities, whilst restored that of IL-10 in poly (I:C)-stimulated mice. In vitro, BPE antagonized poly(I:C)-induced elevation of IL-6, nitric oxide, reactive oxygen species, NF-κB p65 signaling, and transient activation of p38 MAPK in human lung epithelial-like A549 cells. Taken together, BPE ameliorated viral mimic poly(I:C)-induced acute pulmonary inflammation in mice, evidenced by reduced inflammatory cell infiltration and regulation of both pro- and anti-inflammatory cytokines. The mechanism of action might closely associate with NF-κB signaling inhibition.


Assuntos
Musa , Pneumonia , Camundongos , Humanos , Animais , NF-kappa B , Poli I-C/farmacologia , Poli I-C/uso terapêutico , Interleucina-10 , Interleucina-6 , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Citocinas , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Quimiocinas , Anti-Inflamatórios/uso terapêutico
4.
Support Care Cancer ; 32(1): 40, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38110567

RESUMO

PURPOSE: This study explored symptom clusters (SCs) and predominant symptoms in lymphoma survivorships at least 1 month after treatment. METHODS: A cross-sectional trend study design was adopted. Inclusion criteria were participants who were over the age of 20, diagnosed with lymphoma, and 1 month after treatment concluded. The symptoms were assessed by the Functional Assessment of Cancer Therapy Scale-Lymphoma Subscale. Data were analyzed using descriptive statistics, latent profile analysis (LPA), and comparisons of means and frequencies of each symptom in each SC. RESULTS: A total of 234 lymphoma survivors completed this study. Three SCs were identified at < 2 and > 5 years and two SCs at 2-5 years. Worrying about getting new symptoms and infections emerged as predominant symptoms across all SCs over time. This study provides insights into the symptom experiences of survivors of lymphoma and highlights the significant role of worry-related symptoms in their survivorship. CONCLUSION: Through the use of LPA and a trend study design, we identified distinct SCs in lymphoma survivors, providing valuable insights into their longitudinal symptom experiences. The findings emphasize the complexity of symptomatology in lymphoma survivorship and underscore the importance of employing advanced statistical methods to explore and understand these clusters comprehensively, informing targeted interventions and improved care strategies.


Assuntos
Linfoma , Sobrevivência , Humanos , Estudos Transversais , Síndrome , Linfoma/terapia , Sobreviventes , Qualidade de Vida
5.
Nutrients ; 15(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37960146

RESUMO

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.


Assuntos
Produtos Biológicos , Neoplasias da Próstata , Masculino , Humanos , Androgênios/metabolismo , Células PC-3 , Lovastatina/farmacologia , Proliferação de Células , Apoptose , Neoplasias da Próstata/patologia , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Linhagem Celular Tumoral
6.
Ear Nose Throat J ; : 1455613231204206, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872806

RESUMO

Objectives: This study aims to investigate the factors that lead to poor compliance in initiating the treatment in patients with newly diagnosed head and neck cancers. Methods: A total of 193 patients from the head and neck cancer database dated from January 1, 2018 to September 30, 2020, were analyzed. Variables analyzed included age, gender, primary cancer site, T stage, N stage, M stage, overall stage (I-IV), patient's residential distance, and the impact of COVID-19. Univariate and multivariate analyses were used to assess the significance of these variables in relation to the time to receiving on-time treatment as recommended by specialists. Results: Upon multivariate analysis, the advanced stage and residential distance were significantly associated with initial compliance (P < .09). The impact of nasopharyngeal carcinoma (NPC) and COVID-19 shows a borderline significance (P = .224 and P = .184). Conclusions: The overall stage and patient living distance to the healthcare facility, patient with NPC, and the impact of COVID-19 might affect the compliance of initiating a curative-intent treatment in patients with newly diagnosed head and neck cancers.

7.
J Chin Med Assoc ; 86(11): 991-1000, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37697465

RESUMO

BACKGROUND: Donor lymphocyte infusion (DLI) is effective for managing patients with hematologic malignancies after allogeneic hematopoietic stem cell transplant (HSCT). However, few studies have explored its optimal use in pediatric populations. Herein, we report our single-center experiences of DLI and factors for predicting its outcomes. METHODS: This retrospective study included pediatric patients who had received DLI (between June 1998 and December 2022) after allogeneic HSCT. Data regarding patient characteristics, preemptive DLI disease status, and DLI characteristics were collected. The primary outcomes were overall survival (OS), event-free survival (EFS), and graft-vs-host-disease (GVHD) development. RESULTS: The study cohort comprised 17 patients with acute leukemia, 3 with chronic leukemia, and 3 with lymphoma. Prophylactic, preemptive, and therapeutic DLI were used in seven, seven, and nine patients, respectively. Patients' median age and DLI dose were 9 years and 4.6 × 10 7 CD3 + cells/kg, respectively. The 5-year OS, EFS, and nonrelapse mortality were 43.5%, 38.3%, and 13.3%, respectively. Approximately 39% of the patients developed grade III or IV acute GVHD, whereas moderate/severe chronic GVHD (cGVHD) occurred in 30% of the evaluable patients. Patients' disease status before HSCT ( p = 0.009) and DLI ( p = 0.018) were the key factors influencing EFS. The implementation of a dose escalation schedule was associated with a marginal reduction in the risk of moderate/severe cGVHD ( p = 0.051). A DLI dose of ≥5 × 10 7 CD3 + cells/kg was significantly associated with a high moderate to severe cGVHD risk ( p = 0.002) and reduced OS ( p = 0.089). CONCLUSION: Patients' disease status before HSCT and DLI may help predict EFS. The use of DLI as a prophylactic and preemptive modality leads to a favorable 5-year EFS. To safely deliver DLI in children, clinicians must maintain vigilant monitoring and prepare patients in advance when escalating the dose to ≥5 × 10 7 CD3 + cells/kg.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Criança , Estudos Retrospectivos , Transfusão de Linfócitos , Doença Crônica , Linfócitos , Recidiva
8.
Cancer Med ; 12(7): 8089-8101, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36647765

RESUMO

BACKGROUND: Frontline intensification (including consolidative whole-brain radiotherapy or high-dose chemotherapy with autologous stem-cell transplantation after induction therapy) has been proposed to treat primary central nervous system lymphoma (PCNSL). However, no prospective randomized trials have answered whether frontline intensification can offer a survival benefit to PCNSL patients. We aim to clarify the outcomes and survival influence of frontline intensification on real-world patients with different risk-stratified PCNSLs. METHODS: Between January 2003 and December 2016, 110 PCNSL adults were retrospectively included, and 76 patients achieved at least PR after induction therapy, including 38 patients who received frontline intensification. The median follow-up with the 31 survivors was 7.52 years. RESULTS: Of the 38 induction-completed patients who had not received frontline intensification, 95% achieved post-induction therapy CR/CRu; however, all inevitably recurred. In the 38 who received frontline intensification, CR/CRu improved from 45% (pre-frontline intensification) to 84% (post-frontline intensification), and they achieved significantly better PFS (non-reach vs. 522 days, p < 0.001) and OS (non-reach vs. 899 days, p < 0.001). Additionally, patients had similar PFS and OS rates when receiving HDC-ASCT and/or WBRT as frontline intensification. Frontline intensification significantly improved PFS and OS survival in higher-risk patients (intermediate/high IELSG risk, MSKCC group 2/3, or Nottingham/Barcelona score ≥ 2 points) but did not improve OS in lower-risk patients. Among the 38 patients who received frontline intensification, two had treatment-related mortality; 14 recurred after frontline intensification. MTX-based chemotherapy was the main salvage modality, and the median OS was 295 days after recurrence. Progressive disease and infection (especially pneumonia) are two major causes of mortality in patients who receive frontline intensification. CONCLUSIONS: When achieving CR/CRu/PR after induction chemotherapy, frontline intensification should be adopted to improve PFS and OS in real-world PCNSL patients, especially higher-risk patients.


Assuntos
Neoplasias do Sistema Nervoso Central , Transplante de Células-Tronco Hematopoéticas , Linfoma , Adulto , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos Retrospectivos , Transplante Autólogo , Terapia Combinada
9.
Eur J Cancer Care (Engl) ; 31(6): e13741, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36254839

RESUMO

OBJECTIVE: This study aimed to explore the subgroups of symptom severity and impact of their trajectories on quality of life in lymphoma survivors. METHODS: Secondary data were analysed from a prospective study with four-time measures: before treatment (T1), during treatment (T2), treatment completion (T3) and 10 weeks after treatment (T4). Data were analysed using descriptive statistics, group-based trajectory model and generalised estimation equation. RESULTS: Fifty nine of 61 participants completed three-time measure (mean age = 60.43 years, male-predominant). The changes in symptom severity over time were divided into two subgroups: slight-stable group (n = 54, 89%) and mild-fickle group (n = 7, 11%). Pain, tiredness and sleeping trouble were the predominant symptoms. The quality of life change in the slight-stable group was significantly better than that of the mild-fickle group (B = 13.35, SE = 3.53, p < 0.001). The overall quality of life at T2, T3 and T4 was better than it was at T1. CONCLUSION: The different trajectories of symptom severity significantly influenced quality of life changes in lymphoma survivors. Healthcare providers must be aware that there is a group of lymphoma survivors with relatively severe symptoms when newly diagnosed, compared to the opposite. More attention must be paid to this group, in addition to providing in-time symptom management.


Assuntos
Linfoma , Qualidade de Vida , Masculino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Sobreviventes , Fadiga/etiologia
10.
Nutrients ; 14(15)2022 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-35956408

RESUMO

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.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , Células A549/efeitos dos fármacos , Células A549/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/efeitos adversos , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Óleos de Peixe/metabolismo , Óleos de Peixe/farmacologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Células-Tronco Neoplásicas , Fenótipo , Saccharomyces cerevisiae/metabolismo , Selênio/metabolismo , Selênio/farmacologia
11.
J Hematol Oncol ; 15(1): 56, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35545778

RESUMO

Pevonedistat, the first small-molecule inhibitor of NEDD8-activating enzyme, has demonstrated clinical activity in Western patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). We report findings from a phase 1/1b study in East Asian patients with AML or MDS, conducted to evaluate the safety/tolerability and characterize the pharmacokinetics of pevonedistat, alone or in combination with azacitidine, in this population, and determine the recommended phase 2/3 dose for pevonedistat plus azacitidine. Twenty-three adult patients with very high/high/intermediate-risk AML or MDS were enrolled in Japan, South Korea and Taiwan. All 23 patients experienced at least one grade ≥ 3 treatment-emergent adverse event. One patient in the combination cohort reported a dose-limiting toxicity. Eighteen patients discontinued treatment; in nine patients, discontinuation was due to progressive disease. Three patients died on study of causes considered unrelated to study drugs. Pevonedistat exhibited linear pharmacokinetics over the dose range of 10-44 mg/m2, with minimal accumulation following multiple-dose administration. An objective response was achieved by 5/11 (45%) response-evaluable patients in the pevonedistat plus azacitidine arm (all with AML), and 0 in the single-agent pevonedistat arm. This study showed that the pharmacokinetic and safety profiles of pevonedistat plus azacitidine in East Asian patients were similar to those observed in Western patients as previously reported. The recommended Phase 2/3 dose (RP2/3D) of pevonedistat was determined to be 20 mg/m2 for co-administration with azacitidine 75 mg/m2 in Phase 2/3 studies, which was identical to the RP2/3D established in Western patients.Trial registration: clinicaltrials.gov: NCT02782468 25 May 2016. https://clinicaltrials.gov/ct2/show/NCT02782468.


Assuntos
Ciclopentanos , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Pirimidinas , Adulto , Azacitidina/uso terapêutico , Ciclopentanos/efeitos adversos , Ciclopentanos/farmacocinética , Quimioterapia Combinada/efeitos adversos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética
13.
Mar Drugs ; 18(8)2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32751169

RESUMO

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.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Gefitinibe/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Selênio/farmacologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Combinação de Medicamentos , Chaperona BiP do Retículo Endoplasmático , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia
14.
Jpn J Clin Oncol ; 50(6): 693-700, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32303764

RESUMO

BACKGROUND: Cancer-related fatigue (CRF) is an emerging clinical issue, although its prevalence and impact on quality of life (QOL) in cancer patients in Taiwan remain unclear. The present nationwide cross-sectional study was conducted to provide a thorough overview of the prevalence, related factors and impact of CRF in Taiwan. METHODS: In this multi-center survey, data were collected using the International Classification of Diseases 10th Revision (ICD-10) Fatigue evaluation, Brief Fatigue Inventory-Taiwan (BFI-T), the Chinese version of the Symptom Distressed Scale and a fatigue experience survey. Logistic regression was used to determine the correlations between fatigue characteristics and the factors studied. RESULTS: A total of 1207 cancer patients were recruited from 23 hospitals in Taiwan. Fatigue was the most distressing symptom in Taiwanese cancer patients. The distress score was higher if CRF was diagnosed using ICD-10 compared with BFI-T. Rest and nutritional supplementation were the most common non-pharmacological treatments; blood transfusion was the most common pharmacological treatment. There were 45% of patients reported not receiving a timely intervention for fatigue. CONCLUSIONS: Fatigue is the most bothersome symptom reported by Taiwanese cancer patients. Caregivers should be aware of the impact of CRF on QOL in cancer patients, constantly measure the severity of fatigue and provide appropriate interventions.


Assuntos
Fadiga/epidemiologia , Neoplasias/complicações , Qualidade de Vida , Adulto , Idoso , Estudos Transversais , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Taiwan
15.
Immunology ; 160(1): 38-51, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32027025

RESUMO

First discovered on the natural killer (NK) cell, the cell surface inhibitory receptor sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) is known for regulating many important biological activities. However, the detail regulatory mechanism for Siglec-7 expression in NK cells currently remains unclear. In this study, we aimed to investigate how cell surface Siglec-7 expression is regulated and found that, in both NK cell lines and peripheral NK cells, transcription was the main regulatory step. Furthermore, when NK-92MI and peripheral NK cells were treated with DNA methyltransferase (DNMT) inhibitor, the CpG island, with 9 CpG sites, in 5' Siglec-7 promoter became noticeably hypomethylated, and Siglec-7 expression increased in both RNA transcript and surface protein. Within this CpG island, we identified both CpG 8 and CpG 9 as two key regulators responsible for Siglec-7 expression. Additionally, by using histone deacetylases (HDAC) inhibitor, butyric acid, we showed that Siglec-7 expression was also subjected to the histone modification. And a combined treatment with both 5-azacytidine and butyric acid showed an additive effect on Siglec-7 transcript expression in peripheral NK cells.


Assuntos
Antígenos de Diferenciação Mielomonocítica/genética , Epigênese Genética/imunologia , Células Matadoras Naturais/imunologia , Lectinas/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Azacitidina/farmacologia , Ácido Butírico/farmacologia , Linhagem Celular , Ilhas de CpG/genética , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/imunologia , Epigênese Genética/efeitos dos fármacos , Código das Histonas/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Lectinas/metabolismo , Regiões Promotoras Genéticas/genética , RNA-Seq , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/imunologia
16.
Hematol Oncol ; 38(3): 390-398, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32011024

RESUMO

BCR-ABL mutations are associated with resistance to tyrosine kinase inhibitors (TKIs) in Philadelphia chromosome-positive leukaemia. The emergence of these mutations in the era of second-generation TKIs, such as dasatinib and nilotinib, remains an evolving field. We conducted a retrospective study to quantitatively characterize the BCR-ABL transcript and mutation status during treatment with first-generation and second-generation TKI therapies. BCR-ABL mutations were detected by direct sequencing for patients with Philadelphia chromosome-positive leukaemia receiving TKI therapies. The efficacy of TKI therapy was quantitatively assessed by calculating the log reduction of BCR-ABL transcripts, which was measured using real-time quantitative polymerase chain reaction. Fisher's exact test was performed to analyse the associations of log reduction <3 and mutation status. We found 35 patients harbouring 55 mutations of 43 different types, of which 30% occurred in patients receiving imatinib, 27% in nilotinib, and 43% in dasatinib. We found a novel germline mutation, N336 N (AAC➔AAT), and two novel frameshift mutations, Asn358Thr fs*14 and Gly251Ala fs*16. T315I was the most common missense mutation, followed by V299L and F317L. Intron 8 35-bp insertion was the most frequent frameshift mutation. Both missense and multiple BCR-ABL mutations were significantly associated with worse molecular response compared with the molecular response of patients without mutation. Missense mutations, rather than frameshift, were associated with less log reduction, while the T315I, F317L, and T315A mutations were significantly correlated with poor log reduction. Collectively, amino acid substitutions at T315I, F317L, and T315A accounted for the majority of missense mutations and the loss of major molecular response. Mutation analysis is essential for patients receiving TKI therapy who exhibit an unfavourable response. The present study provided a landscape of BCR-ABL mutations in the era of second-generation TKIs.


Assuntos
Biomarcadores Tumorais/antagonistas & inibidores , Proteínas de Fusão bcr-abl/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Mutação , Cromossomo Filadélfia , Inibidores de Proteínas Quinases/uso terapêutico , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Seguimentos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
17.
J Chin Med Assoc ; 83(3): 238-244, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31904659

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are hematological diseases predominantly occurring in older patients. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the curative therapy for refractory AML or high-risk MDS, old age is often a hurdle to the procedure. We conducted a retrospective study to analyze the prognostic factors predicting outcomes of older patients undergoing allo-HSCT for acute leukemia and MDS. METHODS: We collected data from patients diagnosed with acute leukemia or MDS, who underwent allo-HSCT at >50 years of age and reviewed clinical characteristics, including age, sex, underlying disease, European Group for Blood and Bone Marrow Transplantation (EBMT) risk score, and presence of acute graft-versus-host disease (aGVHD) or chronic GVHD (cGVHD). The Cox proportional hazard model was adopted to explore the independent prognostic factors for overall survival (OS), progression-free survival (PFS), and non-relapse mortality (NRM). RESULTS: A total of 85 older patients were included, with the median age at allo-HSCT being 55 years. The significant prognostic factors for worse OS or PFS were an EBMT risk score > 3 and grade III-IV aGVHD, while patients with moderate to severe cGVHD would have better OS or PFS. Interestingly, it is not cGVHD but grade III-IV aGVHD that significantly correlated with NRM. CONCLUSION: This cohort study suggests that an EBMT risk score >3 and grade III-IV aGVHD predict poor outcomes, and careful management of GVHD may allow better survival for older patients undergoing allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transplante Homólogo
18.
J Microbiol Immunol Infect ; 53(2): 274-282, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30082145

RESUMO

BACKGROUND: Mycobacterial infections are important and potentially life-threatening complications after organ transplantations. Notably, for the recipients of allogeneic hematopoietic stem cell transplantation (HSCT), there are a few supporting results to explore post-transplant mycobacterial infections. Taiwan is a high endemic area of the infection. We aim to investigate the incidence, risk factors, and survival of post-transplant mycobacterial infections, including mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterium (NTM). METHODS: We included 422 adult patients undergoing allogeneic HSCT at an Asian tertiary medical center between January 2003 and December 2014. A total 26 subjects developed post-transplant mycobacterial infections. Risk factors, clinical features, and survival for post-transplant mycobacterial infections were collected and analyzed. RESULTS: Post-transplant mycobacterial infections occurred in 26 (6.2%) of 422 HSCT patients. Two-year cumulative incidences in MTB and NTM were 1.4% and 5.4%. In the multivariate analysis, being age >45 years (adjusted HR 2.21, 95% CI 1.01-4.83) and extensive chronic graft-versus-host disease (cGVHD) (adjusted HR 4.95, 95% CI 2.14-11.46) were identified as independent risk factors of infections. There was a trend as a risk factors in relapsed patients (P = 0.088). For patients with cGVHD, there was a significant difference of post-transplant survival between mycobacterial infections and none (P = 0.036). Pneumonia contributed most to mortality (n = 11, 42.3%). CONCLUSION: Mycobacterial infections are worth to note in a high endemic area. Once a high-risk group is identified, much effort is required to target new approaches for prevention, early detection and treatment of infections.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Mycobacterium/complicações , Infecções por Mycobacterium/epidemiologia , Adulto , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mycobacterium , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
19.
Asia Pac J Clin Oncol ; 16(2): e91-e98, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30334366

RESUMO

AIM: To evaluate the prevalence of pain in cancer outpatients in Taiwan and to investigate the impact of pain on quality of life (QoL) and patient satisfaction. Results were compared to those of a similarly designed study conducted in 2008 to identify trends. METHODS: Adult patients with cancer treated as outpatients in hospitals throughout Taiwan were recruited. Pain intensity and the extent to which pain interfered with QoL were self-reported using a modified version of the Brief Pain Inventory. Patients also indicated their level of satisfaction with their physician, as well as with their pain control. RESULTS: A total of 2652 patients were enrolled from 16 sites. Of these, 1167 (44.0%) patients reported experiencing pain during the previous week. Prevalence and severity of pain were highest in patients with progressive disease. A higher pain severity score was significantly associated with greater interference in both physical and psychological functions. Overall, 86.0% of all participants expressed satisfaction with their physician and 84.8% were satisfied with their pain control; satisfaction rates were associated with pain severity. Compared with the findings from the 2008 study, pain prevalence was notably lower and patient satisfaction was significantly greater in the current study. CONCLUSIONS: Prevalence and severity of pain were associated with disease stage. Pain interference on QoL correlated significantly with pain severity. Treatment of pain in cancer patients in Taiwan seems to have improved from 2008 to 2014, possibly attributable to new cancer pain treatment guidelines and the wider availability of novel analgesic therapies.


Assuntos
Dor do Câncer/tratamento farmacológico , Manejo da Dor/métodos , Qualidade de Vida/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
J Clin Med ; 8(10)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31623372

RESUMO

Nasopharyngeal (NP) lymphoma is a rare primary malignancy of the head and neck and represents a minority of malignancies originating from the nasopharynx. For this reason, there are limited data regarding epidemiologic and treatment outcomes. This is a retrospective review of patients diagnosed with NP lymphoma from 1995 to 2017 at a tertiary medical center. The patients' demographic data, clinical presentations, treatment modalities, Epstein-Barr virus (EBV)-encoded small RNA (EBER) staining, and outcomes were investigated. We considered a total of 35 patients, including 20 males and 15 females, diagnosed with NP lymphoma. The age ranged from 17 to 88 years (mean = 59.6). The common presentations were nasal obstruction, epistaxis, and neck mass. In our study, the most common pathological diagnosis of NP lymphoma was diffuse large B cell lymphoma (DLBCL) (n = 17), followed by NK/T cell lymphoma (NKTCL) (n = 9). Other pathologic diagnoses included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma), small lymphocytic lymphoma, mantle cell lymphoma. There were 13 cases showing EBER positivity, including 7 cases of NKTCL, 5 cases of DLBCL, and 1 case of post-transplant lymphoproliferative disorder (PTLD). Most patients received chemotherapy alone, while some patients received both chemotherapy and radiotherapy. Seven patients had local recurrence, and fewer than half of the patients (n = 16) were alive at the time of the study (mean follow-up duration: 54.4 months). The five-year overall survival was 50.4%. NP lymphoma is very rare, and the most common pathologic type is DLBCL. EBER positivity is found in both NKTCL and DLBCL. Identifying more effective therapeutic agents is extremely important to improve patients' survival.

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