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1.
J Pers Med ; 11(11)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34834460

RESUMO

Considering a steady increase in the number of allogeneic hematopoietic stem cell transplantations (allo-HSCT) worldwide and the significant proportion of the world's population that has been exposed to hepatitis B virus (HBV) infection, HBV reactivation following allo-HSCT remains an important issue for post-transplant morbidity and mortality. Antiviral prophylaxis can reduce HBV replication, severity of HBV-related hepatitis, and mortality; therefore, identification of patients at risk is crucial. It is recommended that all recipients and donors should be screened for active or prior HBV infection, including HBsAg, antiHBc, and antiHBs. Adoptive immunity transfer from the donor seems to have protective effects against HBV reactivation. Antiviral prophylaxis should be initiated in all HBsAg-positive patients. HBsAg-negative, antiHBc-positive patients remain at risk; therefore, antiviral prophylaxis should be considered if baseline serum HBV DNA is detectable. In HBsAg-negative, antiHBc-positive patients without detectable HBV DNA, close monitoring of viral load with an on-demand therapy is necessary. Entecavir or tenofovir rather than lamivudine are more appropriate for the emergence of lamivudine resistance. The treatment duration remains unclear, with 6- to 12-month therapy after cessation of immunosuppressive therapy commonly recommended. Here we review the updated evidence and recent recommendations regarding HBV reactivation in patients undergoing allo-HSCT for individualized therapy.

2.
Kaohsiung J Med Sci ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647681

RESUMO

Identification of alloantibodies and achieving a reduction in the rate of red blood cell (RBC) alloimmunization are important issues to prevent transfusion complications. The aim of this study was to identify the antigen and alloantibodies in our patients and to study the association of alloimmunization with previous transfusion. Transfusion records from the blood bank of Kaohsiung Medical University Hospital between 2015 and 2017 were retrospectively enrolled in the study. Antigen and antibody identification was performed using routine blood bank methods. In total, 56,422 transfusion records from 2015 to 2017 were included in the study. Among them, 1858 alloantibody episodes were found in the pre-transfusion survey, and anti-Mia, anti-E, and cold antibodies were the most common alloantibodies, with a prevalence of 3.29% (1858/56,422). Among them, 130 episodes involved newly found alloantibodies with no alloantibodies found in the previous transfusion survey. Tracing back to these newly transfusion-induced alloantibodies, the antibody was found with a mean of 10.8 ± 7.8 units of packed RBC transfusion, a mean of 66.3 ± 52.8 days, and with a mean of 4.3 ± 2.7 times of transfusion from the first transfusion therapy. An antibody survey revealed that Rh-ee (62.1%) was the most common phenotype in these newly identified antibodies. In summary, this hospital-based study revealed that RBC alloantibody rates were present at rates of 3.29%, with anti-Mia, anti-E, and cold antibodies being the most common alloantibodies. Among them, anti-E was the most commonly developed alloantibody. Given that the Rh-ee group is the most common phenotype in our population, the strategy of using Rh-ee blood for Rh-ee recipients is reasonable for transfusion safety.

3.
Biomed Res Int ; 2021: 3291762, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631879

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare lymphoma, and the disease course is often aggressive with poor prognosis outcomes. PCNSL undergoes germinal center reactions and impairs B-cell maturation. However, angiogenesis is also involved in the tumorigenesis and progression of PCNSL. This study investigated the effects of the tumor microenvironment and angiogenesis-associated genomic alterations on the outcomes of PCNSL. The analysis also evaluated the influence of treatment modality and timing on PCNSL survival using partial least squares variance-based path modeling (PLS-PM). PLS-PM can be used to evaluate the complex relationship between prognostic variables and disease outcomes with a small sample of measurements and structural models. A total of 19 immunocompetent PCNSL samples were analyzed by exome sequencing. Our results suggest that the timing of radiotherapy and mutations of ROBO1 and KAT2B are potential indicators of PCNSL outcomes and may be affected by baseline characteristics such as age and sex. Our results also showed that patients with no mutations of ROBO1 and KAT2B, SubRT subgroup showed favorable survival outcomes compared with no SubRT subgroup in short-term follow-up. All SubRT patients have received high-dose methotrexate induction chemotherapy in the initial treatment. Therefore, initial induction chemotherapy combined with subsequent radiotherapy might improve survival outcomes in PCNSL patients who have no ROBO1 and KAT2B somatic mutations in short-term follow-up. The overall findings suggest that the tumor microenvironment and angiogenesis-associated genomic alterations and treatment modalities are potential indicators of overall survival and may be affected by the baseline characteristics of PCNSL patients.

4.
Nutrients ; 13(9)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34579119

RESUMO

Nutritional assessments, including the Geriatric Nutritional Risk Index (GNRI), have emerged as prediction tools for long-term survival in various cancers. This study aimed to investigate the therapeutic strategy and explore the prognostic factors in the elderly patients (≥65 years) with diffuse large B cell lymphoma (DLBCL). The cutoff value of the GNRI score (92.5) was obtained using the receiver operating characteristic curve. Among these patients (n = 205), 129 (62.9%) did not receive standard R-CHOP chemotherapy. Old age (≥80 years), poor performance status, low serum albumin level, and comorbidities were the major factors associated with less intensive anti-lymphoma treatment. Further analysis demonstrated that a lower GNRI score (<92.5) was linked to more unfavorable clinical features. In the patients who received non-anthracycline-containing regimens (non-R-CHOP), multivariate analysis showed that a low GNRI can serve as an independent predictive factor for worse progression-free (HR, 2.85; 95% CI, 1.05-7.72; p = 0.039) and overall survival (HR, 2.98; 95% CI, 1.02-8.90; p = 0.045). In summary, nutritional evaluation plays a role in DLBCL treatment and the GNRI score can serve as a feasible predictive tool for clinical outcomes in frail elderly DLBCL patients treated with non-anthracycline-containing regimens.


Assuntos
Antraciclinas/química , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/química , Feminino , Humanos , Masculino , Avaliação Nutricional , Estado Nutricional
5.
J Pers Med ; 11(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34575621

RESUMO

BACKGROUND: Hepatitis C virus (HCV) in diffuse large B-cell lymphoma (DLBCL) is associated with a higher prevalence and distinctive clinical characteristics and outcomes. METHODS: A retrospective analysis of adult DLBCL patients from 2011 to 2015 was studied. RESULTS: A total of 206 adult DLBCL were enrolled with 22 (10.7%) HCV-positive patients. Compared to HCV-negative patients, the HCV-positive group had a poor performance status (p = 0.011), lower platelet count (p = 0.029), and higher spleen and liver involvement incidences (liver involvement, p = 0.027, spleen involvement, p = 0.026), and they received fewer cycles of chemotherapy significantly due to morbidity and mortality (p = 0.048). Overall survival was shorter in HCV-positive DLBCL (25.3 months in HCV-positive vs. not reached (NR), p = 0.049). With multivariate analysis, poor performance status (p < 0.001), advanced stage (p < 0.001), less chemotherapy cycles (p < 0.001), and the presence of liver toxicity (p = 0.001) contributed to poor OS in DLBCL. Among HCV-positive DLBCL, the severity of liver fibrosis was the main risk factor related to death. CONCLUSION: Inferior survival of HCV-positive DLBCL was observed and associated with poor performance status, higher numbers of complications, and intolerance of treatment, leading to fewer therapy. Therefore, anti-HCV therapy, such as direct-acting antiviral agents, might benefit these patients in the future.

6.
J Pers Med ; 11(9)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34575686

RESUMO

This study aimed to investigate whether the progression risk score (PRS) developed from cytoplasmic immunohistochemistry (IHC) biomarkers is available and applicable for assessing risk and prognosis in oral cancer patients. Participants in this retrospective case-control study were diagnosed between 2012 and 2014 and subsequently underwent surgical intervention. The specimens from surgery were stained by IHC for 16 cytoplasmic target markers. We evaluated the results of IHC staining, clinical and pathological features, progression-free survival (PFS), and overall survival (OS) of 102 oral cancer patients using a novel estimation approach with unsupervised hierarchical clustering analysis. Patients were stratified into high-risk (52) and low-risk (50) groups, according to their PRS; a metric consisting of cytoplasmic PLK1, PhosphoMet, SGK2, and SHC1 expression. Moreover, PRS could be extended for use in the Cox proportional hazard regression model to estimate survival outcomes with associated clinical parameters. Our study findings revealed that the high-risk patients had a significantly increased risk in cancer progression compared with low-risk patients (hazard ratio (HR) = 2.20, 95% confidence interval (CI) = 1.10-2.42, p = 0.026). After considering the influences of demographics, risk behaviors, and tumor characteristics, risk estimation with PRS provided distinct PFS groups for patients with oral cancer (p = 0.017, p = 0.019, and p = 0.020). Our findings support that PRS could serve as an ideal biomarker for clinical use in risk stratification and progression assessment in oral cancer.

8.
J Pers Med ; 11(4)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33918206

RESUMO

Hepatitis B reactivation is a common complication in lymphoma patients under immunosuppressive treatment with potentially serious and life-threating consequences. In this review, we discuss the basis of chronic Hepatitis B virus (HBV) infection, the definition and risk factors for HBV reactivation. We overview the management of HBV reactivation based on virological status and immunosuppressive regimen risk stratification. We also highlight and update information about the HBV reactivation in lymphoma patients under novel agent treatment, including newer monoclonal antibodies, small molecule inhibitors, and even chimeric antigen receptor T-cell immunotherapy.

9.
Int J Mol Sci ; 22(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33806209

RESUMO

Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal plasma-cell proliferation. The survival and prognosis of this condition have been significantly improved by treatment with active anti-MM drugs such as bortezomib or lenalidomide. Further, the discovery of novel agents has recently paved the way for new areas of investigation. However, MM, including myeloma-related bone diseases, remains fatal. Bone disease or bone destruction in MM is a consequence of skeletal involvement with bone pain, spinal cord compression, and bone fracture resulting from osteolytic lesions. These consequences affect disease outcomes, including patients' quality of life and survival. Several studies have sought to better understand MM bone disease (MBD) through the classification of its molecular mechanisms, including osteoclast activation and osteoblast inhibition. Bisphosphonates and the receptor activator of the nuclear factor-kappa B (NF-κB) ligand (RANKL) inhibitor, denosumab, prevent skeletal-related events in MM. In addition, several other bone-targeting agents, including bone-anabolic drugs, are currently used in preclinical and early clinical evaluations. This review summarizes the current knowledge of the pathogenesis of MBD and discusses novel agents that appear very promising and will soon enter clinical development.


Assuntos
Doenças Ósseas/terapia , Mieloma Múltiplo/terapia , Animais , Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas/etiologia , Remodelação Óssea , Osso e Ossos , Bortezomib/farmacologia , Denosumab/farmacologia , Difosfonatos/farmacologia , Humanos , Mieloma Múltiplo/complicações , Subunidade p50 de NF-kappa B/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteólise/complicações , Ligante RANK/metabolismo , Proteínas Wnt/antagonistas & inibidores
10.
Mar Drugs ; 19(4)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921340

RESUMO

Intensive efforts have been undertaken in the fields of prevention, diagnosis, and therapy of lung cancer. Fucoidans exhibit a wide range of biological activities, which are dependent on the degree of sulfation, sulfation pattern, glycosidic branches, and molecular weight of fucoidan. The determination of oversulfation of fucoidan and its effect on anti-lung cancer activity and related signaling cascades is challenging. In this investigation, we used a previously developed fucoidan (SCA), which served as a native fucoidan, to generate two oversulfated fucoidan derivatives (SCA-S1 and SCA-S2). SCA, SCA-S1, and SCA-S2 showed differences in compositions and had the characteristic structural features of fucoidan by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) analyses. The anticancer properties of SCA, SCA-S1, and SCA-S2 against human lung carcinoma A-549 cells were analyzed in terms of cytotoxicity, cell cycle, Bcl-2 expression, mitochondrial membrane potential (MMP), expression of caspase-3, cytochrome c release, Annexin V/propidium iodide (PI) staining, DNA fragmentation, and the underlying signaling cascades. Our findings indicate that the oversulfation of fucoidan promotes apoptosis of lung cancer cells and the mechanism may involve the Akt/mTOR/S6 pathway. Further in vivo research is needed to establish the precise mechanism whereby oversulfated fucoidan mitigates the progression of lung cancer.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Polissacarídeos/farmacologia , Sargassum/metabolismo , Compostos de Enxofre/farmacologia , Células A549 , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Estrutura Molecular , Polissacarídeos/isolamento & purificação , Relação Estrutura-Atividade , Compostos de Enxofre/isolamento & purificação
11.
Antioxidants (Basel) ; 10(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915987

RESUMO

Transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) plays a crucial role in regulating the expression of genes participating in cellular defense mechanisms against oxidative or xenobiotic insults. However, there is increasing evidence showing that hyperactivation of NRF2 is associated with chemoresistance in several cancers, including hepatocellular carcinoma (HCC), thus making NRF2 an attractive target for cancer therapy. Another important issue in cancer medication is the adverse effects of these substances on normal cells. Here, we attempted to identify a dual-selective NRF2 regulator that exerts opposite effects on NRF2-hyperactivated HCC cells and normal keratinocytes. An antioxidant response element driven luciferase reporter assay was established in Huh7 and HaCaT cells as high-throughput screening platforms. Screening of 3,000 crude extracts from the Taiwanese Indigenous Plant Extract Library resulted in the identification of Beilschmiedia tsangii (BT) root extract as a dual-selective NRF2 regulator. Multiple compounds were found to contribute to the dual-selective effects of BT extract on NRF2 signaling in two cell lines. BT extract reduced NRF2 protein level and target gene expression levels in Huh7 cells but increased them in HaCaT cells. Furthermore, notable combinatory cytotoxic effects of BT extract and sorafenib on Huh7 cells were observed. On the contrary, sorafenib-induced inflammatory reactions in HaCaT cells were reduced by BT extract. In conclusion, our results suggest that the combination of a selective NRF2 activator and inhibitor could be a practical strategy for fine-tuning NRF2 activity for better cancer treatment and that plant extracts or partially purified fractions could be a promising source for the discovery of dual-selective NRF2 regulators.

12.
Cancer Med ; 10(9): 2946-2955, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33787078

RESUMO

Most acute myeloid leukemia (AML) cells are argininosuccinate synthetase-deficient. Pegylated arginine deiminase (ADI-PEG20) monotherapy depletes circulating arginine, thereby selectively inducing tumor cell death. ADI-PEG20 was shown to induce complete responses in ~10% of relapsed/refractory or poor-risk AML patients. We conducted a phase I, dose-escalation study combining ADI-PEG20 and low-dose cytarabine (LDC) in AML patients. Patients received 20 mg LDC subcutaneously twice daily for 10 days every 28 days and ADI-PEG20 at 18 or 36 mg/m2 (dose levels 1 and 2) intramuscularly weekly. An expansion cohort for the maximal tolerated dose of ADI-PEG20 was planned to further estimate the toxicity and preliminary response of this regimen. The primary endpoints were safety and tolerability. The secondary endpoints were time on treatment, overall survival (OS), overall response rate (ORR), and biomarkers (pharmacodynamics and immunogenicity detection). Twenty-three patients were included in the study, and seventeen patients were in the expansion cohort (dose level 2). No patients developed dose-limiting toxicities. The most common grade III/IV toxicities were thrombocytopenia (61%), anemia (52%), and neutropenia (30%). One had an allergic reaction to ADI-PEG20. The ORR in 18 evaluable patients was 44.4%, with a median OS of 8.0 (4.5-not reached) months. In seven treatment-naïve patients, the ORR was 71.4% and the complete remission rate was 57.1%. The ADI-PEG20 and LDC combination was well-tolerated and resulted in an encouraging ORR. Further combination studies are warranted. (This trial was registered in ClinicalTrials.gov as a Ph1 Study of ADI-PEG20 Plus Low-Dose Cytarabine in Older Patients With AML, NCT02875093).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/efeitos adversos , Hidrolases/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Polietilenoglicóis/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Arginina/efeitos dos fármacos , Arginina/metabolismo , Argininossuccinato Sintase/deficiência , Citarabina/administração & dosagem , Citarabina/farmacocinética , Esquema de Medicação , Feminino , Humanos , Hidrolases/administração & dosagem , Hidrolases/farmacocinética , Injeções Intramusculares , Injeções Subcutâneas , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacocinética , Trombocitopenia/induzido quimicamente , Resultado do Tratamento
13.
Sci Rep ; 11(1): 1584, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452330

RESUMO

The study aims to evaluate the effectiveness of local injection of autologous platelet rich plasma (A-PRP) as a treatment for women suffering from stress urinary incontinence (SUI). In a prospective intervention study, twenty consecutive women suffering from SUI were treated with A-PRP injection at anterior vaginal wall where mid-urethra locates. Self-reported questionnaires were used to measure pre-treatment, 1 month and 6 months post-treatment symptom severity. Secondary outcomes of sexual function and treatment effect sorted by age were analyzed with valid statistical methods. A-PRP is effective in relieving SUI symptoms at both 1 month and 6 months post-treatment without significant adverse reactions reported. It seems to have a trend that treatment success rate with cured and improved symptoms was slightly higher in the younger group, although it did not reach statistical significance (P = 0.07). No significant changes in sexual function before and after the treatment were reported by the patients. This pilot study is the first to report A-PRP treatment effect for SUI in women. The result suggested that A-PRP is a considerable treatment option for mild to moderate SUI cases. It also opens up further research opportunities for A-PRP's clinical applications.


Assuntos
Transfusão de Plaquetas , Plasma Rico em Plaquetas/química , Incontinência Urinária por Estresse/terapia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Índice de Gravidade de Doença , Transplante Autólogo , Resultado do Tratamento , Uretra/patologia , Incontinência Urinária por Estresse/patologia , Urodinâmica , Vagina/patologia
16.
Kaohsiung J Med Sci ; 37(4): 346-347, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33340392

Assuntos
Infecções por Vírus Epstein-Barr/tratamento farmacológico , Gengiva/patologia , Infecções por HIV/tratamento farmacológico , Mandíbula/patologia , Linfoma Plasmablástico/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Biópsia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Raios gama , Gengiva/diagnóstico por imagem , Gengiva/efeitos dos fármacos , Gengiva/virologia , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/patologia , Infecções por HIV/virologia , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/crescimento & desenvolvimento , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/efeitos dos fármacos , Mandíbula/virologia , Linfoma Plasmablástico/diagnóstico por imagem , Linfoma Plasmablástico/patologia , Linfoma Plasmablástico/virologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prednisona/uso terapêutico , Costelas/diagnóstico por imagem , Costelas/efeitos dos fármacos , Costelas/patologia , Costelas/virologia , Escápula/diagnóstico por imagem , Escápula/efeitos dos fármacos , Escápula/patologia , Escápula/virologia , Vincristina/uso terapêutico
17.
Int J Mol Sci ; 21(18)2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32937821

RESUMO

Osteolytic bone lesions are one of the central features of multiple myeloma (MM) and lead to bone pain, fractures, decreased quality of life, and decreased survival. Dysfunction of the osteoclast (OC)/osteoblast (OB) axis plays a key role in the development of myeloma-associated osteolytic lesions. Many signaling pathways and factors are associated with myeloma bone diseases (MBDs), including the RANKL/OPG and NF-κB pathways. NRF2, a master regulator of inflammatory signaling, might play a role in the regulation of bone metabolism via anti-inflammatory signaling and decreased reactive oxygen species (ROS) levels. The loss of NRF2 expression in OCs reduced bone mass via the RANK/RANKL pathway and other downstream signaling pathways that affect osteoclastogenesis. The NRF2 level in OBs could interfere with interleukin (IL)-6 expression, which is associated with bone metabolism and myeloma cells. In addition to direct impact on OCs and OBs, the activity of NRF2 on myeloma cells and mesenchymal stromal cells influences the inflammatory stress/ROS level in these cells, which has an impact on OCs, OBs, and osteocytes. The interaction between these cells and OCs affects the osteoclastogenesis of myeloma bone lesions associated with NRF2. Therefore, we have reviewed the effects of NRF2 on OCs and OBs in MBDs.


Assuntos
Doenças Ósseas/metabolismo , Doenças Ósseas/patologia , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Humanos , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese/fisiologia , Osteólise/metabolismo , Transdução de Sinais/fisiologia
18.
PeerJ ; 8: e9862, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974098

RESUMO

Background: This study aimed to analyze the clinical outcomes associated with patients with recurrent/metastatic head and neck squamous cell carcinoma (RM HNSCC) who received cetuximab-based chemotherapy in a real-world clinical setting. Methods: Clinical data were extracted from RM HNSCC patients diagnosed between 2016 and 2019. Kaplan-Meier survival estimates and Cox proportional hazards model were used for survival analyses. Results: Of 106 RM HNSCC patients (mean age = 55.1 years), 38.7% exhibited recurrent disease and 61.3% had metastatic disease. The majority of patients showed a habit of addictive substance use, including alcohol (67.0%), betel nuts (71.7%), or tobacco (74.5%). The primary tumor sites included the oral cavity (64.1%), hypopharynx (19.8%), and oropharynx (16.0%). The median number of cetuximab cycles for the 106 patients was 11 (2-24). The disease control rate (DCR) was 48.1%, and the overall response rate (ORR) was 28.3%. The median progression-free survival (PFS) and overall survival (OS) were 5.0 and 9.23 months, respectively. Patients treated with more than 11 cycles of cetuximab exhibited a longer median PFS and median OS than did patients treated with less than 11 cycles (median PFS: 7.0 vs. 3.0 months, p < 0.001; OS: 12.43 vs. 4.46 months, p = 0.001). Patients without previous concurrent chemoradiotherapy (CRT) had a better median PFS than did those with previous CRT (6.0 vs. 4.0 months, p = 0.046). Multivariable analysis revealed that perineural invasion and fewer cycles of cetuximab (<11 cycles) were independent risk factors associated with disease progression. In addition, the reduction in treatment cycles of cetuximab and advanced lymph node metastasis were independent prognostic factors predicting poorer overall survival. Conclusion: Our study provides important real-world data regarding cetuximab-containing treatment in RM HNSCC. Consistent administration of cetuximab could be associated with more favorable outcomes in RM HNSCC in endemic carcinogen exposure areas.

19.
Biomed Pharmacother ; 129: 110348, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32554245

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is currently the most frequently occurring liver disorder in the world. However, a specific drug for the treatment of patients with NAFLD is not available. Therefore, the discovery of novel compounds for the treatment of NAFLD and elucidation of the underlying mechanisms of therapeutic drugs that can be used to treat this disease are urgently needed. 1,2,3,4,6 penta-O-galloyl-ß-d-glucose (PGG) is known to exert anti-inflammatory, antidiabetic, and hepatoprotective effects. However, little is known about the therapeutic potential of PGG in NAFLD. In this study, we investigated the effects of PGG on a high-fat diet (HFD)-induced mouse model of NAFLD. PGG was co-administered along with an HFD to C57BL/6 mice. After eight weeks of treatment, serum biochemistry, liver steatosis, and lipid metabolism-related genes were examined. The results showed that PGG treatment significantly reduced HFD-induced gain in body weight, liver steatosis, and leukocyte infiltration in a dose-dependent manner. Furthermore, PGG treatment markedly reduced serum triglyceride and glucose levels in HFD mice. Moreover, alterations in the mRNA expression of genes involved in lipid metabolism, including Hmgcr, Acc1, Abca1, Mttp, and Cd36, observed in the livers of HFD-treated mice were significantly reversed by PGG treatment. PGG significantly reduced HFD-induced protein expression of CD36, which is associated with fatty acid uptake, insulin resistance, hyperinsulinemia, and increased hepatic steatosis, in the liver of HFD mice. These results suggest that PGG inhibits HFD-induced hepatic steatosis and reverses HFD-induced alterations of gene expression in lipid metabolism. PGG has been shown to be well tolerated; therefore, it has potential uses in NAFLD treatment.


Assuntos
Dieta Hiperlipídica , Taninos Hidrolisáveis/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Homeostase , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia
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