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1.
Anticancer Res ; 39(10): 5345-5352, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570428

RESUMO

BACKGROUND/AIM: Accurate and timely assessment of the human epidermal growth factor receptor 2 (HER2/neu) overexpression is pivotal for the identification of breast cancer (BC) patients that could benefit from HER2-targeted therapy. Currently approved tissue-based HER2 assays (tHER2) are limited to testing HER2 status on tumor samples obtained at a few points in time during the course of the disease. Herein, we assessed serum HER2 (sHER2) status longitudinally in 81 serial samples prospectively collected from 43 consenting patients pre- and post-therapy to revisit the idea of serum testing in the follow-up of BC patients. PATIENTS AND METHODS: The cohort included 11 patients with early BC (EBC), 17 with locally advanced BC (LABC), and 15 with metastatic BC (MBC). sHER2 concentrations were measured using a quantitative ELISA-based technique, using 15 ng/ml as the cut-off for positivity. RESULTS: At baseline, sHER2 was negative in all EBC patients while positive in 1 LABC and 5 MBC patients. Sixteen BC patients (10 LABC, 1 EBC, and 5 MBC) were tHER2 positive. sHER2 and tHER2 results were discordant in 14 patients. Among the 16 tHER2 positive patients, 9 LABC, 1 EBC and 2 MBC patients were sHER2 negative. Conversely, 2 MBC patients were sHER2 positive, despite being tHER2 negative. A rise or drop of sHER2 by >20% correlated with disease progression or pathological response to therapy, respectively. CONCLUSION: The study demonstrated the technical validity and feasibility of the sHER2 assay. Findings suggest that post initial tissue diagnosis (tHER2), sHER2 assay may supplement subsequent tissue tests to monitor disease status and response to therapy. Further studies to assess the role of HER2 targeted therapies in sHER-positive/tHER2-negative cases upon disease progression are warranted.


Assuntos
Neoplasias da Mama/sangue , Receptor ErbB-2/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Mama/patologia , Progressão da Doença , Feminino , Humanos , Oncogenes/genética , Projetos Piloto
2.
Anticancer Res ; 39(10): 5773-5780, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570481

RESUMO

BACKGROUND/AIM: Serum γ-glutamyltransferase (GGT) is reportedly associated with survival and therapeutic response in various malignancies; however, as far as we are aware its impact on metastatic castration-resistant prostate cancer (mCRPC) has never been assessed. PATIENTS AND METHODS: Fifty consecutive men with mCRPC receiving enzalutamide at a single cancer center were retrospectively evaluated. The primary endpoint was overall survival (OS) and the secondary endpoints were prostate-specific antigen (PSA) response, maximal PSA change, and PSA progression-free survival (PSA-PFS). RESULTS: Multivariable analysis demonstrated that elevation of GGT (≥40 U/l) was significantly and independently associated with shorter OS (hazard ratio(HR)=3.61; p=0.004), as were lower hemoglobin (HR=6.04; p<0.001) and higher PSA (HR=4.38; p=0.009). Elevated GGT was also associated with poorer PSA response, maximal PSA change, and shorter PSA-PFS. CONCLUSION: Elevated GGT was an adverse prognostic indicator in men with mCRPC receiving enzalutamide. External validations would improve the generality of our findings.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , gama-Glutamiltransferase/sangue , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Humanos , Masculino , Segunda Neoplasia Primária/sangue , Segunda Neoplasia Primária/tratamento farmacológico , Feniltioidantoína/uso terapêutico , Prognóstico , Antígeno Prostático Específico/sangue , Estudos Retrospectivos , Resultado do Tratamento
3.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(3): 326-333, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31496166

RESUMO

Early diagnosis is the key to improve the prognosis of gastric cancer. How to screen out high-risk subjects of gastric cancer in population is a hot spot. Serum-based early detection of gastric cancer is suitable for high-risk population screening, which is more convenient and safer. This article reviews the diagnostic value of serum biomarkers for gastric cancer, including serum DNA methylation, various RNAs, pepsinogen, gastrin, osteopontin, MG7-Ag and CA724. Until now, there is still lack of ideal biomarkers for gastric cancer, and searching for specific RNAs may be promising for early diagnosis and screening of gastric cancer.


Assuntos
Biomarcadores Tumorais , Detecção Precoce de Câncer , Neoplasias Gástricas , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/tendências , Humanos , Sensibilidade e Especificidade , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico
4.
Curr Urol Rep ; 20(10): 60, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31478113

RESUMO

PURPOSE OF REVIEW: With the long-standing controversy surrounding the use of prostate-specific antigen (PSA) for the detection, evaluation, and surveillance of prostate cancer, there is a need for a minimally invasive technique to identify and risk-stratify these patients. Additionally, in an effort to reduce the number of unnecessary biopsies and identify clinically significant prostate cancer (csPCa), there has been a shift in practice towards the use of multiparametric magnetic resonance imaging (mpMRI) in conjunction with decision-making regarding prostate cancer diagnosis and management. In the current review, we summarize the data regarding the use of mpMRI in the detection, evaluation, and surveillance of csPCa. RECENT FINDINGS: Recent prospective clinical trials have determined that a pre-biopsy mpMRI may rule out insignificant prostate cancers, thereby reducing the number of patients who require a biopsy. The anatomic information gathered from these pre-biopsy mpMRI performed during MRI fusion biopsy in csPCa increases the accuracy of pathologic staging in terms of Gleason scores. In regard to active surveillance, prospective trials suggest little to no clinical utility for mpMRI and fusion biopsy in the surveillance of prostate cancer despite conflicting findings from retrospective studies. Recent trials suggest that mpMRI can play an important role in the detection and evaluation of csPCa. The ideal role for mpMRI in active surveillance remains limited.


Assuntos
Imagem por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Biomarcadores Tumorais/sangue , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Vigilância da População , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Medição de Risco
5.
Medicine (Baltimore) ; 98(37): e17179, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517874

RESUMO

We investigated oxidative stress parameters in the sera of patients with lung cancer and healthy individuals to evaluate their correlations with lung cancer.Ninety-four lung cancer patients and 64 healthy controls were enrolled after obtaining informed consent. Their sera oxidative stress parameters were measured.Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were significantly different between patients and healthy groups (all P < .001). TAS gradually decreased and TOS and OSI gradually increased from stage I to III, but it did not reach statistical significance (all P > .05). TAS and OSI were significantly different between the nonsmoking and smoking groups, radiotherapy and without radiotherapy groups, chemotherapy and without chemotherapy groups (P < .05), but not TOS (P > .05). In a receiver operating characteristic curve analysis comparing patients with lung cancer with healthy controls, the Youden indices of TOS, TAS, and OSI were 0.541, 0.532, and 1, respectively.The oxidative stress may be correlation with lung cancer staging. Smoking, surgery, radiotherapy, and chemotherapy showed correlation with parts oxidative stress parameters.


Assuntos
Antioxidantes/metabolismo , Neoplasias Pulmonares/sangue , Oxidantes/sangue , Biomarcadores Tumorais/sangue , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Curva ROC , Fumar/sangue
6.
Acta Cir Bras ; 34(7): e201900710, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31531530

RESUMO

PURPOSE: To investigate the prognostic value of 17 platelet-based prognostic scores in patients with malignant hepatic tumors after TACE therapy. METHODS: In total, 92 patients were divided into death group and survival group according to long-term follow-up results. The AUC was calculated to determine the optimal cut-off values for predicting prognosis. To determine better prognostic models, platelet-based models were analyzed separately after being showed as binary according to cut-off values. Cumulative survival rates of malignant hepatic tumors were calculated using Kaplan-Meier curves and differences were analyzed by the log-rank test. Univariate and multivariate analyses were performed to identify platelet-based prognostic scores associated with overall survival. RESULTS: Univariate analysis showed that APGA, APRI, FIB-4, FibroQ, GUCI, King's score, Lok index, PAPAS, cirrhosis, number of tumors, vascular cancer embolus, AFP, ALP and APTT were significantly related to prognosis. A multivariate analysis showed that the APGA, number of tumors, ALP and APTT were independently associated with overall survival. CONCLUSION: This study showed that the APGA, a platelet-based prognostic score, was an independent marker of prognosis in patients with malignant hepatic tumors after TACE and was superior to the other platelet-based prognostic scores in terms of prognostic ability.


Assuntos
Aspartato Aminotransferases/sangue , Plaquetas/química , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Curva ROC , Estudos Retrospectivos
7.
Anticancer Res ; 39(8): 4517-4523, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366554

RESUMO

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have dramatically changed the clinical outcomes of advanced tumours. However, biomarkers for monitoring immunological features during immunotherapy remain unclear, especially those in the peripheral blood, which are easily available. This study evaluated the usefulness of nCounter Analysis System in identifying immunological biomarkers in peripheral blood mononuclear cells (PBMCs) during ICI therapy. PATIENTS AND METHODS: PBMCs from two patients who responded well to ICI therapy were used, and the expression levels of immune-related mRNA and extracellular proteins were analyzed. RESULTS: Changes in the expression levels of 55 genes from pre-treatment to on-treatment were bioinformatically similar between the two cases. The expression levels of PD-1 were consistent with those by flow cytometry analysis, a reliable tool for monitoring various markers. CONCLUSION: The nCounter Analysis System may be a potent tool to simultaneously investigate genes and proteins on PBMCs as biomarkers during immunotherapy using a small amount of sample.


Assuntos
Biomarcadores Tumorais/sangue , Imunoterapia , Neoplasias Pulmonares/sangue , Proteínas de Neoplasias/genética , Idoso , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/sangue
8.
Anticancer Res ; 39(8): 4539-4548, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366557

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate PD-L1 expression and its association with prognosis in esophageal squamous cell carcinoma (ESCC) before and after neoadjuvant chemotherapy (5-fluorouracil and cisplatin, NAC-FP). PATIENTS AND METHODS: Using a database of 69 ESCC patients, we analyzed PD-L1 expression on tumor cells (TCs) and immune cells (ICs), as well as the density of CD8+ tumor-infiltrating lymphocytes (TILs) in pretreatment biopsy specimens-versus-surgical specimens after resection. We determined the prognostic significance of these factors. RESULTS: The fraction of ESCC containing ICs expressing PD-L1 and having a high CD8+ TIL density was significantly increased after neoadjuvant treatment. However, PD-L1 expression on TCs or ICs, and CD8+ TIL density, was not significantly associated with patient survival in ESCC patients. CONCLUSION: NAC-FP induced PD-L1 expression on ICs and CD8+ TILs in ESCC patients. This finding suggests that PD-1/PD-L1 blockade could be combined with NAC-FP to treat ESCC patients.


Assuntos
Antígeno B7-H1/genética , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Receptor de Morte Celular Programada 1/genética , Idoso , Antígeno B7-H1/sangue , Linfócitos T CD8-Positivos/efeitos dos fármacos , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Carcinoma de Células Escamosas do Esôfago/sangue , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Fluoruracila/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Prognóstico , Receptor de Morte Celular Programada 1/sangue , Microambiente Tumoral/efeitos dos fármacos
9.
Anticancer Res ; 39(8): 3981-3989, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366479

RESUMO

Uterine sarcomas are rare but very aggressive. Uterine myomas, on the other hand, are the most common benign tumors of the uterus. Currently there is no diagnostic technique available to distinguish them with certainty. This study aimed to summarize the published literature concerning protein-based biomarkers in the peripheral blood that can assist in this difficult differential diagnosis. In total, 48 articles, published between 1990 and 2017, were included. Most studies (n=37) concerned soft tissue sarcomas, while 11 discussed uterine sarcomas specifically. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukins (IL), cancer antigen 125 (CA 125), lactate dehydrogenase, gangliosides (LDH) and growth differentiation factor 15 (GDF-15) are the most studied proteins in soft tissue sarcomas, including uterine sarcomas. Future research on improving sarcoma diagnosis should include these proteins.


Assuntos
Leiomioma/sangue , Neoplasias/sangue , Sarcoma/sangue , Neoplasias Uterinas/sangue , Biomarcadores Tumorais/sangue , Diferenciação Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Leiomioma/patologia , Neoplasias Musculares/sangue , Neoplasias Musculares/patologia , Neoplasias/patologia , Sarcoma/patologia , Neoplasias Uterinas/patologia
10.
Anticancer Res ; 39(8): 4185-4190, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366504

RESUMO

BACKGROUND/AIM: Insulin-like growth factor 1 (IGF-1)-mediated molecular pathway has been implicated in non-small cell lung cancer (NSCLC) pathogenesis and progression. We aimed to evaluate serum levels of IGF-1, IGF-2 and IGF-binding protein 3 (IGF-BP3) before and after standard treatment in patients with advanced NSCLC and their prognostic and predictive correlations. PATIENTS AND METHODS: Seventy-three patients were prospectively included. Analysis and quantification of circulating levels of IGF1, IGF2, IGFBP3 were performed by total ELISA in peripheral blood samples at baseline and 3 months post-treatment. RESULTS: The median values of IGF-1 and IGF-1/IGF-BP3 ratios (125.82 vs. 133.4 ng/ml, p=0.087 and 0.01006 vs. 0.01252, p=0.011) were both decreased after treatment. Importantly, the post-treatment value of the ratio was significantly reduced only among responders to treatment (0.01044 from 0.01255, p=0.02). CONCLUSION: Reduction of IGF-1/IGF-BP3 ratio was statistically significant only among patients with NSCLC who responded to first-line treatment. If validated in larger cohorts, IGF-1/IGFBP3 might be a useful predictive tool for response to chemotherapy in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like I/genética , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pemetrexede/administração & dosagem , Prognóstico , Proteínas Recombinantes , Transdução de Sinais/efeitos dos fármacos
11.
Anticancer Res ; 39(8): 4343-4350, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366528

RESUMO

BACKGROUND/AIM: TAS-102 is recommended as salvage-line therapy for metastatic colorectal cancer (mCRC), but practical predictors for its efficacy are lacking. PATIENTS AND METHODS: In a single-institutional retrospective study of 33 patients treated with TAS-102, we investigated the predictive value of the pretreatment neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-monocyte (LMR) ratios for progression-free (PFS) and overall (OS) survival. Predictive ability using cut-offs of the median value (3.14) and 5 for NLR were compared. RESULTS: In univariate analysis, Eastern Cooperative Oncology Group performance score, NLR, and PLR were negatively significantly associated with PFS and OS. The number of treatment lines was negatively associated with PFS. The NLR cut-off of 5 was superior to the median value. Multivariate analyses showed a significant prognostic impact for NLR at cut-off 5 (hazard ratio(HR)=6.26, p=0.02 for PFS; HR=6.97, p=0.07 for OS). CONCLUSION: The pretreatment NLR is a prognostic biomarker for patients with mCRC who receive TAS-102 treatment.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/tratamento farmacológico , Prognóstico , Trifluridina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neutrófilos/patologia , Contagem de Plaquetas , Intervalo Livre de Progressão , Estudos Retrospectivos
12.
Anticancer Res ; 39(8): 4371-4377, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366532

RESUMO

BACKGROUND/AIM: The purpose of this retrospective study was to identify the predictive biomarkers of response to pretreatment for patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab. MATERIALS AND METHODS: The subjects were 54 patients treated with nivolumab for mRCC with a clear cell component (mccRCC) between September 2016 and February 2018. We analyzed the impact of serum biomarkers (lactate dehydrogenase [LDH], neutrophil-to-lymphocyte ratio, and C-reactive protein) on patients treated with nivolumab. We adopted the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model using six clinical factors (0=favorable, 1 or 2=intermediate, 3 to 6=poor risk groups, respectively). RESULTS: The prognostic risk classification (non-poor vs. poor) and serum LDH levels were correlated with the objective response of nivolumab treatment for mccRCC. Elevated serum LDH levels at baseline were an independent biomarker for progression-free survival (PFS) of mccRCC patients receiving nivolumab [HR=2.268 (95%CI=1.014-5.051), p=0.046]. Notably, high LDH levels were associated with a poorer PFS for patients in the favorable-risk group. CONCLUSION: Serum LDH levels at baseline before nivolumab treatment were associated with the objective response and clinical outcome of nivolumab treatment.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/tratamento farmacológico , L-Lactato Desidrogenase/sangue , Prognóstico , Idoso , Proteína C-Reativa/metabolismo , Carcinoma de Células Renais/sangue , Feminino , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Resultado do Tratamento
13.
Anticancer Res ; 39(8): 4405-4410, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366537

RESUMO

BACKGROUND/AIM: Recent studies have reported the involvement of NADPH oxidases (NOXs) in tumor progression. However, the role of NOX5 in colon cancer is unclear. We examined the clinical significance of NOX5 expression in colon cancer. PATIENTS AND METHODS: NOX5 expression was evaluated by immunohistochemistry in 119 patients with stage II or III colon cancer, and the relationship between NOX5 expression and clinicopathological data was analyzed. RESULTS: Of all tissues, 39.5% were negative and 60.5% were positive for NOX5 expression. Positive expression was significantly associated with undifferentiated histology (p=0.037) and lymph node metastasis (p=0.023). The 5-year progression-free survival rate of NOX5-positive patients was significantly worse than that of NOX5-negative patients (p=0.046). The rates of local recurrence observed in NOX5-positive patients were higher than that in NOX5-negative patients. CONCLUSION: NOX5 expression may be related to poor prognostic factors and could be useful as a prognostic biomarker.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias do Colo/cirurgia , NADPH Oxidase 5/genética , Recidiva Local de Neoplasia/cirurgia , Idoso , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão
14.
N Engl J Med ; 381(8): 727-738, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31433920

RESUMO

BACKGROUND: Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options. METHODS: We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee. Clinical benefit, defined as a minimal response or better, was a secondary end point. RESULTS: A total of 122 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis), and 123 were included in the safety population. The median age was 65 years, and the median number of previous regimens was 7; a total of 53% of the patients had high-risk cytogenetic abnormalities. A partial response or better was observed in 26% of patients (95% confidence interval, 19 to 35), including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months. Fatigue, nausea, and decreased appetite were common and were typically grade 1 or 2 (grade 3 events were noted in up to 25% of patients, and no grade 4 events were reported). Thrombocytopenia occurred in 73% of the patients (grade 3 in 25% and grade 4 in 33%). Thrombocytopenia led to bleeding events of grade 3 or higher in 6 patients. CONCLUSIONS: Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies. (Funded by Karyopharm Therapeutics; STORM ClinicalTrials.gov number, NCT02336815.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/administração & dosagem , Hidrazinas/administração & dosagem , Carioferinas/antagonistas & inibidores , Mieloma Múltiplo/tratamento farmacológico , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Triazóis/administração & dosagem , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/sangue , Dexametasona/efeitos adversos , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Hidrazinas/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Triazóis/efeitos adversos , Adulto Jovem
15.
Anticancer Res ; 39(8): 4561-4568, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366560

RESUMO

BACKGROUND/AIM: Neoplastic spindle cells (NSCs) are believed to play a role in cancer invasion and metastasis, as well as in poor prognosis. The clinicopathological characteristics and prognostic relevance of NSCs was investigated in gallbladder cancer. MATERIALS AND METHODS: Specimens were obtained from 62 patients with gallbladder cancer who underwent surgery. The emergence of NSCs and their correlation with clinicopathological factors, prognosis, and EMT markers was evaluated. RESULTS: The NSC grade correlated with tumor size, preoperative CA19-9, surgical margin, the degree of differentiation, the depth of invasion, lymph node metastasis, lymphatic invasion, vascular invasion, and perineural invasion. Multivariate analysis of overall survival showed that NSCs were an independent prognostic factor. A correlation between NSCs and EMT was also suggested. CONCLUSION: NSCs are an independent prognostic factor for patients with postoperative gallbladder cancer, which also suggests a correlation between NSCs and EMT.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Vesícula Biliar/patologia , Invasividade Neoplásica/patologia , Prognóstico , Adulto , Idoso , Antígeno CA-19-9/sangue , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Invasividade Neoplásica/genética
16.
Medicine (Baltimore) ; 98(35): e16924, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464928

RESUMO

Autoimmune hepatitis (AIH) is a disorder of unknown etiology in which immune-mediated liver damage progresses to cirrhosis or hepatocellular carcinoma (HCC). The mainstay therapy for AIH is steroids and other immunosuppressive treatments. Currently, there are no validated markers for monitoring immune-mediated hepatic inflammation. Galectin-9 has recently been identified as a potential biomarker in patients with chronic liver disease. The objective of this study was to determine whether Galectin-9 and other serum proteins are associated with active disease in AIH patients.We enrolled 77 Japanese patients with well-documented AIH who were identified from the National Hospital Organization-AIH-liver-network database, as well as 32 patients with chronic hepatitis C (CHC), 27 patients with SLE, and 17 healthy control subjects. Serum levels of galectin-9, and markers of liver injury were measured and compared between groups.Serum levels of galectin-9 were significantly higher in AIH patients than in CHC patients (13.8 ±â€Š4.9 ng/mL vs 8.9 ±â€Š3.0 ng/mL, P < .001) or healthy controls (13.8 ±â€Š4.9 ng/mL vs 5.0 ±â€Š1.3 ng/mL, P < .001). In AIH group, serum galectin-9 levels weakly correlated with alanine aminotransferase levels or total bilirubin (TB) and strongly correlated with C-X-C motif chemokine 10 (CXCL10) and Mac-2 binding protein glycosylation isomer (M2BPGi) levels, but did not correlate with the histological grade of liver fibrosis. Steroid treatment of AIH patients significantly reduced serum galectin-9 levels (14.1 ±â€Š4.9 ng/mL vs 8.3 ±â€Š3.8 ng/mL, P < .001). SLE patients exhibited higher galectin-9 levels, whereas the galectin-9 levels did not correlate with liver function tests such as alanine aminotransferase levels.Serum galectin-9 correlated with disease status in AIH patients and could thus be useful biomarkers to detect hepatic autoimmunity. Because circulating galectin-9 reflects autoimmune-mediated inflammation, it may have additional utility as a biomarker for other autoimmune disorders.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Biomarcadores/sangue , Proteínas de Transporte/sangue , Galectinas/sangue , Glicoproteínas/sangue , Hepatite Autoimune/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Hepatite C Crônica/sangue , Hepatite C Crônica/metabolismo , Hepatite Autoimune/sangue , Humanos , Japão , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Esteroides/administração & dosagem , Esteroides/farmacologia , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
17.
Bioengineered ; 10(1): 345-352, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31411110

RESUMO

This study aimed to detect serum miR-203 expression levels in AML and explore its potential clinical significance. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to measure the serum miR-203 levels in 134 patients with AML and 70 healthy controls. The results demonstrated that serum miR-203 expression was significantly reduced in AML patients compared with healthy controls. Receiver operating characteristic curve (ROC) analysis revealed miR-203 could distinguish AML cases from normal controls. Low serum miR-203 levels were associated with worse clinical features, as well as poorer overall survival and relapse free survival of AML patients. Moreover, multivariate analysis confirmed low serum miR-203 expression to be an independent unfavorable prognostic predictor for AML. The bioinformatics analysis showed that the downstream genes and pathways of miR-203 was closely associated with tumorigenesis. Downregulation of miR-203 in AML cell lines upregulated the expression levels of oncogenic promoters such as CREB1, SRC and HDAC1. Thus, these findings demonstrated that serum miR-203 might be a promising biomarker for the diagnosis and prognosis of AML.


Assuntos
Biomarcadores Tumorais/genética , Carcinogênese/genética , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Antagomirs/genética , Antagomirs/metabolismo , Biomarcadores Tumorais/sangue , Carcinogênese/metabolismo , Carcinogênese/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Biologia Computacional/métodos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/sangue , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Perfilação da Expressão Gênica , Ontologia Genética , Histona Desacetilase 1/sangue , Histona Desacetilase 1/genética , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , MicroRNAs/antagonistas & inibidores , MicroRNAs/sangue , Anotação de Sequência Molecular , Análise Multivariada , Proteínas de Neoplasias/sangue , Prognóstico , Curva ROC , Recidiva , Transdução de Sinais , Análise de Sobrevida , Quinases da Família src/sangue , Quinases da Família src/genética
18.
Medicine (Baltimore) ; 98(31): e16685, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374052

RESUMO

The aim of the study was to estimate the prognostic and clinicopathologic significance of miR-125a-5p in human cancers. Eligible studies were obtained from PubMed, Embase, and the Cochrane Library. Combined hazard ratios (HRs) and odds ratios (ORs) were used to evaluate the prognostic and clinicopathologic value of miR-125a-5p. In pan-cancer, high miR-125a-5p expression was associated with better overall survival (OS) (HR = 0.459, 95% confidence interval [CI]: 0.369-0.57, P < .001), and disease-free survival (HR = 0.343, 95% CI: 0.237-0.496, P < .001). Furthermore, favorable OS was also found in lung cancer (HR = 0.343, 95% CI: 0.228-0.517, P < .001) and gastric cancer (HR = 0.341, 95% CI: 0.160-0.725, P = .005) patients with high miR-125a-5p expression. Besides, high miR-125a-5p expression was correlated with early stage (OR = 0.413, 95% CI: 0.228-0.749, P = .004) and negative lymph node metastasis (OR = 0.262, 95% CI: 0.073-0.941, P = .04) in gastric cancer, and was linked with better tumor differentiation in pan-cancer (OR = 1.623, 95% CI: 1.064-2.476, P = .025) and lung cancer (OR = 2.371, 95% CI: 1.358-4.141, P = .002). In conclusion, miR-125a-5p is a tumor suppressor with prognostic and clinicopathologic values for human cancer, and miR-125a-5p overexpression predicted favorable prognosis, early stage, negative lymph node metastasis, and better tumor differentiation. More research should be conducted to test these results.


Assuntos
MicroRNAs/sangue , Neoplasias/sangue , Biomarcadores Tumorais/sangue , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Metástase Linfática , Estudos Observacionais como Assunto , Modelos de Riscos Proporcionais
19.
Medicine (Baltimore) ; 98(31): e16712, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374064

RESUMO

Molecular characterization of lung cancer specimens after radical surgery offers additional prognostic information and may help to guide adjuvant therapeutic procedures. The transcriptional regulators alpha thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) have recently been described in different cancer entities as a useful prognostic biomarker. This study was initiated to explore their protein expression patterns and prognostic value in patients with operable lung cancer disease.The protein abundance (in the following text also named protein expression) of ATRX and DAXX were analyzed by immunohistochemistry in 194 samples of squamous cell lung carcinoma (SQCLC), 111 samples of pulmonary adenocarcinoma (AC) and 40 samples of small cell lung cancer (SCLC). The protein levels of ATRX and DAXX were correlated with clinicopathological characteristics and patient outcome.ATRX showed strong protein expression in 16.2% of AC, 11.9% of SQCLC, and 42.5% of SCLC. DAXX was highly expressed in 54.9% of AC, 76.2% of SQCLC, and 82.5% of SCLC. Immunostaining of both ATRX and DAXX were seen in 14.4% of AC, 11.3% of SQCLC, and 42.5% of SCLC. High protein expression of ATRX was a favorable prognostic marker for patients with AC (hazard ratio 0.38, P = .02). Sub-group analyses showed a significant correlation between ATRX and the clinical stage of SQCLC and SCLC. Histological grading and ATRX were also significantly associated in cases of SQCLC.The presence of ATRX and DAXX are correlated with lung cancer histology. Strong ATRX protein expression is associated with a significantly longer overall survival in patients with AC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , Adenocarcinoma/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Proteínas Nucleares/sangue , Proteína Nuclear Ligada ao X/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
20.
Medicine (Baltimore) ; 98(26): e16051, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261511

RESUMO

MiR-101 plays an important role in tumorigenesis. The aim of this study was to estimate diagnostic potential of serum miR-101 in bladder cancer.Serum level of miR-101 in 122 bladder cancer patients and 110 healthy volunteers was detected using quantitative real-time polymerase chain reaction method. The association between miR-101 expression and clinicopathological characteristic was analyzed via χ test. Then receiver operating characteristic (ROC) curve was plotted to evaluate diagnostic value of serum miR-101 in bladder cancer.MiR-101 expression was statistically down-regulated in bladder cancer patients compared to healthy controls. MiR-101 expression was significantly associated with TNM stage (P = .019), pathological grade (P = .006) and lymph node metastasis (P = .010). ROC analysis suggested that miR-101 had high value in discriminating between bladder cancer patients and healthy individuals with an AUC value of 0.884. The cut-off value for serum miR-101 in bladder cancer diagnosis was 1.645, with a sensitivity of 82.0% and a specificity of 80.9%.MiR-101 is decreased in bladder cancer patients, and shows negative association with aggressive clinical characteristics. MiR-101 may serve as a bio-marker in diagnosing bladder cancer.


Assuntos
MicroRNAs/sangue , Neoplasias da Bexiga Urinária/sangue , Área Sob a Curva , Biomarcadores Tumorais/sangue , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real
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