RESUMEN
BACKGROUND: Differential diagnosis between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains a clinical challenge. OBJECTIVE: The aim of the study is to assess the efficacy of the serum and pleural fluid (PF) miRNA panels in distinguishing MPE from BPE. METHODS: Fourteen candidate miRNAs which were shown aberrant expression in lung cancer based on previous studies were tested by quantitative real-time PCR (qRT-PCR) in 20 MPE patients and 20 BPE patients. Significantly aberrantly expressed miRNAs were further assessed by qRT-PCR in all patients enrolled in this study. A receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to evaluated the diagnostic performance of the miRNAs. RESULTS: miR-21, miR-29c and miR-182 were found to be significantly aberrantly expressed in the serum and PF of MPE patients. The AUCs for the combination of miR-21, miR-29c and miR-182 in serum and PF were 0.832 and 0.89 respectively in distinguishing MPE from infection-associated PE including tuberculous pleurisy and parapneumonia PE, and 0.866 and 0.919 respectively for differentiating MPE from heart failure-associated PE, which were superior to AUC of each individual miRNAs. CONCLUSIONS: miR-21, miR-29c and miR-182 in serum and PF could be useful biomarkers for diagnosis of MPE.
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MicroARNs , Derrame Pleural Maligno , Derrame Pleural , Biomarcadores de Tumor , Diagnóstico Diferencial , Humanos , MicroARNs/genética , Derrame Pleural/diagnóstico , Derrame Pleural/genética , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/metabolismoRESUMEN
Non-small cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) is intrinsic resistance to EGFR-tyrosine kinase inhibitors (TKIs), such as afatinib. Celastrol, a natural compound with antitumor activity, was reported to induce paraptosis in cancer cells. In this study, intrinsic EGFR-TKI-resistant NSCLC cell lines H23 (EGFR wild-type and KRAS mutation) and H292 (EGFR wild-type and overexpression) were used to test whether celastrol could overcome primary afatinib resistance through paraptosis induction. The synergistic effect of celastrol and afatinib on survival inhibition of the NSCLC cells was evaluated by CCK-8 assay and isobologram analysis. The paraptosis and its modulation were assessed by light and electron microscopy, Western blot analysis, and immunofluorescence. Xenografts models were established to investigate the inhibitory effect of celastrol plus afatinib on the growth of the NSCLC tumors in vivo. Results showed that celastrol acted synergistically with afatinib to suppress the survival of H23 and H292 cells by inducing paraptosis characterized by extensive cytoplasmic vacuolation. This process was independent of apoptosis and not associated with autophagy induction. Afatinib plus celastrol-induced cytoplasmic vacuolation was preceded by endoplasmic reticulum stress and unfolded protein response. Accumulation of intracellular reactive oxygen species and mitochondrial Ca2+ overload may be initiating factors of celastrol/afatinib-induced paraptosis and subsequent cell death. Furthermore, Celastrol and afatinib synergistically suppressed the growth of H23 cell xenograft tumors in vivo. The data indicate that a combination of afatinib and celastrol may be a promising therapeutic strategy to surmount intrinsic afatinib resistance in NSCLC cells.
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Afatinib/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Triterpenos Pentacíclicos/farmacología , Animales , Calcio/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Resistencia a Antineoplásicos , Sinergismo Farmacológico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Especies Reactivas de Oxígeno/metabolismo , Respuesta de Proteína Desplegada/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people. METHODS: A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%-95%) were determined for reference ranges in different populations. RESULTS: There was a statistically significant difference in median HE4 levels between the post-menopausal (nâ=â2168) and pre-menopausal groups (nâ=â325) (36.46 vs. 24.04 pmol/L, Zâ=â-14.41, Pâ<â0.001). HE4 increased significantly with age in the post-menopausal groups (Hâ=â408.18, Pâ<â0.001) but not in the pre-menopausal subjects (Zâ=â-0.43, Pâ=â0.67). The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women, 78.17 pmol/L for post-menopausal women, and 73.3 pmol/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age. CONCLUSIONS: Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.
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Neoplasias Ováricas , Proteína 2 de Dominio del Núcleo de Cuatro Disulfuros WAP , Adulto , Beijing , Biomarcadores de Tumor , Antígeno Ca-125 , China , Estudios Transversales , Femenino , Humanos , Masculino , Menopausia , Estudios Prospectivos , Proteína 2 de Dominio del Núcleo de Cuatro Disulfuros WAP/metabolismoRESUMEN
BACKGROUND: High-grade glioma (HGG) is a fatal human cancer. Bortezomib, a proteasome inhibitor, has been approved for the treatment of multiple myeloma but its use in glioma awaits further investigation. This study aimed to explore the chemotherapeutic effect and the underlying mechanism of bortezomib on gliomas. METHODS: U251 and U87 cell viability and proliferation were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, tumor cell spheroid growth, and colony formation assay. Cell apoptosis and cell cycle were detected by flow cytometry. Temozolomide (TMZ)-insensitive cell lines were induced by long-term TMZ treatment, and cells with stem cell characteristics were enriched with stem cell culture medium. The mRNA levels of interested genes were measured via reverse transcription-quantitative polymerase chain reaction, and protein levels were determined via Western blotting/immunofluorescent staining in cell lines and immunohistochemical staining in paraffin-embedded sections. Via inoculating U87 cells subcutaneously, glioma xenograft models in nude mice were established for drug experiments. Patient survival data were analyzed using the Kaplan-Meier method. RESULTS: Bortezomib inhibited the viability and proliferation of U251 and U87 cells in a dose- and time-dependent manner by inducing apoptosis and cell cycle arrest. Bortezomib also significantly inhibited the spheroid growth, colony formation, and stem-like cell proliferation of U251 and U87 cells. When administrated in combination, bortezomib showed synergistic effect with TMZ in vitro and sensitized glioma to TMZ treatment both in vitro and in vivo. Bortezomib reduced both the mRNA and protein levels of Forkhead Box M1 (FOXM1) and its target gene Survivin. The FOXM1-Survivin axis was markedly up-regulated in established TMZ-insensitive glioma cell lines and HGG patients. Expression levels of FOXM1 and Survivin were positively correlated with each other and both related to poor prognosis in glioma patients. CONCLUSIONS: Bortezomib was found to inhibit glioma growth and improved TMZ chemotherapy efficacy, probably via down-regulating the FOXM1-Survivin axis. Bortezomib might be a promising agent for treating malignant glioma, alone or in combination with TMZ.
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Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Proteína Forkhead Box M1/genética , Glioma/tratamiento farmacológico , Survivin/genética , Temozolomida/uso terapéutico , Adolescente , Adulto , Anciano , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Bortezomib/farmacología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Proteína Forkhead Box M1/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioma/genética , Glioma/metabolismo , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Survivin/metabolismo , Temozolomida/farmacología , Adulto JovenRESUMEN
This study compared the efficacy of neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) vs primary surgical treatment (PST) in patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB2/IIA2 cervical cancer.Data of 303 cervical cancer patients who received primary therapy for stage IB2/IIA2 cervical cancer at 7 medical centers in Beijing, China between January 1, 2009 and December 31, 2016 and followed through December 31, 2017 were collected retrospectively. The response rates, surgical characteristics, and overall survival (OS) durations of patients who received NACT followed by RS were compared to those of patients who received PST.An improved short-term complete response rate was observed among patients who received intra-arterial chemotherapy compared with patients who had intravenous chemotherapy (18.3% vs 4.1%, Pdifferenceâ=â.020). Patients who received NACT were more likely to undergo laparoscopic surgery and to have a lower blood loss volume (555.4â±â520.2âml vs PST, 682.5â±â509.8âml; Pâ=â.036) and increased estimated operative time (249.9â±â101.9 vs PST, 225.1â±â76.5âmin; Pâ=â.022). No differences in high-risk factors (HRFs), the effects of supplemental treatment, or 5-year OS were observed between patients who received NACT and PST.Our findings indicate that patients who received NACT for FIGO stage IB2/IIA2 cervical cancer were more likely to undergo laparoscopic surgery. These findings have important implications regarding treatment with curative intent for stage IB2/IIA2 cervical cancer and warrant a further analysis of treatment strategies to ensure adequate treatment and patient-centered care.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cuello del Útero/cirugía , Laparoscopía/mortalidad , Terapia Neoadyuvante/mortalidad , Neoplasias del Cuello Uterino/terapia , Adulto , Quimioterapia Adyuvante/métodos , Quimioterapia Adyuvante/mortalidad , Femenino , Humanos , Laparoscopía/métodos , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
Lumbar disc herniation is a common cause of radicular pain, but the mechanism remains ambiguous and the treatment stays unsatisfied. Many studies revealed a traditional Chinese medicine puerarin may moderate chronic pain from diabetes and nerve injury. Thus far, the role and mechanism of puerarin in radicular pain is still unknown. In this study, by using a rat model of lumbar disc herniation, which was induced by autologous nucleus pulposus (NP) implantation, the analgesic effect of puerarin on radicular pain was tested. Puerarin was delivered intraperitoneally form 1â¯h before surgery, and once daily for 7â¯days. The results demonstrated that NP implantation induced long-lasting pain, characterized by decrease of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in ipsilateral hindpaws, as long as day 20 after surgery. Spinal phosphorylated extracellular signal-regulated kinase (p-ERK) was up-regulated from day 5 to day 20 after surgery in ipsilateral but not contralateral side, and p-ERK was mainly co-localized with microglia. Puerarin decreased p-ERK expression from day 7 to day 20 after surgery. Puerarin or ERK inhibitor PD98059 alleviated pain behaviors, decreased expression of microglia marker ionized calcium-binding adaptor molecule 1 (Iba-1) in rats with NP implantation. The results suggested puerarin may alleviate radicular pain by inhibiting ERK-dependent or accompanied spinal microglia activation.
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Ganglios Espinales/efectos de los fármacos , Desplazamiento del Disco Intervertebral/complicaciones , Isoflavonas/uso terapéutico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Microglía/efectos de los fármacos , Radiculopatía/tratamiento farmacológico , Animales , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ganglios Espinales/metabolismo , Isoflavonas/farmacología , Masculino , Microglía/metabolismo , Dimensión del Dolor , Umbral del Dolor/efectos de los fármacos , Fosforilación/efectos de los fármacos , Radiculopatía/etiología , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: The aim of this study was to compare the incidence of ovarian metastasis (OM) in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) in early-stage cervical cancer and evaluate the safety of ovarian preservation in early-stage ADC. METHODS: To perform a meta-analysis to compare the incidence of OM between early-stage ADC and SCC, we searched PubMed, EMBASE, and Cochrane for observational studies that compared it with pathological evidence after radical hysterectomy and oophorectomy. Odds ratios with 95% confidence intervals were calculated with a fixed effects model. We also found a few articles evaluating the oncological prognosis of patients with ovarian preservation to perform a systematic review. RESULTS: A total of 5 studies were included in the meta-analyses. The incidence of OM of patients with early-stage ADC and SCC were 2% and 0.4%, respectively (odds ratio, 5.27; 95% confidence interval, 2.14-13.45). In 1427 patients with ADC or SCC of the cervix FIGO stage (CIS-IIA) who underwent hysterectomy, no ovarian recurrences were observed after unilateral or bilateral ovarian preservation in ADC patients in the follow-up (30-68 months); however, 15 patients with SCC developed pelvic recurrence. CONCLUSIONS: Although the incidence of OM was higher in early-stage ADC than SCC according to ovarian pathology, it might be relatively safe to perform ovarian preservation with early-stage ADC because of low ovarian recurrence rate in short-term follow-ups.
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Adenocarcinoma/epidemiología , Carcinoma de Células Escamosas/epidemiología , Tratamientos Conservadores del Órgano/estadística & datos numéricos , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/secundario , Neoplasias del Cuello Uterino/epidemiología , Adenocarcinoma/patología , Adenocarcinoma/secundario , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Femenino , Humanos , Incidencia , Estadificación de Neoplasias , Estudios Observacionales como Asunto , Tratamientos Conservadores del Órgano/efectos adversos , Tratamientos Conservadores del Órgano/métodos , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: Gefitinib, an EGFR-tyrosine kinase inhibitor, significantly improve prognosis in patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the usefulness of MUC1 and vascular endothelial growth factor (VEGF) mRNA expression in peripheral blood as means of predicting benefit from gefitinib therapy in NSCLC patients. METHODS: MUC1 and VEGF mRNA expressions were detected in peripheral blood of 66 patients with advanced NSCLC before (B0) and 4 weeks after treatment (B4w) with gefitinib, using real-time quantitative-PCR assay. Correlations between blood MUC1 and VEGF mRNA expression at B0 and B4w and the response to gefitinib treatment and survival were analyzed. RESULTS: Blood levels of MUC1 and VEGF mRNA at B0 and at B4w were significantly higher in patients with progressive disease than in those with partial response and stable disease. Furthermore, blood MUC1 and VEGF mRNA positivity at two time points were strongly associated with shorter progression-free survival (PFS) and overall survival (OS) (P = 0.005 and P = 0.008 at B0, and P < 0.001 and P = 0.001 at B4w, respectively, for MUC1; P = 0.004 and P = 0.009 at B0, and P = 0.001 and P < 0.001 at B4w, respectively, for VEGF). Multivariate analyses demonstrated that blood MUC1 and VEGF mRNA positivity at B0 and B4w were independent factors for predicting worse PFS and OS. CONCLUSIONS: MUC1 and VEGF mRNA positivity in blood seem to be indicators of unfavorable response and poor PFS and OS in patients with advanced NSCLC treated with gefitinib and may be promising noninvasive and repeatable markers for predicting efficacy of gefitinib treatment.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mucina-1/genética , Quinazolinas/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Biomarcadores , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Gefitinib , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mucina-1/sangre , Mutación , Estadificación de Neoplasias , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinazolinas/farmacología , ARN Mensajero/sangre , ARN Mensajero/genética , Factores de Riesgo , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the diagnostic utility of lung-specific X protein (LUNX) mRNA and vascular endothelial growth factor mRNA in differentiating pleural effusion of different origin. METHODS: A total of 136 patients with pleural effusion (46 cases of malignant pleural effusion caused by lung cancer, 30 cases of malignant pleural effusion caused by other cancers and 60 cases of benign pleural effusion) were enrolled in this study. Levels of LUNX mRNA and vascular endothelial growth factor mRNA in pleural fluid were detected by real-time quantitative polymerase chain reaction. Pleural fluid carcinoembryonic antigen and Cyfra21-1 were also measured simultaneously. RESULTS: The LUNX mRNA level was significantly higher in malignant pleural effusion caused by lung cancer than in malignant pleural effusion caused by other cancers and in benign pleural effusion. In malignant pleural effusion caused by cancers of different origin, the vascular endothelial growth factor mRNA level was significantly higher than in benign pleural effusion. For the diagnosis of malignant pleural effusion caused by lung cancer, LUNX mRNA exhibited higher sensitivity (80%), when compared with vascular endothelial growth factor mRNA (65%), carcinoembryonic antigen (67%) and Cyfra21-1 (61%), with the same specificity (95%). The combination of LUNX mRNA and cytology achieved a sensitivity of 85%. The combined use of LUNX mRNA and vascular endothelial growth factor mRNA and cytology raised the sensitivity to 89%, with 95% specificity. In initial cytology-negative pleural effusion from lung cancer, LUNX mRNA achieved the highest positive result (65%) among the four markers. CONCLUSIONS: The detection of LUNX mRNA and vascular endothelial growth factor mRNA in pleural fluid may be a complementary tool for the diagnosis of malignant pleural effusion. In particular, pleural fluid LUNX mRNA provided a valuable adjunct in distinguishing malignant pleural effusion caused by lung cancer from benign pleural effusion.
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Biomarcadores de Tumor/análisis , Glicoproteínas/genética , Neoplasias/complicaciones , Fosfoproteínas/genética , Derrame Pleural Maligno/diagnóstico , Derrame Pleural/diagnóstico , ARN Mensajero/análisis , Factor A de Crecimiento Endotelial Vascular/genética , Biomarcadores de Tumor/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Derrame Pleural/genética , Derrame Pleural Maligno/genética , ARN Mensajero/genéticaRESUMEN
The epidermal growth factor receptor (EGFR) mutations have been proven to be a reliable predictive marker for the response to EGFR-tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, the responses to EGFR-TKIs vary even among patients with EGFR mutation. Recent study showed that survivin overexpression attenuated EGFR-TKI-induced apoptosis and inhibited the antitumor effect of EGFR-TKIs on EGFR mutation NSCLC cells. We investigated the role of survivin mRNA expression in peripheral blood on predicting response and prognosis in NSCLC patients treated with EGFR-TKIs. Survivin mRNA expression levels in blood was detected using quantitative real-time-PCR assay in 62 patients with advanced NSCLC before (D0) and 4 weeks after treatment of EGFR-TKIs (D4w). The associations between survivin mRNA expression in blood and tumor response to treatment, time to progression (TTP), and overall survival (OS) were analyzed. Blood survivin mRNA levels at D0 and D4w were significantly higher in patients with progressive disease than in those with partial response and stable disease. The detections of blood survivin mRNA positivity at D0 and D4w were associated with unfavorable response to EGFR-TKIs treatment and shorter TTP and OS. Multivariate Cox analysis showed that blood survivin mRNA positivity before and 4 weeks after EGFR-TKIs treatment were independent predictor for worse TTP and OS. In conclusion, Blood survivin mRNA positivity was strongly related to a poor treatment outcome of EGFR-TKIs and may be a potential non-invasive biomarker for NSCLC treatment.
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Carcinoma de Pulmón de Células no Pequeñas/sangre , Receptores ErbB/antagonistas & inhibidores , Regulación Neoplásica de la Expresión Génica , Proteínas Inhibidoras de la Apoptosis/sangre , Neoplasias Pulmonares/sangre , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Adulto , Anciano , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Mutación , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Survivin , Resultado del TratamientoRESUMEN
AIM: The diagnostic role of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen, Cyfra 21-1 and neuron-specific enolase (NSE) in the bronchoalveolar lavage fluid (BALF) for lung cancer is still controversial. The aim of this study was to evaluate the diagnostic value of these four tumor markers in BALF for peripheral lung cancer. METHODS: We measured and compared the levels of CEA, SCC, Cyfra21-1 and NSE in BALF in 42 patients with peripheral lung cancer and 22 patients with benign lung disease. In the patients with peripheral lung cancer, the BAL was separately performed in the bronchus of the tumor-bearing lung and in the corresponding bronchus of the opposite healthy lung. RESULTS: The levels of CEA, SCC, Cyfra21-1 and NSE were significantly elevated in BALF from the tumor-bearing lung compared with the opposite healthy lung in the lung cancer patients (P < 0.001) or the benign lung disease patients (P < 0.005). The diagnostic sensitivities of Cyfra21-1 (86 and 76%), with a specificity of 91%, were the highest among the four tumor markers for the tumor-bearing lung versus the opposite healthy lung and benign lung disease. The combination of Cyfra21-1 and CEA increased the sensitivity to 93 and 86 percent, respectively. CONCLUSION: The assay of these tumor markers in BALF may be used as a diagnostic tool to complement a cytological examination in the diagnosis of peripheral lung cancer.
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Biomarcadores de Tumor/análisis , Líquido del Lavado Bronquioalveolar/química , Neoplasias Pulmonares/metabolismo , Adulto , Anciano , Antígenos de Neoplasias/análisis , Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Antígeno Carcinoembrionario/análisis , Antígeno Carcinoembrionario/metabolismo , Femenino , Humanos , Queratina-19/análisis , Queratina-19/metabolismo , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Fosfopiruvato Hidratasa/análisis , Fosfopiruvato Hidratasa/metabolismo , Serpinas/análisis , Serpinas/metabolismoRESUMEN
LUNX is a lung-specific gene whose messenger ribonucleic acid (mRNA) expression is strictly limited to normal lung tissue and nonsmall cell lung cancer (NSCLC) tissue. The aim of this study was to investigate whether the detection of LUNX mRNA-positive circulating tumor cells (CTC)s in peripheral blood at different time points is useful for predicting disease recurrence, disease-free survival (DFS), and overall survival (OS) in NSCLC patients undergoing surgery. Serial blood samples from 68 patients with stage I-IIIA NSCLC were examined by real-time quantitative polymerase chain reaction assay targeting LUNX mRNA before (T0) and after surgery (T1) and after the completion of adjuvant chemotherapy (T2). Results showed that LUNX mRNA-positive CTCs were detected in 40 of 68 NSCLC patients (58.8%) before surgery; the detection rates of LUNX mRNA-positive CTCs at T1 and T2 time points were 32.4% (22/68) and 33.3% (20/60), respectively. The detection of LUNX mRNA-positive CTC at 3 time points was associated with lymph node status and pathologic stage. During the follow-up period, patients with LUXN mRNA-positive CTC at 3 time points had a higher relapse rate and a shorter DFS and OS than those without. Multivariate analysis revealed that presence of LUNX mRNA-positive CTC at T1 and T2 time points was an independent unfavorable factor for DFS and OS. In conclusion, detection of LUNX mRNA-positive CTC after surgery and the completion of adjuvant chemotherapy in patients with stage I-IIIA NSCLC are highly predictive for DFS and OS. This technique could aid in the prediction of prognosis and design of tailored treatment.
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Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Glicoproteínas/genética , Neoplasias Pulmonares/mortalidad , Fosfoproteínas/genética , ARN Mensajero/análisis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
The purpose of this study was to investigate the diagnostic value of the deletion of fragile histidine triad (FHIT) and p16INK4a (p16) mRNA in biopsies obtained by bronchoscopy. Biopsies were analyzed using RT-PCR in 52 patients with lung cancer and 19 patients with benign lung disease. The results showed that the detection rates of FHIT and p16 gene transcript deletion were significantly higher in lung cancer patients than in patients with benign lung disease (65.4% versus 10.5%, p=0.001 and 59.6% versus 5.3%, p<0.001, respectively). The sensitivities for detecting FHIT and p16 transcript deletion in biopsies were 65.4% and 59.6% (combined 80.8%), respectively, which were markedly better than those of histology and cytology (42.3% and 34.6%, respectively; combined 57.7%). In 22 lung cancer patients with negative histology and cytology at initial bronchoscopy, FHIT and p16 mRNA loss was detected in 40.9% (9/22) and 36.4% (8/22) cases, respectively. FHIT mRNA loss was associated with smoking status in lung cancer patients. In conclusion, deletion of FHIT and p16 mRNA can be identified in biopsies obtained during bronchoscopic procedures. FHIT and p16 mRNA deletion can be used as biomarkers in the clinical diagnosis of lung cancer and may serve as adjuncts to histology and cytology in lung cancer diagnosis.
Asunto(s)
Ácido Anhídrido Hidrolasas/genética , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , ARN Mensajero/genética , Ácido Anhídrido Hidrolasas/metabolismo , Anciano , Biopsia , Broncoscopía/métodos , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Femenino , Genes p16 , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Estudios Prospectivos , ARN Mensajero/metabolismoRESUMEN
OBJECTIVE: To investigate the effects of postoperative adjuvant chemotherapy (CT) and chemoradiotherapy (CRT) or radiotherapy(RT) for Ib-IIa cervical cancer with risk factors. METHODS: From March 1995 to June 2010, there were 137 patients underwent radical hysterectomy and systematic pelvic lymphadenectomy for stage Ib-IIa cervical cancer admitted at Peking University First Hospital. These patients had risk factors, intermediate risk factors including bulky tumor ( > 4 cm) , lymph vascular space invasion, deep stromal invasion; high risk factors including positive surgical margin, parametrial invasion, lymph node involvement. Of the all patients, 79 cases of them were treated with CT, 58 of them were treated with RT or CRT. The 5-year survival and prognosis factors were analyzed retrospectively, the prognosis was compared between two adjuvant therapy groups. RESULTS: The univariate analysis shown that types of pathology, different grade of risk factors, stroma invasion and lymph node involvement were prognostic factors of 5-year overall survival. Patients with squamous cell carcinoma, intermediate risk factors, no parametrial invasion, and no lymph node involvement had better prognosis(P < 0.05). Whether patients with high-risk factors or intermediate-risk factors, the 5-year overall survival and 3-year disease-free survival had no difference between CT and RCT or RT groups respectively. Cox regression multivariate analysis of survival indicated that clinical stages, types of histology, different grade of risk factors were independent prognostic indicator. Patients with early stage, squamous cell carcinoma, intermediate risk factors had better prognosis. Univariate and multivariate analysis indicated that different postoperative adjuvant therapies had no effects on the prognosis. The 5-year overall survival was 88.6% in patients treated with CT, and 89.7% in patients treated with RT or CRT (P = 0.455) . CONCLUSION: There are equivalent therapeutic results between CT and RT or CRT for patients with risk factors after radical surgery, CT may be as one choice of postoperative adjuvant therapy for stage Ib-IIa cervical carcinoma with risk factors.
Asunto(s)
Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/terapia , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Quimioterapia Adyuvante , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Histerectomía , Escisión del Ganglio Linfático , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Periodo Posoperatorio , Pronóstico , Radioterapia Adyuvante , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Adulto JovenRESUMEN
OBJECTIVE: To assess the clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma (EOC). METHODS: A retrospective study of young EOC inpatients (≤40 years old) was performed during January 1994 and December 2010 in eight institutions. RESULTS: Data were analyzed from 94 patients treated with fertility-sparing surgery with a median follow-up time of 58.7 months. As histologic grade increased, overall survival (OS) and disease-free survival (DFS) of patients receiving fertility-sparing surgery declined. Neither staging surgery nor laparoscopy of early stage EOC with conservative surgery had a significant effect on OS or DFS. Normal menstruation recommenced after chemotherapy in 89% of the fertility-sparing group. Seventeen pregnancies among twelve patients were achieved by the end of the follow-ups. CONCLUSIONS: Fertility-sparing treatment for patients with EOC Stage I Grade 1 could be cautiously considered for young patients. The surgical procedure and surgical route might not significantly influence the prognosis. Standard chemotherapy is not likely to have an evident impact on ovarian function or fertility in young patients.
Asunto(s)
Preservación de la Fertilidad , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Ováricas/cirugía , Adulto , Carcinoma Epitelial de Ovario , Supervivencia sin Enfermedad , Femenino , Fertilidad/efectos de los fármacos , Humanos , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/fisiopatología , Ovario/efectos de los fármacos , Ovario/fisiología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: To discuss the death affairs of gynecological patients and find the measurements of down-regulating the mortality. METHODS: We conducted a retrospective study on the 54 death in-patients in our gynecological department during January 1993 and June 2008. Associated with literature, the data were analyzed according to primary diseases, death causes and clinical demonstrations, in order to probe into the rule of death in gynecological in-patients. RESULTS: The main death causes were gynecological cancers, such as ovarian carcinoma, cervical carcinoma, choriocarcinoma, invasive mole and endometrial carcinoma, which accounted for 79.6 percent (43/54) of gynecological death. Sudden death took up 24 percent (13/54), with death causes of cardio-cerebral vascular events, such as myocardium infarction, pneumonia embolism and cerebral embolism. CONCLUSION: Gynecological oncology is still the main disease threatening women's lives. Emphasis should be put on the physical and surgical complications of the patients. We should attach more importance to the observation and associated treatment of post-operative and post-chemotherapeutic patients with high risks.
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Causas de Muerte , Enfermedades de los Genitales Femeninos/mortalidad , Neoplasias Ováricas/mortalidad , Neoplasias del Cuello Uterino/mortalidad , Neoplasias Uterinas/mortalidad , Adulto , Anciano , Coriocarcinoma/epidemiología , Coriocarcinoma/mortalidad , Muerte Súbita , Femenino , Enfermedades de los Genitales Femeninos/epidemiología , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/epidemiología , Estudios Retrospectivos , Neoplasias del Cuello Uterino/epidemiología , Neoplasias Uterinas/epidemiología , Adulto JovenRESUMEN
Cervical cancer is the first malignant disease of the women all over the world. Although the incidence of cervical cancer has been decreasing due to increased availability of screening tests, the diagnosis, management and prognosis of pregnancy associated with cervical cancer are still complex problems for clinical doctors. Here we report two cases of pregnancy associated with cervical cancer in our hospital and analyze the screening tests, the management, the neoadjuvant chemotherapy and the prognosis of the cases. Besides, we also review some literature and conclude by relating with our case reports that: cervical cytological test is significant for the prenatal examination and doing the test can obviously decrease the incidence of cervical cancer for pregnant women; In the clinical process, the doctors should take the social, ethical, medical condition etc. into account in the management for each trimester at presentation; The neoadjuvant chemotherapy has become a blessing for the pregnant women associated with cervical cancer and there is no bad result reported in the literature; The main factor influencing prognosis of pregnancy associated with cervical cancer is in the tumor stage.
Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Complicaciones Neoplásicas del Embarazo/diagnóstico , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Embarazo , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Complicaciones Neoplásicas del Embarazo/cirugía , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/cirugía , Displasia del Cuello del Útero/tratamiento farmacológico , Displasia del Cuello del Útero/cirugíaRESUMEN
Primary fallopian tube carcinoma (PFTC) is a rare malignant carcinoma among all genital tract malignancies. It occurs most commonly in postmenopausal women and is similar to ovarian malignancy historically and clinically. Because of its insidious onset and silent course, the diagnosis is made usually postoperatively. Liquid-based cytology (LBC) is a type of method for cervical cancer screening, but sometimes it may aid in making PFTC diagnosis. We report a 47-year-old woman with PFTC, whose diagnosis was made with the aid of LBC.
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Citodiagnóstico/métodos , Neoplasias de las Trompas Uterinas/diagnóstico , Antígeno Ca-125/sangre , Neoplasias de las Trompas Uterinas/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To develop the rationales for ovarian cancer-specific protein profiles in serum and to analyze the protein profiles of multidrug resistance P-glucoprotein (MDR1) and multidrug resistance-associated protein (MRP) positive and negative expression sets for a rapid and sensitive serum protein pattern. METHOD: Serum protein profiles from 36 epithelial ovarian cancer cases were compared with 30 healthy controls using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (DELDI-TOF-MS). Blinded test was conducted subsequently for identification of the protein pattern. Expression of MDR and MRP were detected in set of training cases by immunohistochemistry. The spectra were analyzed statistically between positive and negative groups. RESULTS: Twenty-nine peaks were significantly different between ovarian cancer and healthy controls (P < 0.01, 15 peaks up-regulated and 14 down-regulated). A set of three peaks, at 5 486, 6 463 and 8 575 m/z respectively, were selected from 29 sense peaks as an ovarian cancer biomarker. The sensitivity was 100% and specificity 93.33%. Identification by blinded validation indicated a positive predictive value of 90%. MDR1 expression in ovarian cancer was 69.4 %. Twenty peaks were significantly different between positive and negative sets (P < 0.01). MRP expression in ovarian cancer was 63.8%. But one peak was detected (P < 0.01). CONCLUSION: It was an ideal pattern for employing the SELDI mass spectrum approach to diagnose ovarian cancer and select the multidrug resistance cases. Serum biomarkers for detecting drug resistance in ovarian cancer can be established on the basis of MDR1 immunohistochemistry.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/sangre , Biomarcadores de Tumor/sangre , Proteínas Sanguíneas/análisis , Resistencia a Antineoplásicos , Neoplasias Ováricas/sangre , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Mapeo Peptídico , ProteómicaRESUMEN
A series of substituted 2,5-diaryl-1,3,4-thiadiazole derivatives are prepared by microwave-assisted synthesis in the absence of an organic solvent. All derivatives are well characterized by (1)H and (13)C NMR, MS, and elemental analyses. The X-ray crystal structure of 2,5-di-(4-decyloxyphenyl)-1,3,4-thiadiazole reveals the tilt lamellar arrangement of rod-shaped molecules, which are stabilized by a variety of weak non-covalent interactions. The liquid crystalline properties are studied by polarized-light optical microscopy (POM), differential scanning calorimetry (DSC), and in situ variable temperature X-ray diffraction (VTXRD). By variations in the peripheral n-alkoxy chains, the calamitic mesogens exhibit enantiotropic smectic (SmC and/or SmA) mesophases with wide mesomorphic temperature ranges, whilst the disc-like mesogens form hexagonal columnar mesophase (Col(h)) at room temperature. The bulk electrical conductivity values of the smectic mesophases of 1-3 are in the range of 10(-3)-10(-4) S cm(-1), which are slightly higher than that of their solid films. In contrast, the solid film made from 2,5-di-(3,4,5-trioctyloxyphenyl)-1,3,4-thiadiazole shows poor conductivity (2x10(-7) S cm(-1)).