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1.
BMC Med ; 19(1): 269, 2021 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-34784919

RESUMEN

BACKGROUND: There is no consensus regarding the clinical target volume (CTV) margins in radiotherapy for glioma. In this study, we aimed to perform a complete macropathologic analysis examining microscopic tumor extension (ME) to more accurately define the CTV in glioma. METHODS: Thirty-eight supra-total resection specimens of glioma patients were examined on histologic sections. The ME distance, defined as the maximum linear distance from the tumor border to the invasive tumor cells, was measured at each section. We defined the CTV based on the relationships between ME distance and clinicopathologic features. RESULTS: Between February 2016 and July 2020, a total of 814 slides were examined, corresponding to 162 slides for low-grade glioma (LGG) and 652 slides for high-grade glioma (HGG). The ME value was 0.69 ± 0.43 cm for LGG and 1.29 ± 0.54 cm for HGG (P < 0.001). After multivariate analysis, tumor grade, O6-methylguanine-DNA-methyltransferase promoter methylated status (MGMTm), isocitrate dehydrogenase wild-type status (IDHwt), and 1p/19q non-co-deleted status (non-codel) were positively correlated with ME distance (all P < 0.05). We defined the CTV of glioma based on tumor grade. To take into account approximately 95% of the ME, a margin of 1.00 cm, 1.50 cm, and 2.00 cm were chosen for grade II, grade III, and grade IV glioma, respectively. Paired analysis of molecularly defined patients confirmed that tumors that had all three molecular alterations (i.e., MGMTm/IDHwt/non-codel) were the most aggressive subgroups (all P < 0.05). For these patients, the margin could be up to 1.50 cm, 2.00 cm, and 2.50 cm for grade II, grade III, and grade IV glioma, respectively, to cover the subclinical lesions in 95% of cases. CONCLUSIONS: The ME was different between the grades of gliomas. It may be reasonable to recommend 1.00 cm, 1.50 cm, and 2.00 cm CTV margins for grade II, grade III, and grade IV glioma, respectively. Considering the highly aggressive nature of MGMTm/IDHwt/non-codel tumors, for these patients, the margin could be further expanded by 0.5 cm. These recommendations would encompass microscopic disease extension in 95% of cases. TRIAL REGISTRATION: The trial was registered with Chinese Clinical Trial Registry ( ChiCTR2100049376 ).


Asunto(s)
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Glioma/genética , Glioma/radioterapia , Humanos , Isocitrato Deshidrogenasa/genética , Mutación
2.
World J Surg Oncol ; 19(1): 297, 2021 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-34645481

RESUMEN

BACKGROUND: Inflammation markers have an important effect on tumor proliferation, invasion, and metastasis. Oligometastatic disease (OMD) is an intermediate state between widespread metastases and locally confined disease, where curative strategies may be effective for some patients. We aimed to explore the predictive value of inflammatory markers in patients with oligometastatic colorectal cancer (OMCC) and build a nomogram to predict the prognosis of these patients. METHODS: Two hundred nine patients with OMCC were retrospectively collected in this study. The Kaplan-Meier survival curves and Cox regression analysis were used to estimate overall survival (OS) and progression-free survival (PFS). A multivariate Cox analysis model was utilized to establish the nomogram. The concordance index (C-index), calibration curve, and receiver operating characteristics (ROC) were established to verify the validity and accuracy of the prediction model. RESULTS: According to the multivariate analysis, decreased platelet-to-lymphocyte ratio (PLR) might independently improve OS in patients with OMCC (HR = 2.396, 95% CI 1.391-4.126, P = 0.002). Metastases of extra-regional lymph nodes indicated poor OS (HR = 2.472, 95% CI 1.247-4.903, P = 0.010). While the patients with early N stage had better OS (HR = 4.602, 95% CI 2.055-10.305, P = 0.001) and PFS (HR = 2.100, 95% CI 1.364-3.231, P = 0.007). Primary tumor resection (HR = 0.367, 95% CI 0.148-0.908, P = 0.030) and lower fibrinogen (HR = 2.254, 95% CI 1.246-4.078, P = 0.007) could significantly prolong the OS in patients with OMCC. PLR, metastases of extra-regional lymph nodes, N stage, primary tumor resection, and fibrinogen were used to make up the nomogram. The C-index and area under the curve (AUC) of the ROC in nomogram were 0.721 and 0.772 respectively for OS, showed good consistency between predictive probability of OS and actual survival. CONCLUSIONS: Decreased PLR could predict a good prognosis in patients with OMCC. The nomogram including inflammatory factors and clinicopathological markers was credible and accurate to predict survivals in patients with OMCC.


Asunto(s)
Neoplasias Colorrectales , Linfocitos , Plaquetas , Humanos , Nomogramas , Pronóstico , Estudios Retrospectivos
3.
Front Oncol ; 11: 709511, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34336697

RESUMEN

Background: Gastric cancer (GC) is one of the most common causes of malignant tumors in the world. Due to the high heterogeneity of GC and lack of specificity of available chemotherapy regimens, these tumors are prone to resistance, recurrence, and metastasis. Here, we formulated an individualized chemotherapy regimen for GC using a modified individual conditional reprogramming (i-CR) system. We established a primary tumor cell bank of GC cells and completed drug screening in order to realize individualized and accurate GC treatment. Methods: We collected specimens from 93 surgical or gastroscopy GC cases and established a primary tumor cell bank using the i-CR system and PDX models. We also completed in vitro culture and drug sensitivity screening of the GC cells using the i-CR system. Whole-exome sequencing (WES) of the i-CR cells was performed using P0 and P5. We then chose targeted chemotherapy drugs based on the i-CR system results. Results: Of the 72 cases that were collected from surgical specimens, 26 cases were successfully cultured with i-CR system, and of the 21 cases collected from gastroscopy specimens, seven were successfully cultured. Among these, 20 cases of the PDX model were established. SRC ± G3 had the highest culture success rate. The i-CR cells of P0 and P5 appeared to be highly conserved. According to drug sensitivity screening, we examined the predictive value of responses of GC patients to chemotherapeutic agents, especially in neoadjuvant patients. Conclusion: The i-CR system does not only represent the growth characteristics of tumors in vivo, but also provides support for clinical drug use. Drug susceptibility results were relatively consistent with clinical efficacy.

4.
Cancer Manag Res ; 13: 6411-6428, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34429650

RESUMEN

Purpose: The Y-box binding protein 1 (YBX1) gene encodes the multifunctional protein YB1 that is associated with the dysregulation of numerous cancer-related genes. However, the prognostic value of YBX1 and its correlation with immune cell infiltration in breast cancer (BRCA) remain unclear. Methods: YBX1 expression data in various malignancies were obtained from Oncomine, Tumor Immune Estimation Resource (TIMER), Cancer Cell Line Encyclopedia, UALCAN and cBio Cancer Genomics Portal databases. Survival data were analyzed with Kaplan-Meier plotter. Immune cell infiltration and its association with YBX1 expression level were assessed with TIMER and LinkedOmics. YB1 expression was evaluated by immunohistochemistry and Western blotting, and changes in cancer cell viability and T cell activity following YBX1 knockdown were assessed with an immunocyte-tumor cell co-culture assay. Results: YBX1 was downregulated in the BRCA cohort, which was closely associated with worse prognosis in the luminal A subtype (overall survival [OS]: hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.22-3.05, P = 0.0042; recurrence-free survival [RFS]: HR 1.85, 95% CI 1.51-2.28, P = 3.1e-9) and luminal B subtype (OS: HR 1.08, 95% CI 0.68-1.70, P = 0.75; RFS: HR 1.29, 95% CI 1.02-1.62, P = 0.03). YBX1 expression was positively correlated with the M2 macrophage infiltration and expression of T cell exhaustion markers such as indoleamine 2,3-dioxygenase 1 (IDO1) (rs = 0.388, P = 4.93e-37) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) (rs = 0.321, P = 2.54e-25) in luminal BRCA. Kaplan-Meier analysis revealed a correlation between YBX1 expression, M2 infiltration and survival outcome. Co-culture with macrophages or T cells enhanced the decrease in luminal BRCA cell viability induced by YBX1 knockdown. Conclusion: High YBX1 mRNA levels predict a poor prognosis in luminal BRCA, which is correlated with M2 macrophage infiltration and T cell exhaustion in the tumor microenvironment. Combining classic therapeutics with immune checkpoint inhibitors and M1 polarization agents may be an effective treatment strategy for luminal BRCA with YBX1 overexpression.

5.
Radiat Oncol ; 16(1): 97, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34098965

RESUMEN

INTRODUCTION: In this study, we performed a consecutive macropathologic analysis to assess microscopic extension (ME) in high-grade glioma (HGG) to determine appropriate clinical target volume (CTV) margins for radiotherapy. MATERIALS AND METHODS: The study included HGG patients with tumors located in non-functional areas, and supratotal resection was performed. The ME distance from the edge of the tumor to the microscopic tumor cells surrounding brain tissue was measured. Associations between the extent of ME and clinicopathological characteristics were evaluated by multivariate linear regression (MVLR) analysis. An ME predictive model was developed based on the MVLR model. RESULTS: Between June 2017 and July 2019, 652 pathologic slides obtained from 30 HGG patients were analyzed. The mean ME distance was 1.70 cm (range, 0.63 to 2.87 cm). The MVLR analysis identified that pathologic grade, subventricular zone (SVZ) contact and O6-methylguanine-DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status were independent variables predicting ME (all P < 0.05). A multivariable prediction model was developed as follows: YME = 0.672 + 0.513XGrade + 0.380XSVZ + 0.439XMGMT + 0.320XIDH + 0.333X1p/19q. The R-square value of goodness of fit was 0.780. The receiver operating characteristic curve proved that the area under the curve was 0.964 (P < 0.001). CONCLUSION: ME was heterogeneously distributed across different grades of gliomas according to the tumor location and molecular marker status, which indicated that CTV delineation should be individualized. The model could predict the ME of HGG, which may help clinicians determine the CTV for individual patients. Trial registration The trial was registered with Chinese Clinical Trial Registry (ChiCTR2100046106). Registered 4 May 2021-Retrospectively registered.

7.
FASEB J ; 35(4): e21531, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33769605

RESUMEN

Lymphangiogenesis is thought to contribute to promote tumor cells to enter lymphatic vessels and plant at a secondary site. Endothelial cells are the cornerstone of the generation of new lymphatic vessels. NADPH oxidase 4 (Nox4) is the most abundant one of NADPH oxidases in endothelial cells and the most studied one in relevance with cancer. Our purpose is to analyze the relationship between Nox4 and lymphangiogenesis and find out whether the newborn lymphatic vessels lead to cancer metastasis. We first explored the expression of Nox4 in lymphatic endothelial cells of primary invasive breast tumors and human normal mammary glands using GEO databases and found that Nox4 was upregulated in primary invasive breast tumors samples. In addition, its high expression correlated with lymph node metastasis in breast cancer patients. Nox4 could increase the tube formation and lymphatic vessel sprouting in a three-dimensional setting. In vivo, inhibition of Nox4 in 4T1 tumor-bearing mice could significantly decrease the tumor lymphangiogenesis and metastasis. Nox4 may increase tumor lymphangiogenesis via ROS/ERK/CCL21 pathway and attract CCR7-positive breast cancer cells to entry lymphatic vessels and distant organs. In conclusion, our results show that Nox4 is a factor that promotes lymphangiogenesis and is a potential target of antitumor metastasis.


Asunto(s)
Neoplasias de la Mama/metabolismo , Células Endoteliales/metabolismo , Linfangiogénesis/fisiología , Metástasis Linfática/patología , NADPH Oxidasa 4/antagonistas & inhibidores , Línea Celular Tumoral , Células Endoteliales/efectos de los fármacos , Humanos , Linfangiogénesis/efectos de los fármacos , Vasos Linfáticos/metabolismo , NADPH Oxidasa 4/metabolismo
8.
Clin Epigenetics ; 12(1): 162, 2020 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-33126908

RESUMEN

BACKGROUND AND AIMS: Stool DNA testing is an emerging and attractive option for colorectal cancer (CRC) screening. We previously evaluated the feasibility of a stool DNA (sDNA) test of methylated SDC2 for CRC detection. The aim of this study was to assess its performance in a multicenter clinical trial setting. METHODS: Each participant was required to undergo a sDNA test and a reference colonoscopy. The sDNA test consists of quantitative assessment of methylation status of SDC2 promoter. Results of real-time quantitative methylation-specific PCR were dichotomized as positive and negative, and the main evaluation indexes were sensitivity, specificity, and kappa value. All sDNA tests were performed and analyzed independently of colonoscopy. RESULTS: Among the 1110 participants from three clinical sites analyzed, 359 and 38 were diagnosed, respectively, with CRC and advanced adenomas by colonoscopy. The sensitivity of the sDNA test was 301/359 (83.8%) for CRC, 16/38 (42.1%) for advanced adenomas, and 134/154 (87.0%) for early stage CRC (stage I-II). Detection rate did not vary significantly according to age, tumor location, differentiation, and TNM stage, except for gender. The follow-up testing of 40 postoperative patients with CRC returned negative results as their tumors had been surgically removed. The specificity of the sDNA test was 699/713 (98.0%), and unrelated cancers and diseases did not seem to interfere with the testing. The kappa value was 0.84, implying an excellent diagnostic consistency between the sDNA test and colonoscopy. CONCLUSION: Noninvasive sDNA test using methylated SDC2 as the exclusive biomarker is a clinically viable and accurate CRC detection method. CHINESE CLINICAL TRIAL REGISTRY: Chi-CTR-TRC-1900026409, retrospectively registered on October 8, 2019; http://www.chictr.org.cn/edit.aspx?pid=43888&htm=4 .

9.
Mol Cancer ; 19(1): 62, 2020 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-32192494

RESUMEN

Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. Advanced gastric cancer patients can notably benefit from chemotherapy including adriamycin, platinum drugs, 5-fluorouracil, vincristine, and paclitaxel as well as targeted therapy drugs. Nevertheless, primary drug resistance or acquisition drug resistance eventually lead to treatment failure and poor outcomes of the gastric cancer patients. The detailed mechanisms involved in gastric cancer drug resistance have been revealed. Interestingly, different noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are critically involved in gastric cancer development. Multiple lines of evidences demonstrated that ncRNAs play a vital role in gastric cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically summarized the emerging role and detailed molecular mechanisms of ncRNAs impact drug resistance of gastric cancer. Additionally, we propose the potential clinical implications of ncRNAs as novel therapeutic targets and prognostic biomarkers for gastric cancer.


Asunto(s)
Biomarcadores de Tumor/genética , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , Neoplasias Gástricas/patología , Animales , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética
11.
Biomed Pharmacother ; 118: 109335, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31452513

RESUMEN

In this study, we aimed to evaluate the antiviral effect of total flavonoids extracted from Robinia pseudoacacia cv. idaho (RPTF) in vivo and its toxicity on rats with oral gavage. RPTF was prepared by percolation with 70% ethanol for 24 h and its antiviral effect on different kinds of viruses was evaluated in vitro by MTT staining. The long-term toxicity of RPTF on rats was evaluated through the detection of general behavior, body weight, food intake and related organ tissue sections of experimental animals. We found that RPTF produced significantly inhibitory effects on HSV-1 and EV-71 viruses with the therapeutic index TI values 113.8 and 46.2, respectively. Moreover, toxicity evaluation in vivo showed no significantly adverse effects in rats, indicating that RPTF was safe in use. In conclusion, we demonstrated that RPTF, natural compounds in the Chinese traditional medicine, could act as promising and effective antiviral therapeutics with relative safety in use.


Asunto(s)
Antivirales/farmacología , Antivirales/toxicidad , Flavonoides/farmacología , Flavonoides/toxicidad , Robinia/química , Pruebas de Toxicidad , Animales , Antivirales/aislamiento & purificación , Peso Corporal/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Femenino , Flavonoides/aislamiento & purificación , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratas Wistar
12.
Medicine (Baltimore) ; 97(22): e10859, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29851800

RESUMEN

RATIONALE: Despite the approval of antiangiogenic therapy for high grade glioma (HGG) patients, survival benefits are still limited. New treatment plans have always been developed to improve the survival. PATIENT CONCERNS: A 26-year-old woman was admitted to our hospital for distending pain of head and eye. DIAGNOSES: Resonance imaging (MRI) revealed a large spherical heterogeneously enhancing, mixed cystic and solid mass in the right frontal region, and the midline shifted. INTERVENTION: The patient received apatinib therapy for positive vascular endothelial growth factor. OUTCOMES: A partial response was observed after 4 weeks and remains sustained until now. LESSONS: It suggests that apatinib might be a feasible option for the treatment in advanced HGG patients or patients with poor physical condition.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Piridinas/uso terapéutico , Adulto , Neoplasias Encefálicas/química , Neoplasias Encefálicas/diagnóstico por imagen , Femenino , Lóbulo Frontal/diagnóstico por imagen , Glioma/química , Glioma/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Clasificación del Tumor , Recurrencia Local de Neoplasia/química , Recurrencia Local de Neoplasia/diagnóstico por imagen , Factor A de Crecimiento Endotelial Vascular/análisis
13.
Medicine (Baltimore) ; 96(44): e8490, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29095309

RESUMEN

Lymphatic vessel invasion (LVI) is promising in determining prognosis and treatment strategies, but the application of LVI as a histopathological criterion in breast cancer patients especially those of different subgroups is controversial. This research aims to evaluate the prognostic value of LVI assessed by D2-40 not only in patients with early invasive breast cancer but also in lymph node-negative, lymph node-positive, luminal A-like, luminal B-like, HER2-enriched, and triple-negative subgroups.The study cohort included 255 patients with a median follow-up of 101 months. Immunohistochemical staining for D2-40 was performed to identify LVI.LVI was present in 64 (25.1%), 15 (12.1%), 49 (37.4%), 19 (20.9%), 23 (27.7%), 13 (31.7%), and 9 (22.5%), respectively, in the whole cohort, lymph node-negative, lymph node-positive, luminal A-like, luminal B-like, HER2-enriched, and triple-negative patients. LVI was associated with large tumor size (P = .04), high histological grade (P = .004), involved lymph node (P < .001), and high expression of Ki-67 (P = .003). No significant difference was found among patients with different subtypes and LVI status. The presence of LVI was significantly associated with adverse disease-free survival in the whole cohort (P < .001), lymph node-negative (P < .001), lymph node-positive (P < .001), luminal A-like (P < .001), and luminal B-like patients (P < .001) in both of the univariate and multivariate survival analysis.This study indicated that the presence of LVI stained by D2-40 provided independent prognostic information not only in the whole cohort but also in the subgroup of patients with lymph node-negative, lymph node-positive, luminal A-like, and luminal B-like diseases, which may make a case for routine clinical assessment of LVI using D2-40.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/análisis , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Vasos Linfáticos/patología , Adulto , Anciano , Biomarcadores de Tumor , China , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Metástasis Linfática , Vasos Linfáticos/inmunología , Persona de Mediana Edad , Invasividad Neoplásica/inmunología , Pronóstico
14.
World J Surg Oncol ; 14(1): 183, 2016 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-27422708

RESUMEN

BACKGROUND: The liver is a common site of metastases, followed by the bone and lung in breast cancer. The symptoms of hepatic metastases are similar to intrahepatic cholangiocarcinoma (ICC). ICC is rare, with an overall incidence rate of 0.95 cases per 100,000 adults. The incidence of ICC for patients with breast cancer is very uncommon. Breast cancer patient with ICC is easily misdiagnosed as hepatic metastases. CASE PRESENTATION: We report a breast cancer patient postoperatively who was hospitalized because of having continuous irregular fever for 1 month. Antibiotics were given for 1 week without any significant effect. Her admission bloods revealed elevated levels of carcino-embryonic antigen. Magnetic resonance imaging diagnosis showed multiple liver metastases. We believed that the woman had hepatic metastases until biopsy guided by computed tomography. The liver biopsy pathology analysis considered the possibility of primary intrahepatic cholangiocarcinoma. CONCLUSIONS: Breast cancer patient with space-occupying lesions in the liver is easily considered to be progressed hepatic metastases. Image-guided biopsy is the best diagnostic method for breast cancer with liver mass to avoid misdiagnosis and classify the molecular subtypes to make appropriate treatment.


Asunto(s)
Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/terapia , Colangiocarcinoma/complicaciones , Errores Diagnósticos/prevención & control , Antibacterianos/uso terapéutico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/patología , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Femenino , Fiebre/tratamiento farmacológico , Fiebre/etiología , Humanos , Biopsia Guiada por Imagen , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética , Mastectomía , Persona de Mediana Edad , Estadificación de Neoplasias , Tomografía Computarizada por Rayos X
15.
Tumour Biol ; 37(7): 9979-87, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26819207

RESUMEN

Hypoxia promotes tumor invasion and metastasis via multiple mechanisms, including epithelial-mesenchymal transition (EMT). Twist, an EMT regulator, has been disclosed to associate with invasion and metastasis as well as poor prognosis of many malignancies. However, it remains undefined whether Twist is involved in invasion and metastasis of hypoxic non-small cell lung cancer (NSCLC). In this study, protein levels of Twist, hypoxia-inducible factor-1α (HIF-1α), and EMT markers (E-cadherin and vimentin) were examined by immunohistochemistry in 76 lung cancer tissues from NSCLC patients. Expression of Twist and its correlation with HIF-1α, E-cadherin, and vimentin were analyzed. Small interfering RNA (siRNA) against Twist was used to knockdown Twist expression in hypoxic NSCLC cells, A549 and NCI-H460. Cellular invasion and protein levels of Twist, E-cadherin, and vimentin were evaluated by matrigel invasion assay and Western blot, respectively. Our results showed that in clinical samples, there was a significant association between Twist expression and differentiation degree, lymph node metastasis, and TNM stage. Correlation analysis demonstrated that expression of Twist was negatively correlated with E-cadherin expression, but positively associated with HIF-1α and vimentin expression. In cultured NSCLC cells, Twist messenger RNA (mRNA) and protein levels were upregulated under hypoxia, while knockdown of Twist suppressed potentiated invasion and expression of mesenchymal marker vimentin induced by hypoxia. Protein level of increased epithelial marker E-cadherin was shown along with Twist downregulation. These findings suggest that Twist promoting hypoxic invasion and metastasis of NSCLC may be associated with altered expression of EMT markers. Inhibition of Twist may be of therapeutic significance.


Asunto(s)
Adenocarcinoma/secundario , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Células Escamosas/secundario , Hipoxia/patología , Neoplasias Pulmonares/patología , Proteínas Nucleares/metabolismo , Proteína 1 Relacionada con Twist/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Anciano , Antígenos CD , Apoptosis , Biomarcadores de Tumor/genética , Western Blotting , Cadherinas/genética , Cadherinas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Movimiento Celular , Proliferación Celular , Femenino , Estudios de Seguimiento , Humanos , Hipoxia/genética , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/genética , Pronóstico , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Proteína 1 Relacionada con Twist/antagonistas & inhibidores , Proteína 1 Relacionada con Twist/genética , Vimentina/genética , Vimentina/metabolismo
16.
Cancer Lett ; 371(2): 182-6, 2016 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-26656954

RESUMEN

The purpose of this study was to assess the usefulness of rapid on-site evaluation (ROSE) during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and the interpretation of its results. Based on the criterion of using ROSE or not, 236 patients with known or suspected lung cancer undergoing EBUS-TBNA were allocated into the ROSE group (122 patients with 252 lymph nodes) and non-ROSE group (114 patients with 260 lymph nodes). In the ROSE group, the percentages of the suspicious specimens on cytology and non-diagnostic specimens on pathology were both significantly lower than that in the non-ROSE group (8.7% vs. 14.6%, p = 0.038; and 0.9% vs. 4.4%, p = 0.018, respectively), and 13 out of 22 suspicious lesions on ROSE were confirmed with definite diagnoses on TBNA pathology. The diagnostic yield stratified by pathology was significantly higher in the ROSE group than that in the non-ROSE group (90.5% vs. 81.2%, p = 0.003). These results suggest that ROSE during EBUS-TBNA allows for a low rate of suspicious results and therefore improves the diagnostic yield stratified by pathology when sampling hilar or mediastinal lymphadenopathy in patients with lung cancer.


Asunto(s)
Broncoscopía , Detección Precoz del Cáncer/métodos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Neoplasias Pulmonares/patología , Ganglios Linfáticos/patología , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Humanos , Neoplasias Pulmonares/epidemiología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Prevalencia , Reproducibilidad de los Resultados , Estudios Retrospectivos
17.
Onco Targets Ther ; 8: 1823-30, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26244020

RESUMEN

Follicular dendritic cell sarcoma (FDCS) is a rare malignant tumor recognized in recent years. It accounts for only 0.4% of soft-tissue sarcomas, and its underlying causes are largely unknown. A correct diagnosis can be difficult to make. Diagnosis of FDCS depends on the combined clinical examination, histopathologic features, electron microscopic examination and confirmation with immunohistochemical studies. Here, we report two rare cases of FDCS: one case involving multiple bones, and the other involving extensive abdominal and pelvic cavities. Clinical, histopathological, and immunohistochemical aspects, therapeutic options, and a related literature review of the two cases are discussed. As the prevalence of FDCS is increasing, the details of these rare cases may highlight the importance and facilitate treatment of similar diseases.

18.
Radiother Oncol ; 116(1): 100-6, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26142269

RESUMEN

PURPOSE: To construct an anatomical atlas of thoracic lymph node regions of esophageal cancer (EC) based on definitions from The Japan Esophageal Society (JES) and generate a consensus to delineate the nodal clinical target volume (CTVn) for elective nodal radiation (ENI) of esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: An interdisciplinary group including two dedicated radiation oncologists, an experienced radiologist, a pathologist and two thoracic surgeons were gathered to generate a three-dimensional radiological description for the mediastinal lymph node regions of EC on axial CT scans. Then the radiological boundaries of lymph node regions were validated by a relatively large number of physicians in multiple institutions. RESULTS: An atlas of detailed anatomic boundaries of lymph node station No. 105-114 was defined on axial CT, along with illustrations. From the previous work, the study provided a guide of CTVn contouring for ENI of thoracic ESCC from a single center. CONCLUSION: It is feasible to use such an atlas of thoracic lymph node stations for radiotherapy planning. A phase III study based on the atlas is ongoing in China to measure quantitatively the ENI received by patients with ESCC.


Asunto(s)
Neoplasias Esofágicas/patología , Neoplasias Esofágicas/radioterapia , Ganglios Linfáticos/patología , China , Humanos , Mediastino/patología , Tomografía Computarizada por Rayos X
19.
Asian Pac J Cancer Prev ; 16(3): 875-80, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25735376

RESUMEN

Mediator 19 (Med19) is a component of the mediator complex which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II. Accumulating evidence has shown that Med19 plays important roles in cancer cell proliferation and tumorigenesis. The involvement of Med19 in sensitivity to the chemotherapeutic agent cisplatin was here investigated. We employed RNA interference to reduce Med19 expression in human non-small cell lung cancer (NSCLC) cell lines and analyzed their phenotypic changes. The results showed that after Med19 siRNA transfection, expression of Med19 mRNA and protein was dramatically reduced (p<0.05). Meanwhile, impaired growth potential, arrested cell cycle at G0/G1 phase and enhanced sensitivity to cisplatin were exhibited. Apoptosis and caspase-3 activity were increased when cells were exposed to Med19 siRNA and/or cisplatin. The present findings suggest that Med19 facilitates tumorigenic properties of NSCLC cells and knockdown of Med19 may be a rational therapeutic tool for lung cancer cisplatin sensitization.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Resistencia a Antineoplásicos/genética , Neoplasias Pulmonares/tratamiento farmacológico , Complejo Mediador/antagonistas & inhibidores , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Ciclo Celular/efectos de los fármacos , Citometría de Flujo , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Complejo Mediador/genética , Complejo Mediador/metabolismo , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas
20.
Contemp Oncol (Pozn) ; 18(4): 260-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25258584

RESUMEN

AIM OF THE STUDY: FaDu human squamous cell carcinoma (FaDu-hSCC) demonstrated accelerated tumor repopulation during fractionated irradiation with pathological validation in a xenograft model system. Previous studies showed that the selective cyclooxygenase (COX)-2 inhibitor celecoxib can enhance the tumor response to radiotherapy. So we aimed to explore the effect of celecoxib in inducing apoptosis and inhibiting repopulation of FaDu tumors in nude mice during fractionated radiotherapy. MATERIAL AND METHODS: FaDu-hSCC was transplanted into the right hind leg of BALB/C nude mice. Mice were treated with celecoxib and/or fractionated irradiation. Celecoxib (100 mg/kg/day) was administered by daily gavage. Irradiation was delivered with 12 to 18 fractions of 3.0 Gy daily or every second day based on Petersen's repopulation model. At different time points, tumors were excised for immunohistochemistry staining. RESULTS: Significant tumor repopulation occurred after about 18 days of radiotherapy. On average, Ki-67 and bromodeoxyuridine (BrdUrd) labeling indices (LI) decreased with daily irradiation (both p < 0.05) and increased with every-second-day irradiation (both p > 0.05), suggesting accelerated repopulation. Ki-67 LI decreased in celecoxib concurrent with radiotherapy for 12 fractions in 24 days and 18 fractions in 36 days compared with irradiated alone (p = 0.004 and 0.042, respectively). BrdUrd LI values were lower in the concurrent groups than irradiated alone (p = 0.001 and 0.006, respectively). Epithelial growth factor receptor (EGFR) expression score decreased in the concurrent groups than irradiated alone (p = 0.037 and 0.031, respectively). Caspase-3 expression scores were higher in the concurrent groups than irradiated alone (p = 0.05 and 0.006, respectively). CONCLUSIONS: Celecoxib concurrent radiotherapy could inhibit tumor repopulation and increase tumor apoptosis during the treatment in FaDu squamous cell carcinoma.

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