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Introduction: Many randomized controlled trials have indicated that immuno-chemotherapy could generate clinical benefits, though the cost of immuno-chemotherapy was so prohibitive and the options were varied. This investigation aimed at evaluating effectiveness, safety, and cost-effectiveness for immuno-chemotherapy as a first-line therapeutic option for ES-SCLC patients. Methods: Multiple scientific literature repositories were searched for clinical studies where immuno-chemotherapy was regarded as the first-line treatment for ES-SCLC, which were published in English between Jan 1, 2000, and Nov 30, 2021. This study conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based upon US-resident payer perspectives. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated through NMA. In addition, costings, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-benefit ratio (ICER) were estimated by CEA. Results: We identified 200 relevant search records, of which four randomized controlled trials (RCTs) (2,793 patients) were included. NMA demonstrated that the effect of atezolizumab plus chemotherapy was ranked at a more elevated position in comparison to other immuno-chemotherapy options and chemotherapy alone, within the general population. The influence of atezolizumab plus chemotherapy and durvalumab plus chemotherapy was ranked higher within populations experiencing non-brain metastases (NBMs) andbrain metastases (BMs), respectively. The CEA revealed that the ICERs of immuno-chemotherapy over chemotherapyalone were higher than the willingness-to-pay (WTP) threshold of $150,000/QALY in any population. However, treatment with atezolizumab plus chemotherapy and durvalumab plus chemotherapy were more favorable health advantages than other immuno-chemotherapy regimens and chemotherapy alone, and the results were 1.02 QALYs and 0.89 QALYs within overall populations and populations with BMs, respectively. Conclusion: The NMA and cost-effectiveness investigation demonstrated that atezolizumab plus chemotherapy could be an optimal first-line therapeutic option for ES-SCLC when compared with other immuno-chemotherapy regimens. Durvalumab plus chemotherapy is likely to be the most favorable first-line therapeutic option for ES-SCLC with BMs.

Asunto(s)

Análisis de Costo-Efectividad , Neoplasias Pulmonares , Humanos , Metaanálisis en Red , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Análisis Costo-Beneficio , Neoplasias Pulmonares/tratamiento farmacológico

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INTRODUCTION: The CLEAR trial indicated that survival benefits were generated with lenvatinib plus pembrolizumab (LP) or everolimus (LE) than with sunitinib for advanced renal cell carcinoma (aRCC). However, the high cost of immuno-target and dual-targeted treatment, we assessed the cost-effectiveness of lenvatinib plus pembrolizumab or everolimus in the first-line setting for treatment of patients with aRCC from the United States (US) payers' perspective. MATERIALS AND METHODS: A comprehensive Markov model was developed to evaluate the cost and effectiveness of LP or LE in first-line therapy for aRCC. We estimated life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Utility values and direct costs related to the treatments were gathered from the published studies. Then, one-way and probabilistic sensitivity analyses were performed. Additional subgroup analyses were considered. RESULTS: Treatment with LP and LE provided an additional 0.67 QALYs (0.62 LYs) and 0.66 QALYs (0.90 LYs) compared with sunitinib, resulting in ICER of $131,656 per QALY and 201,928 per QALY, respectively. The most influential factor in this model was the cost of pembrolizumab with LP. Probabilistic sensitivity analysis showed there was a 58.97% and 28.91% probability that LP and LE were cost-effective at WTP values of $150,000 per QALY in the US. Subgroup analyses demonstrated that LP was more cost-effective for patients from Western Europe and North America, intermediate risk of the International risk group of Metastatic Renal Cell Carcinoma Database Consortium (IMDC), favorable and intermediate risk group of Memorial Sloan Kettering Cancer Center (MSKCC) and PD-L1 combined positive score greater than or equal to 1%. CONCLUSION: From the perspective of the US payer, LP is a cost-effective option as first-line treatment for patients with aRCC at a WTP threshold of $150,000 per QALY, but LE is the opposite.

Asunto(s)

Carcinoma de Células Renales , Neoplasias Renales , Humanos , Estados Unidos , Carcinoma de Células Renales/patología , Sunitinib/uso terapéutico , Everolimus/uso terapéutico , Análisis de Costo-Efectividad , Neoplasias Renales/patología , Análisis Costo-Beneficio , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico

RESUMEN

Introduction: Two targeted drugs (apatinib and lenvatinib) show clinical efficacy in first-line treatment of Chinese patients with radioactive advanced iodine-refractory differentiated thyroid cancer (RAIR-DTC) and are recommended by the Chinese Society of Clinical Oncology guidelines. Considering the high clinical cost of long-term vascular endothelial growth factor receptor inhibitor administration and to determine which of the two targeted drugs is preferable, we opted to conduct a cost-effectiveness analysis (CEA) and network meta-analysis (NMA). Material and Methods: The results of NMA and CEA included in the two phase III randomized clinical trials REALITY (NCT03048877) and Study-308 (NCT02966093), in which Bayesian NMA and CEA were performed on 243 and 149 Chinese patients, respectively, were retrieved. Overall survival and progression-free survival (PFS) for apatinib versus lenvatinib were determined by NMA. CEA involved the development of a 20-year Markov model to obtain the total cost and quality-adjusted life-years (QALYs), and this was followed by sensitivity and subgroup analyses. Results: Compared with lenvatinib, apatinib therapy provided a 0.837 improvement in QALY and $6,975 reduction in costs. The hazard ratio of apatinib versus lenvatinib and the cost of the targeted drugs had a significant impact on the model. According to the sensitivity analysis, apatinib was more cost-effective and had no correlation with willingness-to-pay in China. Subgroup analysis showed that apatinib maintained PFS more economically. Conclusion: NMA and CEA demonstrated that apatinib was more cost-effective compared to lenvatinib in the first-line treatment of Chinese RAIR-DTC patients.

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Adenocarcinoma , Neoplasias de la Tiroides , Adenocarcinoma/tratamiento farmacológico , Teorema de Bayes , Análisis Costo-Beneficio , Humanos , Radioisótopos de Yodo/uso terapéutico , Metaanálisis en Red , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/radioterapia , Factor A de Crecimiento Endotelial Vascular

RESUMEN

INTRODUCTION: In 2021, KEYNOTE-590 (NCT03189719) showed that pembrolizumab plus 5-fluorouracil and cisplatin (PPF) has more benefits than 5-fluorouracil and cisplatin (PF) as a first-line regimen to treat individuals with advanced esophageal cancer. However, given that it is expensive, controversies over the value of using this compared to competitive strategies remain. Hence, we conducted a cost-effectiveness evaluation of pembrolizumab plus chemotherapy. METHODS: A Markov model was applied in evaluating the efficacy and cost of PPF and PF over a 7-year horizon and measured the health outcomes in life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). The economic data included were relevant to patients in the USA and China. We also performed one-way and probabilistic sensitivity analyses to determine the uncertainties relevant to the model. Willingness to pay thresholds (WTP) of $150,000/QALY (USA) and $35,673/QALY (China) were used to calculate a probability for the cost-effectiveness of PPF. RESULTS: PPF yielded 0.386-0.607 QALYs (0.781-1.195 LYs) compared with PF. In our analysis, compared with receiving PF, patients with advanced esophageal cancer receiving PPF had an ICER of $577,461/QALY in the USA and $258,261/QALY in China, those for esophageal squamous cell carcinoma were $550,211/QALY in the USA and $244,580/QALY in China, and a programmed cell death ligand 1 combined positive score (PD-L1 CPS) ≥ 10 was associated with a cost of $479,119/QALY in the USA and $201,355/QALY in China. Sensitivity analysis found the price of pembrolizumab to be the biggest influence. CONCLUSION: From the economic perspectives of the USA and China, a first-line regimen of PPF for esophageal cancer therapy may not be as cost-effective as PF. However, patients with esophageal cancer and PD-L1 CPS ≥ 10 may gain the most LYs from initial PPF treatment.

Asunto(s)

Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1 , Cisplatino , Análisis Costo-Beneficio , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Humanos , Años de Vida Ajustados por Calidad de Vida

RESUMEN

A solid acid catalyst prepared by sulfonated Sargassum horneri carbon was utilized for the esterification reaction of oleic acid and methanol. The formed amorphous carbon layers during carbonization and the access of sulfonic acid groups during sulfonation can catalyze the esterification reaction for biodiesel preparation efficiently. The catalyst was characterized by various methods to investigate its physical and chemical properties. With carbonization at 300 °C for 2 h followed by sulfonation at 90 °C for 5 h, the catalyst reached acid density of 1.40 mmol/g. The catalyst dosage, methanol/oleic acid (molar ratio), reaction temperature, and reaction time were optimized to 10 wt%, 15:1, 70 °C, and 3 h, respectively. Under the optimal condition, the conversion of oleic acid reached 96.4%. Additionally, the catalyst was regenerated after four cycles, with the conversion of oleic acid still reaching 95.4%.

Asunto(s)

Biocombustibles , Sargassum , Carbono , Catálisis , Esterificación

RESUMEN

OBJECTIVE: There are multiple treatment options for hiccups, including non-pharmacological therapies, but little evidence of superiority of one treatment over another. The aim of this study was to investigate the effects of acupuncture on persistent hiccups after arthroplasty. METHODS: From April 2010 to December 2015, 15 patients with primary unilateral total hip/knee arthroplasty were diagnosed with persistent hiccups and given acupuncture at PC6, CV12 and ST36. Each acupuncture session lasted 30 min. The total number of treatment sessions was determined by the persistence of symptoms, but acupuncture was administered no more than three times over the course of a week. The hiccups assessment instrument (HAI) was used to assess the severity of hiccups pre-treatment and post-treatment. Adverse events were also recorded. RESULTS: Absolute resolution was observed in all 15 patients after less than three acupuncture sessions. Of these, 10 patients required only one acupuncture session, 3 patients required two sessions and 2 patients required three sessions. The HAI score improved after each round of acupuncture treatment (P<0.05). The average HAI score improved significantly post-acupuncture compared to baseline values pre-treatment (P<0.05). Symptoms accompanying the hiccups included pain in the diaphragmatic area (five patients), mild dyspnoea (three patients), dysphagia (two patients) and nausea/vomiting (one patient). All these accompanying symptoms disappeared at the point of resolution of the hiccups. There were no adverse effects related to acupuncture during the study period. CONCLUSION: Based on our results, acupuncture may represent a potential treatment option for hiccups after arthroplasty. Caution must be exercised, however, given the lack of a control group. Accordingly, randomised controlled trials will be required to verify the efficacy and effectiveness of acupuncture for the treatment of hiccups.

Asunto(s)

Terapia por Acupuntura , Artroplastia/efectos adversos , Hipo/terapia , Complicaciones Posoperatorias/terapia , Puntos de Acupuntura , Anciano , Femenino , Hipo/etiología , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento

RESUMEN

Recent studies have suggested that puerarin may impede osteoclastogenesis and facilitate bone regeneration, in addition to attenuating tissue inflammation. The present study investigated the therapeutic effects of puerarin on inflammatory responses and monocyte recruitment in in vitro and in vivo osteoarthritis (OA) models. Puerarin treatment increased the proliferation of OA chondrocytes, as determined by Cell Counting Kit­8 assay. In addition, the present results suggested that puerarin suppressed the interleukin­1ß­induced production of inflammatory cytokines in OA chondrocytes and monocytes/macrophages, as assessed by ELISA. In a mouse model of mono­iodoacetate­induced OA, the present histological analyses suggested that administration with puerarin attenuated the inflammatory profile of OA joints and reduced cartilage destruction. Using flow cytometry, a decreased number of myeloid­derived C­C chemokine receptor 2+/lymphocyte Ag 6C+ monocytes was identified in the blood of OA mice treated with puerarin compared with control OA mice. Furthermore, quantitative real­time polymerase chain reaction analysis suggested that puerarin treatment decreased C­C chemokine ligand 2 expression in arthritic tissues. Collectively, the results suggested that puerarin treatment limited the recruitment of inflammatory monocytes. In summary, the present study provided pre­clinical evidence that puerarin may serve as a potential target in the treatment of OA.

Asunto(s)

Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Isoflavonas/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Sustancias Protectoras/farmacología , Animales , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , Cartílago Articular/patología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-1beta/metabolismo , Masculino , Ratones

RESUMEN

The oxidative cleavage of vegetable oils and their derivatives to produce bio-based aldehydes is a potentially useful process, although the aldehyde products are readily oxidized to carboxylic acids and thus seldom obtained in high yields. The present study developed a room-temperature method for the synthesis of bio-aldehydes via the oxidative cleavage of vegetable oil-derived epoxides, using H2WO4 as the catalyst, H2O2 as the oxidant, and t-BuOH as the solvent. Reactions were carried out at temperatures ranging from 25 to 35 °C for 3.5-10.5 h, and provided >99% conversion and >90% aldehyde yield. In particular, an approximately 97% yield was obtained at 25 °C after 10.5 h. As the reaction proceeded, the H2WO4 dissolved to form a W-containing anion. Several mesoporous Al-MCM-41 materials having different Si/Al ratios were hydrothermally synthesized and used as adsorbents to recover the catalyst by adsorbing these anions. The adsorption capacity of the Al-MCM-41 was found to increase with decreases in the Si/Al ratio. The Al-MCM-41 had little effect on the oxidative cleavage reaction at 25 °C, and thus could be directly added to the reaction system. The excellent anion adsorption performance of the Al-MCM-41 greatly improved the reusability of the H2WO4 catalyst. When using the Al-MCM-41 with the best adsorption performance, there was no significant decrease in the activity of the catalyst following five reuses.

RESUMEN

OBJECTIVES: To investigate the roles of miR-149 in the progression of human osteosarcoma (OS). RESULTS: miR-149 level was upregulated in tissues from OS patients more than in normal subjects. Cell proliferation and apoptosis assays revealed that miR-149 increased cell proliferation and inhibited cell apoptosis in OS cell line (MG63). An increase of Bcl-2 gene expression and a decrease of cleaved-caspase-3, and cleaved-PARP expression were observed in MG63 cells with transfection of miR-149. Additionally, bone morphogenetic protein 9 (BMP9) was identified as a target of miR-149 in MG63 cells, and BMP9 expression was negatively correlated with miR149 level in OS clinical samples. Co-overexpression of BMP9 with miR-149 in MG63 cells prohibited miR-149-mediated promotive effects on OS progression. Importantly, overexpression of miR-149 conferred chemoresistance in MG63 cells. CONCLUSIONS: miR-149 promotes OS progression via targeting BMP9.

Asunto(s)

Factores de Diferenciación de Crecimiento/biosíntesis , MicroARNs/metabolismo , Osteosarcoma/fisiopatología , ADP Ribosa Transferasas/análisis , Apoptosis , Caspasa 3/análisis , Línea Celular Tumoral , Proliferación Celular , Perfilación de la Expresión Génica , Factor 2 de Diferenciación de Crecimiento , Humanos , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Reacción en Cadena en Tiempo Real de la Polimerasa , Transfección

RESUMEN

BACKGROUND: Due to the adverse effects of cemented hip arthroplasty, uncemented stems with hydroxyapatite (HA) coating reduces these risks and enhanced integration. The concept of an extensive HA coating for the fixation of a tapered femoral stem (Corail®) was introduced, which can achieve durable biological fixation and preserve normal periprosthetic bone activity. Here we describe the clinical and radiological outcome in patients with the Corail® stem. METHODS: 92 total hip replacements in 81 patients using the Corail® stem were followed-up. 47 patients were women, and the mean age at surgery was 62.9 ± 8.7 (34-71) years. The indications included: osteoarthritis of the hip (71.1%), avascular necrosis (13.6%), femur neck fractures in elderly (9.7%) and post-traumatic osteoarthritis (6.8%). FINDINGS: Eight patients died during follow-up. The revision was only found in two patients due to line wear and resulted in an 10-year Kaplan-Meier estimated overall survival rate of 97.83%. The clinical results were good, with a mean Harris hip score of 92.3 ± 5.6 (72-100). The mean total Merle d'Aubigné and Postel score was 6.8 ± 0.5 pre-operatively and 16.1 ± 1.4 at latest follow-up. All unrevised implants were radiographically stable, with a mean liner wear of 0.07 mm/year. CONCLUSION: This long-term analysis confirmed the durability of the functional and radiographic results. Our findings suggest the long-term results of Corail® HA-coated stem are more satisfactory which is preferable to any other system.

RESUMEN

Primitive neuroectodermal tumor (PNET) is most commonly encountered in the soft tissue or bone in children and young adults, and its involvement in the intestines is exceedingly rare. To the best of our knowledge, eighteen cases have been reported to date. The present study reports three cases of PNET arising in the mesentery and ileocecum in 59- and 22-year-old males and a 36-year-old female. Computed tomography revealed a solid mass in the lower abdomen, with areas of cystic changes. Microscopically, the tumors were composed of small round cells arranged in sheets and rosettes with scant cytoplasm, hyperchromatic nuclei and a high mitotic rate. The tumor cells were immunopositive for CD99 and FLI1. EWS/FLI1 translocations were detected in all cases. Case 1 and case 2 underwent tumor resection without any preoperative radiotherapy, chemotherapy or biological therapy. Case 3 underwent tumor resection and received eight cycles of IAP chemotherapy (2.0 mg ifosfamide, 80 mg epirubicin, 30 mg cisplatin 30mg). Case 3 was followed up for 34 months until they succumbed to peritoneal recurrence, whereas the other cases were not followed up. The incidence of these small round-cell tumors in the intestinal system, their clinical and pathological features and differential diagnosis are discussed with a review of the literature.

RESUMEN

OBJECTIVE: To investigate the effects of total flavonoids from astragalus complanatus (FAC) on paraquat poisoning-induced pulmonary fibrosis in rats. METHODS: The rats were divided into six groups randomly: control group, paraquat group, prednisolone group and FAC low-dose, middle-dose, high-dose group. Pulmonary fibrosis model was replicated by intratracheal injection of paraquat. In the mext day,the rats were treated by intragastric administration once a day. After 28 days, the rats were sacrificed. The lung index and the levels of HYP and T-AOC were measured, and the pathologic changes of the lung tissue were obtained by HE staining. The levels of TGF-ß, Smad2, α-SMA protein were analyzed by Western blot. RESULTS: FAC improved the activity of T-AOC in serum and reduced pulmonary index and the content of HYP as well (P<0.05 or P<0.01), the alveolitis and fibrosis extent were attenuated. The expression of Smad2 significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.31±0.11, 0.45±0.12 and 0.30±0.05) as compared with that of the PQ group (0.85±0.34) (P<0.05). The expression of α-SMA significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.31±0.11, 0.35±0.07 and 0.32±0.10) as compared with that of the PQ group (0.45±0.08) (P<0.05). The expression of TGF-ß significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.35±0.04, 0.27±0.05 and 0.18±0.04)as compared with that of the PQ group (0.63±0.11) (P<0.05). CONCLUSION: FAC can alleviate PQ-induced pulmonary fibrosis in rats through inhibiting TGF-ß/Smad signaling pathway.

Asunto(s)

Planta del Astrágalo/química , Flavonoides/farmacología , Paraquat/envenenamiento , Fibrosis Pulmonar/tratamiento farmacológico , Actinas/metabolismo , Animales , Pulmón/patología , Fitoquímicos/farmacología , Fibrosis Pulmonar/inducido químicamente , Ratas , Proteína Smad2/metabolismo , Factor de Crecimiento Transformador beta/metabolismo

RESUMEN

OBJECTIVE: To investigate the effect of total flavonoids from astragalus complanatus (FAC) on attenuating lung injury resulted from paraquat (PQ) poisoning by inhibiting excessive endoplasmic reticulum stress (ERS) and c-Jun N-terminal kinase (JNK) pathway in rat. METHODS: Forty-eight Sprague-Dawley (SD) rats were randomly divided into six groups (n=8 in each group), including control group, model group, dimethyl sulfoxide (DMSO) vehicle control group, and FAC in low, medium, and high dosage groups. The model was reproduced by giving PQ 80 mg/kg orally to induce lung injury. The rats in control group were treated with saline by gavage. The rats in DMSO group were given 10% DMSO 20 mL/kg by gavage 2 hours before intraperitoneal injection of PQ, and those in FAC low, medium and high dosage groups received 40, 80, 160 mg×kg(-1)×d(-1) of FAC solution intraperitoneally after the PQ administration. The rats were sacrificed 72 hours after giving PQ, and the left lung tissue was harvested 72 hours after the reproduction of experimental model. The ratio of wet/dry weight (W/D) and total lung water content (TLW) were determined. The pathohistological changes of the left lung was observed under light microscope, and scored with alveolar damage index of quantitative assessment (IQA). The mRNA expressions of JNK and glucose regulated protein 78 (GRP78) were determined by reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression of JNK, phosphorylation-JNK (p-JNK), and GRP78 were determined by Western Blot. RESULTS: Compared with control group, the W/D ratio, TLW and IQA were increased significantly in model group and DMSO group, and the mRNA expressions of JNK and GRP78 and the protein expressions of JNK, p-JNK and GRP78 were markedly increased. Compared with the model group, the W/D ratio, TLW and IQA, and the expressions of JNK mRNA and p-JNK protein were significantly decreased in the FAC groups, especially in FAC high dosage group [W/D ratio: 3.0±0.3 vs. 5.5±0.5, TLW: 2.2±0.3 vs. 4.7±0.4, IQA: (15.4±3.0)% vs. (40.0±5.7)%, JNK mRNA: 0.21±0.08 vs. 0.82±0.27, p-JNK protein: 0.31±0.09 vs. 0.78±0.25, all P<0.01]. The mRNA expression of GRP78 and the protein expressions of JNK and GRP78 were highly expressed in FAC low, medium and high dosage groups, and there was no significant difference compared with those in model group (GRP78 mRNA: 0.54±0.18 vs. 0.74±0.20, JNK protein: 0.76±0.27 vs. 0.80±0.28, GRP78 protein: 0.51±0.18 vs. 0.69±0.21, all P>0.05). CONCLUSIONS: PQ induces excessive ERS in the lung tissue resulting in lung injury. FAC has a protective effect on lung against PQ injury, and it may be related with inhibition JNK pathway in ERS.

Asunto(s)

Planta del Astrágalo/química , Flavonoides/farmacología , Lesión Pulmonar/prevención & control , Paraquat/envenenamiento , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Lesión Pulmonar/inducido químicamente , Masculino , Ratas , Ratas Sprague-Dawley , Transducción de Señal

RESUMEN

Erythropoietin-producing hepatocyte (Eph) receptor family constitutes the largest family of tyrosine kinase receptors in the human genome. Loss of EphB6, a kinase-deficient receptor, correlated with a negative outcome in several carcinomas. This study aimed to investigate the expression of EphB6 protein and mRNA levels in colorectal cancers (CRCs) and possible correlations with clinicopathological variables and prognosis. To assess protein expression level, 124 CRCs and 57 colorectal adenomas samples were examined by immunostaining, the mRNA level of 43 paired CRC and the adjacent normal tissues were detected by using SYBR Green real-time PCR method. Decreased expression of EphB6 protein was found in CRC as compared with adenoma and normal tissues (χ(2) = 10.146, P = 0.001 and χ(2) = 45.333, P < 0.001, respectively). Low EphB6 mRNA expression was detected in 83.8% of cancers with negative or low EphB6 protein expression. The loss of EphB6 protein in CRC was positively associated with poorly differentiation (P < 0.001), lymph node metastasis (P = 0.006), Dukes stage (P = 0.002) and depth of invasion (P = 0.016). The patients with lymph node metastasis had a worse prognosis independently of gender, age, tumor site, stage and differentiation (RR = 0.404, CI 0.267-0.213, P < 0.001). Low levels of EphB6 protein expression are associated with a shorter mean duration of survival in colorectal cancer. Our results demonstrated that EphB6 may represent a novel, useful tissue biomarker for the prediction of survival rate in CRC.

Asunto(s)

Adenoma/genética , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Tirosina Quinasas Receptoras/genética , Adenoma/metabolismo , Adenoma/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Regulación hacia Abajo , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Tirosina Quinasas Receptoras/biosíntesis , Receptores de la Familia Eph , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa

RESUMEN

The erythropoietin-producing hepatocellular (Eph) family of receptor tyrosine kinases regulates a multitude of physiological and pathological processes. EphA1 is the first member of Eph superfamily and is involved in carcinogenesis. The aim of this study was to investigate the expression of EphA1 in prostate cancers cell lines and the tissues, then explore the correlation with the clinicopathologic parameters. The EphA1 transcript expression in prostate cancer cell lines was detected by Quantitative real-time PCR. The expression of EphA1 protein in 138 prostate cancer tissue samples and 21 benign prostate hyperplasia samples were checked by using immunohistochemical staining. EphA1 mRNA was high expressed in LNCap, moderately expressed in 22RV1 and Du145, and lost in PC3. Loss of expression of EphA1 transcript was related to hypermethylation of CpG island around the translation start site. EphA1 protein was differentially expressed in prostate cancers and hyperplasia. Increased expression of EphA1 protein was more frequently detected in prostate cancers than in hyperplasia (P = 0.02), and more often detected in prostate cancer with high Gleason score (P < 0.001). Our data indicate that EphA1 receptor may have roles in carcinogenesis and progression of prostate cancer, and can be a potentially useful target for prognostic and therapeutic application.

Asunto(s)

Neoplasias de la Próstata/metabolismo , Receptor EphA1/metabolismo , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Codón Iniciador , Islas de CpG , Metilación de ADN , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Hiperplasia Prostática/genética , Hiperplasia Prostática/mortalidad , Hiperplasia Prostática/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , ARN Mensajero/metabolismo , Receptor EphA1/genética , Regulación hacia Arriba

RESUMEN

We report a case of diffuse hyperplastic mesothelial cells in multiple lymph nodes. Microscopically, the lymph nodes had a normal follicular pattern. The lymphatic sinus was extremely expanded, within the sinuses the epithelial-like cells proliferated actively in the form of sheets and clusters. Epithelioid-like cells had eosinophilic cytoplasm, prominent nucleoli and vesicular nuclei. Mitotic figures were rarely observed. These cells were immunopositive for Calretinin, CK5/6, D2-40, MC and Ckpan and immunonegative for S-100, HMB45, MelanA, TTF-1, CDX-2, Villin, ALK, CD30, CD20, CD3, CD1a and CD68. In addition, during a 22 months follow-up period failed to identify any malignant neoplasms, thus confirming the benign nature of these cells. It is the first reported case of diffuse hyperplastic of mesothelial cells mainly in the cervical lymph nodes associated with systemic multiple lymph node involvement. Awareness of this event is important for the pathologist in preventing the misdiagnosis of malignancy.

Asunto(s)

Células Epiteliales/patología , Ganglios Linfáticos/patología , Niño , Diagnóstico Diferencial , Humanos , Hiperplasia , Metástasis Linfática/diagnóstico , Masculino

RESUMEN

INTRODUCTION: Pulpitis has been associated with abundant inflammatory cells, dilated blood vessels, and thickening nerve fibers histopathologically with or without severe pain clinically. On the basis of EphA7 receptor expression in inflammatory cells, the developing mouse dental pulp, and trigeminal nerve system, EphA7 may possibly be involved in local inflammatory response and sensory innervation of adult dental pulp as well as odontogenic pain conducted through the trigeminal system. The purpose of the study was to analyze the expression of EphA7 gene in healthy and inflamed human dental pulps and to elucidate the roles of EphA7 gene in dental pulp inflammation response and odontogenic pain. METHODS: Twelve healthy controls, 5 acute pulpitis from dental trauma, 21 symptomatic, and 20 asymptomatic irreversible pulpitis human dental pulps were involved in the study. The protein expression, subcellular localization, and mRNA level of EphA7 gene were detected by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction, respectively. RESULTS: In healthy samples, immunohistochemical staining showed positive EphA7 expression only in vascular endothelial cells and odontoblasts with cytoplasm staining. Under inflammatory conditions, in addition to the above cells, EphA7 staining began to occur in fibroblasts, nerve fiber tissues, and inflammatory cells. Compared with healthy samples, EphA7 expressions at both mRNA and protein levels increased significantly in acute and irreversible pulpitis samples. In asymptomatic irreversible pulpitis samples, EphA7 expressions were significantly lower than those in symptomatic ones but still higher than those in healthy ones. There was no significant difference between acute and symptomatic irreversible pulpitis groups. CONCLUSIONS: The results suggest that EphA7 gene may be a marker reflecting inflammatory activity and pain state for human dental pulp.

Asunto(s)

Pulpitis/patología , Receptor EphA7/análisis , Adolescente , Adulto , Enfermedades Asintomáticas , Biomarcadores/análisis , Citoplasma/ultraestructura , Pulpa Dental/citología , Exposición de la Pulpa Dental/patología , Células Endoteliales/patología , Endotelio Vascular/patología , Femenino , Fibroblastos/patología , Humanos , Incisivo/lesiones , Incisivo/patología , Masculino , Persona de Mediana Edad , Fibras Nerviosas/patología , Odontoblastos/patología , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor EphA7/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Fracciones Subcelulares/patología , Fracturas de los Dientes/patología , Odontalgia/patología , Adulto Joven

RESUMEN

Eph receptors play important roles in the development of cancer. The present study aimed to investigate the expression of EphA1 and its clinicopathologic significance in esophageal squamous cell carcinoma (ESCC). The expression levels of the EphA1 transcript and protein were compared between ESCC and matched normal mucosa in the same patient. High expression levels of the EphA1 transcript and protein were detected in 25.6% (21/82) and 23.2% (19/82) of tumors compared with matched normal mucosa. The up-regulation of EphA1 transcript in tumors was positively associated with differentiation (p = 0.002), disease stage (p = 0.034), and lymph node metastasis (p = 0.042). Increased expression of EphA1 protein in tumors was more often observed in patients with well-differentiated tumors (p = 0.004), lymph node metastasis (p = 0.028), and advanced tumor stage (p = 0.008). EphA1 protein expression was detected in intraepithelial neoplasias as well. Decreased expression of EphA1 protein was detected in 65.2% (15/23) of samples with low-grade neoplasia and in 85.3% (8/15) of samples with high-grade intraepithelial neoplasia. Increased staining of EphA1 protein was not detected in low-grade intraepithelial neoplasia samples, but was detected in 21.3% (2/15) of high-grade intraepithelial neoplasia samples. Taken together, our results show that EphA1 appears to be a differentiation marker for esophageal squamous cells, and its increased expression is positively associated with lymph node metastasis and advanced disease stage.

Asunto(s)

Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Receptor EphA1/biosíntesis , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Distribución de Chi-Cuadrado , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor EphA1/genética

RESUMEN

OBJECTIVE: The aims of this study were to evaluate the clinical utility of a fluorescence in situ hybridization (FISH) assay as a non-invasive molecular test to distinguish urothelial carcinoma (UC) in the upper urinary tract (UUT) from benign lesions presenting with hematuria. STUDY DESIGN: The chromosomal abnormalities of chromosomes 3, 7, 17 and 9 (p16) in hematuria specimens from 34 patients with UUT-UC and 33 patients with benign disorders were detected using a set of fluorescently labeled DNA probes. The abnormalities of the chromosomes were determined and analyzed between UUT-UC and benign disorders. RESULTS: Chromosomal abnormalities were detected in 25 of 34 (73.5%) patients with UUT-UC and in 2 of 33 (6.1%) patients with benign disorders (p < 0.001). CONCLUSIONS: FISH of chromosomes 3, 7, 9 and 17 performed on exfoliated cells from voided urine specimens may serve as a non-invasive tool to distinguish UUT-UC from benign disorders presenting with hematuria.

Asunto(s)

Carcinoma de Células Transicionales/genética , Hematuria/genética , Hibridación Fluorescente in Situ/métodos , Enfermedades Urológicas/genética , Neoplasias Urológicas/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/diagnóstico , Aberraciones Cromosómicas , Cromosomas Humanos Par 17/genética , Cromosomas Humanos Par 3/genética , Cromosomas Humanos Par 7/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Diagnóstico Diferencial , Femenino , Hematuria/diagnóstico , Humanos , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Enfermedades Urológicas/diagnóstico , Neoplasias Urológicas/diagnóstico , Adulto Joven

RESUMEN

BACKGROUND: Paraquat (PQ) is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Currently, there are many studies on lung injury after PQ poisoning. But the kidney as the main excretory organ after PQ poisoning is rarely studied and the mechanisms of this poisoning is not very clear. In this study, we observed the expression of caspase-3 and livin protein in rat renal tissue after PQ poisoning as well as the therapeutic effects of ulinastatin. METHODS: Fifty-four Sprague-Dawley (SD) rats were randomly divided into three experimental groups: control group (group A), paraquat poisoning group (group B) and ulinastatin group (group C), with 18 rats in each group. Rats in group B and group C were administered intragastrically with 80 mg/kg PQ, rats in group C were injected peritoneally with 100 000 U/kg ulinastatin once a day, while rats in group A were administered intragastrically with the same volume of saline as PQ. At 24, 48, 72 hours after poisoning, the expression of livin in renal tissue was detected by Westen blotting, the expression of caspase-3 was detected by immunohistochemistry, and the rate of renal cell apoptosis was tested by TUNEL detection. The histopathological changes were observed at the same time. RESULTS: Compared to group A, the expression of caspase-3 in the renal tissue of rats in groups B and C increased significantly at any time point. Compared with group B, the expression of caspase-3 in renal tissue of rats in group C decreased. Compared with group A, the expression of livin in renal tissue in rats of groups B and C increased significantly at any time point (P<0.01), especially in group C (P<0.01). TUNEL method showed that the rate of renal cell apoptosis index was higher in group B at corresponding time points than in group A (P<0.01), and was lower in group C at corresponding time points than in group B (P<0.01). CONCLUSION: UTI has a protective effect on the renal tissue of rats after paraquat poisoning through up-regulating the expression of livin and down-regulating the expression of caspase-3, but the regulation path still needs a further research.