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BACKGROUND: Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation. METHODS: This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method. DISCUSSION: APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022).
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Adenocarcinoma , Neoplasias Encefálicas , Neoplasias Colorrectales , Síndromes Neoplásicos Hereditarios , Neoplasias Pancreáticas , Neoplasias del Recto , Humanos , Canal Anal , Protocolos de Quimioterapia Combinada Antineoplásica , Irinotecán , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como AsuntoRESUMEN
BACKGROUND: More efficient instruments for body constitution identification are needed for clinical practice. We aimed to develop the short-form version of the Constitution in Chinese Medicine Questionnaire (CCMQ) and evaluate for health management. METHODS: First, the short forms were developed through expert survey, classical test theory (CTT), and modern item response (IRT) based on the CCMQ. A combination of e-mail and manual methods was used in expert survey. Then, five indexes of CTT including criteria value-critical ratio, correlation coefficient, discrete tendency, internal consistency, and factor loading were used. And, IRT method was used through analyzing the discrimination and difficulty parameters of items. Second, the three top-ranked items of each constitution scale were selected for the simplified CCMQ, based on the three combined methods of different conditions and weights. Third, The psychometric properties such as completion time, validity (Construct, criterion, and divergent validity), and reliability (test-retest and internal consistency reliability) were evaluated. Finally, the diagnostic validity of the best short-form used receiver operating characteristic (ROC) curve. RESULTS: Three short-form editions were developed, and retained items 27, 23 and 27, which are named as WangQi nine body constitution questionnaire of Traditional Chinese Medicine (short-form) (SF-WQ9CCMQ)- A, B, and C, respectively. SF-WQ9CCMQ- A is showed the best psychometric property on Construct validity, Criterion validity, test-retest reliability and internal consistency reliability. The diagnostic validity indicated that the area under the ROC curve was 0.928 (95%CI: 0.924-0.932) for the Gentleness constitution scale, and were 0.895-0.969 and 0.911-0.981 for unbalance constitution scales using the cut-off value of the original CCMQ as 40 ("yes" standard) and 30 ("tendency" standard), respectively. CONCLUSIONS: Our study successfully developed a well short-form which has good psychometric property, and excellent diagnostic validity consistent with the original. New and simplified instrument and opportunity are provided for body constitution identification, health management and primary care implementation.
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Cuproptosis, a new type of programmed cell death (PCD), is closely related to cellular tricarboxylic acid cycle and cellular respiration, while hypoxia can modulate PCD. However, their combined contribution to tumor subtyping remains unexplored. Here, we applied a multi-omics approach to classify TCGA_COADREAD based on cuproptosis and hypoxia. The classification was validated in three colorectal cancer (CRC) cohorts and extended to a pan-cancer analysis. The results demonstrated that pan-cancers, including CRC, could be divided into three distinct subgroups (cuproptosis-hypoxia subtypes, CHSs): CHS1 had active metabolism and poor immune infiltration but low fibrosis; CHS3 had contrasting characteristics with CHS1; CHS2 was intermediate. CHS1 may respond well to cuproptosis inducers, and CHS3 may benefit from a combination of immunotherapy and anti-fibrosis/anti-hypoxia therapies. In CRC, the CHSs also showed a significant difference in prognosis and sensitivity to classic drugs. Organoid-based drug sensitivity assays validated the results of transcriptomics. Cell-based assays indicated that masitinib and simvastatin had specific effects on CHS1 and CHS3, respectively. A user-friendly website based on the classifier was developed (https://fan-app.shinyapps.io/chs_classifier/) for accessibility. Overall, the classifier based on cuproptosis and hypoxia was applicable to most pan-cancers and could aid in personalized cancer therapy.
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Neoplasias Colorrectales , Multiómica , Humanos , Inmunoterapia , Apoptosis , Perfilación de la Expresión Génica , Hipoxia , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genéticaRESUMEN
OBJECTIVE: To develop the best short form of constitution in Chinese medicine questionnaire (CCMQ) and evaluate its psychometric properties in Chinese population. METHODS: A total of 21 948 subjects were used to refine the short form. Correlation coefficient, exploratory factor analysis (EFA) and Cronbach's alpha coefficient were used to analyze and select items to form the short form. Separate sample of 205 subjects were collected to further evaluate the short from. EFA, confirmatory factor analysis (CFA), item-scale correlation, discriminant validity, internal consistency reliability and split-half reliability were carried out to evaluate the short form. RESULTS: The short form CCMQ included 26 items. Seven common factors of characteristic root > 1 were extracted to explain 58.488% of the total variation. Result of CFA was consistent with the 9-factors structure. The mean differences of Blood-stasis body constitution and Qi-stagnation body constitution had statistical significance in body mass index differentiation. Cronbach's alpha coefficient of short form CCMQ was 0.863. The split-half reliability of total scale was 0.813, and each scale was 0.568-0.770. The item-scale correlations ranged from 0.620-0.849. CONCLUSION: The short form CCMQ consisted of 26 items with good psychometric properties. The short form should be recommended for the measurement of health of Chinese population in any clinical trial.
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Medicina Tradicional China , China , Análisis Factorial , Humanos , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
Radiotherapy for liver cancer can affect the level of autophagy in cells, and effective autophagy regulation can increase the radiosensitivity of liver cancer cells.Saikosaponin-d (SSd) is an effective active ingredient extracted from traditional Chinese medicine Bupleurum. We have confirmed previously in vitro and in vitro experiments that SSd can significantly induce apoptosis of liver cancer cells, increase the radiosensitivity of liver cancer cells.This study explored the role of autophagy in SSd-mediated radiosensitivity of liver cancer cells. MTT and clone formation experiments showed that radiation can inhibit the proliferation of hepatoma cells and reduce the colony formation of hepatoma cells. After the addition of SSd, the inhibitory effect of radiation on the proliferation and clonal formation of hepatoma cells was further enhanced. However, the addition of the autophagy inhibitor chloroquine or mTOR agonist can partially reverse the inhibitory effect of the combined treatment of SSd with radiation on the proliferation of hepatoma cells. Similarly, transmission electron microscopy and laser confocal microscopy showed that after the addition of SSd, the number of radiation-induced autophagosomes increased significantly in hepatoma cells and the intervention of mTOR agonist can reduce the formation of autophagosomes in hepatoma cells.In addition,Western blot analysis presented that radiation significantly increased LC3-II levels. Especially when SSd is added, LC3-II levels is further increased. Our data indicate that SSd can inhibit the growth of liver cancer cells and enhance cell radiosensitivity by inducing autophagy formation.
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OBJECTIVE: To develop a health-evaluating scale from a Chinese medicine (CM) perspective and reflecting CM conception of health. METHODS: The Traditional Chinese Medicine Health Self-Evaluation Scale (TCM-50) was developed by verification of dimensions, formation of item pool, verification of scoring methodology, and pilot test of scale and item analysis. RESULTS: TCM-50 composed of 50 items that could be classified into 4 dimensions including physiology and health, psychology and health, nature and health, and society and health. An examination of reliability and validity of TCM-50 yielded Cronbach's α coefficient of 0.927, and half coefficient of was 0.876. The intraclass correlation coefficient of total score was 0.912. After using SF-36 questionnaire to evaluate the criterion validity, the Pearson of the score of the two scales from the same participant was 0.740. CONCLUSIONS: TCM-50 has good reliability and validity, and can yield similar levels of efficacy as SF-36 in terms of evaluating people's overall health level. As a scale based on CM theory, TCM-50 is suitable for self-measuring the general health of Chinese patients.
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Autoevaluación Diagnóstica , Medicina Tradicional China , Adolescente , Adulto , Anciano , Calibración , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to investigate the effects of Saikosaponin-d (SSd) combined with radiotherapy on SMMC-7721 hepatoma cell lines and its mechanism. MATERIAL/METHODS: SMMC-7721 hepatoma cell lines are selected in our research. With MTT (methylthiazolyldiphenyl-tetrazolium-bromide) method, the effects of SSd and radiation on inhibiting SMMC-7721 cell growth were investigated. We also used transmission electron microscopy (TEM) to observe ultrastructural changes of cells. Colorimetry methods were used to measure content changes of glutathione (GSH) and malondialdehyde (MDA) in cells. RESULTS: Both SSd and radiation inhibited the growth of SMMC-7721 cells. The combination of SSd and radiotherapy had a time-dependent synergistic effect. Radiation caused ultrastructural damage to cells, and the damage was enhanced in combination with SSd. Radiation decreased the GSH content and increased the MDA content in cells, and this effect was suppressed after the intervention of SSd. CONCLUSIONS: SSd can inhibit the growth of SMMC-7721 hepatoma cell lines in vitro. Additionally, it significantly enhances the effects of radiation on inhibiting the growth of SMMC-7721 hepatoma cell lines, and up-regulates the antioxidant level after the radiotherapy. Thus, SSd could be an ideal radiotherapy sensitizer for the treatment of liver cancer.
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Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/radioterapia , Ácido Oleanólico/análogos & derivados , Fármacos Sensibilizantes a Radiaciones/farmacología , Saponinas/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Humanos , Técnicas In Vitro , Microscopía Electrónica de Transmisión , Ácido Oleanólico/farmacología , Sales de Tetrazolio , TiazolesRESUMEN
Electrochemical codeposition of vanadium oxide (V2O5) and polypyrrole (PPy) is conducted from vanadyl sulfate (VOSO4) and pyrrole in their aqueous solution to get V2O5-PPy composite, during which one-dimensional growth of polypyrrole (PPy) is directed. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) are used to characterize the composite, while scanning electron microscopy (SEM) is used to investigate their morphologies. Cyclic voltammetry (CV), chronopotentiometry (CP) for galvanostatic charge-discharge and electrochemical impedance spectroscopy (EIS) are used to study electrochemical activities and pseudocapacitive properties of the composite. The influences of VOSO4 to pyrrole ratio in the electro-codeposition solution on morphologies and pseudocapacitive properties of the composite are discussed. Due to the organic-inorganic synergistic effect, V2O5-PPy composite exhibits good charge-storage properties in a large potential window from -1.4 to 0.6 V vs SCE, with a specific capacitance of 412 F/g at 4.5 mA/cm(2). A model supercapacitor assembled by using the V2O5-PPy composite as the electrode materials displays a high operating voltage of 2 V and so a high energy density of 82 Wh/kg (at the power density of 800 W/kg).
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BACKGROUND: Our previous study revealed that the combination of Saikosaponin-d ( SSd) and radiation is more effective in the treatment of liver cancer than the application of either of these monotherapeutic methods. However, the molecular mechanisms of the radiosensitizing effect of SSd on liver cancer remained ill defined. METHODS: Cells were treated with different interventions; afterward, cell viability, apoptosis, and cell survival of SMMC-7721 and HepG2 hepatoma cells were examined. Xenograft tumor models were established by subcutaneously injecting SMMC-7721 cells. The molecular mechanism was assessed by western blot. RESULTS: SSd dose-dependently increased radiosensitivity of hepatoma cells under hypoxic condition. The growth inhibitory effect of the combined treatment was correlated with cell apoptosis. Further mechanistic analysis indicated that SSd induced the upregulation of p53 and Bax as well as the downregulation of Bcl-2 by attenuating HIF-1α expression under hypoxic condition. These effects were enhanced when the HIF-1α inhibitor PX-478 was introduced. In vivo data also presented a more significant suppression of tumor xenograft growth from the combined therapy than from either of the monotherapeutic methods. CONCLUSIONS: Our study provides evidence for a radiosensitizing effect of SSd on hepatoma cells under hypoxic conditions by inhibiting HIF-1α expression. Thus, SSd can be used as a potential sensitizer in hepatoma radiotherapy. © 2014 S. Karger AG, Basel.
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Carcinoma Hepatocelular/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Neoplasias Hepáticas/patología , Ácido Oleanólico/análogos & derivados , Tolerancia a Radiación/efectos de los fármacos , Saponinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/metabolismo , Hipoxia de la Célula/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Saponinas/química , Ensayo de Tumor de Célula Madre , Proteína p53 Supresora de Tumor/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: Saikosaponin-d (SSd), a monomer terpenoid purified from the Chinese herbal drug Radix bupleuri, has multiple effects, including anticancer properties. However, the effect of SSd on tumors exposed to radiation is largely unknown. To investigate the radiosensitizing effect of SSd and its possible mechanism, we combined SSd with radiation therapy to treat SMMC-7721 hepatocellular carcinoma cells under oxia and hypoxia. METHODS: Cell growth, apoptosis, and cell cycle distribution were examined after treatment with SSd alone, radiation alone, and their combinations under oxia and hypoxia. The protein and mRNA levels of p53, Bcl2, and BAX were measured using western blot analysis and RT-PCR, respectively. RESULTS: Treatment with SSd alone and radiation alone inhibited cell growth and increased apoptosis rate at the concentration used. These effects were enhanced when SSd was combined with radiation. Moreover, SSd potentiated the effects of radiation to induce G0/G1 arrest in SMMC-7721 cells, and reduced the G2/M-phase population under hypoxia. However, under oxia, SSd only potentiated the effects of radiation to induce G0/G1 arrest, but not G2/M-phase arrest. These effects of SSd alone, radiation alone, and their combination, were accompanied by upregulated expression of p53 and BAX and downregulation of Bcl2 expression under oxia and hypoxia. CONCLUSION: SSd potentiates the effects of radiation on SMMC-7721 cells; thus, it is a promising radiosensitizer. The radiosensitizing effect of SSd may contribute to its effect on the G0/G1 and G2/M checkpoints of the cell cycle.
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Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/radioterapia , Puntos de Control del Ciclo Celular/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/radioterapia , Ácido Oleanólico/análogos & derivados , Fármacos Sensibilizantes a Radiaciones/farmacología , Saponinas/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Carcinoma Hepatocelular/patología , Puntos de Control del Ciclo Celular/efectos de la radiación , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/patología , Ácido Oleanólico/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Rayos X , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Esophageal duplication cysts are benign, asymptomatic anomalies of foregut formation. We report a case of esophageal duplication cyst with esophageal squamous cancer. An upper endoscopy visualized with esophageal scan disclosed a stenotic lesion in the lower esophagus. Computed tomography images revealed a cystic mass in the inferior mediastinum, which was on the right wall of the esophagus. The postoperative pathology report confirmed the diagnosis of esophageal squamous cancer (ulcer type) and esophageal duplication cyst with calcification.
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Carcinoma de Células Escamosas/complicaciones , Quiste Esofágico/congénito , Neoplasias Esofágicas/complicaciones , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirugía , Diagnóstico Diferencial , Endoscopía Gastrointestinal , Quiste Esofágico/complicaciones , Quiste Esofágico/diagnóstico , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/cirugía , Esofagectomía , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Radiation-induced skin injury is a common complication of radiotherapy. The RHIZOMA COPTIDIS and COPTIS CHINENSIS aqueous extract (RCE) can ameliorate radiation-induced skin injury in our clinical observation. But, the protective mechanism of RHIZOMA COPTIDIS and COPTIS CHINENSIS in radiation-induced skin injury remains unclear. METHODS: In this experiment, we developed a radiation-induced skin injury rat model to study the mechanism. The animals were randomly divided into control group, treatment group, radiation group, and treatment and radiation group. 5 rats in each group were separately executed on 2 d and 49 d post-radiation. The semi-quantitative skin injury score was used to measure skin reactions by unblinded observers, and hematoxylin and eosin staining was used to evaluate the damage areas by irradiation. The MDA content, SOD activity of skin and serum were measured to detect the oxidative stress. RESULTS: Acute skin reactions were caused by a single dose of 45 Gy of ß-ray irradiation, and the skin injury could be found in all rats receiving irradiation based on the observation of HE staining of skin at different time-points, while RCE could significantly ameliorate those changes. The MDA content in serum and skin of control rats was 4.13±0.12 mmol/ml and 4.95±0.35 mmol/mgprot on 2 d post-radiation. The rats receiving radiation showed an increased content of MDA (5.54±0.21 mmol/ml and 7.10±0.32 mmol/mgprot), while it was 4.57±0.21 mmol/ml and 5.95±0.24 mmol/mgprot after treated with RCE (p<0.05). Similar changes of the MDA content could be seen on 49 d post-radiation. However, the SOD activity of rats receiving radiation decreased compared with control group on both time-points, which was inhibited by RCE (p<0.05). Meanwhile, no valuable changes could be found between control group and treatment group on 2 d and 49 d. CONCLUSIONS: Our study provides evidences for the radioprotective role of RCE against radiation-induced skin damage in rats by modulating oxidative stress in skin, which may be a useful therapy for radiation-induced skin injury.
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Coptis/química , Medicamentos Herbarios Chinos/administración & dosificación , Traumatismos por Radiación/tratamiento farmacológico , Rizoma/química , Animales , Coptis chinensis , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Traumatismos por Radiación/enzimología , Traumatismos por Radiación/metabolismo , Traumatismos por Radiación/prevención & control , Ratas , Piel/efectos de los fármacos , Piel/enzimología , Piel/metabolismo , Piel/efectos de la radiación , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVE: This study systematically investigated the effect of chronic stress on the hippocampus and its damage mechanism at the whole genome level. METHODS: The rat whole genome expression chips (Illumina) were used to detect gene expression differences in the hippocampus of rats subjected to chronic immobilization stress (daily immobilization stress for 3 h, for 7 or 21 days). The hippocampus gene expression profile was studied through gene ontology and signal pathway analyses using bioinformatics. A differentially expressed transcription regulation network was also established. Real-time quantitative polymerase chain reaction (RT-PCR) was used to verify the microarray results and determine expression of the Gabra1, Fadd, Crhr2, and Cdk6 genes in the hippocampal tissues. RESULTS: Compared to the control group, 602 differentially expressed genes were detected in the hippocampus of rats subjected to stress for 7 days, while 566 differentially expressed genes were expressed in the animals experiencing stress for 21 days. The stress significantly inhibited the primary immune system functions of the hippocampus in animals subjected to stress for both 7 and 21 days. Immobilization activated the extracellular matrix receptor interaction pathway after 7 day exposure to stress and the cytokine-cytokine receptor interaction pathway. The enhanced collagen synthesis capacity of the hippocampal tissue was the core molecular event of the stress regulation network in the 7-day group, while the inhibition of hippocampal cell growth was the core molecular event in the 21-day group. For the Gabra1, Fadd, Crhr2, and Cdk6 genes, RT-PCR results were nearly in line with gene chip assay results. CONCLUSION: During the 7-day and 21-day stress processes, the combined action of polygenic, multilevel, and multi-signal pathways leads to the disorder of the immunologic functions of the hippocampus, hippocampal apoptosis, and proliferation disequilibrium.
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Hipocampo/metabolismo , Inmovilización , Estrés Fisiológico/genética , Transcriptoma , Animales , Regulación hacia Abajo/genética , Matriz Extracelular/genética , Redes Reguladoras de Genes/genética , Masculino , Anotación de Secuencia Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/genética , Transcripción Genética , Regulación hacia Arriba/genéticaRESUMEN
The arcuate nucleus (ARC) in the basal of hypothalamus plays an important role in appetite regulation and energy balance. We sought to investigate the central neuroendocrine mechanism of appetite decrease and weight loss under chronic stress by observing the regulatory effects of Xiaoyaosan decoction in the expression of leptin receptor (ob-R) and neuropeptide Y (NPY) in the ARC. Our results showed that bodyweight and food intake of rats in the 21-day stress group increased slower than those of the normal group. Higher contents of Leptin and ob-R were noted in the 21-day stress group compared with control rats, while NPY expression was not statistically different. Xiaoyaosan powder can significantly downregulate the contents of leptin and ob-R in the hypothalamus of stressed rats. These findings suggest that increase of ob-R expression in the ARC is possibly one key central neuroendocrine change for the somatic discomfort. Weight loss and decreased food intake in rats caused by the binding of leptin to ob-R in hypothalamus do not appear to utilize the NPY pathway. This study also suggests that ob-R in the ARC may act as the target of Xiaoyaosan in regulating the symptoms such as appetite decrease and bodyweight loss under chronic stress.
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AIM: To explore the relationship between the expression of PTEN gene and the expression of PPARgamma, and the human pancreatic cancer cells PANC-1 were cultured in vitro. METHODS: The effects of rosiglitazone and GW9662 on the expression of PTEN gene and PTEN protein in the human pancreatic cancer cells PANC-1 were detected by RT-PCR and immunohistochemistry respectively. In addition, the percentage of the expression of PTEN protein was analyzed by flow cytometry. RESULTS: The expression of PTEN gene and PTEN protein in human pancreatic cancer cells PANC-1 were all increased significantly after treated with rosiglitazone. While those were markedly reduced in GW9662 treated groups, and it has a dose-effect relationship between them. CONCLUSION: The expression of PTEN gene were paralleled with the expression of PPARgammain human pancreatic cancer cells PANC-1, which may be related to its inhibitory effects on pancreatic tumor cells.
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PPAR gamma/metabolismo , Fosfohidrolasa PTEN/metabolismo , Neoplasias Pancreáticas/metabolismo , Anilidas/farmacología , Línea Celular Tumoral , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunohistoquímica , PPAR gamma/antagonistas & inhibidores , Fosfohidrolasa PTEN/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rosiglitazona , Tiazolidinedionas/farmacologíaRESUMEN
AIM: To construct pcDNA3.1-Egr.1p-p16 recombinant plasmid and investigate the expression of p16 in pancreatic cancer JF305 cells induced by radiation and the feasibility of gene radiotherapy for pancreatic carcinoma. METHODS: Human p16 cDNA was ligated to the downstream of Egr-1 promotor to construct pcDNA3.1-Egr.1p-p16 plasmid by restriction enzyme digested. The recombined plasmids were transfected into pancreatic cancer JF305 cells with lipofectamine. p16 mRNA level was detected by RT-PCR. The expression of p16 after different doses of X-ray radiation was detected by Western blot technique. Cell survival was assessed by clonogenic assays and cell viability was analysed by trypen blue exclusion. Flow cytometry was performed to study the apoptosis of JF305 cells. RESULTS: Restriction enzyme digestion showed the correctly constructed pcDNA3.1-Egr.1p-p16. The p16 expression in cells transfected with pcDNA3.1-Egr.1p-p16 induced by different doses of radiation was higher than that in the control group (P < 0.05). Eight hours after 2 Gy X-ray radiation, the expression reached its peak (87.00 ng/L), and was significantly higher than that in the control group (P < 0.0.5). Clonogenic analysis and trypan blue extraction test showed that the pcDNA3.1-Egr.1p-p16 transfer enhanced radiation-induced cell killing in p16-null JF305 cell lines. The induction of apoptosis was lower in combined transfection and irradiation group than that in irradiation alone. CONCLUSION: X-ray can induce the recombinant plasmid pcDNA3.1-Egr.1p-p16 expression in JF305 cells. The detection of dose and time provides an experimental basis for in vivo study in future.
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Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Vectores Genéticos/genética , Neoplasias Pancreáticas/metabolismo , Plásmidos/genética , Apoptosis/genética , Apoptosis/efectos de la radiación , Línea Celular Tumoral , Supervivencia Celular/genética , Supervivencia Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Humanos , Neoplasias Pancreáticas/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , TransfecciónRESUMEN
AIM: To determine the survival of advanced pancreatic cancer patients treated with intraoperative radiotherapy (IORT) combined with external beam radiation therapy (EBRT) following internal drainage (cholecystojejunostomy or choledochojejunostomy). METHODS: Eighty-one patients with advanced pancreatic cancer who received IORT combined with EBRT following internal drainage (ID) between 1996 and 2001 were retrospectively analyzed. Among the 81 patients, 18 underwent ID+IORT, 25 ID+IORT+EBRT (meanwhile, given 5-Fu 300 mg/m(2) i.v. drip, 2f/w), 16 EBRT, 22 had undergone simple internal drainage. The IORT dose was 15-25Gy in a single fraction. The usual EBRT dose was 30-40Gy with a daily fraction of 1.8-2.0 Gy. RESULTS: The complete remission rate, partial remission rate of patients with backache and abdominal pain treated with ID+IORT were 55.5%, 33.3% respectively. Alleviation of pain was observed 2 or 3 wk after IORT. The median survival time (MST) of ID+IORT group was 10.7 mo. The pain remission rate of patients treated with ID+IORT+EBRT was 92%, and their MST was 12.2 mo. The MST of patients treated with EBRT and simple internal drainage was 5.1 mo and 7.0 mo, respectively. The survival curve of ID+IORT group and ID+IORT+EBRT group was significantly better than that of EBRT group (P<0.05). The difference between the ID+IORT+EBRT group and ID group was significant (P<0.05). CONCLUSION: IORT combined with EBRT following internal drainage can alleviate pain, improve quality of life and prolong survival time of patients with advanced pancreatic cancer.