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1.
World J Gastrointest Surg ; 16(3): 731-739, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38577073

RESUMO

BACKGROUND: Hemorrhoids are among the most common and frequently encountered chronic anorectal diseases in anorectal surgery. They are venous clusters formed by congestion, expansion, and flexion of the venous plexus in the lower part of the rectum. Mixed hemorrhoids bleed easily and recurrently, and this can result in severe anemia. Hence, they may have a negative effect on the health of the patient and surgical treatment is required. Milligan-Morgan hemorrhoidectomy has been widely used since 1937 for the treatment of grade III and IV hemorrhoids. However, most patients experience different degrees of postoperative pain that may cause anxiety. AIM: To assess the factors influencing pain scores and quality of life (QoL) in patients with mixed hemorrhoids post-surgery. METHODS: The clinical data of patients with mixed hemorrhoids who underwent Milligan-Morgan hemorrhoidectomy were collected retrospectively. The basic characteristics of the enrolled patients with mixed hemorrhoids were recorded, and based on the Goligher clinical grading system, the hemorrhoids were classified as grades III or IV. The endpoint of this study was the disappearance of pain in all patients. Quantitative data were presented as mean ± SD, such as age, pain score, and QoL score. Student's t-test was used to compare the groups. RESULTS: A total of 164 patients were enrolled. The distribution of the visual analog scale pain scores of all patients at 3, 7, 14 and 28 d after surgery showed that post-surgery pain was significantly reduced with the passage of time. Fourteen days after the operation, the pain had completely disappeared in some patients. Twenty-eight days after the surgery, none of the patients experienced any pain. Comparing the World Health Organization Quality of Life - BREF self-reporting questionnaire scores of patients between 14 and 28 d after surgery, we observed that the quality-of-life scores of the patients post-surgery had significantly improved. There were six items that were compared at 14- and 28-d post-surgery. The mean QoL score 28 d after surgery (4.79 ± 0.46) was higher than that at 14 d post-surgery (3.79 ± 0.57). The mean health condition score 28 d after surgery (4.80 ± 0.41) was also higher than that at 14 d post-surgery (4.01 ± 0.62). The mean physical health score 28 d after surgery (32.10 ± 2.96) was significantly higher than that at 14 d post-surgery (23.41 ± 2.85). The mean psychological health score 28 d after surgery (27.22 ± 1.62) was significantly higher than that at 14 d post-surgery (21.37 ± 1.70). The mean social relations score 28 d after surgery (12.21 ± 1.59) was significantly higher than that at 14 d post-surgery (6.32 ± 1.66). The mean surrounding environment score 28 d after surgery (37.13 ± 2.88) was significantly higher than that at 14 d post-surgery (28.42 ± 2.86). The differences in quality-of-life scores at day 14 and day 28 post-surgery were observed to be statistically significant (P < 0.001). CONCLUSION: Milligan-Morgan hemorrhoidectomy can significantly improve the postoperative QoL of patients. Age, sex, and the number of surgical resections were important factors influencing Milligan-Morgan hemorrhoidectomy.

2.
Int J Cardiol ; 371: 397-401, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36103945

RESUMO

BACKGROUND: The aim of this study was to investigate the relationship between day-1 urine cadmium excretion and 30-day mortality in patients with acute myocardial infarction (AMI) at two centers. METHODS: A total of 286 patients (222 males and 64 females) with AMI from Huashan Hospital, Shanghai and Chang Gung Memorial Hospital, Taiwan were enrolled. Basic vital signs, history, laboratory results, and day-1 urine excretion of cadmium (D1UECd) were recorded. Disease severity was assessed during the first hospitalization using Killip score, APACHE II score, and SOFA score. The main endpoint was 30-day mortality. RESULTS: Among the 286 patients, 218 were from Chung Gung Memorial Hospital and 68 were from Huashan Hospital with an average age of 64.2 years. Forty (14%) patients died within 30 days after AMI. The average 24-h urine cadmium level among the Chung Gung Memorial Hospital cohort was 1.5 ± 2.4 µg compared to 1.7 ± 1.7 µg among Huashan Hospital cohort, both higher than the local populations. A higher D1UECd level was significantly associated with a greater risk of 30-day mortality (odds ratio 1.68, 95% confidence interval 1.30-2.16) after controlling for a number of covariates. The ability of D1UECd to discriminate 30-day mortality was excellent, with a very high area under the curve (87.2%, 95% CI 82.0-92.5%). CONCLUSION: D1UECd was positively correlated and an independent predictor of 30-day mortality in the enrolled AMI patients. D1UECd may be a simple, objective prognostic scoring system in AMI patients.


Assuntos
Cádmio , Infarto do Miocárdio , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , China , Estudos de Coortes , Mortalidade Hospitalar , Estudos Retrospectivos
3.
Medicine (Baltimore) ; 100(4): e21370, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530152

RESUMO

ABSTRACT: A number of studies have demonstrated that exosomes were involved in important physiological and pathological processes through cell-to-cell communication in cardiovascular disease, which contained nucleic acids, proteins, and lipid contents. In our study, we found that the protein platelet endothelial cell adhesion molecule-1 (PECAM1) was an extracellular vesicle in the blood of high blood pressure patients (HBPP).Isolated the vesicles from the blood of HBPP and health examiners and detected its size and morphology with nanoparticle tracking analysis, then we identified its surface protein CD63, CD81, and the protein expression of PECAM1 in the exosome with western blot. Furthermore, we analyzed the correlation between the expression of PECAM1 and the high blood degree with linear regression analysis.Our results showed that the morphology of extracellular vesicles was more evident in high blood pressure groups than healthy controls, and the protein expression of PECAM1 was also abundant in the vesicles of HBPP, however, there were no extracellular vesicles in the blood samples of healthy controls. Besides, linear regression showed the linear correlation coefficient R = 0.901, P < .01 between the expression of PECAM1 and the systolic blood pressure of the high blood patients. Therefore, the exosome of protein of PECAM1 was a potential risking star in HBPP.


Assuntos
Exossomos/genética , Hipertensão/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/sangue , Adulto , Western Blotting , Vesículas Extracelulares/genética , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hipertensão/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Nanopartículas/metabolismo , Tetraspanina 28/metabolismo , Tetraspanina 30/metabolismo
4.
J Cancer ; 11(22): 6582-6590, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33046979

RESUMO

Aim: Malignant melanoma (MM) is a highly aggressive cutaneous cancer with undetermined underlying genetic disposition. We aim to evaluate prognostic and mechanistic role of ACSM3 in MM. Methods: In silico reproduction of TCGA MM dataset, GEO dataset, GDSC dataset and human protein atlas was performed to establish differential expression of ACSM3. In vitro and in vivo validation using A375 and SKMEL1 MM cells were performed to profile tumorigenic role and functional attribution of the gene. Results: ACSM3 expression was significantly downregulated in MM. Lower expression of ACSM3 conferred worsened prognosis of MM. Lower ACSM3 was observed in Asian ethnicity. Knock-down (KD) and overexpression (OE) of ACSM3 resulted in significant increased and decreased proliferation, invasion and colony formation in MM cells, respectively. Pathway annotation revealed significantly active immune response invoked by ACSM3. Lower ACSM3 expression was associated with decreased CD8+, macrophage and dendritic cell infiltration. Cox regression revealed loss of survival contribution of ACSM3 in the presence of immune infiltrates supporting immune regulatory role of ACSM3. Drug sensitivity analysis revealed BRAF inhibitor PLX-4720 was sensitive in both MM cells. ACSM3 expression showed no correlation with immune checkpoint molecules. Combined ACSM3-OE and PLX-4720 in MM cells showed synergistic inhibition in MM cells and xenograft murine models with no significant toxicity. Conclusion: Loss of ACSM3 was associated with poor prognosis in MM. Overexpression of ACSM3 synergistically inhibited MM with PLX-4720. ACSM3 was potentially associated with immune exclusion in MM. Further validation was warranted in future studies.

5.
J Cardiothorac Surg ; 15(1): 276, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993717

RESUMO

BACKGROUND: In this study, we sought to evaluate the feasibility of improved transcatheter aortic valve implantation (TAVI) in noncalcified aortic valve by using the novel concept of double-layer ChenValve prosthesis. TAVI was initially considered as an alternative treatment for high-risk patients with aortic stenosis. However, non noncalcified aortic valve disease was considered as a contraindication to TAVI. METHODS: ChenValve prosthesis, which consisted of a self-expanding Nitinol ring, a balloon-expandable cobalt-chromium alloy stent and a biological valve, was implanted at the desired position under fluoroscopic guidance in a transapical approach through a 20F sheath in 10 goats. Aortic angiography was performed to measure the diameter of the aotic annulus and assess the performance of the artificial valve. The ultrasound was used to evaluate the regurgitation or paravalvular leakage and trans-prosthetic vascular flow velocity postoperatively. The aortogram and transthoracic echocardiography were applied to observe whether the valve stent was implanted at the desired position. RESULTS: ChenValve prosthesis was successfully transppical implanted in all animals. The aortogram and transthoracic echocardiography performed immediately after implantation revealed that the valve stent was implanted at the desired position. There was no significant paravalvular leakage, obstruction of coronary artery ostia, stent malpositioning or dislodgement occurred. CONCLUSIONS: This preliminary trial with the novel double-layer ChenValve prosthesis demonstrated the feasibility of improved TAVI in noncalcified aortic valve. The mechanism of Nitinol ring-guided locating the aortic sinus enables us to anatomically correct position the artifact valve. This improved strategy seems to make the TAVI process more safe and repeatable in noncalcified aortic valve.


Assuntos
Insuficiência da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Stents , Substituição da Valva Aórtica Transcateter/métodos , Animais , Valva Aórtica/diagnóstico por imagem , Ecocardiografia , Feminino , Fluoroscopia , Cabras , Próteses Valvulares Cardíacas , Masculino , Desenho de Prótese , Substituição da Valva Aórtica Transcateter/instrumentação , Ultrassonografia
6.
Medicine (Baltimore) ; 99(37): e22153, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925773

RESUMO

BACKGROUND: Immune checkpoint blockade (ICB) brings hope to many late-stage cancer patients yet its marker for response remains elusive. METHODS: We developed a hypothesis that treatment-related adverse events (TrAEs) could predict objective response rate (ORR) to ICB. We plotted ORR against corresponding any and grade 3 to 5 (G3-5) TrAEs across a variety of cancer types by performing a meta-analysis using linear regression. RESULTS: We identified 113 eligible studies encompassing 25 types of malignancies that were treated with ICB or ICB-based regimes. A significant linear correlation was observed for any and severe TrAEs, respectively. The correlation coefficient was 0.57 (r = 0.324) for any TrAE and 0.61 (r = 0.37) for G3-5 TrAE. For melanoma, the correlation coefficient was 0.81 (r = 0.57) for any TrAE and 0.65 (r = 0.42) for G3-5 TrAEs. For RCC, the correlation coefficient was 0.86 (r = 0.74) for any TrAE and 0.91 (r = 0.83) for G3-5 TrAE. For NSCLC, the correlation coefficient was 0.55 (r = 0.3) for any TrAE and 0.74 (r = 0.86) for G3-5 TrAE. For UC, the correlation coefficient was 0.47 (r = 0.68) for any TrAE and 0.27 (r = 0.52) for G3-5 TrAE, yet the correlation was insignificant for severe AEs. CONCLUSION: Our findings suggest that over half of ICB responses could be reflected by any adverse events and ∼60% of responses could be reflected by severe AEs. Further validation is needed in individual trials.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Humanos , Estadiamento de Neoplasias , Neoplasias/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Análise de Sobrevida , Resultado do Tratamento
7.
Cancer Med ; 9(16): 6020-6029, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32628820

RESUMO

BACKGROUND: Chromosomal rearrangements are common in clear cell renal cell carcinoma (ccRCC) and their roles in mediating sensitivity to tyrosine kinase inhibitors (TKIs) and mTOR inhibitors (mTORi) remain elusive. METHODS: We developed an in silico strategy by screening copy number variance (CNV) that was potentially related to TKI or mTORi sensitivity in ccRCC by reproducing the TCGA and GDSC datasets. Candidate genes should be both significantly prognostic and related to drug sensitivity or resistance, and were then validated in vitro. RESULTS: ADCYAP1 loss and GNAS gain were associated with sensitivity and resistance and to Cabozantinib, respectively. ACRBP gain and CTBP1 loss were associated with sensitivity and resistance and to Pazopanib, respectively. CDKN2A loss and SULT1A3 gain were associated with sensitivity and resistance and to Temsirolimus, respectively. CCNE1 gain was associated with resistance to Axitinib and LRP10 loss was associated with resistance to Sunitinib. Mutivariate analysis showed ADCYAP1, GNAS, and CCNE1 remained independently prognostic when adjusted for the rest. CONCLUSION: Here we show CNVs of several genes that are associated with sensitivity and resistance to commonly used TKIs and mTORi in ccRCC. Further validation and functional analyses are therefore needed.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Variações do Número de Cópias de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Anilidas/uso terapêutico , Antineoplásicos , Arilsulfotransferase/genética , Axitinibe/uso terapêutico , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Cromograninas/genética , Simulação por Computador , Ciclina E , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Indazóis/uso terapêutico , Proteínas Oncogênicas , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Sulfonamidas/uso terapêutico , Sunitinibe/uso terapêutico
8.
Int J Clin Exp Pathol ; 12(11): 4232-4241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933823

RESUMO

MicroRNAs (miRNAs) have been revealed to be involved in dysfunction and inflammatory conditions of vascular endothelial cells (ECs). However, the role of miR-499a in inflammatory responses and apoptosis of human umbilical vein endothelial cells (HUVECs) remains unclear. The expression of miR-499a and signal transducer and activator of transcription 1 (STAT1) was analyzed using quantitative real-time polymerase chain reaction or western blot assay, respectively. Cells apoptosis was determined by Flow cytometry. Western blot was used to evaluate the protein expression of STAT1, interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), B cell lymphoma (Bcl-2), Bcl-2 associated X (Bax) and Cleaved Caspase-3. The interaction between miR-499a and STAT1 was confirmed by bioinformatics analysis and luciferase reporter assay. The expression of miR-499a was significantly down-regulated, while the STAT1 level was obviously up-regulated in LPS-induced HUVECs. Overexpressed miR-499a inhibited LPS-activated expression of IL-6, VCAM-1 and ICAM-1, and protected HUVECs against LPS-induced apoptosis by suppressing the expression of Bax and cleaved caspase 3 expressions. However, STAT1 promoted LPS-induced inflammatory injury and apoptosis in HUVECs. In addition, STAT1 was predicted and confirmed to be a target of miR-499a, and rescue experiment indicated that STAT1 was involved in the miR-499a mediated protection on LPS-induced HUVECs inflammatory injury and apoptosis. MiR-499a protects HUVECs from LPS-induced inflammatory injury and apoptosis by regulating STAT1 expression, which providing a novel insight to assist researchers and clinicians in developing potential therapeutic strategies for sepsis.

9.
Oncol Lett ; 16(4): 4407-4417, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30214575

RESUMO

Although liver transplantation (LT) lengthens the survival time of patients with hepatocellular carcinoma (HCC), LT patients exhibit a high recurrence rate; particularly those that had advanced HCC associated with the tumor biological characteristics and long-term application of immunosuppressants. A consensus on optimal prophylaxis and treatment for recurrent HCC following LT does not currently exist. The present study retrospectively analyzed data from 36 non-University of California at San Francisco criteria-eligible patients with advanced HCC who underwent LT, and then treated them with sirolimus (SRL)-based therapy with thymalfasin and huaier granules (SRL+, n=18), or with tacrolimus-based therapy (controls; n=18). The SRL+ group had significantly longer recurrence times (P=0.008) and survival times (P<0.0001) (OS, 1-year: 100%, 3-year: 94.4%, 5-year: 77.8%; DFS, 1-year: 88.9%, 3-year: 55.6%, 5-year: 50.0%). Furthermore, compared with pre-LT values and the control group, the SRL+ group had significantly lower serum α-fetoprotein (AFP) levels (both P<0.0001) and percentage of Forkhead box P3 (FoxP3)+ Treg lymphocytes (P<0.001) during the first year. In the SRL+ group, FoxP3+/cluster of differentiation (CD)8+ Treg lymphocyte percentages decreased significantly following LT (P<0.001); however, CD8+/CD3+ T-cells significantly increased (P<0.001). Levels of serum AFP and FoxP3+ Treg cells increased when tumors relapsed, and decreased to near-normal when relapse foci were cured or stabilized. SRL+ therapy may decrease AFP and Treg levels, while increasing CD8+ T cells, indicating an associated mechanism among them. In conclusion, SRL+ therapy appears to be safe and effective in preventing HCC recurrence following LT with no significant adverse events, and warrants further investigation.

10.
Oncol Lett ; 14(6): 7817-7824, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29344227

RESUMO

There is currently no consensus on the most suitable therapeutic approach for psoriasis (PS) co-existing with posthepatic cirrhosis (PCs) and hepatocellular carcinoma (HCC) following liver transplantation (LT). The present study provides an analysis of the therapeutic experience of such patients. Five LT recipients (two with PC and three with HCC) with accompanying PS were included. The induction program consisted of methylprednisolone plus basiliximab treatment. The initial postoperative treatment scheme consisted of tacrolimus (FK506) plus mycophenolate mofetil (MMF) and hormone; the latter was withdrawn 1 week after LT. The patients with PC had been using FK506 with or without a postoperative MMF program; the patients with HCC and recurrence of PS had been switched to a sirolimus (SRL)-based replacement therapy. Furthermore, all patients received anti-hepatitis B virus (HBV) therapy. The patients were followed up after 8.3±1.5 years. There was a positive correlation between HBV-DNA copy numbers, and psoriatic area and severity index (PASI) scores (r=0.97; P=0.006). The PASI scores were decreased significantly at 6 months following surgery compared with pre-transplantation (P<0.05). The patients who had received the FK506-based treatment experienced PS recurrence two years post-transplantation. The PASI scores increased significantly (P<0.05) and then declined gradually, maintaining a stable level (P<0.05) by 1 year after switching to the SRL-based treatment. The patients who had received the SRL-based treatment exhibited no recurrence of PS. The results of the present study suggest that SRL therapy provides a promising novel treatment method for patients with PS following LT that may be superior to tacrolimus treatment. When co-existing HBV is present pre-transplantation, regular injection of human hepatitis B immunoglobulin should be used to prevent the HBV from relapsing or aggravating the PS.

11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 31(6): 744-8, 2015 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-26062414

RESUMO

OBJECTIVE: To explore the impact of triple anti-tumor therapy based on thymosin α1 (Tα1) combined with Huaier granule(HG) and sirolimus on the level of serum alpha-fetoprotein (AFP) in rat models of liver cancer. METHODS: Ninety Sprague-Dawley rats were randomly divided into triple anti-tumor therapy group, Tα1 group, HG group, sirolimus group, positive control and blank control groups, with 15 rats in each group. Except the blank control group, the rats in the other groups were induced using diethylnitrosamine (DEN) to establish liver cancer models. After DEN treatment, the triple therapy group underwent 0.8 mg/kg Tα1 subcutaneous injection (from once a day for two weeks to twice a week since the third week), 0.35 g/kg HG gavage (three times a day) and 1 mg/kg sirolimus gavage (once a day). The dose of the rest single drug groups were the same with that of the triple therapy group. The positive control and blank control groups were not treated with the drugs. The treatment lasted 20 weeks. Then, the behavior of the rats were observed at the different time points, and the level of serum AFP in the rats were detected at 6, 16, 18, 20 weeks, respectively. RESULTS: The typical symptoms of liver cancer were seen in the DEN-induced rats at 16 weeks. Since the tenth week, 6 rats died one after another. Pathological section of rat liver tissue suggested that the rat models were established successfully. According to the incidence rate of liver cancer and the survival rate at 20 weeks, the triple anti-tumor therapy was significantly superior to the single drug treatments. In addition, the triple anti-tumor therapy significantly reduced the level of serum AFP in the rats. CONCLUSION: The triple anti-tumor therapy can significantly prolong the survival time of rats with liver cancer, decrease the cancer incidence rate and the level of serum AFP.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Timosina/análogos & derivados , alfa-Fetoproteínas/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Sirolimo/administração & dosagem , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Análise de Sobrevida , Timalfasina , Timosina/administração & dosagem , Timosina/farmacologia , Timosina/uso terapêutico
12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 30(10): 1099-102, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25270216

RESUMO

OBJECTIVE: To explore the efficacy of the modified extracorporeal photochemotherapy (ECP) in improving the apoptotic rate of lymphocytes in vitro. METHODS: The spleens which were obtained from liver transplantation donor under aseptic condition were used as experimental materials. Splenic lymphocytes (SPs) suspensions were prepared by modified and traditional ECP method, respectively. And then the isolated SPs were treated by the irradiation of 8-methoxypsoralen (8-MOP) combined with ultraviolet A (UVA) named PUVA, 8-MOP and UVA, and compared with a blank group meanwhile. The treated SPs were cultured overnight in an incubator at 37 Degrees Celsius, in a humidified atmosphere of 50 mL/L CO2 for 6-8 hours. The morphological changes of cells were observed using an inverted microscope, the apoptotic rates of SPs were detected by flow cytometry, and the difference between groups was analyzed finally. RESULTS: The apoptotic rate at early stage and the total apoptotic rate of SPs prepared by the modified ECP method were respectively (95.33±3.03)% and (97.10±2.12)% after treated by PUVA, (23.39±4.55)% and (36.32±6.63)% after treated by 8-MOP, and (66.98±3.60)% and (68.65±4.35)% by UVA. Compared with control group (12.82±1.86% and 13.4±2.65%), there were statistically significant differences (P<0.01). The apoptotic rate at early stage and the total apoptotic rate of SPs prepared by the traditional ECP method were respectively (79.73±4.21)% and (82.70±4.13)%, (61.42±2.28)% and (68.91±2.18)%, (19.30±1.78)% and (28.06±1.88)%, (10.84±0.98)% and (12.77±1.22)%, and the statistical comparisons between groups also had significant difference (P<0.01). In addition, there was a significant difference in the early and total apoptosis between the modified and traditional ECP (P<0.01), but no obvious variation in the end-stage apoptosis in the two groups (P>0.05). CONCLUSION: The modified ECP method can promote apoptosis of SPs in vitro conveniently, safely and efficiently, especially in the early stage. This can lay a foundation for the further study on dendritic cell immunomodulation induced by ECP method.


Assuntos
Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linfócitos/efeitos dos fármacos , Linfócitos/efeitos da radiação , Fotoquimioterapia/métodos , Células Cultivadas , Humanos , Metoxaleno/farmacologia , Terapia PUVA/métodos , Fármacos Fotossensibilizantes/farmacologia , Reprodutibilidade dos Testes , Baço/citologia , Fatores de Tempo , Raios Ultravioleta
13.
Nat Genet ; 44(10): 1117-21, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22922871

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. HCC is associated with multiple risk factors, including hepatitis B virus (HBV) infection, which is especially prevalent in China. Here, we used exome sequencing to identify somatic mutations in ten HBV-positive individuals with HCC with portal vein tumor thromboses (PVTTs), intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations. Notably, ARID1A, which encodes a component of the SWI/SNF chromatin remodeling complex, was mutated in 14 of 110 (13%) HBV-associated HCC specimens. We used RNA interference to assess the roles of 91 of the confirmed mutated genes in cellular survival. The results suggest that seven of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity to HCC cells. This study provides a view of the landscape of somatic mutations that may be implicated in advanced HCC.


Assuntos
Carcinoma Hepatocelular/genética , Exoma , Vírus da Hepatite B , Hepatite B/complicações , Neoplasias Hepáticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/secundário , Carcinoma Hepatocelular/virologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Cromossomos Humanos X/genética , Quinases Ciclina-Dependentes/genética , Proteínas de Ligação a DNA , Feminino , Estudos de Associação Genética , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Veia Porta/patologia , Análise de Sequência de DNA , Fatores de Transcrição/genética , Molécula 1 de Adesão de Célula Vascular/genética , Trombose Venosa/genética , Trombose Venosa/virologia
14.
Biochem Biophys Res Commun ; 395(4): 540-6, 2010 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-20394727

RESUMO

Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-gamma by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naïve T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4(+)CD25(high)Foxp3(+) regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.


Assuntos
Células Dendríticas/imunologia , Rejeição de Enxerto/terapia , Transplante de Coração/imunologia , Imunomodulação , Linfócitos T Reguladores/imunologia , Animais , Antígenos CD4/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/efeitos da radiação , Regulação para Baixo , Fatores de Transcrição Forkhead/imunologia , Interferon gama/imunologia , Interleucina-10/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Metoxaleno/farmacologia , Fagocitose , Fotoferese , Ratos , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Baço/imunologia , Células Th2/imunologia , Raios Ultravioleta
15.
BMC Genomics ; 10: 109, 2009 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19284880

RESUMO

BACKGROUND: The pituitary is a critical neuroendocrine gland that is comprised of five hormone-secreting cell types, which develops in tandem during the embryonic stage. Some essential genes have been identified in the early stage of adenohypophysial development, such as PITX1, FGF8, BMP4 and SF-1. However, it is likely that a large number of signaling molecules and transcription factors essential for determination and terminal differentiation of specific cell types remain unidentified. High-throughput methods such as microarray analysis may facilitate the measurement of gene transcriptional levels, while Expressed sequence tag (EST) sequencing, an efficient method for gene discovery and expression level analysis, may no-redundantly help to understand gene expression patterns during development. RESULTS: A total of 9,271 ESTs were generated from both fetal and adult pituitaries, and assigned into 961 gene/EST clusters in fetal and 2,747 in adult pituitary by homology analysis. The transcription maps derived from these data indicated that developmentally relevant genes, such as Sox4, ST13 and ZNF185, were dominant in the cDNA library of fetal pituitary, while hormones and hormone-associated genes, such as GH1, GH2, POMC, LHbeta, CHGA and CHGB, were dominant in adult pituitary. Furthermore, by using RT-PCR and in situ hybridization, Sox4 was found to be one of the main transcription factors expressed in fetal pituitary for the first time. It was expressed at least at E12.5, but decreased after E17.5. In addition, 40 novel ESTs were identified specifically in this tissue. CONCLUSION: The significant changes in gene expression in both tissues suggest a distinct and dynamic switch between embryonic and adult pituitaries. All these data along with Sox4 should be confirmed to further understand the community of multiple signaling pathways that act as a cooperative network that regulates maturation of the pituitary. It was also suggested that EST sequencing is an efficient means of gene discovery.


Assuntos
Etiquetas de Sequências Expressas , Regulação da Expressão Gênica no Desenvolvimento , Hipófise/crescimento & desenvolvimento , Adulto , Animais , DNA Complementar/metabolismo , Feto/metabolismo , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sequência com Séries de Oligonucleotídeos , Hipófise/metabolismo , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo
16.
Di Yi Jun Yi Da Xue Xue Bao ; 22(8): 734-5, 2002 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-12376265

RESUMO

OBJECTIVE: To investigate the effect of superselective intra-arterial infusion chemotherapy in the treatment of advanced recurrent cancer in the remnant stomach after previous partial gastrectomy. METHODS: Eighteen patients with advanced recurrent cancer in the remnant stomach that were non-resectable as confirmed in the operations were included in this study, who subsequently received superselective intra-arterial infusion chemotherapy. RESULTS: Improvement of the symptoms to various degrees were achieved in all patients after the therapy, with the total rate of tumor reduction of 77.8% and pathologically confirmed improvement rate of 83.3%. The 0.5-, 1.0-, 1.5- and 2.0-year survival rates were 94.4%, 66.7%, 50.0% and 27.8% respectively. CONCLUSION: Superselective catheterization is effective in treatment of advanced recurrent cancer in the remnant stomach, which can significantly prolong the tumor-bearing survival period of the patients.


Assuntos
Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Seguimentos , Coto Gástrico , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
17.
Zhonghua Zhong Liu Za Zhi ; 24(2): 167-9, 2002 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-12015040

RESUMO

OBJECTIVE: To evaluate the value of infusion chemotherapy by pump implantation via hepatic artery or portal vein or both (double-pump chemotherapy, DPC) for hepatic metastasis from colorectal cancer. METHODS: Thirty patients with hepatic metastasis from colorectal cancer were divided into three groups: 1. Group I-DPC (12 patients). 2. Group II-hepatic artery implantation chemotherapy (10 patients) and 3. Group III-portal vein implantation chemotherapy (8 patients). RESULTS: Response rate was 66.7% in group I, 60% in group II and 37.5% in group III. The 0.5-, 1-, 2-year survival rates were 100.0%, 75.0%, 41.7% in group I, 90.0%, 60.0%, 30.0% in group II and 87.5%, 50.0%, 25.0% in group III. CONCLUSION: Double pump implantation chemotherapy is effective in treating hepatic metastasis from colorectal cancer. It is better than hepatic artery or portal vein pump-implantation chemotherapy alone.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Bombas de Infusão Implantáveis , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Neoplasias Colorretais/patologia , Tratamento Farmacológico/métodos , Feminino , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Infusões Intravenosas , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Veia Porta , Terapêutica
18.
Zhonghua Wai Ke Za Zhi ; 40(1): 37-9, 2002 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-11955376

RESUMO

OBJECTIVE: To evaluate the effect of operative selective pump-insertion into the tumorous target artery, postoperative regional infusion chemotherapeutant and immunizator for treatment the latter gastrointestinal cancer. METHODS: The effect of operative super-selective pump-insertion into the tumorous nutritious artery, postoperative regional infusion chemotherapeutant and immunizator for treatment 88 cases patients suffering from irremovable gastrointestinal cancer was observed. Of them, 45 cases were gastric cancer, 31 cases were rectal cancer, 11cases were colic cancer. RESULTS: Complete response 2 case; Part response 77 cases, 11 cases patients had received secondary resection after intraarterial chemotherapy. Non chang 9 cases; effective rates reach to 89.8%. One, two and three years survival rates were 86.4%, 30.7% and 10.2%. Average survival period were 21.5 mouths. CONCLUSION: Super-selective pump-insertion into the artery and regional intraarterial chemotherapy is an efficient way in treatment of the latter gastrointestinal cancer, which can delay the survival period of patients with tumor, and increase the resectable rate.


Assuntos
Neoplasias Gastrointestinais/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateteres de Demora , Terapia Combinada , Feminino , Neoplasias Gastrointestinais/mortalidade , Humanos , Imunoterapia , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade
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