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In this randomized controlled trial, 74 patients scheduled for gynecological laparoscopic surgery (American Society of Anesthesiologists grade I/II) were enrolled and randomly divided into two study groups: (i) Group C (control), received sufentanil (0.3 µg/kg) and saline, followed by sufentanil (0.1 µg/kgâh) and saline; and (ii) Group F (OFA), received esketamine (0.15 mg/kg) and lidocaine (2 mg/kg), followed by esketamine (0.1 mg/kgâh) and lidocaine (1.5 mg/kgâh). The primary outcome was the 48-h time-weighted average (TWA) of postoperative pain scores. Secondary outcomes included time to extubation, adverse effects, and postoperative sedation score, pain scores at different time points, analgesic consumption at 48 h, and gastrointestinal functional recovery. The 48-h TWAs of pain scores were 1.32 (0.78) (95% CI 1.06-1.58) and 1.09 (0.70) (95% CI 0.87-1.33) for Groups F and C, respectively. The estimated difference between Groups F and C was - 0.23 (95% CI - 0.58 - 0.12; P = 0.195). No differences were found in any of the secondary outcomes and no severe adverse effects were observed in either group. Balanced OFA with lidocaine and esketamine achieved similar effects to balanced anesthesia with sufentanil in patients undergoing elective gynecological laparoscopic surgery, without severe adverse effects.Clinical Trial Registration: ChiCTR2300067951, www.chictr.org.cn 01 February, 2023.
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Analgésicos Opioides , Procedimentos Cirúrgicos em Ginecologia , Ketamina , Lidocaína , Dor Pós-Operatória , Sufentanil , Humanos , Sufentanil/administração & dosagem , Sufentanil/efeitos adversos , Feminino , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Lidocaína/administração & dosagem , Lidocaína/efeitos adversos , Adulto , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Pessoa de Meia-Idade , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Anestesia/métodos , Anestesia/efeitos adversos , Anestésicos Locais/administração & dosagem , Medição da DorRESUMO
Photosynthesis of H2O2 from seawater represents a promising pathway to acquire H2O2, but it is still restricted by the lack of a highly active photocatalyst. In this work, we propose a convenient strategy of regulating the number of benzene rings to boost the catalytic activity of materials. This is demonstrated by ECUT-COF-31 with adding two benzene rings as the connector, which can result in 1.7-fold enhancement in the H2O2 production rate relative to ECUT-COF-30 with just one benzene ring as the connector. The reason for enhancement is mainly due to the release of *OOH from the surface of catalyst and the final formation of H2O2 being easier in ECUT-COF-31 than in ECUT-COF-30. Moreover, ECUT-COF-31 provides a stable photogeneration of H2O2 for 70 h, and a theoretically remarkable H2O2 production of 58.7 mmol per day from seawater using one gram of photocatalyst, while the cost of the used raw material is as low as 0.24 $/g.
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OBJECTIVE: Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC. SUBJECTS AND METHODS: This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC). RESULTS: The median follow-up was 5.2 years. Compared with instillation for 1-2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3-6 months and > 6 months were 3.57ã1.57 and 0.22(95% CI 1.27-12.41;0.26-9.28;0.07-0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC. CONCLUSIONS: In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC.
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Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Administração Intravesical , Quimioterapia de Manutenção , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/patologia , Vacina BCG/uso terapêutico , Invasividade NeoplásicaRESUMO
OBJECTIVE: To investigate the therapeutic effects of total glucosides of paeony (TGP) on psoriasis based on the immunomodulatory effect of dermal mesenchymal stem cells (DMSCs). METHODS: A total of 30 male BALB/c mice were divided into 6 groups (n=5 in each) by a random number table method, including control, psoriasis model (model, 5% imiquimod cream 42 mg/d), low-, medium- and high-dose TGP (50, 100, and 200 mg/kg, L, M-, and H-TGP, respectively), and positive control group (2.5 mg/kg acitretin). After 14 days of continuous administration, the skin's histopathological changes, apoptosis, secretion of inflammatory cytokines, and proportion of regulatory T cells (Treg) and T helper cell 17 (Th17) were evaluated using hematoxylin-eosin (HE) staining, TdT-mediated dUTP nick end labeling staining, enzyme-linked immunosorbent assay, and flow cytometry, respectively. DMSCs were further isolated from the skin tissues of normal and psoriatic mice, and the cell morphology, phenotype, and cycle were observed. Furthermore, TGP was used to treat psoriatic DMSCs to analyze the effects on the DMSCs immune regulation. RESULTS: TGP alleviated skin pathological injury, reduced epidermis layer thickness, inhibited apoptosis, and regulated the secretion of inflammatory cytokines and the proportion of Treg and Th17 in the skin tissues of psoriatic mice (P<0.05 or P<0.01). There was no significant difference in cell morphology and phenotype between control and psoriatic DMSCs (P>0.05), however, more psoriatic DMSCs remained in G0/G1 phase compared with the normal DMSCs (P<0.01). TGP treatment of psoriatic DMSCs significantly increased cell viability, decreased apoptosis, relieved inflammatory response, and inhibited the expression of toll-like receptor 4 and P65 (P<0.05 or P<0.01). CONCLUSION: TGP may exert a good therapeutic effect on psoriasis by regulating the immune imbalance of DMSCs.
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Células-Tronco Mesenquimais , Paeonia , Psoríase , Masculino , Animais , Camundongos , Psoríase/tratamento farmacológico , Citocinas , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: This study aimed to evaluate the role of intravenous lidocaine as a adjuvant anesthetics in patients undergoing gynecological surgery. EVIDENCE ACQUISITION: We conducted a meta-analysis of randomized controlled trials (RCTs) from PUMED/MELINE, EMBASE and clinic trails.gov involving the use of intravenous lidocaine in gynecological surgery. We used a more comprehensive search strategy to adequately screen for randomized controlled trials involving intravenous lidocaine infusion in gynecological surgery. First outcomes were postoperative pain scores. And secondary outcomes included 24 h postoperative opioids consumption, time to first flatus, and incidence of postoperative nausea and vomiting. EVIDENCE SYNTHESIS: A total of 6 RCTs comprising 375 patients were included in the meta-analysis. There were statistically significant between postoperative pain scores. The consumption of opioids and anesthetics during surgery and 24 hours after surgery was statistically significant when compared with the control group. Postoperative pain scores were similar at 2,4,6,8,10,12,24,48 hour between groups. No statistical differences were found in postoperative complications including nausea, vomiting and restoration of the intestinal function. CONCLUSIONS: Our results indicated that the current literature supports the perioperative use of intravenous lidocaine as part of multimodal analgesia and beneficial to patients in early postoperative analgesia, reduced opioid consumption.
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BACKGROUND: Extramedullary plasmacytoma (EMP), a variant form of myeloma, is a rare solid plasma cell tumor that originates from the bone marrow hematopoietic tissue and accounts for about 3% of all plasma cell tumors. EMP can affect various tissues and organs, about 90% of which is found in the head and neck. However, EMP in the reproductive organs is rare, and is difficult to be distinguished from other primary or metastatic genital tumors according to clinical symptoms and imaging findings. CASE SUMMARY: Herein, we report a case with coexistence of EMP and squamous cell carcinoma in the cervix. The first histopathological report of neoplasms on the surface of the cervix and vagina showed an EMP. Both ultrasound and pelvic enhanced magnetic resonance imaging (MRI) indicated that there was a tumor in the cervix. Thus, another cervical biopsy and pathological examination were performed, which indicated EMP combined with squamous cell carcinoma. Then, the patient underwent extensive total hysterectomy (type C1) + systemic lymph node dissection and received 25 external pelvic irradiations with a dose of 50 Gy following surgery. During 2-year follow-up, no recurrence was reported. CONCLUSION: In conclusion, EMP involving the reproductive system is relatively rare. In this case, MRI, B-ultrasound, and cervical canal scraping were used to further determine the diagnosis of EMP combined with squamous cell carcinoma. The patient had improved prognosis after appropriate treatments.
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AbstractããCurrently, hematopoietic stem cell (HSC) transplantation is widely used in the therapy of hematological malignancies, non-malignant refractory anemia, genetic diseases and certain tumors with satisfactory therapeutic efficacy. HSC sources used for transplantation include bone marrow, mobilized peripheral blood and neonate umbilical cord blood. However, for many patients, sufficient number of human leukocyte antigen (HLA) -matched HSC cannot be found for transplantation, because the number of HSC in these tissues is small and HLA-identical donors are rare. Thus, in vitro generation of HSC has recently been focused. At present, the origin of HSC is hPSC, including hESC and hiPSC, which is worth to be the new origin of HSC transplantation. However, to generate functional hematopoietic stem cells which have efficient multi-lineage differentiation and in vivo engraftment potentials still is a big challenge to be confronted. In this review, the recent technical progress in HSC generation is summarizd, and the problems to be solved and new challenges to be confronted were discussed.
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Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Medula Óssea , Sangue Fetal , Células-Tronco Hematopoéticas , HumanosRESUMO
Lysosomal-associated protein transmembrane 4 beta (LAPTM4B), a proto-oncogene, has been shown to be a positive modulator in cancer progression. However, the mechanism of LAPTM4B regulation is not fully elucidated. Aberrant microRNAs (miRNAs) can regulate gene expression by interfering with target transcripts and/or translation to exert tumor-suppressive or oncogenic effects in breast cancer. In the present study, miR-132-3p, which was predicted by relevant software, was confirmed to directly bind to the 3' untranslated region (3'UTR) of LAPTM4B and negatively regulate its expression in luciferase reporter and western blot assays. Subsequently, we validated that miR-132-3p was downregulated in breast cancer tissues. Receiver-operating characteristic curve analysis indicated that miR-132-3p had accurate diagnostic value, and a Kaplan-Meier and Cox regression model showed that miR-132-3p was a potential prognostic marker for recurrence, showing low levels in breast cancer patients. In addition, we showed that miR-132-3p was inversely correlated with LAPTM4B expression in the above samples. Functionally, miR-132-3p suppressed the migration and invasion of breast carcinoma cells through LAPTM4B by mediating epithelial-mesenchymal transition signals, and partially reversed the carcinogenic effects of LAPTM4B by inhibiting the PI3K-AKT-mTOR signaling pathway. Taken together, these findings provide the first comprehensive analysis of miR-132-3p as a direct LAPTM4B-targeted miRNA, and shed light on miR-132-3p/LAPTM4B as a significant functional axis involved in the oncogenesis and metastasis of breast cancer.
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Neoplasias da Mama/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/genética , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Regiões 3' não Traduzidas , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Invasividade Neoplásica , Estadiamento de Neoplasias , Proto-Oncogene Mas , Curva ROC , Transdução de Sinais , Análise de SobrevidaRESUMO
BACKGROUND: Lysosomal-associated protein transmembrane-4 beta (LAPTM4B), a novel oncogene, promotes tumorigenesis and may be a potential prognostic biomarker in several cancers. This study was to determine the clinical significance and biological roles of LAPTM4B in lung adenocarcinoma (LAC). METHODS: LAPTM4B expression was analyzed by immunohistochemistry (IHC) of 63 LAC tumors. Serum levels of LAPTM4B were measured by enzyme-linked immuosorbent assays (ELISA). The study included untreated group (n = 216), chemotherapy group (n = 29), chemotherapy efficacy group (n = 179), EGFR-TKIs group (n = 57) and 68 healthy controls. Statistical analysis was performed to explore the correlation between LAPTM4B expression and clinicopathological parameters in LAC. Kaplan-Meier analysis was performed to assess the prognostic significance of LAPTM4B in LAC. In vitro assays were performed to assess the biological roles of LAPTM4B in LAC cells. Western blotting assays were examined to identify the underlying pathways involved in the tumor-promoting role of LAPTM4B. RESULTS: We found LAPTM4B was upregulated in LAC tissues and high LAPTM4B expression was significantly correlated with poor prognosis. Serum LAPTM4B levels were significantly decreased after chemotherapy. Patients in invalid response group showed higher LAPTM4B levels than the valid response group. Overexpression of LAPTM4B promoted, while silencing of LAPTM4B inhibited proliferation, invasion and migration of LAC cells via PI3K/AKT and EMT signals. LAPTM4B expression level was associated with epidermal growth factor receptor (EGFR) gene mutations. In addition, LAPTM4B plays important roles in EGFR-promoted cell proliferation, migration and invasion and gefitinib-induced apoptosis. CONCLUSIONS: Collectively, our data propose that LAPTM4B may be a cancer biomarker for LAC and a potential therapeutic target which facilitates the development of a novel therapeutic strategy against LAC.
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Adenocarcinoma de Pulmão/diagnóstico , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/diagnóstico , Proteínas de Membrana/genética , Proteínas Oncogênicas/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Receptores ErbB/genética , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Mutação , Proteínas Oncogênicas/sangue , Prognóstico , Adulto JovemRESUMO
4'-Demethylepipodophyllotoxin (DMEP) derivatives are broad-spectrum and potent antitumor leading compound. Because of their unacceptable toxicity, DMEP derivatives often failed in the development of new drug. Until now, there was no report on the millimolar-potency toxicity of DMEP derivatives by modifying the molecule structure of DMEP. For the first time, this work discovered leading compounds with millimolar-potency toxicity by modifying the molecule structure of DMEP. The IC50 value of 4ß-S-(5-fluorobenzoxazole-2-)-4-deoxy-4'-demethylepipodophyllotoxin (Compound 2) was around 323.4-2000.9⯵M on human healthy cells (i.e., HL-7702, H8, MRC-5 and HMEC), which was significantly reduced by 171-1999 times than podophyllotoxin (1.0-2.6⯵M) and 9-80 times than etoposide (21.5-75.4⯵M). Compared with the treatment of etoposide, DNA repair proteins HMGB1 and PARK7 were specifically activated and the expression of anti-apoptotic proteins were up-regulated in HL-7702â¯cells after the treatment of Compound 2. These indicated the toxicity of Compound 2 was synergistically reduced by DNA repair and anti-apoptosis pathway.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Desenho de Fármacos , Podofilotoxina/análogos & derivados , Apoptose/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Halogenação , Células Hep G2 , Humanos , Modelos Moleculares , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Oxazóis/química , Oxazóis/farmacologia , Podofilotoxina/química , Podofilotoxina/farmacologiaRESUMO
Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a novel oncogene, whose overexpression is involved in cancer occurrence and progression. However, the mechanism of LAPTM4B transcriptional regulation remains unclear. In this study, the results of transcription factor (TF) profiling plate arrays indicated that AP4 was a potential transcription factor regulating LAPTM4B expression. LAPTM4B was positively correlated with AP4 and they were both associated with poor overall and disease-free survival. Luciferase and electrophoretic mobility shift assay assays confirmed that AP4 directly bound to the polymorphism region of LAPTM4B promoter and modulated its transcription. Functionally, AP4 promoted cell proliferation, migration, invasion, and assisted drug resistance in part through upregulation of LAPTM4B. Taken together, these findings identify LAPTM4B as a direct AP4 target gene and the interaction of AP4 and LAPTM4B plays an important role in breast cancer progression.Implications: This study demonstrates that AP4 promotes cell growth, migration, invasion, and cisplatin resistance through upregulation of LAPTM4B expression, thus representing an attractive therapeutic target for breast cancer. Mol Cancer Res; 16(5); 857-68. ©2018 AACR.
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Antineoplásicos/farmacologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Cisplatino/farmacologia , Proteínas de Membrana/biossíntese , Proteínas Oncogênicas/biossíntese , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinogênese , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Proteínas de Ligação a DNA , Resistencia a Medicamentos Antineoplásicos , Feminino , Xenoenxertos , Humanos , Células MCF-7 , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Fenótipo , Proteínas de Ligação a RNA , TransfecçãoRESUMO
BACKGROUND: Prostate is susceptible to infection and pro-inflammatory agents in a man's whole life. Chronic inflammation might play important roles in the development and progression of prostate cancer. Mesenchymal stem cells (MSCs) are often recruited to the tumor microenvironment due to local inflammation. We have asked whether stimulation of MSCs by pro-inflammatory cytokines could promote prostate tumor growth. The current study investigated the possible involvement of MSCs stimulated by pro-inflammatory cytokines in promotion and angiogenesis of prostate cancer through relative pathway in vitro and in vivo. METHODS: A syngeneic mouse model of C57 was established. The murine prostate cancer cells (RM-1) mixing with MSCs treated with tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) or vehicle were subcutaneously injected into C57 mice. Tumor volume of C57 mouse model was estimated and serum level of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) was test by Enzyme-linked Immunosorbent Assay (ELISA). A hen egg test-chorioallantoic membrane (HET-CAM) assay was applied to test the effect of conditioned media of stimulated MSCs in chorioallantoic membrane angiogenesis. Short interfering RNA (siRNA) knocked down either hypoxia-inducible factor-1alpha (HIF-1α) or nuclear factor-erythroid-2-related factor 2 (NRF2) were employed. mRNA of PDGF and VEGF in MSCs, as well as NRF2 and HIF-1α was test by Real time polymerase chain reaction (PCR) analyses. Protein expression levels of PDGF and VEGF from conditioned medium, NRF2, HIF-1α, as well as PDGF and VEGF in MSCs were detected by Western blot analysis. RESULTS: MSCs treated with TNF-α and IFN-γ promote tumor growth in C57 syngeneic mouse model, correlating with increased serum level of PDGF, VEGF. HET-CAM assay shows the angiogenic effect of conditioned medium of MSCs pre-treated with the pro-inflammatory cytokines. mRNA and protein levels of two pro-angiogenic factors (PDGF and VEGF) and key hypoxia regulators (HIF-1α and NRF2) in MSCs were induced after MSCs' pretreatment. siRNA knockdown either HIF-1α or NRF2 results reduction of PDGF and VEGF expression. CONCLUSIONS: MSCs stimulated by pro-inflammatory cytokines increase the expression of PDGF and VEGF via the NRF2-HIF-1α pathway and accelerate prostate cancer growth in mice.
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Indutores da Angiogênese/metabolismo , Medula Óssea/patologia , Citocinas/farmacologia , Mediadores da Inflamação/farmacologia , Células-Tronco Mesenquimais/patologia , Neoplasias da Próstata/patologia , Animais , Apoptose/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Medula Óssea/metabolismo , Proliferação de Células/efeitos dos fármacos , Galinhas , Membrana Corioalantoide/efeitos dos fármacos , Membrana Corioalantoide/patologia , Meios de Cultivo Condicionados/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/metabolismo , Carga Tumoral , Células Tumorais Cultivadas , Microambiente TumoralRESUMO
Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a potential proto-oncogene, whose overexpression is involved in cancer occurrence and progression. Its transcript is up-regulated in various types of solid tumors including breast cancer. However, its transcriptional regulation mechanism is still unclear. To investigate the mechanism of transcriptional regulation of LAPTM4B in human breast cancer cells, a series of luciferase reporter constructs and construct with mutated binding site for cAMP responsive element binding protein-1 (CREB1) were generated by PCR amplification and transiently transfected into breast cancer cells to determine the transcriptional activities of different promoter regions. The +10+292 promoter region was possessed the highest transcriptional activity. The ability of CREB1 to bind the LAPMT4B promoter was confirmed by electrophoretic mobility shift assay, super-shift and RNA interference experiments. Our study identified the core promoter region responsible for constitutive expression of LAPTM4B and clarified that CREB1 played an important role in LAPTM4B transcriptional regulation in human breast cancer cells.
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Neoplasias da Mama/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Bases , Western Blotting , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Primers do DNA , Ensaio de Desvio de Mobilidade Eletroforética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Regiões Promotoras Genéticas , Proto-Oncogene Mas , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: To evaluate the efficacy and safety of Kuntai Capsule and Estrogen for Menopausal Syndrome. METHODS: Related randomized controlled trials about Kuntai capsule and estrogen in recent 10 years were collected by various kinds of database according to strict inclusion and exclusion criteria. Valid data were extracted to conduct meta-analysis by RevMan5.0. RESULTS: A total of 196 articles were retrieved, but only 6 were finally included. Meta-analysis showed that no significant differences were observed in Kupperman score between Kuntai group and estrogen [WMD = 0.22, 95%CI (-1.14, 1.58), P > 0.05]. While E(2) level was significantly higher in estrogen group than that in Kuntai [WMD = -59.59, 95%CI(-87.35, -31.83), P < 0.01]. The incidence of adverse effects was significantly lower in Kuntai group compared to the estrogen group [RR = 0.61, 95%CI(0.45,0.83), P < 0.01]. CONCLUSION: Kuntai can improve symptoms of menopausal syndrome effectively as the same as estrogen and tends to have lower incidence of adverse effects.
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Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Estrogênios/efeitos adversos , Estrogênios/uso terapêutico , Feminino , Humanos , Menopausa , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Tumor-specific antigens (TSA) are central elements in the immune control of cancers. To systematically explore the TSA genome, we developed a computational technology called heterogeneous expression profile analysis (HEPA), which can identify genes relatively uniquely expressed in cancer cells in contrast to normal somatic tissues. Rating human genes by their HEPA score enriched for clinically useful TSA genes, nominating candidate targets whose tumor-specific expression was verified by reverse transcription PCR (RT-PCR). Coupled with HEPA, we designed a novel assay termed protein A/G-based reverse serological evaluation (PARSE) for quick detection of serum autoantibodies against an array of putative TSA genes. Remarkably, highly tumor-specific autoantibody responses against seven candidate targets were detected in 4% to 11% of patients, resulting in distinctive autoantibody signatures in lung and stomach cancers. Interrogation of a larger cohort of 149 patients and 123 healthy individuals validated the predictive value of the autoantibody signature for lung cancer. Together, our results establish an integrated technology to uncover a cancer-specific antigen genome offering a reservoir of novel immunologic and clinical targets.
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Antígenos de Neoplasias/isolamento & purificação , Estudos de Associação Genética/métodos , Genômica/métodos , Imunoterapia , Terapia de Alvo Molecular , Neoplasias/terapia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Imunoterapia/métodos , Masculino , Análise em Microsséries , Terapia de Alvo Molecular/métodos , Neoplasias/genética , Neoplasias/imunologia , Especificidade de Órgãos/genética , Integração de SistemasRESUMO
Breast cancer (BC) screening is important for early detection, but conventional tumor markers lack the desired sensitivity. Aberrant microRNA (miRNA) expression plays an important role in tumor formation and development. Thus, serum miRNAs represent potential BC biomarkers. microRNA-181a (miR-181a) is deregulated in many types of human cancer and is a key oncogenic regulator, but the relationship between serum miR-181a and BC diagnosis has not been investigated. This study investigated serum miR-181a levels in BC patients and healthy controls and compared the diagnostic value of serum miR-181a as a BC tumor marker with the conventional tumor markers CA153 and CEA. Serum miR-181a and miR-16 (as a control) were quantified by real-time quantitative RT-PCR in 20 plasma samples. The promising results prompted analysis of 227 additional samples. The levels of CA153 and CEA were measured using electrochemiluminescence assays. Median miR-181a levels were significantly lower in patients with BC compared to healthy controls (P=0.001). ROC analysis demonstrated the sensitivity and specificity of miR-181a for BC diagnosis at 70.7 and 59.9%, respectively, whereas the sensitivities of CA153 and CEA were 10.53 and 9.21%. As a tumor marker, serum miR-181a expressed a higher level of sensitivity [55.28% (68/123)] in the early stage of BC diagnosis (ductal carcinoma in situ, TNM I and II) than the CA153 and CEA markers (8.13 and 7.32%, respectively). There were no significant associations between miR-181a levels and other clinicopathological parameters. These results suggest that serum miR-181a may represent a novel biomarker for primary BC as well as for early stage BC diagnosis. In combination with other markers, serum miR-181a may improve the sensitivity of BC screening.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer , MicroRNAs/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Antígeno Carcinoembrionário/sangue , Antígeno Carcinoembrionário/genética , Estudos de Casos e Controles , Feminino , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sensibilidade e Especificidade , Adulto JovemRESUMO
OBJECTIVE: Plasminogen activator inhibitor-1 (PAI-1), one crucial component of the plasminogen activator system, is a major player in the pathogenesis of many vascular diseases as well as in cancer. High levels of PAI-1 in breast cancer tissue are associated with poor prognosis. The aim of this study is to evaluate rigorously the potential of serum PAI-1 concentration functioning as a general screening test in diagnostic or prognostic assays. METHODS: A protein-microarray-based sandwich fluorescence immunoassay (FIA) was developed to detect PAI-1 in serum. Several conditions of this microarray-based FIA were optimized to establish an efficacious method. Serum specimens of 84 healthy women and 285 women with breast cancer were analyzed using the optimized FIA microarray. RESULTS: The median serum PAI-1 level of breast cancer patients was higher than that of healthy women (109.7 ng/ml vs. 63.4 ng/ml). Analysis of covariance revealed that PAI-1 levels of the two groups were significantly different (P<0.001) when controlling for an age effect on PAI-1 levels. However, PAI-1 values in TNM stage I-IV patients respectively were not significantly different from each other. CONCLUSION: This microarray-based sandwich FIA holds potential for quantitative analysis of tumor markers such as PAI-1.
RESUMO
AIM: To prepare and characterize monoclonal antibodies against ASNS for the research of ASNS function. METHODS: To induce the expression of the fusion protein MS2-ASNS, Hybridomas were generated by the fusion with Sp2/0 myelomas and spleen cells, which were obtained from mice immunized with MS2-ASNS recombinant proteins. The specificity and titer of mAb were identified by ELISA methods, and then used to detect the affinity of ASNS in cancer cells by Western blot. The expression of ASNS was detected in some cancer lines and tissues by IHC. RESULTS: Two hybridoma cell lines F4-15 and F4-16, which stably secret anti-ASNS mAbs were produced. Both cell lines produce IgG2a monoclonal antibody. ELISA demonstrated that anti-ASNS mAbs had high specificity and titer. The titers of anti-ASNS mAbs produced by hybridoma cell lines were up to 1:5×10(5);. Western blot demonstrated that ASNS was expressed in some cancer lines, including human lymphoma cell line K562 and cervical cancer cell line HeLa. The expression of ASNS was also detected by IHC in several tumor cell lines, such as stomach cancer cell line SGC-7901 and liver cancer cell lines SMMC-7721, BEL-7402, HepG2 as well as lung and esophageal carcinoma tissue. CONCLUSION: The monoclonal antibodies against ASNS have been successfully prepared, which provides a tool for the following research of nasal type NK/T cell lymphoma.
Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Aspartato-Amônia Ligase/biossíntese , Aspartato-Amônia Ligase/imunologia , Neoplasias/enzimologia , Proteínas ADAM/genética , Proteínas ADAM/imunologia , Animais , Anticorpos Monoclonais/biossíntese , Especificidade de Anticorpos , Antígenos CD/genética , Antígenos CD/imunologia , Aspartato-Amônia Ligase/genética , Western Blotting/métodos , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Células HeLa , Humanos , Hibridomas/imunologia , Imunoglobulina G/biossíntese , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Células K562 , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/química , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologiaRESUMO
OBJECTIVE: Programmed cell death 5 (PDCD5) is an apoptosis related gene and plays an important role in the pathogenesis and development of cancer. Whether PDCD5 is present in peripheral blood serum has not been reported. The aim of this study is to determine the contents of PDCD5 protein in peripheral blood serum of cancer patients, as well as normal subjects. METHODS: ELISA was used to detect the serum PDCD5 concentrations in 100 normal persons, 83 patients with breast cancer, 74 patients with gastrointestinal tract cancer and 41 patients with lung cancer. The results were statistically analyzed and discussed. RESULTS: PDCD5 could be detected in peripheral blood serum in both normal subjects and cancer patients. The serum PDCD5 contents in normal persons ranged from 3.8 to 6.1 ng/ml with a median of 4.70±0.68 ng/ml. For cancer patients the PDCD5 levels were 4.59±0.90, 4.79±1.14 and 10.43±22.34 ng/ml for breast cancer, gastrointestinal cancer and lung cancer patients respectively. There was no statistically significant difference between the serum PDCD5 concentrations of normal persons and cancer patients. CONCLUSION: PDCD5 is present in peripheral blood. The PDCD5 levels in cancer patients are not statistically different from that of normal persons, though decreased expression of PDCD5 in malignant tissues has been found.
RESUMO
OBJECTIVE: To investigate the effects of curcumin on the expressions of TNF-alpha, IL-6 and IL-8 in rats with chronic nonbacterial prostatitis. METHODS: Sixty healthy adult male SD rats with the body weight of 200 -220 g were equally and randomly divided into a normal control, a positive control, a model, an oral curcumin and an intraperitoneal curcumin group. The rat models of chronic nonbacterial prostatitis were made by hypodermic injection of estradiol benzoate at the dose of 0.25 mg/(kg x d) for 30 days after castration, and then treated with curcumin at 200 mg/(kg x d) by gavage or intraperitoneal injection. The positive controls received oral celebrex at 250 mg/(kg x d), while the normal control and model groups were given saline by gavage. After a week of treatment, the levels of TNF-alpha, IL-6 and IL-8 in the serum and prostate tissues of the rats were detected by ELISA assay. RESULTS: The levels of TNF-alpha and IL-8 in the serum and prostate tissues were significantly lower in the intraperitoneal curcumin than in the positive control group (P < 0.05), but the expression of IL-6 showed no significant difference between the two groups (P > 0.01). CONCLUSION: Curcumin is efficacious for chronic nonbacterial prostatitis in rats, and the action mechanism may be associated with its decreasing effect on the proinflammatory cytokines IL-8 and TNF-alpha in the blood and tissues.