RESUMO
Gallbladder polyp is a common disease of gallbladder, the incidence of gallbladder polyp in China is about 5%~10%, and the trend is increasing year by year. The patients with gallbladder polyps had no obvious clinical symptoms, which was more than that found by ultrasonography during physical examination. At present, the diameter of gallbladder polyps>10 mm is still used by clinicians as the main surgical indication for cholecystectomy. According to the data, about 80% to 90% of gallbladder polyps are cholesterol type polyps and benign gallbladder polyps. For these patients whose gallbladder is removed due to benign gallbladder polyps, we consider that we can continue to observe or retain the gallbladder, without having to bear the adverse consequences that may be caused by gallbladder removal. Based on the literature analysis at home and abroad, this paper discusses the surgical treatment of gallbladder polyps and the results of postoperative pathological diagnosis, and reminds the majority of clinicians to be careful when removing gallbladder polyps.
Assuntos
Colecistectomia , Doenças da Vesícula Biliar , Pólipos , Humanos , Pólipos/cirurgia , Doenças da Vesícula Biliar/cirurgia , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/cirurgiaRESUMO
Objective: To investigate the clinicopathological features and possible mechanisms of burned-out testicular germ cell tumors. Methods: The clinical and imaging data, histology and immunophenotypic characteristics of three cases of burned-out testicular germ cell tumors diagnosed at the Ruijin Hospital, Medical College of the Shanghai Jiaotong University, from 2016 to 2020 were retrospectively analyzed. The relevant literature was reviewed. Results: The mean age of the three patients was 32 years. Case 1 had an elevated preoperative alpha-fetoprotein level (810.18 µg/L) and underwent "radical pancreaticoduodenectomy and retroperitoneal lesion resection" for a retroperitoneal mass. Postoperative pathology showed embryonal carcinoma, which needed to exclude gonadal metastasis. Color Doppler ultrasound showed a solid mass of the right testis, with hypoechoic lesion and scattered calcification in some areas. Case 2 was a "right supraclavicular lymph node biopsy specimen." Chest X-ray showed multiple metastases in both lungs. The biopsy showed metastatic embryonic carcinoma and bilateral testicular color Doppler ultrasound revealed abnormal calcifications in the right testicle. Case 3 showed a cystic mass of the right testis with calcification and solid areas. All 3 patients underwent radical right orchiectomy. Grossly, borders of the testicular scar areas were well defined. Cross sectioning of the tumors showed a gray-brown cut surface and single focus or multiple foci of the tumor. The tumor maximum diameter was 0.6-1.5 cm. Microscopically, lymphocytes, plasma cells infiltration, tubular hyalinization, clustered vascular hyperplasia and hemosiderin laden macrophages were found in the scar. Atrophic and sclerotic seminiferous tubules, proliferation of clustered Leydig cells and small or coarse granular calcifications in seminiferous tubules were present around the scar. Seminoma and germ cell neoplasia in situ were seen in case 1, germ cell neoplasia in situ was seen in case 2 and germ cells with atypical hyperplasia were seen in case 3. Immunohistochemistry showed that embryonic carcinoma expressed SALL4, CKpan(AE1/AE3) and CD30, seminoma and germ cell tumor in situ expressed OCT3/4, SALL4 and CD117, and spermatogenic cells with atypical hyperplasia expressed CD99 and SALL4. The Ki-67 positive index was about 20%, while OCT3/4 and CD117 were both negative. Conclusions: Burned-out testicular germ cell tumors are rare. The possibility of gonad testicular metastasis should be considered first for extragonadal germ cell tumor. If fibrous scar is found in testis, it must be determined whether it is a burned-out testicular germ cell tumor. The burned-out mechanisms may be related to the microenvironment of tumor immune-mediated and local ischemic injury.
Assuntos
Calcinose , Carcinoma , Neoplasias Embrionárias de Células Germinativas , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Adulto , Seminoma/diagnóstico , Seminoma/patologia , Seminoma/secundário , Cicatriz/patologia , Hiperplasia , Estudos Retrospectivos , China , Neoplasias Testiculares/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Microambiente TumoralRESUMO
OBJECTIVE: Atherosclerosis, a kind of peripheral arterial disease with chronic inflammation, leads to the dysfunction of the vascular system and many other diseases. Hypoxia has been proven to participate in the progression of atherosclerosis, while curcumin can inhibit hypoxia-inducible factor 1α (HIF-1α). However, the underlying mechanisms are still elusive. PATIENTS AND METHODS: qRT-PCR was used to examine the expression of HIF-1α, IL-6 and TNFα of macrophages under hypoxic condition. Western blot was applied to examine the changes of HIF-1α, ERK and p-ERK after treatment with curcumin. Oli Red O staining and enzymatic assay were used to examine the lipid and total cholesterol in macrophages, respectively. ELISA was used to examine the release of IL-6 and TNFα by macrophages. FACS and MTT assays were applied to examine the apoptosis and proliferation of macrophages. RESULTS: Here, we found curcumin inhibited the expression of HIF-1α at the protein level in macrophages under hypoxic condition and curcumin and HIF-1α inhibitors repressed the total cholesterol and lipid level in macrophage under hypoxic condition. Moreover, curcumin also decreased the expression of HIF-1α downstream genes, VEGF, HMOX1, ROS and PDGF. Then, the data show the HIF-1α-induced apoptosis and inflammation of macrophages were inhibited by curcumin. Curcumin also rescued the proliferation defect of macrophages caused by hypoxia. Furthermore, we found it inhibited the expression of HIF-1α via ERK signaling pathway. CONCLUSIONS: We describe that curcumin inhibited the HIF-1α-induced apoptosis and inflammation of macrophages via ERK signaling pathways. These results suggest curcumin can be used for the treatment of atherosclerosis.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Inflamação/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Células Cultivadas , Colesterol/análise , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/metabolismo , Células THP-1RESUMO
OBJECTIVE: Vitamin D receptor (VDR) has potent anti-inflammatory activities. VDR gene polymorphism has been linked with systemic lupus erythematosus (SLE). However, its expression in the kidney has not been evaluated. This study aimed to investigate the relationship between VDR expression and renal pathology as well as clinical manifestations in lupus nephritis (LN). METHODS: A total of 20 renal biopsy specimens from 35 patients with LN were classified according to the International Society of Nephrology/Renal Pathology Society 2003 LN-type standards pathological type, and the activity index and chronicity index were determined. Five normal renal tissue samples were obtained from surrounding areas distal to nephronophthisis or renal tumors (>2 cm). The expression of VDR was assessed by immunohistochemistry. The relationships between VDR expression and histological injury index, proteinuria and Systemic Lupus International Collaborating Clinics (SLICC) renal activity scores were analyzed. RESULTS: As compared to the control group, the expression of VDR in the LN group was lower ( p < 0.001) and negatively correlated with activity index (r = -0.548, p = 0.012) but not with chronicity index (r = -0.277, p = 0.236). The expression of VDR in renal tissue was also associated with SLICC renal activity scores (r = -0.470, p = 0.037). CONCLUSION: The down-regulation of VDR expression in renal tissues of LN patients was negatively correlated with renal activity and injury severity.
Assuntos
Rim/lesões , Nefrite Lúpica/genética , Receptores de Calcitriol , Adulto , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Humanos , Rim/patologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Proteinúria/genética , Índice de Gravidade de DoençaRESUMO
Objective:To investigate the expression of Nrf2 and Keap1 in nasopharyngeal carcinoma (NPC) and to analyze the relationship between the expression of Nrf2 and Keap1 and the clinicopathological features and prognosis of patients with nasopharyngeal carcinoma. Method:A total of 108 patients with biopsy-proven nonkeratinizing squamous cell carcinoma-undifferentiated type with available biopsy specimens for tissue microarray (TMA) construction were selected. The relationship between Nrf2 and Keap1 protein expression and the prognosis of radiotherapy in patients with nasopharyngeal carcinoma was analyzed. Result: The overall 5-year disease free survival (DFS) and overall survival(OS) rates were 57.4% and 70.2%, respectively. The 5-year DFS rate was 59.4% in the low nuclear Nrf2 expression group, and 53.8% in the high nuclear Nrf2 expression group. The 5-year DFS rate was 42.2% in the low cytoplasmic Keap1 expression group, and 68.2% in the high cytoplasmic Keap1 expression group. The 5-year OS rate was 70.8% in the low nuclear Nrf2 expression group, and 69.2% in the high nuclear Nrf2 expression group. The 5-year OS rate was 55.6% in the low cytoplasmic Keap1 expression group, and 80.9% in the high cytoplasmic Keap1 expression group.Conclusion:We found that nuclear Nrf2 or cytoplasmic Keap1 expression had no significant association with clinicopathological features. The high expression of cytoplasmic Keap1 had higher DFS and OS. Keap1 is an independent prognostic factor for DFS and OS in NPC patient.
Assuntos
Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Carcinoma , Humanos , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , PrognósticoRESUMO
Chromosomal abnormalities are an attractive avenue for the screening of various disorders especially related to carcinogens like acute myeloid leukemia (AML). The cytogenetic findings like Karyotypic patterns are common in pediatric patients. On the other hand, monosomal karyotype (MK) and complex karyotype (CK) are more common in older patients. Further, recent studies have revealed direct proportion between the number of chromosome abnormalities and mortality rates in both pediatric as well as old patients affected by AML. Moreover, to be specific 5q, 7q and/or 17p loss lead to higher mortality rates in comparison to loss of to MK. The present review article would put light on current views of important chromosomal changes during AML, especially in pediatric patients.
Assuntos
Envelhecimento/genética , Aberrações Cromossômicas/estatística & dados numéricos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Humanos , Cariótipo , CariotipagemRESUMO
Objective: To investigate the feasibility and diagnostic value of preoperative transthoracic echocardiography guided three dimensional printing model (TTE Guided 3DPM) on the assessment of structural heart disease (SHD). Methods: From February 2016 to October 2016, 44 patients underwent cardiac surgery in Tianjin Chest Hospital, forty-four patients were assessed preoperatively using TTE Guided 3DPM, including 25 males and 19 females, aged 3-75 years, with an average of (44±22) years. compared to conventional three dimensional transthoracic echocardiography (3D-TTE), and took direct intraoperative findings as "Golden Standard" simultaneously. There are twelve patients with SHD, including four cases with mitral prolapse, two cases with partial endocardial cushion defect, two cases with secondary atrial septal defect, two cases with rheumatic mitral stenosis, one case with tetralogy of Fallot, one case with ventricular septal defect (VSD), thirty-two patients without SHD were designed as negative control. Results: The sensitivity and specificity of TTE Guided 3DPM were greater than or equal to 3D-TTE, P value of McNemar test of 3D-TTE was greater than 0.05, the difference was not statistically significant, kappa=0.745, P<0.01, indicated that the results of 3DTTE and the gold standard were generally consistent.P value of McNemar test of TTE Guided 3DPM was greater than 0.05, the difference was not statistically significant, kappa=0.955, P<0.01, indicated that the results of TTE Guided 3DPM and gold standards were consistent. Compared with 3D-TTE and TTE Guided 3DPM, P value was greater than 0.05, the difference was not statistically significant, kappa=0.879, P<0.01, indicated that the results of 3D-TTE and TTE Guided 3DPM were consistent. TTE Guided 3DPM displayed the three-dimensional structure of SHD cardiac lesions clearly, which were consistent with intraoperative findings. Conclusion: TTE Guided 3DPM provides essential information for the preoperative evaluation and decision of SHD.
Assuntos
Ecocardiografia Tridimensional , Ecocardiografia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Comunicação Interatrial , Comunicação Interventricular , Humanos , Masculino , Pessoa de Meia-Idade , Impressão Tridimensional , Adulto JovemRESUMO
BACKGROUND: Geniposide (GEN) is the major ingredient of Gardenia jasminoides Ellis, which has anti-inflammatory and anti-apoptotic activities and is widely used to treat ischemia disease. Inflammation and apoptosis play an important role in hepatic ischemia/reperfusion (I/R) injury. The current study was conducted to explore the effects of geniposide on hepatic I/R injury and its potential molecular mechanism in mice. METHODS: Fifty Sprague-Dawley rats were randomly divided into 5 groups: the sham group (sham), the hepatic I/R injury group (IRI) and the GEN groups (low, middle, and high). In the GEN and IRI groups, hepatic IRI by was induced by means of clamping the left and median liver lobes for 30 minutes with noninvasive endoclips. The GEN groups were pretreated with GEN (5, 10, 20 mg/kg) at 30 minutes before ischemia by use of intraperitoneal injection. Rats in the IRI group and sham group were administrated with same dosage of saline at the same time. After reperfusion for 6 hours, the hepatic pathology and the expression of alanine aminotransferase (ALT), AST aspartate aminotransferase, LDH lactic acid dehydrogenase, PI3K, AKT, p-AKT, m-TOR, Bax, BCL-2, interleukin (IL)-6, MCP-1, and tumor necrosis factor (TNF)-α were examined. RESULTS: Compared with the sham group, the IRI group had higher expression of ALT, AST, LDH, Bax, IL-6, MCP-1, and TNF-α and lower expression of BCL-2, PI3K, p-AKT, and mammalian target of rapamycin (mTOR), with more inflammatory cell infiltration, cellular swelling, and vacuolar degeneration. Compared with the IRI group, the GEN group had lower expression of ALT, AST, LDH, Bax, IL-6, MCP-1, and TNF-α and higher expression of BCL-2, PI3K, p-AKT, and mTOR, with less inflammatory cell infiltration, cellular swelling, and vacuolar degeneration. There were no differences in the expression of AKT among several groups. CONCLUSIONS: GEN can protect rats against hepatic I/R injury and partly relies on suppressing inflammation and apoptosis by inducing the activation of the PI3K/Akt/mTOR signaling pathway.
Assuntos
Iridoides/farmacologia , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Alanina Transaminase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Interleucina-6/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: Liver cancer is a common malignant tumor in the digestive system. Curcumin is a kind of phenolic pigment, which is extracted from herbage and has a plenty of physiological roles in anti-inflammation, anti-oxidation and anti-tumor. In our study, human hepatoma SMMC-7721 cell lines were selected and treated with curcumin to detect its effects on the apoptosis and AMPK signaling pathway. MATERIALS AND METHODS: Human liver cancer cell strain SMMC-7721 was cultured and treated with different curcumin concentrations for different times followed by measuring the changes of cell proliferation activity and cycle by MTT and flow cytometry, respectively. Protein expression of Bcl-2, Bax and Caspase-3 were tested by Western blot, and the activation level of AMPK was also detected. RESULTS: Different concentrations of curcumin could inhibit the proliferation of tumor cells in a dose-dependent manner. After 48 h inhibition by curcumin with a concentration of 40 mmol/L, the inhibitory effect was more obvious with statistically significant (p<0.05). The number of human liver cancer SMMC-7721 cells increased in G1 stage and decreased in S stage after treated with different concentrations of curcumin. During the G1 stage to the S stage, inhibition occurred and the effect of curcumin intervention group with 40 mmol/L was more evident than that of 10 mmol/L group, 20 mmol/L group and the control group with statistically significant (p<0.05). SMMC-7721 cell stains had been intervening by curcumin with concentrations of 10 mmol/L, 20 mmol/L and 40 mmol/L for 12 h, 24 h and 48 h, as the drug concentration increased, the reaction time prolonged, the protein expressions of Bcl-2 and Survivin were significantly decreased and Bax protein expression was significantly increased (p<0.05). CONCLUSIONS: Curcumin decreased the proliferation activity of tumor cells, increased the cell quantities in G1 stage and decreased the cell numbers in S stage in human liver cancer SMMC-7721 cells. The Bcl-2 and Survivin proteins were downregulated and Bax protein was upregulated; furthermore, the AMPK signaling pathway was activated.
Assuntos
Proteínas Quinases Ativadas por AMP , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular , Curcumina/farmacologia , Neoplasias Hepáticas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: The mammalian target of rapamycin (mTOR) inhibitor is an immunosuppressive drug used in kidney transplantation. Whether the mTOR inhibitor is associated with reduced risk of cancer development and mortality after kidney transplantation is controversial. METHODS: We conducted a nationwide population-based study. Patients who did not have malignancy history and received kidney transplantation between 2010 and 2013 were enrolled. Recipients who had mTOR inhibitors (n = 430) for more than 30 days comprised the study group; 1720 recipients who did not have mTOR inhibitors comprised the control group. The primary outcome is the development of cancer after kidney transplantation. These patients were followed until the first-time admission with diagnosis of cancer, death, or the end of 2014. A Cox proportional-hazard model was used to determine the risk of cancer development and all-cause mortality. RESULTS: During the 35-month median duration of observation, there were 16 and 61 patients with cancer development in the study group and the control group, respectively. The cancer incidence was 12.8 and 12.4 per 1000 person-years. There were 10 and 135 mortality cases, with the incidence rate of 7.8 and 26.9 per 1000 person-years. After multivariable adjustment, the mTOR inhibitors users were not associated with reduced risk of new cancer development as compared with control (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.46-1.60; P = .63), nor risk of all-cause mortality (HR, 0.70; 95% CI, 0.33-1.46; P = .34). CONCLUSIONS: The use of mTOR inhibitors was not associated with a reduction in the risk of cancer development and all-cause mortality in kidney transplantation recipients.
Assuntos
Inibidores Enzimáticos/efeitos adversos , Transplante de Rim/efeitos adversos , Neoplasias/epidemiologia , Vigilância da População , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Modelos de Riscos Proporcionais , Taiwan/epidemiologia , Adulto JovemRESUMO
Non-small cell lung cancer (NSCLC) is the most common cancer globally. The XRCC1 protein interacts with ligase and poly(ADP-ribose) polymerase to repair cisplatin-induced DNA damage. The authors of previous studies have reported XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms and advanced NSCLC prognosis, but the results are inconclusive. We investigated the association between clinical outcome and XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms in advanced NSCLC patients treated with cisplatin. We recruited 252 patients with advanced NSCLC (TNM stages: IIIB and IV) and used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to genotype the polymorphisms. Patients with the TT genotype of XRCC1 Arg194Trp showed a significantly better response to chemotherapy than those with the CC genotype. The GA+AA genotype of Arg194Trp was correlated with better response to chemotherapy than the wild-type form. The TT genotype of Arg194Trp was associated with longer survival time than the CC genotype. The TT genotype of Arg194Trp was correlated with lower risk of death from all causes than the CC genotype. The Arg194Trp polymorphisms interacted with squamous cell carcinoma and affected overall survival of advanced NSCLC. However, there was no association between Arg399Gln and Arg280His polymorphisms and response to cisplatin-based chemotherapy and overall survival in advanced NSCLC. The results suggest that the TT genotype of Arg194Trp is significantly associated with better response to chemotherapy and longer overall survival of advanced NSCLC patients than the wild-type form. Our investigation offers insight into the influence of XRCC1 gene polymorphisms on the treatment outcome of advanced NSCLC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Ligação a DNA/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Polimorfismo Genético , Alelos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Genótipo , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Resultado do Tratamento , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
OBJECTIVE: Ischemic heart disease is the most common cause of cardiovascular morbidity and mortality in the industrialized world, and the incidence has been increasing in developing countries. Stem cell transplantation has emerged as a potent new therapeutic strategy for acute/chronic ischemic heart disease and has been explored extensively. The present study aimed to investigate whether hypoxic preconditioning of endothelial progenitor cells (EPCs) before transplantation could ameliorate their survival and engraftment in ischemic tissue and the potential mechanisms. MATERIALS AND METHODS: EPCs extracted were subjected to increasing hypoxia for 24-72 h, survival and function of the preconditioned EPCs were assayed in both in vitro and in vivo. RESULTS: Hypoxia for 24 h caused significant enhancements in formation of tube like structure and motility of BM-EPCs (p < 0.05), as well as mRNA expressions of CXCR4, PI3K, AKT, and NF-κB, while these effects were reversed by prolonged hypoxia (48 and 72 h, p < 0.05). Hypoxia of BM-EPCs for 24 h did not result in increased apoptosis resistance, and cell apoptosis was even enhanced by prolonged hypoxia. In vivo transplantation experiments demonstrated the beneficial effect of hypoxic EPCs on left ventricular (LV) functions after acute myocardial ischemia (AMI). CONCLUSIONS: Shorter-term hypoxia showed better survival, differentiation and function of BM-EPCs in vivo, further study was still needed to optimize the hypoxic pattern of BM-EPCs so as to better protect heart from myocardial ischemic injury. The present study showed evidence suggested that hypoxic preconditioning did exert further beneficial effects of BM-EPCs on preservation of LV function after AMI. Short-term exposure to hypoxia for about 24 h provided better condition for survival and function of BM-EPCs.
Assuntos
Transplante de Medula Óssea/métodos , Células Progenitoras Endoteliais/transplante , Isquemia Miocárdica/terapia , Transplante de Células-Tronco/métodos , Função Ventricular Esquerda/fisiologia , Animais , Hipóxia Celular/fisiologia , Células Cultivadas , Células Progenitoras Endoteliais/metabolismo , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patologia , Neovascularização Fisiológica/fisiologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
BACKGROUND: Squamous cell lung cancer (SqCC) is the second most common type of lung cancer in the United States. Previous studies have used gene-expression data to classify SqCC samples into four subtypes, including the primitive, classical, secretory and basal subtypes. These subtypes have different survival outcomes, although it is unknown whether these molecular subtypes predict response to therapy. METHODS: Here, we analysed RNAseq data of 178 SqCC tumour samples and characterised the features of the different SqCC subtypes to define signature genes and pathway alterations specific to each subtype. Further, we compared the gene-expression features of each molecular subtype to specific time points in models of airway development. We also classified SqCC-derived cell lines and their reported therapeutic vulnerabilities. RESULTS: We found that the primitive subtype may come from a later stage of differentiation, whereas the basal subtype may be from an early time. Most SqCC cell lines responded to one of five anticancer drugs (Panobinostat, 17-AAG, Irinotecan, Topotecan and Paclitaxel), whereas the basal-type cell line EBC-1 was sensitive to three other drugs (PF2341066, AZD6244 and PD-0325901). CONCLUSION: Compared with the other three subtypes of cell lines, the secretory-type cell lines were significantly less sensitive to the five most effective drugs, possibly because of their low proliferation activity. We provide a bioinformatics framework to explore drug repurposing for cancer subtypes based on the available genomic profiles of tumour samples, normal cell types, cancer cell lines and data of drug sensitivity in cell lines.
Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Carcinoma de Células Escamosas/patologia , Processos de Crescimento Celular/efeitos dos fármacos , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Biologia Computacional , Resistencia a Medicamentos Antineoplásicos , Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , RNA Neoplásico/química , RNA Neoplásico/genéticaRESUMO
BACKGROUND: Data on the efficacy and safety of sorafenib in combination with transarterial chemoembolization (TACE) in patients with advanced hepatocellular carcinoma (HCC) are lacking. PATIENTS AND METHODS: In this multicenter retrospective study, 222 consecutive HCC patients receiving combination therapy were enrolled between June 2008 and July 2011. RESULTS: Chronic hepatitis B was the predominant cause of HCC (86%). Eighty percent patients were at Barcelona Clinic Liver Cancer (BCLC) stage C, and 86% patients were in Child-Pugh (CP) A class. The overall median survival was 12 months (95% CI 10.1-13.9). The overall incidence of adverse events (AEs) was 87%. In 177 BCLC-C patients, performance status, the number of HCC nodules, Child-Pugh score and macrovascular invasion were significantly associated with overall survival (OS) and were included in the final risk scores (R), where R = 5 × (vascular invasion: 0 if no, 1 yes) + 6 × (CP: 0 if A, 1 if B) + 7 × (no. of lesions: 0 if 1-2, 1 ≥3) + 8 × ( Eastern Cooperative Oncology Group, ECOG: 0 if 0, 1 ≥1). CONCLUSIONS: Sorafenib in combination with TACE should be considered a safe and effective therapy for advanced HCC. Further validation of the new subgroup of BCLC-C stage is warranted in an independent patient cohort.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Terapia Combinada , Diarreia/induzido quimicamente , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Sorafenibe , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate the effects of ß-(3,4-dihydroxyphenyl)lactic acid on oxidative stress stimulated by high glucose levels in human peritoneal mesothelial cells (HPMCs) in vitro. METHODS: HPMCs were incubated with 100 mol/l glucose followed by 0.625-20 mg/ml ß-(3,4-dihydroxyphenyl)lactic acid. Reactive oxygen species (ROS) were quantified by flow cytometry. Relative levels of fibronectin-1 (FN1), collagen-I α(1) (COL1A1), endothelin-1 (EDN1) and haem oxygenase-1 (HMOX1) mRNA and protein were quantified by real-time reverse transcription-polymerase chain reaction and Western blotting, respectively. Absolute levels of FN1 and COLIA1 were quantified by enzyme-linked immunosorbent assay. RESULTS: ß-(3,4-Dihydroxyphenyl)lactic acid significantly decreased ROS levels, and EDN1 mRNA and protein levels, in dose- and time-dependent manners. HMOX1 mRNA and protein levels were significantly increased by ß-(3,4-dihydroxyphenyl)lactic acid in dose-dependent manners. COL1A1 and FN1 mRNA and protein levels were significantly decreased by ß-(3,4-dihydroxyphenyl)lactic acid in dose- and time-dependent manners. CONCLUSIONS: ß-(3,4-Dihydroxyphenyl)lactic acid inhibited oxidative stress and reversed increases in FN1 and COLIA1 induced by high glucose levels in HPMCs. This may contribute to a protective role in peritoneal fibrosis.
Assuntos
Glucose/metabolismo , Lactatos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Peritônio/efeitos dos fármacos , Sequência de Bases , Western Blotting , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Primers do DNA , Relação Dose-Resposta a Droga , Endotelina-1/genética , Endotelina-1/metabolismo , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/metabolismo , Fibronectinas/genética , Fibronectinas/metabolismo , Citometria de Fluxo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Peritônio/citologia , Peritônio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Growth hormone (GH) supplementation may help to preserve erectile function. We assessed whether serum insulin-like growth factor 1 (IGF-1) levels, a surrogate for GH levels, correlate with sexual function scores in 65 men who completed the Sexual Health Inventory for Men (SHIM) and Expanded Prostate Cancer Index Composite (EPIC) questionnaires, and had serum IGF-1 and testosterone levels determined. Median±s.d. IGF-1 level, SHIM and EPIC scores were 235.0±86.4, 19.5±8.7 and 56.4±28.3 mg ml(-1), respectively. IGF-1 levels and total SHIM score correlate significantly (r=0.31, P=0.02), as do IGF-1 levels and all individual SHIM question scores, and IGF-1 levels and the sexual domain of the EPIC questionnaire (r=0.30, P=0.02). No correlation was observed between IGF-1 levels and Gleason score, IGF-1 and testosterone level or SHIM score and testosterone level. These data support a potential role for the GH axis in erectile function.
Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Disfunções Sexuais Fisiológicas/sangue , Idoso , Comorbidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Disfunções Sexuais Fisiológicas/epidemiologia , Testosterona/sangue , Estados Unidos/epidemiologiaRESUMO
UNLABELLED: There is increasing interest in the development of new in vitro tissue models. In this study, a tissue model of periodontal ligament (PDL) was established by 3-D-culturing human PDL cells in a thin sheet of porous poly (lactic-co-glycolic acid) scaffold. Growth of the model was evidenced by MTT assay and various microscopies. After being subjected to static compression of 5 ~ 35 g/cm(2) for 6 hrs, the RANKL mRNA expression was significantly up-regulated by force ≥ 25 g/cm(2) in the model. After being subjected to static compression of 25 g/cm(2) for 6 ~ 72 hrs, the mRNA expression of PTHrP, IL-11, IL-8, and FGF-2, potential osteoclastogenesis inducers, was significantly up-regulated in the model, which was further verified by the compression of human PDL in vivo. However, when human gingival fibroblasts were substituted for PDL cells in the model, almost no osteoclastogenesis inducers were up-regulated by compression. This tissue model can serve as an effective tool for the study of PDL mechanoresponse. ABBREVIATIONS: periodontal ligament, PDL; periodontal ligament cells, PDLCs; poly (lactic-co-glycolic acid), PLGA; orthodontic tooth movement, OTM; extracellular matrix, ECM.