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CONTEXT: Taiwanofungus camphoratus is a parasitic mushroom found in the heartwood of Cinnamomum kanehirai and is used as a nutritional supplement. It has an anticancer action, both alone and synergistically with amphotericin B (AmB). OBJECTIVE: The study intended to assess the efficacy of a T camphoratus ethanol extract (TCEE) combined with AmB for patients with metastatic cancer whose cancer did not respond to multiline chemotherapy or who were unwilling to receive chemotherapy. DESIGN: The research team performed a retrospective analysis as a pilot study. SETTING: The study took place at a single hospital (Taipei Medical University Hospital, Taipei, Taiwan). PARTICIPANTS: Participants were 9 patients at the hospital who were terminally ill with metastatic cancer. INTERVENTIONS: The participants had received daily doses of 2-3 g of the TCEE in combination with a weekly dose of 20-25 mg of AmB in 500 cc of 5% glucose water, given intravenously in 4-6 h. OUTCOME MEASURES: Outcome measures included (1) a primary evaluation index measuring the efficacy of the treatment; (2) a measure of tumor burden that was estimated using the response evaluation criteria in solid tumors (RECIST 1.1), (3) a secondary evaluation index measuring survival duration, and (4) safety. RESULTS: The mean treatment time was 54.4 ± 18.3 wk. At the end of the study, 2 patients showed a continued complete response, 1 patient had a continued partial response, and 1 patient showed a stable disease. The other 5 participants had times to progression ranging from 24 to 48 wk, with a mean of 35.6 wk. The mean survival time was 57.8 ± 18.5 wk, and 5 patients were still alive at the end of the study. CONCLUSIONS: For patients whose metastatic cancer did not respond to multiline chemotherapy or who were unwilling to receive chemotherapy, the use of TCEE as an adjuvant therapy to AmB resulted in tumor suppression and a delay in time to disease progression. The preliminary results reported here can be used to guide a future, more extensive clinical study of the combination.
Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Antrodia/química , Produtos Biológicos/farmacologia , Metástase Neoplásica/patologia , Neoplasias/tratamento farmacológico , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Produtos Biológicos/administração & dosagem , Etanol , Humanos , Neoplasias/patologia , Projetos Piloto , Estudos Retrospectivos , Taiwan , Resultado do TratamentoRESUMO
The main problem in the treatment of non-small cell lung cancer (NSCLC) is metastasis. Epithelial-mesenchymal transition (EMT) is known as the critical signaling in tumor progression, metastasis, and also the drug resistance. In this study, we reported a novel gene Polymerase delta-interacting protein 2 (POLDIP2) was downregulated in NSCLC tissues and first demonstrated that overexpression of POLDIP2 increased the anchorage-independent growth (AIG) and invasiveness of H1299 cells. In addition, we examined that knockdown of POLDIP2 in H1299 and A549 cells reduced tumorigenicity and metastatic capacity in vitro and also in vivo. Moreover, downregulation of the cell proliferation marker cyclin D1 and EMT markers CDH2, Slug, and Twist was showed in H1299 cells by POLDIP2 knockdown, suggesting that the inhibition of malignancy was affected by modulating key genes for tumor growth and invasiveness. Taken together, our study is the first study that demonstrated that POLDIP2 gene was function as an oncogene in NSCLC and implied the oncogenic ability might be through promoting cell proliferation or EMT.
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Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Invasividade Neoplásica/genética , Proteínas Nucleares/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Invasividade Neoplásica/patologia , Proteínas Nucleares/metabolismoRESUMO
PURPOSE: To assess the reduction of 6 and 12 months postoperatively of Framingham risk score in morbidly obese patients with laparoscopic sleeve gastrectomy (LSG). MATERIAL AND METHODS: In total, 870 morbid obesity patients received LSG in Taipei Medical University Hospital from June 2007 to June 2014 were retrospectively studied preoperatively, 6 and 12 months after surgery. The coronary heart disease risk was calculated using Framingham risk score. RESULTS: The body mass index in men and women decreased from 43.3 ± 6.9, 39.2 ± 6.0 kg/m2 preoperatively to 32.9 ± 6.7, 31.0 ± 5.2 kg/m2 and to 30.4 ± 5.6 , 28.2 ± 4.7 kg/m2, respectively, at 6 and 12 months after surgery (P < 0.0001). At 6 and 12 months after LSG, there was a marked improvement on lipid profile as well as a significant decline in the prevalence of diabetes mellitus, systemic hypertension, and smoking. The Framingham risk score in men and women reduced from 3.2 ± 5.7, 6.1 ± 5.7 preoperatively to 1.4 ± 5.9, 3.3 ± 5.9 and 0.1 ± 6.2, 2.8 ± 6.1, respectively, at 6 and 12 months after surgery (P < 0.0001). CONCLUSIONS: Laparoscopic sleeve gastrectomy is efficient not only in the reduction of obesity and its related comorbidities but also in decreasing the long-term coronary event risk. Early intervention for the high-risk group is strongly recommended.
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Doença das Coronárias/epidemiologia , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologia , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Adulto , Índice de Massa Corporal , Comorbidade , Doença das Coronárias/etiologia , Feminino , Seguimentos , Gastrectomia/métodos , Humanos , Laparoscopia , Lipídeos/sangue , Masculino , Obesidade Mórbida/complicações , Prevalência , Estudos Retrospectivos , Medição de Risco , Fumar/epidemiologia , Taiwan/epidemiologia , Resultado do Tratamento , Redução de PesoRESUMO
BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) signaling reportedly promotes tumor malignancy and recurrence in nonsmall cell lung cancer (NSCLC). It was demonstrated previously that the STAT3 pathway maintains the tumorigenicity and therapeutic resistance of malignant tumors as well as cancer stem cells (CSCs). The objective of the current study was to investigate the effect of the strong STAT3 inhibitor, cucurbitacin I, in prominin-1 (CD133)-positive lung cancer cells. METHODS: CD133-positive and CD133-negative NSCLC-derived cells were isolated from 7 patients with NSCLC. CD133-positive NSCLC cells that were treated with or without cucurbitacin I were evaluated for their expression of phosphorylated STAT3 (p-STAT3), tumorigenicity, stemness properties, and resistance to chemotherapeutic drugs and ionizing radiation. RESULTS: Compared with parental or CD133-negative NSCLC cells, CD133-positive NSCLC cells had greater tumorigenicity, greater radioresistance, and higher expression of octamer-binding transcription factor 4 (Oct-4), Nanog homeobox, and sex-determining region Y, box 2 (Sox2) at high p-STAT3 levels. Cucurbitacin I treatment at 100 nM effectively abrogated STAT3 activation, tumorigenic capacity, sphere formation ability, radioresistance, and chemoresistance in CD133-positive NSCLC cells. Microarray data suggested that cucurbitacin I inhibited the stemness gene signature of CD133-positive NSCLC cells and facilitated the differentiation of CD133-positive NSCLC cells into CD133-negative NSCLC cells. It is noteworthy that 150 nM cucurbitacin I effectively blocked STAT3 signaling and downstream survival targets, such as B-cell chronic lymphocytic leukemia/lymphoma 2 (Bcl-2) and Bcl-2-like 1 (Bcl-xL) expression and induced apoptosis in CD133-positive NSCLC cells. Finally, xenotransplantation experiments revealed that cucurbitacin I plus radiotherapy or chemotherapeutic drugs significantly suppressed tumorigenesis and improved survival in NSCLC-CD133-positive-transplanted, immunocompromised mice. CONCLUSIONS: Targeting STAT3 signaling in CD133-positive NSCLC cells with cucurbitacin I suppressed CSC-like properties and enhanced chemoradiotherapy response. The potential of cucurbitacin I should be verified further in future anti-CSC therapy.
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Antígenos CD/análise , Carcinoma Pulmonar de Células não Pequenas , Glicoproteínas/análise , Neoplasias Pulmonares , Células-Tronco Neoplásicas/efeitos dos fármacos , Peptídeos/análise , Fator de Transcrição STAT3/antagonistas & inibidores , Triterpenos/farmacologia , Antígeno AC133 , Idoso , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Proliferação de Células , Separação Celular , Resistencia a Medicamentos Antineoplásicos , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Camundongos , Pessoa de Meia-Idade , Proteína Homeobox Nanog , Metástase Neoplásica , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos da radiação , Fator 3 de Transcrição de Octâmero/biossíntese , Fator 3 de Transcrição de Octâmero/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Tolerância a Radiação , Fatores de Transcrição SOXB1/biossíntese , Fatores de Transcrição SOXB1/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Proteína bcl-X/genéticaRESUMO
BACKGROUND: Histone deacetylases and histone acetyl transferases covalently modify histone proteins, consequentially altering chromatin architecture and gene expression. METHODS: The effects of suberoylanilide hydroxamic acid, a HDAC inhibitor, on 320 HSR colon cells were assessed in 320 HSR colon cancer cells. RESULTS: Concentration and time-dependent inhibition of 320 HSR cell proliferation was observed. Treatment of 320 HSR cells with 5 µM SAHA for 72 h significantly inhibited their growth by 50% as compared to that of the control. Fluorescence-activated cell sorting analysis demonstrated significant inhibition of cell cycle progression (sub-G1 arrest) and induction of apoptosis upon various SAHA concentrations after 48 h. In addition, the anti-apoptosis proteins, survivin and Bcl-xL, were significantly inhibited by SAHA after 72 h of treatment. Immunocytochemistry analysis revealed that SAHA-resistant cells were positive for cyclin A (85%), ki-67 (100%), p53 (100%), survivin (100%), and p21 (90%) expression. Furthermore, a significant increase cyclin A-, Ki-67-, p53-, survivin-, and p21-positive cells were noted in SAHA-resistant tumor cells. CONCLUSION: Our results demonstrated for the first time in 320 HSR colon adenocarcinoma cells that SAHA might be considered as an adjuvant therapy for colon adenocarcinoma.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Fase G1/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/fisiologia , Proliferação de Células/efeitos dos fármacos , Separação Celular , Quimioterapia Adjuvante , Citometria de Fluxo , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , VorinostatRESUMO
OBJECTIVE: The purpose of this study was to analyse the lesion characteristics and the patterns of dilated ducts on ultrasonography (US) to determine the appropriateness of the Breast Imaging Reporting and Data System (BI-RADS) categories. MATERIALS AND METHODS: From July 2001 to June 2006, 172 consecutive pathologically proved lesions with dilated ducts on US were reviewed retrospectively. All the lesions were classified into four types according to their US features, and in combination with the size, location, margins and number of lesions, the corresponding positive predictive values (PPVs) were obtained. RESULTS: Of the 172 lesions, 55 (32%) were classified as type I, 68 (40%) as type II, 14 (8%) as type III and 35 (20%) as type IV. The PPVs for malignancy were 9% for type I, 13% for type II, 43% for type III and 17% for type IV. There was a significantly higher frequency of malignancy among type III lesions than among type I (43% vs 9%, respectively, P = 0.002; chi (2) test) or type II lesions (43% vs 13%, respectively, P = 0.009; chi (2) test). Lesions with a nonsubareolar location and noncircumscribed margins had a high probability of malignancy (P < 0.001 and P = 0.03, respectively). CONCLUSION: The four types of US classifications used in our study establish reliable references for the dilated duct patterns when stratified according to BI-RADS categories, and they clarify the indications for biopsy of these lesions.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Ultrassonografia Mamária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Dilatação Patológica/diagnóstico por imagem , Dilatação Patológica/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Radiografia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia Pré-Natal , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Primary spontaneous pneumothorax (PSP) is a common condition that typically affects young adults. With recent advances in techniques, VATS is now a safe and accepted procedure for treating PSP. Lung isolation techniques have been commonly used to facilitate surgical procedures in the past. The purpose of this study was to evaluate the feasibility of using a single-lumen endotracheal tube for thoracoscopic surgery in patients with PSP. METHODS: A series of 121 consecutive patients with PSP, who underwent VATS using a double-lumen or single-lumen endotracheal tube between January 2000 and December 2002, were assessed retrospectively. The clinical features, operation times, complications, hospital stays and recurrences of PSP in these patients were recorded and analysed. RESULTS: There were no significant differences in gender, BMI, smoking habits, blebs/bullae on CT, duration of surgery or recurrence of PSP between the two groups. Patients in the single-lumen endotracheal tube group had a shorter duration of anaesthesia (15.4 +/- 2.6 vs 25.6 +/- 3.2 min, P < 0.001), lower early complication rates, lower costs and shorter hospital stays (3.6 +/- 3.0 vs 4.5 +/- 2.8 days, P = 0.02) compared with those in the double-lumen endotracheal tube group. The follow-up period was 40-68 months (mean 54 months). There were two recurrences in each group (3.1% vs 3.4%). CONCLUSIONS: VATS for the treatment of PSP was easily performed using a single-lumen endotracheal tube, and resulted in lower intubation-related costs, fewer complications and equivalent outcomes, compared with procedures performed using double-lumen endotracheal tube anaesthesia.
Assuntos
Anestesia Endotraqueal , Anestésicos/administração & dosagem , Intubação Intratraqueal/efeitos adversos , Pneumotórax/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Intubação Intratraqueal/economia , Tempo de Internação , Pulmão/cirurgia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Due to widespread use of low-dose computed tomography (LDCT) screening, increasing number of patients are found to have subsolid nodules (SSNs). The management of SSNs is a clinical challenge and primarily depends on CT imaging. We seek to identify risk factors that may help clinicians determine an optimal course of management. METHODS: We retrospectively reviewed the characteristics of 83 SSN lesions, including 48 pure ground-glass nodules and 35 part-solid nodules, collected from 83 patients who underwent surgical resection. RESULTS: Of the 83 SSNs, 16 (19.28%) were benign and 67 (80.72%) were malignant, including 23 adenocarcinomas in situ (AIS), 16 minimally invasive adenocarcinomas (MIA), and 28 invasive adenocarcinomas (IA). Malignant lesions were found to have significantly larger diameters (P<0.05) with an optimal cut-off point of 9.24 mm. Significant indicators of malignancy include female sex (P<0.05), air bronchograms (P<0.001), spiculation (P<0.05), pleural tail sign (P<0.05), and lobulation (P<0.05). When compared with AIS/MIA combined, IA lesions were found to be larger (P<0.05) with an optimal cut-off of 12 mm, and have a higher percentage of part-solid nodules (P<0.001), pleural tail sign (P<0.001), air bronchograms (P<0.05), and lobulation (P<0.05). Further multivariate analysis found that lesion size and spiculation were independent factors for malignancy while part-solid nodules were associated with IA histology. CONCLUSIONS: East Asian females are at risk of presenting with a malignant lesion even without history of heavy smoking or old age. Nodule features associated with malignancy include larger size, air bronchograms, lobulation, pleural tail sign, spiculation, and solid components. A combination of patient characteristic and LDCT features can be effectively used to guide management of patients with SSNs.
RESUMO
CD133-expressing glioma cells play a critical role in tumor recovery after treatment and are resistant to radiotherapy. Herein, we demonstrated that glioblastoma-derived CD133-positive cells (GBM-CD133(+)) are capable of self-renewal and express high levels of embryonic stem cell genes and SirT1 compared to GBM-CD133(-) cells. To evaluate the role of SirT1 in GBM-CD133(+), we used a lentiviral vector expressing shRNA to knock-down SirT1 expression (sh-SirT1) in GBM-CD133(+). Silencing of SirT1 significantly enhanced the sensitivity of GBM-CD133(+) to radiation and increased the level of radiation-mediated apoptosis. Importantly, knock-down of SirT1 increased the effectiveness of radiotherapy in the inhibition of tumor growth in nude mice transplanted with GBM-CD133(+). Kaplan-Meier survival analysis indicated that the mean survival rate of GBM-CD133(+) mice treated with radiotherapy was significantly improved by Sh-SirT1 as well. In sum, these results suggest that SirT1 is a potential target for increasing the sensitivity of GBM and glioblastoma-associated cancer stem cells to radiotherapy.
Assuntos
Apoptose , Glioma/radioterapia , Tolerância a Radiação/genética , Sirtuínas/genética , Antígeno AC133 , Antígenos CD/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Glioma/genética , Glicoproteínas/metabolismo , Humanos , Peptídeos/metabolismo , Sirtuína 1RESUMO
Patterns of global histone modifications have been recently suggested as outcome predictors in cancer patients. To date, there has been no report on the prognostic significance of global histone modifications in esophageal squamous cell carcinoma. We investigated the role of global histone modification as outcome predictor in patients undergoing esophagectomy for esophageal squamous cell carcinoma. A retrospective clinicopathologic analysis was undertaken of 97 patients with esophageal squamous cell carcinoma who recovered from esophagectomy. Immunohistochemical expression of five histone modification markers, acetylated histone 3 lysine 18 (H3K18Ac), acetylated histone 4 lysine 12 (H4K12Ac), dimethylated histone 4 arginine 3 (H4R3diMe), dimethylated histone 3 lysine 4 (H3 K4diMe), and trimethylated histone 3 lysine 27 (H3K27triMe) was assessed in paraffin-embedded tumor samples. Results were analyzed in relation to patients' clinicopathologic parameters. There was a positive relationship between tumor differentiation and H3K18Ac (P<0.001), H4R3diMe (P=0.003), and H3K27triMe (P<0.001). Expression of H3K27triMe correlated positively with nodal (N) status (P=0.012) and stage (P=0.025). Univariate analysis showed that better survival in patients with low expression of H3K18Ac (P=0.038) and H3K27triMe (P=0.003). Multivariate analysis showed that nodal status, metastasis status (M), and expression of H3K27triMe predicted survival independently (P<0.001, P=0.016, and 0.048, respectively). Low expression of H3K18Ac and H3K27triMe correlated with better prognosis of patients with esophageal squamous cell carcinoma, especially for those of early stages. We hypothesize that expression of H3K27triMe may be considered as a significant survival predictor for patients with esophageal squamous cell carcinoma.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/química , Neoplasias Esofágicas/química , Esofagectomia , Histonas/análise , Processamento de Proteína Pós-Traducional , Acetilação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Diferenciação Celular , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Lisina , Masculino , Metilação , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: Our study investigates the significance of the expression of Wnt pathway proteins including beta-catenin, Axin, beta-transducin-repeat-containing protein (beta-TrCP), and adenomatous polyposis coli (APC) in squamous cell carcinoma of the esophagus (ESCC). METHODS: Immunohistochemical analysis was performed on paraffin-embedded tissue specimens from 128 resected ESCC tumors to detect the expression of beta-catenin, Axin, beta-TrCP, and APC. Correlation between immunoexpression, clinicopathological parameters, and patient survival was analyzed. RESULTS: Increased beta-catenin expression was noted in 22 (18.2%) of 121 tumor specimens. Reduced expression of Axin, beta-TrCP, and APC was observed in 57 (46.0%) of 124, 29 (24.4%) of 119, and 54 (48.2%) of 119 specimens, respectively. No correlation was found among these protein expressions. Axin protein expression was inversely correlated with tumor invasion depth (P = 0.033). Reduced Axin protein expression, lymph node involvement, and distant metastasis were significant negative predictors for overall survival and disease-free survival on univariate analysis. In multivariate analysis, reduced Axin expression remained a significant prognostic factor for patients with ESCC (P = 0.005). CONCLUSIONS: Reduced Axin expression was observed in 46% of ESCC tumor specimens and was associated with poor prognosis in patients with ESCC. Further study is mandatory to elucidate the underlying mechanism responsible for loss of Axin expression and the role of Axin in ESCC tumorigenesis.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Linfonodos/patologia , Proteínas Repressoras/metabolismo , Proteína da Polipose Adenomatosa do Colo/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína Axina , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Técnicas Imunoenzimáticas , Linfonodos/metabolismo , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , beta Catenina/metabolismo , Proteínas Contendo Repetições de beta-Transducina/metabolismoRESUMO
Microfluidic-based tumor models that mimic tumor culture environment have been developed to understand the cancer metastasis mechanism and discover effective antimetastatic drugs. These models successfully recapitulated key steps of metastatic cascades, yet still limited to few metastatic steps, operation difficulty, and small molecule absorption. In this study, we developed a metastasis system made of biocompatible and drug resistance plastics to recapitulate each metastasis stage in three-dimensional (3D) mono- and co-cultures formats, enabling the investigation of the metastatic responses of cancer cells (A549-GFP). The plug-and-play feature enhances the efficiency of the experimental setup and avoids initial culture failures. The results demonstrate that cancer cells tended to proliferate and migrate with circulating flow and intravasated across the porous membrane after a period of 3 d when they were treated with transforming growth factor-beta 1 (TGF-ß1) or co-cultured with human pulmonary microvascular endothelial cells (HPMECs). The cells were also observed to detach and migrate into the circulating flow after a period of 20 d, indicating that they transformed into circulating tumor cells for the next metastasis stage. We envision this metastasis system can provide novel insights that would aid in fully understanding the entire mechanism of tumor invasion.
Assuntos
Técnicas de Cocultura/instrumentação , Técnicas de Cocultura/métodos , Metástase Neoplásica/patologia , Células A549 , Movimento Celular , Endotélio Vascular/citologia , Desenho de Equipamento , Humanos , Hidrogéis , Dispositivos Lab-On-A-Chip , Células Neoplásicas Circulantes/patologia , Fator de Crescimento Transformador beta1/farmacologia , Microambiente TumoralRESUMO
We aimed to investigate the role of CCND1 G870A polymorphism genetic and transcriptomic effects susceptibility in association with breast cancer carcinogenesis and clinical prognosis. A case-control study was conducted with the enrollment of 992 sporadic breast cancer patients and the corresponding 960 normal controls from routine mammographic or sonographic screening for breast cancer between 1995 and 2003 in Taiwan. The 167 fragment spanning the G870A polymorphism in exon 4-intron 4 boundary was amplified to identify genotype of CCND1 (G870A) polymorphism. Competitive RT-PCR were further performed to investigate alternative transcript in four different specimens in association with immunohistochemistry markers. The results showed that AG and AA subgroup were at increased risk for developing breast cancer compared with the GG genotype by 19% (OR 1.19 (0.85-1.67)) and by 34% (OR 1.34 (0.04-1.74)), respectively. A870 allele revealed a recessive tendency while GG and AA/AG subgroup was compared (OR 1.35 (1.07-1.70)). AA genotype also had a higher risk in premenopausal women than postmenopausal ones. The recurrence-free survival was longer in patients with GG+AG than that in patients with AA (P = 0.034). A870 allele produced more transcript b both in malignant. There were significant correlations between several immunohistochemistry markers (such as Ki-67) and cyclin D1 or CDk4. We concluded CCND1 G870A polymorphism make significant contribution to breast cancer in the country with the preponderance of breast cancer in young women. The role of G870A polymorphism in alternative transcript was not only implicated in CCND1 alternative splicing but also correlated with immunohistochemistry markers.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Ciclina D1/genética , Predisposição Genética para Doença , Polimorfismo Genético , Prognóstico , Adulto , Alelos , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , Éxons , Humanos , Imuno-Histoquímica/métodos , Íntrons , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , TaiwanRESUMO
Hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF) are important angiogenic factors in human cancers. Relative to VEGF-C, prognostic significance of VEGF-D expression and its association with HIF-1alpha expression remain elusive in esophageal squamous cell cancer (ESCC). We studied expression of HIF-1alpha and VEGF-D using immunohistochemistry in 85 resected ESCC specimens and correlated results with patients' clinicopathologic parameters and survival. Association between expression of HIF-1alpha and VEGF-D was investigated using a concordance analysis. High expression of HIF-1alpha and VEGF-D was observed in 52 (61.2%) and 56 (65.9%) patients, respectively. HIF-1alpha expression correlated well with tumor stage (P = 0.041), whereas VEGF-D expression correlated with tumor stage (P = 0.027) and N status (P = 0.019). Groups of high HIF-1alpha and VEGF-D showed worse survivals than those of low expression (P = 0.002 and 0.001, respectively). Multivariate analysis supported expression of HIF-1alpha and VEGF-D as significant survival predictors (P = 0.044 and 0.035, respectively). A concordance rate of 69.5% was observed between expression of HIF-1alpha and VEGF-D. In conclusion, protein expression of HIF-1alpha and VEGF-D are independent prognostic predictors. An association between expression of HIF-1alpha and VEGF-D suggests that these two angiogenic factors are essential in progression of ESCC.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator D de Crescimento do Endotélio Vascular/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
PURPOSE: Lung cancer cells frequently exhibit marked chromosome instability. We postulated that alterations of the double-strand break repair genes (BRCA1, BRCA2, and XRCC5) might be involved in lung cancer. PATIENTS AND METHODS: We examined the loss of protein and mRNA expression and the 5'CpG hypermethylation and allelic imbalance of the BRCA1, BRCA2, and XRCC5 genes in 98 non-small cell lung cancer (NSCLC) samples. Anchorage-dependent growth after reexpression of these genes was examined in a lung cancer cell line that originally lacked BRCA1 and BRCA2 expression. RESULTS: The data indicated that low protein expression of BRCA1 and BRCA2 was frequent in lung adenocarcinomas (42-44%), whereas low XRCC5 protein expression was more prevalent among squamous cell carcinoma (32%). In addition, low BRCA1 expression was significantly associated with low RB expression, especially in lung adenocarcinoma. Concurrent alterations in XRCC5 and p53 were the most frequent profiles in smoking patients. Importantly, low mRNA and protein expressions of BRCA1, BRCA2, and XRCC5 were significantly associated with their promoter hypermethylation. 5-Aza-2'-deoxycytidine treatment of NSCLC cells showed demethylation and reexpression of the BRCA1 and BRCA2 genes and reduced anchorage-independent growth. CONCLUSIONS: Our retrospective study provides compelling evidence that low mRNA and protein expression in the BRCA1/BRCA2 and XRCC5 genes occur in lung adenocarcinoma and squamous cell carcinoma, respectively, and that promoter hypermethylation is the predominant mechanism in deregulation of these genes. Alteration of the double-strand break repair pathway, perhaps by interacting with p53 and RB deregulation, is important in the pathogenesis of a subset of NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , DNA Helicases/genética , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Genes BRCA1 , Genes BRCA2 , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Adenocarcinoma/metabolismo , Sequência de Bases , Carcinoma de Células Grandes/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Metilação de DNA , Reparo do DNA , Humanos , Autoantígeno Ku , Dados de Sequência Molecular , Metástase Neoplásica , Regiões Promotoras Genéticas , Estudos RetrospectivosRESUMO
Fistula formation between the bronchi and peritoneal cavity is extremely rare. In previous reports, fistulas have occurred secondary to thoraco-abdominal trauma, subphrenic abscess, suppurative biliary tract obstruction, malignancy and iatrogenically through procedures such as biliary surgery or percutaneous biliary drainage. The direction of fistula formation has always been thought to be from the peritoneal cavity to the bronchi: there are no reports of a fistula with a bronchial origin. This case report presents a patient who presented with sepsis and a bronchoperitoneal fistula and pneumoperitoneum secondary to lung abscess.
Assuntos
Fístula Brônquica/etiologia , Abscesso Pulmonar/complicações , Doenças Peritoneais/etiologia , Adulto , Antibacterianos/uso terapêutico , Fístula Brônquica/diagnóstico , Fístula Brônquica/cirurgia , Tubos Torácicos , Diagnóstico Diferencial , Drenagem/instrumentação , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/terapia , Fístula/diagnóstico , Fístula/etiologia , Fístula/cirurgia , Seguimentos , Humanos , Infecções por Klebsiella/complicações , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/terapia , Klebsiella pneumoniae/isolamento & purificação , Laparotomia/métodos , Abscesso Pulmonar/diagnóstico , Abscesso Pulmonar/terapia , Masculino , Doenças Peritoneais/diagnóstico , Doenças Peritoneais/cirurgia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: While primary spontaneous pneumothorax (PSP) is common in adolescents and young adults, simultaneous bilateral PSP (SBPSP) is rare and can be life-threatening if it progresses to tension pneumothorax. This study reviewed cases of PSP to identify the clinical features of SBPSP. METHODS: All patients with PSP diagnosed and treated between June 1996 and June 2006 were reviewed, and the clinicoradiological features and outcomes were evaluated. RESULTS: Of the 616 patients with 807 episodes of PSP, 13 had SBPSP (1.6%) at first presentation, and all were male (mean age 20.9 +/- 4.7 years, range 16-25 years). Compared with the non-SBPSP patients, SBPSP patients had significantly lower body weight and BMI (P = 0.018 and <0.001, respectively) and higher body height/body weight ratio (P = 0.004). There was no significant difference in their age, sex, smoking habits or body height. Patients with SBPSP had a significantly higher incidence of bleb/bullae seen in HRCT of the lung compared with non-SBPSP (88.5% vs 63.5%, P = 0.016). In multiple logistic regression analysis, BMI and presence of blebs/bullae were independent risk factors for SBPSP. All patients with SBPSP received bilateral video-assisted thoracoscopic surgery and recovered uneventfully. The mean follow-up period was 3.7 years (range 10 months-7 years). CONCLUSION: Patients with PSP having a lower BMI, and bilateral bleb/bullae formation are at higher risk for the development of SBPSP. SBPSP needs urgent assessment and management, and bilateral video-assisted thoracoscopic surgery is a safe and effective treatment.
Assuntos
Pneumotórax/etiologia , Pneumotórax/terapia , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Masculino , Pneumotórax/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Taiwan , Cirurgia Torácica Vídeoassistida , Resultado do TratamentoRESUMO
BACKGROUND: Primary spontaneous pneumothorax (PSP) is a common disease in young adults. With advances in its surgical treatment, ipsilateral recurrence is < 5%. However, contralateral recurrence remains a significant problem. The purpose of this retrospective study was to identify the factors associated with contralateral recurrence of PSP. METHODS: From January 1997 to December 1999, 231 patients with PSP were reviewed and evaluated after an average of 92-months of follow-up. The clinical features and treatment of these patients were analyzed retrospectively. RESULTS: Thirty-three of these patients had contralateral recurrence (14.3%). The average time of contralateral recurrence was 22.94 months. In the univariate analysis (after Bonferroni correction), patients with contralateral recurrence of PSP had lower a body mass index (BMI) [p < 0.001], and higher frequency of contralateral blebs/bullae on high-resolution CT (HRCT) of the lung (p < 0.001). Multiple logistic regression was performed on 128 patients with contralateral blebs/bullae on HRCT of the lung, and the results indicate that being underweight (BMI < 18.5 kg/m(2)) is an independent risk factor for contralateral recurrence (odds ratio, 5.327). All patients with contralateral recurrence of PSP received surgical treatment. Two patients had unilateral recurrences of pneumothorax during follow-up (2 of 64 video-assisted thoracoscopic surgeries, 3%). CONCLUSIONS: Contralateral recurrence of PSP is significantly more common in patients with underweight and blebs/bullae in the contralateral lung. Single-stage bilateral surgery may be considered for these patients to circumvent the need for subsequent anesthetic and operative procedures, and additional hospitalization.
Assuntos
Vesícula/epidemiologia , Pneumotórax/epidemiologia , Pneumotórax/cirurgia , Magreza , Adulto , Índice de Massa Corporal , Feminino , Humanos , Modelos Logísticos , Masculino , Recidiva , Estudos Retrospectivos , Fatores de Risco , Cirurgia Torácica VídeoassistidaRESUMO
The discovery of candidate biomarkers from biological materials coupled with the development of detection methods holds both incredible clinical potential as well as significant challenges. However, the proteomic techniques still provide the low dynamic range of protein detection at lower abundances. This review describes the current development of potential methods to enhance the detection and quantification in proteome studies. It also includes the bioinformatics tools that are helpfully used for data mining of protein ontology. Therefore, we believe that this review provided many proteomic approaches, which would be very potent and useful for proteome studies and for further diagnostic and therapeutic applications.
Assuntos
Proteoma/análise , Proteômica/métodos , Biomarcadores/análise , Biologia Computacional/métodos , Proteoma/química , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: We sought to determine whether Charlson comorbidity index (CCI) or Kaplan-Feinstein index (KFI) is a better predictor of prognosis in patients with stage I NSCLC after surgical resection. METHODS: A retrospective study of medical records of 426 patients with stage I lung cancer having complete surgical resection from 1995 to 2000 was performed. Data collected included age, gender, smoking history, resection type, pleural invasion status, and tumor type and size. Comorbidity score was determined using Charlson comorbidity index and Kaplan-Feinstein index. Both univariate and multivariate analyses were used to evaluate prognostic factors. RESULTS: Three hundred and twenty-eight male (76.99%) and 98 female (23.01%) patients had a mean age of 67.07 years (range 19-88 years). Median duration of follow-up was 60.32 months. Total follow-up rate was 95.1%. Distribution of CCI score was: 0, 236 (55.40%); 1, 112 (26.29%); >or=2, 78 (18.31%). Overall KFI score was: none, 247 (57.98%); mild, 126 (29.58%); moderate, 43 (10.09%); and severe, 10 (2.35%). In univariate analyses, patients aged>or=65 years, male, smokers, CCI score>or=2, extensive resection and pathological stage IB cancer had poorer 5-year survival. In multivariate logistic regression analysis, age>or=65 years, pneumonectomy, CCI score>or=2, and stage IB cancer were independent prognostic factors for poorer 5-year survival. CONCLUSIONS: Patients with CCI>or=2 had higher perioperative mortality and death from non-cancer causes after surgery compared to patients with CCI<2. However, KFI score had no impact on operative mortality and non-cancer death during follow-up.