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1.
Int J Surg Case Rep ; 97: 107368, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35841758

RESUMO

INTRODUCTION AND IMPORTANCE: Juvenile polyposis of the stomach (JPST) is a very rare disease and has been reported to have malignant potential. Total gastrectomy has been recommended as a standard treatment. Recently, the usefulness of laparoscopic surgery for this disease has been reported; however, in laparoscopic surgery, maintaining the surgical space is difficult because of the distended and thickened stomach wall that polyposis causes. CASE PRESENTATION: A 64-year-old woman was admitted to our hospital because she became malnourished due to loss of appetite. She had no family history of gastrointestinal polyposis and was diagnosed with gastric polyposis and polyp-related anemia eight years previously. She received endoscopic submucosal dissection of early gastric cancer twice in another hospital. Thereafter, the patient received an annual upper gastrointestinal endoscopy and took iron supplements for anemia due to occasional bleeding from polyps. However, the number of polyps increased over time. Enhanced computed tomography showed gastric wall thickening and multiple gastric polyps. She was diagnosed as having JPST and underwent laparoscopic total gastrectomy. She was discharged on postoperative Day 10. CLINICAL DISCUSSION: In the present case, similar to previous cases, standard laparoscopic surgery could be performed although the patient had excessive distention and congestion of the stomach. This report suggests that laparoscopic surgery is a safe and feasible option for patients with JPST and is preferable because of better cosmetic effects, especially for young female patients. CONCLUSION: We successfully performed laparoscopic surgery to treat a rare case of JPST.

2.
J Adv Nurs ; 77(4): 1825-1838, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33368578

RESUMO

AIM: To analyse the interactions of associated factors with post stroke fatigue (PSF) after discharge home and determine the predictors of PSF and their impact on stroke survivors. DESIGN: A prospective observational study. METHODS: A total of 94 patients with acute stroke were recruited between May 2019 -July 2020. The main outcomes were fatigue, depression, insomnia, sarcopenia, and health-related quality of life (HRQOL) and were assessed at admission and 1 month after discharge. Fatigue was measured using the Fatigue Assessment Scale. Depression and Insomnia were assessed using the Hospital Anxiety and Depression Scale-Depression and Insomnia Severity Index, respectively. Sarcopenia was measured using the SARC-F questionnaire, and HRQOL was assessed using the Short Form-8. RESULTS: Acute phase PSF was an independent predictor of PSF after discharge home. Moreover the path analysis revealed that this effect is mediated through both the direct effect of acute-phase PSF on PSF after discharge home and through the indirect effect of interaction with pre-stroke SARC-F, acute phase depression, and acute phase insomnia, which remains a separate predictor of acute-phase PSF. In total, 17% of the survivors had persistent PSF. Persistent PSF was significantly associated with depression, insomnia, sarcopenia, and a lower quality of life scores. CONCLUSIONS: Post-stroke fatigue may occur in the acute phase and persists after discharge, it will not only affect later depression, insomnia, and quality of life, but also sarcopenia. IMPACT: Acute phase PSF was found to be an independent predictor of PSF after discharge home. In addition, the interaction with pre-stroke SARC-F, acute phase depression and insomnia had an indirect connection with PSF after discharge home, which remains a separate predictor of acute-phase PSF. Thus, early assessment and management of mental status, sleep problems, and sarcopenia during hospitalization might be an important step in post-stroke rehabilitation and home transition.


Assuntos
Qualidade de Vida , Acidente Vascular Cerebral , Depressão/etiologia , Fadiga/etiologia , Hospitais , Humanos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações
3.
Surg Case Rep ; 6(1): 200, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32761395

RESUMO

BACKGROUND: Gastric hamartomatous inverted polyp (GHIP) is a pathological condition where enlarged gastric glands with cystic dilatation grow in the submucosa. It is difficult to excise the tissue due to its location. In addition, even if the tissue is taken correctly, making an accurate diagnosis is difficult due to foveolar epithelium in the tissue, which can be misdiagnosed as gastric mucosal epithelium. Thus, an accurate diagnosis of GHIP is rarely established from a biopsy alone preoperatively. We here report a case of GHIP with a central dimple, which was diagnosed and treated using a modified combination of laparoscopic and endoscopic approaches to neoplasia with a non-exposure technique (modified CLEAN-NET). CASE PRESENTATION: A 60-year-old man with a submucosal tumor (SMT) in the stomach was referred to our hospital by a primary care doctor. On examination, a gastrointestinal stromal tumor was suspected. Modified CLEAN-NET was performed for diagnostic and therapeutic purposes. The histopathological examination of the resected specimen showed an enlarged gland duct in the submucosal layer. This finding, along with immunostaining results, led to the diagnosis of GHIP. The postoperative course was uneventful without any symptoms. CONCLUSIONS: GHIP should be considered among the differential diagnoses of SMT of the stomach. Modified CLEAN-NET may be beneficial in the removal of SMTs such as GHIP with a central dimple because it can avoid stomach deformation of the stomach and tumor dissemination.

4.
Breast Cancer (Auckl) ; 14: 1178223420983843, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33447040

RESUMO

BACKGROUND: Clinical studies have shown that palbociclib improves progression-free survival in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) patients with advanced breast cancer (ABC). However, there are insufficient data on its use in a real-world setting in Japan. The aim of this study was to investigate the effectiveness, predictive factors, and safety of palbociclib among Japanese patients in routine clinical practice. METHODS: Between December 1, 2017, and April 30, 2019, we recruited patients from 9 hospitals and retrospectively evaluated the data on HR+/HER2- patients with ABC who received palbociclib for at least 1 week. The correlation between time-to-treatment discontinuation (TTD) and clinical background was investigated via univariate and multivariate analyses using Cox hazards models. RESULTS: A total of 177 women were available for analysis. Of these patients, 58 (33%) patients were treated with palbociclib with an aromatase inhibitor and 117 (66%) patients were treated with palbociclib and a selective estrogen receptor degrader. Approximately three-fourths of the patients (n = 130, 73%) received palbociclib as third- or later-line therapy. One-third of the patients had 3 or more metastatic sites (n = 59, 33%), and one-third of the patients had liver metastasis (n = 59, 33%). The median follow-up duration at the time of data cutoff was 8.9 months, the median TTD was 6.3 months, and the median overall survival was not reached. Liver metastasis (hazard ratio [HR]: 1.54 [95% confidence interval {CI}: 1.03-2.27]), high serum lactate dehydrogenase (LDH) level (>300 U/L) (HR: 2.58 [95% CI: 1.49-4.26]), and high neutrophil-to-lymphocyte ratio (NLR) (⩾3.0) (HR: 1.76 [95% CI: 1.13-2.69]) were significantly associated with shorter TTD. The most common hematologic adverse event was neutropenia, which occurred in 93% of the patients. CONCLUSION: Based on the results of the pivotal phase 3 trials, the median TTD recorded in this study was shorter than expected. Our results suggest that liver metastasis, serum LDH level, and NLR may be predictive factors for HR+/HER2- ABC treatment outcomes.

5.
Microb Cell Fact ; 18(1): 194, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699086

RESUMO

BACKGROUND: 5'-Aminolevulinic acid (ALA) is widely used in the pharmaceutical industry, healthcare, and food production, and is a substrate for the biosynthesis of heme, which is required for respiration and photosynthesis. Enhancement of ALA biosynthesis has never been developed in Saccharomyces cerevisiae, which is a well-known model microorganism used for bioproduction of many value-added compounds. RESULTS: We demonstrated that metabolic engineering significantly improved ALA production in S. cerevisiae. First, we found that overexpression of HEM1, which encodes ALA synthetase, increased ALA production. Furthermore, addition of an optimal amount of glycine, a substrate for ALA biosynthesis, or levulinic acid, an inhibitor of ALA dehydrogenase, effectively increased ALA production. Next, we developed an assay for multiple metabolites including ALA and found that aconitase, encoded by ACO1 and ACO2, is the rate-limiting enzyme of ALA biosynthesis when sufficient glycine is supplied. Overexpression of ACO2 further enhanced ALA production in S. cerevisiae overexpressing HEM1. CONCLUSIONS: In this study, ALA production in S. cerevisiae was enhanced by metabolic engineering. This study also shows a strategy to identify the rate-limiting step of a target synthetic pathway by assay for multiple metabolites alongside the target product. This strategy can be applied to improve production of other valuable products in the well-studied and well-industrialized microorganism S. cerevisiae.


Assuntos
Ácidos Levulínicos/metabolismo , Engenharia Metabólica/métodos , Organismos Geneticamente Modificados/metabolismo , Saccharomyces cerevisiae , Aconitato Hidratase/genética , Aconitato Hidratase/metabolismo , Fermentação , Glicina/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Ácido Aminolevulínico
6.
Gan To Kagaku Ryoho ; 42(12): 2130-2, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26805287

RESUMO

Case 1: A 53-year-old woman had a positive fecal occult blood test during an examination performed in June 2014, and she visited our department in August. Colonoscopic examination showed a type 2 rectal cancer 4 cm from the anal verge. CT showed situs inversus totalis. We performed laparoscopic abdominoperineal resection (D2) for a diagnosis of cT1b, N0, M0, Stage Ⅰrectal cancer. Case 2: A 60-year-old man had a positive fecal occult blood test. Colonoscopic examination showed a type 2 cancer of the ascending colon. Chest radiography showed dextrocardia, but the arrangement of the organs in the abdomen was normal. We performed laparoscopic ileocecal resection (D3) for a diagnosis of cT2, N0, M0, StageⅠ colon cancer. Laparoscopic surgery can be performed safely in patients with situs inversus totalis.


Assuntos
Colo Ascendente/cirurgia , Neoplasias do Colo/cirurgia , Laparoscopia , Neoplasias Retais/cirurgia , Situs Inversus/complicações , Colectomia , Neoplasias do Colo/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/complicações , Situs Inversus/cirurgia
7.
Breast Cancer ; 22(4): 399-405, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24000037

RESUMO

BACKGROUND: The impact of body mass index (BMI) on the risk of postmenopausal estrogen receptor (ER)-positive breast cancers has been well documented. However, the mechanism for the impact of BMI on the etiology of luminal A and luminal B subtypes has not yet been identified. METHODS: We analyzed associations between BMI and breast cancers stratified by immunohistochemically defined intrinsic subtypes, and 1,297 Japanese women (615 breast cancer patients and 682 healthy women from a breast cancer screening program) were enrolled in a case-control study. ER-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancers were classified into luminal A and B subtypes according to Ki67 expression levels. RESULTS: Higher BMI was significantly positively associated with postmenopausal breast cancer risk for one-unit increase in BMI (adjusted odds ratio (aOR) 1.09, 95 % confidence interval (CI) 1.04-1.15; P = 0.0008). Analyses of postmenopausal women revealed that BMI was consistently and exclusively associated with luminal A incidence (aOR 1.18, 95 % CI 1.10-1.26; P < 0.0001). When BMI was divided into three categories corresponding to those of controls, among postmenopausal women, the observed positive association was confined to luminal A (high vs low, aOR 2.98, 95 % CI 1.53-5.80; P < 0.005), but not luminal B (aOR 0.95, 95 % CI 0.47-1.91) subtypes. CONCLUSIONS: We observed that BMI was significantly positively associated with increased risk of postmenopausal breast cancer for Japanese women with luminal A, but not with luminal B tumor subtype.


Assuntos
Índice de Massa Corporal , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Pós-Menopausa , Fatores de Risco , Adulto Jovem
8.
Breast Cancer ; 21(1): 52-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22359195

RESUMO

BACKGROUND: Estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancers can be divided into luminal A and luminal B subtypes based on Ki67 expression levels. However, the biological differences in ER and progesterone receptor (PR) expression levels between these luminal subtypes are not clear. METHODS: We examined immunohistochemical expression levels of ER, PR, and Ki67 in 180 ER-positive/HER2-negative breast cancers while taking menopausal status into account. Breast cancers were divided according to ER and PR levels (H: >50%, L: ≤ 50%), and luminal A and B were classified by the Ki67 labeling index (A: Ki67 <14%, B: Ki67 ≥ 14%). RESULTS: When breast cancers were classified based on ER and PR levels, the distribution of pre- and postmenopausals was significantly different for luminal A (P < 0.0001), but not for luminal B cancers. As for luminal A, ER-H/PR-L cancers were rare among premenopausals (8%), but frequent among postmenopausals (54%). Correlation between ER and PR levels among luminal A cancers was strong in premenopausals but weak in postmenopausals. Since crosstalk with growth factor signaling is unlikely in luminal A, we speculate that intratumoral estrogen insufficiency contributed to the characteristics of postmenopausal ER-H/PR-L cancers. CONCLUSION: We speculate that the biological characteristics of luminal A cancers are influenced by the estrogen environment, but its influence on luminal B cancers may be limited. We believe these considerations constitute useful information for a better understanding of the biology of ER-positive-HER2-negetive breast cancers.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Pós-Menopausa , Pré-Menopausa
9.
Cancer Lett ; 321(1): 65-72, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22388174

RESUMO

Extracellular adenosine induced apoptosis of MCF-7 human breast cancer cells in a concentration (10µM-10mM)- and treatment time (24-72h)-dependent manner, and the effect was inhibited by the adenosine transporter inhibitor dipyridamole, but not an inhibitor of adenosine kinase, an inhibitor of AMP-activated protein kinase, or inhibitors for A(1), A(2a), A(2b), and A(3) adenosine receptors. No significant activation of caspase-7, -8, or -9 was obtained with adenosine. Adenosine promoted translocation of apoptosis-inducing factor (AIF)-homologous mitochondrion-associated inducer of death (AMID) from the cytosol into the nucleus, although the total amount of AMID was not affected. Adenosine-induced MCF-7 cell death was abrogated by knocking-down AMID. The results of the present study indicate that intracellularly transported adenosine induces MCF-7 cell apoptosis by accumulating AMID in the nucleus in a caspase-independent manner.


Assuntos
Adenosina/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias da Mama/metabolismo , Proteínas Mitocondriais/metabolismo , Apoptose , Proteínas Reguladoras de Apoptose/genética , Transporte Biológico , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Proteínas Mitocondriais/genética , Transdução de Sinais
10.
Gan To Kagaku Ryoho ; 38(7): 1217-9, 2011 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-21772116

RESUMO

A 62-year-old male was admitted to our hospital because of anal pain and bloody stool. After careful examination, a locally advanced rectal cancer was found, and an invasion of the prostate was suspected. The prevention of pelvic recurrence and downstaging for S-1/oxaliplatin (SOX), combined with preoperative chemoradiation (CRT) make, PR decision (reduction rate 70%), and surgery (APR+central D3) were performed. The postoperative course was uneventful and the patient was discharged 18 hospital days after surgery. The outpatient is receiving the adjuvant chemotherapy by single S-1 now. Advanced lower rectal cancer S-1/oxaliplatin (SOX), combined with preoperative chemoradiation (CRT), have fewer adverse events and are considered to be useful.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Tegafur/uso terapêutico , Biópsia , Terapia Combinada , Combinação de Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Ácido Oxônico/administração & dosagem , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Tegafur/administração & dosagem
11.
Cell Physiol Biochem ; 26(2): 125-34, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20798496

RESUMO

BACKGROUND/AIMS: Adenosine 5'-triphosphate (ATP) mediates a variety of signal transductions via ATP receptors such as P2X and P2Y receptors. The present study aimed at understanding the mechanism underlying extracellular ATP-induced suppression of Caco-2 human colonic cancer cell proliferation. METHODS: Caco-2 cells were cultured. To examine cell viability and cell cycling, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, fluorescent cytochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and flow cytometry were carried out. To see mRNA expression of ATP receptors, reverse transcription-polymerase chain reaction (RT-PCR) was performed. To examine PKC activity and mitogen-activated protein (MAP) kinase activity, in situ PKC assay and Western blotting using an anti-extracellular signal-regulated kinase 1 (ERK1)-antibody and an anti-phospho-ERK antibody were carried out. RESULTS: Extracellular ATP or the unhydrolyzed ATP analogue 5'-adenylyimido-diphosphate (AMP-PNP) reduced Caco-2 cell viability in a concentration (10 microM-10 mM)-dependent manner at 48-h treatment, and the effect was not affected by caspase inhibitors. Caco-2 cells were little reactive to propidium iodide and Hoechst 33342 or little positive to TUNEL after 48-h treatment with ATP (1 mM). In the flow cytometry, 48-h treatment with ATP (1 mM) arrested cell cycling at the S phase in Caco-2 cells. P(2) purinoceptor agonists reduced Caco-2 cell viability with the order of potency: 2-methylthio ATP>UTP>beta, gamma-methylene ATP, and the ATP effect was partially inhibited by suramin, a non-selective inhibitor of P(2) purinoceptors. The PKC inhibitor GF109203X or the MAP kinase kinase inhibitor PD98059 reduced Caco-2 cell viability to an extent similar to that achieved by ATP (1 mM), and no further reduction was obtained with co-treatment with ATP. ATP and its ATP analogues such as AMP-PNP and ATPgammaS, at higher concentrations (1-10 mM), inhibited PKC activation in Caco-2 cells in a fashion that mimics the effect of GF109203X, but PD98059 exhibited no effect on PKC activation. The inhibitory effect of ATP on PKC activation was not found with SK-N-SH cells, a human neuroblastoma cell line, but the cells expressed all the mRNAs for P2X and P2Y receptors that Caco-2 cells did. ATP (10 mM) or GF109203X inhibited activation of ERK, a MAP kinase, in Caco-2 cells. CONCLUSION: Extracellular ATP, at higher concentrations, suppresses Caco-2 cell proliferation at the S phase of cell cycling by inhibiting PKC, possibly as mediated via an unknown ATP receptor, followed by MAP kinase.


Assuntos
Trifosfato de Adenosina/farmacologia , Antineoplásicos/farmacologia , Neoplasias do Colo/enzimologia , Proteína Quinase C/antagonistas & inibidores , Trifosfato de Adenosina/análogos & derivados , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Flavonoides/farmacologia , Humanos , Indóis/farmacologia , Maleimidas/farmacologia , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase C/metabolismo , Agonistas do Receptor Purinérgico P2/farmacologia , Receptores Purinérgicos P2X/química , Receptores Purinérgicos P2X/metabolismo , Receptores Purinérgicos P2Y/química , Receptores Purinérgicos P2Y/metabolismo
12.
Med Mol Morphol ; 43(4): 193-6, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21267694

RESUMO

The most critical step for initiation and progression of estrogen receptor-α (ERα)-positive breast cancers is thought to be upregulation of ERα expression. There are several factors involved in this mechanism, i.e., increased promoter activity of the ERα gene (ESR1) at the transcriptional level, ESR1 gene amplification, and diminished degradation of ERα protein through ubiquitination and proteasomal pathways. Mediating these factors, ERα protein levels seem to be controlled, although the details of the mechanism remain to be clarified. In addition, for upregulation of estrogen signaling, functional changes in its action in cancer cells originating from normal epithelial cells, i.e., estrogen stimulation, which then leads to proliferation of ERα-positive cancer cells, has been recognized, but this action has not been observed in normal epithelial cells. These alterations are therefore likely to contribute to the pathogenesis of ERα-positive breast cancers.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Regulação Neoplásica da Expressão Gênica , Animais , Receptor alfa de Estrogênio/biossíntese , Feminino , Humanos , Regulação para Cima
13.
Digestion ; 81(1): 62-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20029210

RESUMO

BACKGROUND/AIMS: Adenosine deaminase (ADA)-deficient disease, a severe combined immunodeficiency, is most commonly associated with gastrointestinal disorders such as ulcer. The present study investigated the role of ADA in the pathogenesis of gastric ulcer. METHODS: ADA activity was measured in a variety of organs and tissues from rats and in human gastric biopsy samples from patients who underwent gastrofiberscope. An MTT assay and TUNEL staining were carried out, and activity of caspase-3 and -4 was enzymatically measured in MKN45 human gastric cancer cells. In the Western blot analysis, caspase-4 activation was identified in gastric biopsy samples. RESULTS: In rat organs and tissues, the epithelium of the gastrointestine exhibited higher ADA activity. The ADA inhibitor EHNA reduced cell viability, increased TUNEL-positive cells, and activated caspase-3 and -4 in MKN45 cells. For gastric biopsy samples, much lower ADA activity was found in gastric ulcer tissues, with a tendency of caspase-4 activation. CONCLUSION: A decline in ADA activity and the ensuing increase in intracellular adenosine concentrations for the stomach could induce gastric epithelial cell apoptosis by activating caspase-4 and the effector caspase-3. This may represent a fresh pathogenetical pathway for gastric ulcer relevant to ADA activity and caspase-4 activation.


Assuntos
Adenosina Desaminase/metabolismo , Caspase 3/metabolismo , Úlcera Gástrica/etiologia , Estômago/enzimologia , Adenina/análogos & derivados , Adenina/farmacologia , Adenosina/metabolismo , Adulto , Idoso , Animais , Apoptose , Caspases Iniciadoras/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Mucosa Gástrica/enzimologia , Humanos , Mucosa Intestinal/enzimologia , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Ratos
14.
Cancer Lett ; 290(2): 211-5, 2010 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-19822392

RESUMO

Extracellular adenosine-induced apoptosis of CW2 human colonic cancer cells by activating caspase-3, -8 and -9, and the effect was enhanced by adding EHNA, an adenosine deaminase inhibitor. Adenosine-induced CW2 cell death was inhibited by 8-CPT, an A(1) adenosine receptor inhibitor, but otherwise 2-chloroadenosine, an A(1) adenosine receptor agonist, and MDL-12330A, an inhibitor of adenylate cyclase, mimicked the adenosine effect. For mice inoculated with CW2 cells, intraperitoneal injection with adenosine reduced tumor growth and more prominent reduction was obtained with co-injection with EHNA. Adenosine, thus, suppresses CW2 human colonic cancer growth by inducing apoptosis as mediated via A(1) adenosine receptors.


Assuntos
Adenosina/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/patologia , Receptor A1 de Adenosina/efeitos dos fármacos , Animais , Caspases/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Ativação Enzimática/efeitos dos fármacos , Humanos , Camundongos , Receptor A1 de Adenosina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Breast Cancer ; 17(2): 86-91, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19806427

RESUMO

The classic action that leads to transcriptional activation of estrogen response genes mediated through estrogen receptors (ER) and the estrogen complex plays a pivotal role in the development of ER-positive breast cancers. In addition to this pathway, non-classic action and non-genomic action, both estrogen-dependent and estrogen-independent genomic actions have also been found to contribute to ER-positive tumor growth. Although the details of these mechanisms are not well known, participation of the growth factor signaling pathway is likely to be the most significant factor for acquisition of resistance to hormonal therapy. This resistance is mediated not only directly through cell growth promotion by growth factor signaling, but also through enhancement of alternative ER signaling pathways in addition to classic action. The reason why tamoxifen-insensitive ER-positive breast cancers respond to aromatase inhibitors may be explained, at least in part, by the different estrogen-related signaling pathways in which aromatase inhibitors may block estrogen signaling. In this paper we discuss the molecular mechanisms for resistance to hormonal therapy based on an understanding of estrogen signaling pathways.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Receptores de Estrogênio/metabolismo , Animais , Neoplasias da Mama/patologia , Feminino , Humanos , Prognóstico
16.
J Gastroenterol ; 44(1): 56-65, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19159073

RESUMO

BACKGROUND: Extracellular adenosine has been shown to induce apoptosis in a variety of cells via an intrinsic pathway linked to adenosine uptake into cells and the ensuing signaling cascades and an extrinsic pathway linked to adenosine receptors. The present study was designed to understand the mechanism underlying adenosine-induced apoptosis of Caco-2 human colonic cancer cells. METHODS: To observe cell viability, an MTT assay was carried out in Caco-2 cells untransfected or transfected with the A(2a) adenosine receptor pcDNA3.1. Apoptotic cell death was assessed with flow cytometry using propidium iodide and annexin V and internucleosomal DNA fragmentation analysis. Activities of caspase-3, -8, and -9 were measured using a caspase fluorometric assay kit. Mitochondrial membrane potentials were monitored using a DePsipher kit. Expression of adenosine receptors was examined with the reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: Extracellular adenosine induced Caco-2 cell apoptosis in a concentration-dependent (1-20 mM) and treatment time-dependent (24-72 h) manner. The adenosine effect was inhibited by DMPX, an inhibitor of A(2a) adenosine receptors and SQ22536, an inhibitor of adenylate cyclase. CGS21680, an agonist of A(2a) adenosine receptors, and forskolin, an adenylate cyclase activator, mimicked the adenosine action. Caco-2 cell death was still induced by overexpressing A(2a) adenosine receptors, and adenosine further promoted the cell death. Adenosine disrupted mitochondrial membrane potentials and activated caspase-9 and -3, but not caspase-8. CONCLUSIONS: Extracellular adenosine induces apoptosis in Caco-2 cells by activating caspase-9 and the downstream effector caspase caspase-3 in association with mitochondrial damage via A(2a) adenosine receptors.


Assuntos
Adenosina/fisiologia , Apoptose/fisiologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Receptor A2A de Adenosina/metabolismo , Células CACO-2 , Caspase 8/metabolismo , Sobrevivência Celular , Relação Dose-Resposta a Droga , Citometria de Fluxo , Regulação da Expressão Gênica , Humanos , Potencial da Membrana Mitocondrial , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo
17.
Artigo em Inglês | MEDLINE | ID: mdl-19163856

RESUMO

Three classes of walking patterns, normal, caution and danger, were simulated by tying elastic bands to joints of lower body. In order to distinguish one class from another, four local motions suggested by doctors were investigated stepwise, and differences between levels were evaluated using t-tests. The human adaptability in the tests was also evaluated. We improved average classification accuracy to 84.50% using multiclass support vector machine classifier and concluded that human adaptability is a factor that can cause obvious bias in contiguous data collections.


Assuntos
Inteligência Artificial , Marcha/fisiologia , Interpretação de Imagem Assistida por Computador/métodos , Perna (Membro)/fisiologia , Modelos Biológicos , Reconhecimento Automatizado de Padrão/métodos , Caminhada/fisiologia , Imagem Corporal Total/métodos , Simulação por Computador , Diagnóstico por Computador/métodos , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Oncol Rep ; 18(5): 1329-34, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17914593

RESUMO

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine (PC) to generate phosphatidic acid (PA) and choline. PA acts as a second messenger in cell proliferation; therefore PLD is believed to play an important role in carcinogenesis. PLD activity has been reported to be elevated in human breast, gastric, renal cell and colorectal carcinomas, compared with adjacent non-neoplastic tissues. The activity of PLD was also correlated with nuclear grade in breast cancer, tumor size in gastric carcinoma, and nodal involvement and deeper invasion in colorectal carcinoma. However, the number of cases in each study was small. The aim of this study was to investigate the expression level of PLD2 and its association with clinicopathological features in human colorectal carcinoma. Ninety-seven colorectal carcinomas were obtained from surgery. Expression level of PLD2 was assessed by real-time PCR. The prognostic relevance of PLD2 expression level in patients with colorectal carcinoma was also analyzed by the survival analysis of mortality follow-up data covering the period 2000-2004. PLD expression level was varied from tumor to tumor. Expression level of PLD was significantly correlated with tumor size (P<0.05); it was independent of lymph node metastasis, extent of invasion, pathological classification, distant metastasis and Dukes' stage. PLD expression level was also significantly correlated with survival of patients with colorectal carcinoma (P<0.05). These findings suggested that PLD2 plays an important role in progression of colorectal carcinoma and that PLD2 could be a target for therapy in colorectal carcinoma.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/enzimologia , Fosfolipase D/metabolismo , Adenocarcinoma Mucinoso/enzimologia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fosfolipase D/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida
19.
Biochem Biophys Res Commun ; 360(2): 418-22, 2007 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-17603016

RESUMO

Many physiological, biochemical, and behavioral processes are under circadian regulation, which is generated by an internal time-keeping mechanism referred to as biological clock. The regulators of circadian rhythm in human plasma have not been completely elucidated. Here we demonstrated that the isolated protein from human plasma, which down-regulated expression level of cry1 in Jurkat cells, was apoprotein H (ApoH). Further, mRNA expression level of ApoH indicated circadian rhythm in Jurkat cells. The concentration of ApoH was subject to circadian rhythm in human plasma. These experimental results suggested that ApoH may be one of the members of the regulator of circadian rhythm and that ApoH expression level was also dependent on circadian rhythm in Jurkat cells and in human plasma.


Assuntos
Relógios Biológicos/fisiologia , Ritmo Circadiano/fisiologia , Regulação da Expressão Gênica/fisiologia , beta 2-Glicoproteína I/sangue , Humanos , Células Jurkat , Oscilometria/métodos
20.
Ann Thorac Cardiovasc Surg ; 12(1): 37-41, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16572073

RESUMO

PURPOSE: The purpose of the present study was to evaluate the stability of a high-porosity expanded polytetrafluoroethylene (ePTFE) graft, which has been shown to possess excellent biocompatibility and tissue integration. METHODS: The graft used in the present study was a high-porosity ePTFE graft , which had an average internodal distance of approximately 60 microm and a random node architecture with tortuous path channels extending from the outer to the inner surface. Eleven beagle dogs (each group n = 3 or 4) weighing 10-12 kg were used. The graft, with a 6 mm inside diameter and a 30-40 mm length, was implanted into the canine abdominal aorta and retrieved after 2-80 weeks. The deformation of the graft was evaluated by conventional computed tomography (CT). The radial tensile strength, longitudinal tensile strength, and suture retention strength of the graft were measured after 2-80 weeks. RESULTS: CT studies showed no anastomotic aneurysm or deformation of the graft. Physical tests demonstrated no significant deterioration in suture retention strength, radial tensile strength or longitudinal tensile strength for periods ranging from 2-80 weeks compared to pre-implantation grafts. CONCLUSION: The graft possesses adequate stability that ensures safe and effective clinical use.


Assuntos
Prótese Vascular , Politetrafluoretileno/uso terapêutico , Animais , Cães , Feminino , Masculino , Porosidade , Desenho de Prótese , Resistência à Tração
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