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1.
AJNR Am J Neuroradiol ; 43(1): 40-47, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34824097

RESUMO

BACKGROUND AND PURPOSE: The microenvironment of lymphomas is known to be highly variable and closely associated with treatment resistance and survival. We tried to develop a physiologic MR imaging-based spatial habitat analysis to identify regions associated with treatment resistance to facilitate the prediction of tumor response after initial chemotherapy in patients with primary central nervous system lymphoma. MATERIALS AND METHODS: Eighty-one patients with pathologically confirmed primary central nervous system lymphoma were enrolled. Pretreatment physiologic MR imaging was performed, and K-means clustering was used to separate voxels into 3 spatial habitats according to ADC and CBV values. Associations of spatial habitats and clinical and conventional imaging predictors with time to progression were analyzed using Cox proportional hazards modeling. The performance of statistically significant predictors for time to progression was assessed using the concordance probability index. RESULTS: The 3 spatial habitats of hypervascular cellular tumor, hypovascular cellular tumor, and hypovascular hypocellular tumor were identified. A large hypovascular cellular habitat was most significantly associated with short time to progression (hazard ratio, 2.83; P = . 017). The presence of an atypical finding (hazard ratio, 4.41; P = . 016), high performance score (hazard ratio, 5.82; P = . 04), and high serum lactate dehydrogenase level (hazard ratio, 1.01; P = .013) was significantly associated with time to progression. A predictive model constructed using the habitat score and other imaging parameters showed a concordance probability index for prediction of time to progression of 0.70 (95% CI, 0.54-0.87). CONCLUSIONS: A hypovascular cellular tumor habitat is associated with treatment resistance in primary central nervous system lymphoma, and its assessment may refine prechemotherapy imaging-based response prediction for patients with primary central nervous system lymphoma.


Assuntos
Linfoma , Imageamento por Ressonância Magnética , Sistema Nervoso Central , Humanos , Linfoma/diagnóstico por imagem , Linfoma/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Microambiente Tumoral
2.
Br J Surg ; 108(6): 644-651, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-33982068

RESUMO

BACKGROUND: No effective treatment exists for anterior resection syndrome (ARS) following sphincter-saving surgery for rectal cancer. This RCT assessed the safety and efficacy of a 5-HT3 receptor antagonist, ramosetron, for ARS. METHODS: A single-centre, randomized, controlled, open-label, parallel group trial was conducted. Male patients with ARS 1 month after rectal cancer surgery or ileostomy reversal were enrolled and randomly assigned (1 : 1) to 5 µg of ramosetron (Irribow®) daily or conservative treatment for 4 weeks. Low ARS (LARS) score was calculated after randomization and 4 weeks after treatment. The study was designed as a superiority test with a primary endpoint of the proportion of patients with major LARS between the groups. Primary outcome analysis was based on the modified intention-to-treat population. Safety was assessed by monitoring adverse events during the study. RESULTS: : A total of 100 patients were randomized to the ramosetron (49 patients) or conservative treatment group (51 patients). Two patients were excluded, and 48 and 50 patients were analysed in the ramosetron and control groups, respectively. The proportion of major LARS after 4 weeks was 58 per cent (28 of 48 patients) in the ramosetron group versus 82 per cent (41 of 50 patients) in the control group, with a difference of 23.7 per cent (95 per cent c.i. 5.58 to 39.98, P = 0.011). There were minor adverse events in five patients, which were hard stool, frequent stool or anal pain. These were not different between the two groups. There were no serious adverse events. CONCLUSION: : Ramosetron could be safe and feasible for male patients with ARS. TRIAL REGISTRATION NUMBER: NCT02869984 (http://www.clinicaltrials.gov).


Assuntos
Benzimidazóis/uso terapêutico , Protectomia/efeitos adversos , Neoplasias Retais/cirurgia , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Protectomia/métodos , Reto/cirurgia , Síndrome , Resultado do Tratamento
3.
Colorectal Dis ; 22(4): 399-407, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31698537

RESUMO

AIM: Preoperative factors predictive of permanent stoma creation were investigated in a long-term follow-up of patients with mid or low rectal cancer. METHOD: We included patients who underwent radical resection for mid or low rectal cancer with available data for preoperative anal function measured by manometry and Faecal Incontinence Severity Index questionnaire between January 2005 and December 2015 in three tertiary referral hospitals. A permanent stoma was defined as a stoma present until the patient's last follow-up visit or death. Preoperative factors that predicted permanent stoma creation were analysed. RESULTS: Over a median follow-up of 57.4 months (range 12-143 months), a permanent stoma was created in 144/577 (25.0%) patients, including 89 (15.4%) who underwent abdominoperineal resection, one (0.2%) who underwent Hartmann's operation without reversal, 15 (2.6%) with a diverting ileostomy at the time of initial sphincter-preserving surgery without undergoing stoma reversal, and 39 (6.8%) who underwent permanent ileostomy formation after sphincter-preserving surgery. Patients with permanent stoma creation had a shorter tumour distance from the anal verge (P < 0.001), larger tumour size (P = 0.020) and higher preoperative Faecal Incontinence Severity Index score (P = 0.020). On multivariable analysis, tumour distance from the anal verge predicted permanent stoma formation (relative risk 0.53 per centimetre increase; 95% confidence interval 0.46-0.60; P < 0.001) but preoperative anal function did not. CONCLUSION: Tumour distance from the anal verge was the only preoperative determinant of permanent stoma creation in rectal cancer patients. These data may help mid and low rectal cancer patients understand the need for permanent stoma.


Assuntos
Neoplasias Retais , Estomas Cirúrgicos , Canal Anal/cirurgia , Estudos de Coortes , Humanos , Ileostomia , Neoplasias Retais/cirurgia
4.
Int J Surg Case Rep ; 65: 119-123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31704662

RESUMO

INTRODUCTION: During an anatomical dissection of the distal upper extremities, numerous muscular and nervous anomalies were found in the forearm and hand of a 94-year-old cadaver. These anomalies are clinically relevant with regard to medical or surgical interventions. PRESENTATION OF CASE: The presence of a "flexor digiti minimi longus" muscle was observed passing through Guyon's canal; to our knowledge this passageway has never been previously reported. An aberrant first lumbrical with three origins was noted. Additionally, numerous atypical nerves were found innervating the hand; the dorsal branch of the ulnar nerve contributed to cutaneous innervation of the palm of the hand (Kaplan's anastomosis), the superficial ulnar nerve provided muscular innervation to the flexor digiti minimi brevis muscle, and two connections between the common palmar digital branches of the median and superficial ulnar nerves were observed (Berrettini anastomosis). DISCUSSION: Here, we describe an extranumerary muscle associated with the hypothenar group of muscles. We also describe unusual origins of the first lumbrical muscle, and atypical cutaneous and muscular innervation to the palm of the hand. CONCLUSION: Clinically, understanding the existence of these anatomical variations may influence medical care or surgical procedures.

5.
Oncogene ; 38(22): 4427-4428, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30718918

RESUMO

The original version of this article contained error in Figure 2e. In Figure 2e, the 6th colony image of T47D cells treated with shMSI2 was inadvertently replaced with a duplicate of 7th colony image. However, the conclusions reported in the manuscript are not affected by figure replacement. The authors regret that these errors were made and apologize for the confusion and inconvenience. The correct version of this figure panel appears in the Author Correction associated with this Article.

6.
Mol Oral Microbiol ; 32(1): 48-59, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-26792079

RESUMO

Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway and is a possible mechanism in inflammatory disease. Periodontitis is an inflammatory disease caused by periodontal pathogens. Porphyromonas gingivalis, an important periodontal pathogen, activates cellular autophagy to provide a replicative niche while suppressing apoptosis in endothelial cells. However, the molecular basis for a causal relationship between P. gingivalis and autophagy is unclear. This research examines the involvement of P. gingivalis in autophagy through light chain 3 (LC3) and autophagic proteins, and the role of P. gingivalis-induced autophagy in the clearance of P. gingivalis and inflammation. To investigate the molecular mechanism of autophagy induced by P. gingivalis, PMA-differentiated THP-1-derived macrophages were infected with live P. gingivalis. The P. gingivalis increased the formation of autophagosomes in a multiplicity of infection-dependent manner, as well as autophagolysosomes. Porphyromonas gingivalis activated LC3-I/LC3-II conversion and increased the conjugation of autophagy-related 5 (ATG5) -ATG12 and the expression of Beclin1. The expressions of Beclin1, ATG5-ATG12 conjugate, and LC3-II were significantly inhibited by the presence of 3-methyladenine, an autophagy inhibitor. Interestingly, 3-methyladenine increased the survival of P. gingivalis and proinflammatory cytokine interleukin-1ß production. The data indicate that P. gingivalis induces autophagy in PMA-differentiated THP-1-derived macrophages and in turn, macrophages eliminate P. gingivalis through an autophagic response, which can lead to the restriction of an excessive inflammatory response by downregulating interleukin-1ß production. The induction of autophagy by P. gingivalis may play an important role in the periodontal inflammatory process and serve as a target for the development of new therapies.


Assuntos
Autofagia/fisiologia , Macrófagos/microbiologia , Porphyromonas gingivalis/patogenicidade , Animais , Autofagossomos , Autofagia/imunologia , Diferenciação Celular , Citocinas/imunologia , Citocinas/metabolismo , Células HEK293 , Humanos , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia , Lisossomos , Macrófagos/patologia , Camundongos , Periodontite/metabolismo , Periodontite/microbiologia
7.
Oncogene ; 36(12): 1745-1752, 2017 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-27593929

RESUMO

Musashi RNA-binding protein 2 (MSI2) has important roles in human cancer. However, the regulatory mechanisms by which MSI2 alters breast cancer pathophysiology have not been clearly identified. Here we demonstrate that MSI2 directly regulates estrogen receptor 1 (ESR1), which is a well-known therapeutic target and has been shown to reflect clinical outcomes in breast cancer. Based on gene expression data analysis, we found that MSI2 expression was highly enriched in estrogen receptor (ER)-positive breast cancer and that MSI2 expression was significantly correlated with ESR1 expression, including expression of ESR1 downstream target genes. In addition, MSI2 levels were associated with clinical outcomes. MSI2 influenced breast cancer cell growth by altering ESR1 function. MSI2 alters ESR1 by binding specific sites in ESR1 RNA and by increasing ESR1 protein stability. Taken together, our findings identified a novel regulatory mechanism of MSI2 as an upstream regulator of ESR1 and revealed the clinical relevance of the RNA-binding protein MSI2 in breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Receptor alfa de Estrogênio/metabolismo , Proteínas de Ligação a RNA/metabolismo , Biomarcadores , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Análise por Conglomerados , Receptor alfa de Estrogênio/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Ligação Proteica , Estabilidade Proteica , Proteínas de Ligação a RNA/genética
8.
Skin Res Technol ; 23(1): 79-87, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27440551

RESUMO

BACKGROUND/PURPOSE: The growing demand for a youthful appearance, including a favorable body shape, has motivated recent developments in noninvasive body contouring techniques. Our aim was to investigate the efficacy and safety of a new version of a 4D handpiece-mounted cooling device for cryolipolysis with or without tumescent injections. METHODS: We conducted a side-by-side comparative study using two female porcine models. Two areas of each pig's left abdomen were treated using a conventional device and the new cooling device, and two areas of the right abdomen were also treated using the conventional and new cooling device, but both were combined with tumescent-solution injections. RESULTS: The conventional method alone yielded a 75.25% reduction in skin thickness, while the new cooling device alone yielded a 81.63% reduction. When paired with tumescent injections, the conventional device yielded a 86.3% reduction in skin thickness and the cooling device yielded a 85.9% reduction. Using histological analysis with H&E, oil red O, and toluidine blue stain, we confirmed that selective cryolipolysis was able to induce selective apoptosis of fat cells. CONCLUSION: This in vivo study presents a new 4D handpiece-assisted cooling device with tumescent anesthesia that is safe and effective for fat reduction.


Assuntos
Tecido Adiposo/patologia , Tecido Adiposo/cirurgia , Técnicas Cosméticas/instrumentação , Criocirurgia/instrumentação , Procedimentos Cirúrgicos Dermatológicos/instrumentação , Lipectomia/instrumentação , Animais , Criocirurgia/métodos , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Lipectomia/métodos , Miniaturização , Suínos
9.
Br J Surg ; 102(12): 1581-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26331459

RESUMO

BACKGROUND: Many surgical instruments have been replaced with powered devices in open gastrointestinal and laparoscopic surgery. The production of smoke as a result of vaporization of surgical tissue is inevitable, and exposure to surgical smoke is a long-standing concern. These vapours are potentially hazardous to patients and surgical teams. The present research was designed to compare various surgical devices to determine whether viable cells exist in their surgical smoke. METHODS: The search for viable cells in surgical smoke was conducted using both in vitro and in vivo experiments. Various cancers were cauterized with electrocautery, radiofrequency ablation and ultrasonic scalpels, and the resulting surgical smoke was aspirated with Transwell(®) membrane; viable cells were sought in the surgical smoke. In an in vivo experiment, samples of SCC7 were cauterized with an ultrasonic scalpel and the sediment from the rinsed Transwell(®) membrane liquid after centrifugation was injected subcutaneously into the lower back of mice. RESULTS: Viable cells were found only in the smoke from ultrasonic scalpels (in all 25 samples taken 5 cm from the cautery; 2 of 25 samples at 10 cm). Viable cells in the surgical smoke from ultrasonic scalpels implanted in mice grew in 16 of 40 injection sites. Histological and biochemical analyses revealed that these cancer cells were identical to the cancer cells cauterized by the ultrasonic scalpel. CONCLUSION: Viable tumour cells are produced in the surgical smoke from tumour dissection by ultrasonic scalpel. Surgical relevance Surgical smoke is a byproduct of dissection using a number of powered devices. Hazards to operating room personnel and patients are unclear. This study has shown that use of an ultrasonic dissection device can produce smoke that contains viable tumour cells. Although the model is somewhat artificial, a theoretical risk exists, and measures to evacuate surgical smoke efficiently are important.


Assuntos
Ablação por Cateter/instrumentação , Eletrocoagulação/instrumentação , Neoplasias Experimentais/cirurgia , Exposição Ocupacional/efeitos adversos , Fumaça/efeitos adversos , Instrumentos Cirúrgicos/efeitos adversos , Animais , Camundongos , Neoplasias Experimentais/patologia , Salas Cirúrgicas , Células Tumorais Cultivadas
10.
Ann Oncol ; 26(9): 1974-1980, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26116430

RESUMO

BACKGROUND: In this study, we aimed to identify demographic and clinical variables that correlate with perceived information provision among cancer patients and determine the association of information provision with decisional conflict (DC). PATIENTS AND METHODS: We enrolled a total of 625 patients with cancer from two Korean hospitals in 2012. We used the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-INFO26) to assess patients' perception of the information received from their doctors and the Decisional Conflict Scale (DCS) to assess DC. To identify predictive sociodemographic and clinical variables for adequate information provision, backward selective logistic regression analyses were conducted. In addition, adjusted multivariate logistic regression analyses were carried out to identify clinically meaningful differences of perceived level of information subscales associated with high DC. RESULTS: More than half of patients with cancer showed insufficient satisfaction with medical information about disease (56%), treatment (73%), other services (83%), and global score (80%). In multiple logistic regression analyses, lower income and education, female, unmarried status, type of cancer with good prognosis, and early stage of treatment process were associated with patients' perception of inadequate information provision. In addition, Information about the medical tests with high DCS values clarity [adjusted odds ratio (aOR), 0.54; 95% confidence interval (CI) 0.30-0.97] and support (aOR, 0.53; 95% CI 0.33-0.85) showed negative significance. For inadequate information perception about treatments and other services, all 5 DCS scales (uncertainty, informed, values clarity, support, and effective decision) were negatively related. Global score of inadequate information provision also showed negative association with high DCS effective decision (aOR, 0.43; 95% CI 0.26-0.71) and DCS uncertainty (aOR, 0.46; 95% CI 0.27-0.77). CONCLUSION: This study found that inadequate levels of perceived information correlated with several demographic and clinical characteristics. In addition, sufficient perceived information levels may be related to low levels of DC.


Assuntos
Comunicação , Conflito Psicológico , Tomada de Decisões , Relações Médico-Paciente , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Educação de Pacientes como Assunto , Qualidade de Vida , Fatores Socioeconômicos , Inquéritos e Questionários
11.
Cell Death Dis ; 5: e1303, 2014 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-24967965

RESUMO

The increased mitochondrial DNA damage leads to altered functional capacities of retinal pigment epithelial (RPE) cells. A previous study showed the increased autophagy in RPE cells caused by low concentrations of rotenone, a selective inhibitor of mitochondrial complex I. However, the mechanism by which autophagy regulates RPE cell death is still unclear. In the present study, we examined the mechanism underlying the regulation of RPE cell death through the inhibition of mitochondrial complex I. We report herein that rotenone induced mitotic catastrophe (MC) in RPE cells. We further observed an increased level of autophagy in the RPE cells undergoing MC (RPE-MC cells). Importantly, autophagy inhibition induced nonapoptotic cell death in RPE-MC cells. These findings indicate that autophagy has a pivotal role in the survival of RPE-MC cells. We next observed PINK1 accumulation in the mitochondrial membrane and parkin translocation into the mitochondria from the cytosol in the rotenone-treated RPE-MC cells, which indicates that increased mitophagy accompanies MC in ARPE-19 cells. Noticeably, the mitophagy also contributed to the cytoprotection of RPE-MC cells. Although there might be a significant gap in the roles of autophagy and mitophagy in the RPE cells in vivo, our in vitro study suggests that autophagy and mitophagy presumably prevent the RPE-MC cells from plunging into cell death, resulting in the prevention of RPE cell loss.


Assuntos
Autofagia/fisiologia , Complexo I de Transporte de Elétrons/metabolismo , Células Epiteliais/metabolismo , Mitocôndrias/metabolismo , Mitose/fisiologia , Epitélio Pigmentado da Retina/metabolismo , Linhagem Celular , Sobrevivência Celular/fisiologia , Células Epiteliais/citologia , Humanos , Transporte Proteico/fisiologia , Epitélio Pigmentado da Retina/citologia , Ubiquitina-Proteína Ligases/metabolismo
13.
Cell Death Differ ; 21(1): 146-60, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24141722

RESUMO

PTEN is one of the most frequently mutated or deleted tumor suppressors in human cancers. NEDD4-1 was recently identified as the E3 ubiquitin ligase for PTEN; however, a number of important questions remain regarding the role of ubiquitination in regulating PTEN function and the mechanisms by which PTEN ubiquitination is regulated. In the present study, we demonstrated that p34, which was identified as a binding partner of NEDD4-1, controls PTEN ubiquitination by regulating NEDD4-1 protein stability. p34 interacts with the WW1 domain of NEDD4-1, an interaction that enhances NEDD4-1 stability. Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination. Notably, an inverse correlation between PTEN and p34/NEDD4-1 levels was confirmed in tumor samples from colon cancer patients. Thus, p34 acts as a key regulator of the oncogenic behavior of NEDD4-1 and PTEN.


Assuntos
Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Proteínas Nucleares/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Transativadores/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Complexos Endossomais de Distribuição Requeridos para Transporte/antagonistas & inibidores , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Células HEK293 , Humanos , Células MCF-7 , Ubiquitina-Proteína Ligases Nedd4 , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , PTEN Fosfo-Hidrolase/genética , Estabilidade Proteica , Estrutura Terciária de Proteína , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transativadores/antagonistas & inibidores , Transativadores/genética , Fatores de Transcrição , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
14.
Nuklearmedizin ; 52(4): 121-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23928981

RESUMO

AIM: Many investigators have reported an inverse relationship between iodine and glucose utilization of differentiated thyroid carcinoma (DTC) according to its degree of differentiation; however, not every DTC is compatible with this phenomenon. This study was conducted to evaluate the clinical implication of iodine and glucose uptake at distant metastatic lesions in DTC patients. PATIENTS, METHODS: 64 DTC patients (women 47; mean age 49.9 ± 16.4 years) with distant metastasis who underwent post (131)I treatment whole-body scan (RxWBS) and FDG PET/CT were included in the study. Radioiodine (RAI) and FDG uptake of metastatic lesions were evaluated. TSH stimulated serum thyroglobulin (s-Tg) were obtained. RESULTS: 53 of 64 patients (82.8%) were RAI(+) group, and 37 patients (57.8%) were FDG(+) group. Patients in the RAI(-) group showed a higher rate of FDG uptake than RAI(+) group (100.0% vs. 49.1%, p = 0.002). Patients in the FDG(-) group showed a higher rate of RAI uptake than FDG(+) group (100.0% vs. 70.3%, p = 0.002). Patients with s-Tg < 100 ng/ml were frequently observed in the FDG(-)/RAI(+) group and the FDG(+)/RAI(-) group (p = 0.023). And patients with s-Tg ≥ 500 ng/ml were more frequently observed in the FDG(+)/RAI(+) group, compared with the FDG(+)/RAI(-) group (p = 0.036). Reduced disease-specific survival (DSS) was observed in patients with RAI(-) (p = 0.003), FDG(+) (p = 0.006), SUVmax > 3.6 (p<0.001), and s-Tg > 75.8 ng/ml (p = 0.009). In multivariate analysis, only a SUVmax > 3.6 was significantly predictive of DSS (p = 0.006). CONCLUSION: An inverse relationship between RAI and FDG uptake, flip-flop phenomenon, was observed in patients with metastatic lesions of DTC. Reduced disease-specific survival was observed in patients with FDG(+), RAI(-) in metastatic lesions, or high s-Tg value.


Assuntos
Carcinoma/radioterapia , Carcinoma/secundário , Fluordesoxiglucose F18 , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia , Carcinoma/diagnóstico por imagem , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Neoplasias da Glândula Tireoide/metabolismo , Resultado do Tratamento
15.
Br J Cancer ; 108(10): 1978-84, 2013 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-23652310

RESUMO

BACKGROUND: There have been controversies in prognostic impact of mucinous histology on colorectal cancer, and its implication in patients treated with adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is unclear. METHODS: Stage II and III colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Patients were grouped according to the mucinous content: >50%, mucinous adenocarcinoma (MAC); <50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, non-MAC (NMA). Clinicopathological features and disease-free survival (DFS) were compared. RESULTS: Among a total of 521 patients, 27 patients (5.2%) had MAC, 41 patients (7.9%) had AIM, and 453 patients (86.9%) had NMA. Mucinous adenocarcinoma and AIM had higher frequency of proximal location and microsatellite instability, but lower frequency of angiolymphatic invasion. Disease-free survival was significantly worse in the MAC compared with NMA (3-year DFS 57% and 86%, respectively; P<0.001) and AIM (3-year DFS 87%, P=0.01 vs MAC). Multivariate analysis revealed MAC as an independent negative prognostic factor of DFS (adjusted hazard ratio 7.96, 95% confidence interval 3.76-16.8). CONCLUSION: Adenocarcinoma with intermediated mucinous component and MAC have distinct clinicopathological features compared with NMA. Mucinous adenocarcinoma has an adverse prognostic impact on stage II or III colorectal cancer treated with adjuvant FOLFOX.


Assuntos
Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mucinas/análise , Mucinas/metabolismo , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Prognóstico , Estudos Retrospectivos
16.
Br J Cancer ; 108(7): 1425-31, 2013 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-23481187

RESUMO

BACKGROUND: We aimed to determine the role of palliative resection in metastatic colorectal cancer (mCRC) and ascertain which patient populations would benefit most from this treatment. METHODS: A total of 1015 patients diagnosed with mCRC at Seoul National University Hospital between 2000 and 2009 were retrospectively studied. RESULTS: Of the 1015 patients, 168 patients with only liver and/or lung metastasis received curative resection. The remaining 847 patients were treated with palliative chemotherapy and/or palliative resection combined with best supportive care. Palliative resection was performed in 527 (62.2%) cases (complete resection with negative margin (R0) in 93, R1/2 in 434). Resected patients had a more prolonged median overall survival (OS) than unresected patients (21.3 vs 14.1 months; P<0.001). In multivariate analysis, R0 resection was found to be associated with a superior OS compared with R1/2 resection (51.3 vs 19.1 months; P<0.001) and no resection (51.3 vs 14.1 months; P<0.001). When we performed propensity score matching, palliative resection was found to be related to prolonged OS (hazard ratio=0.72, 95% confidence interval=0.59-0.89; P=0.003). CONCLUSION: Palliative resection without residual disease and chemotherapy confers a longer-term survival outcome than palliative chemotherapy alone in mCRC patient subset.


Assuntos
Neoplasias Colorretais/cirurgia , Cuidados Paliativos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Ann Oncol ; 23(10): 2731-2737, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22553194

RESUMO

BACKGROUND: We conducted a population-based retrospective cohort study to investigate the influence of hospital volume, delay of surgery, and both together on the long-term survival of postoperative cancer patients. METHODS: Using information from the Korea Central Cancer Registry from 2001 through 2005 and the National Health Insurance claim database, we determined survival for 147 682 patients who underwent definitive surgery for any of six cancers. RESULTS: Regardless of cancer site, surgical patients in low- to medium-volume hospitals showed significantly worse survival [adjusted hazard ratio (aHR) = 1.36-1.86] than those in high-volume hospitals in multivariable analyses. Among the latter, treatment delays > 1 month were not associated with worse survival for stomach, colon, pancreatic, or lung cancer but were for rectal [aHR = 1.28; 95% confidence interval (CI), 1.17-1.40] and breast (aHR = 1.59; 95% CI, 1.37-1.84) cancer. For patients in low- to medium-volume hospitals, treatment delay was associated with worse survival for all types of cancer (aHR = 1.78-3.81). CONCLUSION: Our findings suggest that the effect of hospital volume and surgical treatment delay on overall survival of cancer patients should be considered in formulating or revising national health policy.


Assuntos
Neoplasias/cirurgia , Taxa de Sobrevida , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , República da Coreia , Estudos Retrospectivos , Listas de Espera , Adulto Jovem
18.
Mol Oral Microbiol ; 27(3): 149-59, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22520385

RESUMO

Streptococcus mutans, a major etiological agent of dental caries, frequently causes systemic disease, such as subacute bacterial endocarditis, if it enters the bloodstream. In this study, the production pathways of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), induced by S. mutans in mouse macrophage were examined using a quantitative real-time polymerase chain reaction and an enzyme-linked immunosorbent assay. The S. mutans stimulated the expression of TNF-α and IL-1ß mRNA at a multiplicity of infection of 1 : 100, which increased at 2 and 4 h, respectively, to 24 h. It also induced the production of high levels of the TNF-α and IL-1ß proteins, which increased at 2 h and reached a peak at 4 and 24 h, respectively. Nuclear factor-κB (NF-κB) was activated and reached a maximum level 30 min after the S. mutans treatment. The expression of TNF-α and IL-1ß mRNA and protein was suppressed by the treatment with pyrrolidine dithiocarbamate, an NF-κB inhibitor. The S. mutans-induced TNF-α expression was suppressed by the presence of SB203580, a p38 mitogen-activated protein (MAP) kinase inhibitor, or SP600125, a Jun N-terminal kinase (JNK) MAP kinase inhibitor. On the other hand, IL-1ß expression was inhibited by extracellular signal-regulated kinase (ERK)/p38/JNK MAP kinase inhibitor pretreatment. In addition, TNF-α production was suppressed more in the Toll-like receptor 2(-/-) (TLR2(-/-)) macrophages than in the TLR4(-/-) macrophages, whereas IL-1ß production was suppressed more in the TLR4(-/-) macrophages than in the TLR2(-/-) macrophages. These results show that S. mutans stimulates the production of TNF-α and IL-1ß in the mouse macrophage cell line, RAW 264.7, by activating ERK/p38/JNK, and NF-κB through TLR2 and TLR4, respectively.


Assuntos
Interleucina-1beta/imunologia , Macrófagos/microbiologia , Streptococcus mutans/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Antracenos/farmacologia , Antioxidantes/farmacologia , Linhagem Celular , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Ensaio de Imunoadsorção Enzimática , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Imidazóis/farmacologia , Mediadores da Inflamação/imunologia , Interleucina-1beta/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Macrófagos/enzimologia , Macrófagos/imunologia , Macrófagos Peritoneais/enzimologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Subunidade p50 de NF-kappa B/antagonistas & inibidores , Subunidade p50 de NF-kappa B/imunologia , Piridinas/farmacologia , Pirrolidinas/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Tiocarbamatos/farmacologia , Fatores de Tempo , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
19.
Nuklearmedizin ; 50(5): 204-13, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21727990

RESUMO

UNLABELLED: The aim of this study is to evaluate the usefulness of (18)F-FDG PET/CT for preoperative stratification of high-risk and low-risk carcinomas in patients with endometrial cancer. PATIENTS, METHODS: 60 women (mean age 53.8±9.9 years) with endometrial cancer, who underwent (18)F-FDG PET/CT for preoperative staging work-up, followed by primary cytoreductive surgery, were enrolled in this study. Maximum and mean standardized uptake values (SUVmax, SUVmean) of endometrial tumors were measured, and compared with the various clinicopathologic findings obtained after surgery. Tumour aggressiveness was classified as high-risk and low-risk carcinomas. Patients with stage I or II, endometrioid adenocarcinoma, histologic grade 1 or 2, invasion of less than half of the myometrium, maximum tumor size less than 2.0 cm, and absence of cervical invasion and lymphovascular space involvement (LVSI) were classified as the low-risk carcinoma group. The remaining patients were classified as the high-risk carcinoma group. RESULTS: In univariate analysis, SUVmax of the primary endometrial tumor was significantly higher in patients who were in a postmenopausal state (p=0.047), large (>2 cm) primary tumor (p<0.001), nonendometrioid subtype (p=0.024), invasion of more than half of the myometrium (p=0.020), or LVSI (p=0.004). SUVmax differed significantly according to FIGO stage (p=0.013) and histologic grade (p<0.001). In multivariate analysis, FIGO stage, histologic grade, LVSI, and maximum tumor size demonstrated a significant association with SUVmax (p<0.001; r=0.843, r(2)=0.711). SUVmean showed similar results. Forty-one (68.3%) patients were diagnosed postoperatively as high-risk and 19 patients (31.7%) as low-risk carcinoma. Patients with high-risk carcinoma (12.1±6.1) showed significantly higher SUVmax than patients with low-risk carcinoma (5.8±2.8, p<0.001). The optimal SUVmax cut-off value of 8.7, determined by ROC analysis, revealed 75.6% sensitivity, 89.5% specificity, and 81.7% accuracy for risk stratification. CONCLUSION: High-risk endometrial cancer might be differentiated by means of higher SUVmax from low-risk endometrial cancer. (18)F-FDG FDG PET/CT can be applied preoperatively for stratification of risk in patients with endometrial cancer.


Assuntos
Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Fluordesoxiglucose F18 , Cuidados Pré-Operatórios/métodos , Medição de Risco/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Técnica de Subtração , Tomografia Computadorizada por Raios X/métodos
20.
AJNR Am J Neuroradiol ; 32(7): 1178-81, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21757523

RESUMO

BACKGROUND AND PURPOSE: Only 1 ultrasonography study that described the variation of the VN had been published at the time our research was begun. The purpose of this study was to evaluate the incidence and type of variation in the course of the cervical VN on thyroid ultrasonography. MATERIALS AND METHODS: From August 2009 to September 2010, 163 consecutive patients were evaluated by sonography for the screening and characterization of thyroid nodules (mean age, 49.0 ± 14.4 years, male:female, 20:143). Two types of variation were defined as follows: 1) anterior variation, when the course of the VNs changed from the typical location to an anterior location in front of the CCA; and 2) medial variation, when the course of the VNs changed from the typical location to a location medial to the CCA (between CCA and thyroid gland). The incidence of the each variation was studied. RESULTS: Variation in the course of the VN occurred in 5.5% (18/326) of cases. The anterior variation was observed in 4.3% (14/326, right:left = 4:10), and the medial variation was observed in 1.2% (4/326, right:left = 3:1). For both variations, the VN was close to or nearly abutted the thyroid gland after it changed course. CONCLUSIONS: Variation in the course of the cervical VN could be assessed by ultrasonography. Two variations were observed in 5.5% of cases. The anterior variation was more common than the medial variation.


Assuntos
Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia/métodos , Nervo Vago/anormalidades , Nervo Vago/diagnóstico por imagem , Adulto , Artérias Carótidas/diagnóstico por imagem , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/estatística & dados numéricos , Nódulo da Glândula Tireoide/epidemiologia , Ultrassonografia/estatística & dados numéricos
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