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1.
Anticancer Res ; 39(8): 4315-4324, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366523

RESUMO

BACKGROUND/AIM: This study aimed to obtain accurate differential diagnosis (DDx) of multicentric carcinogenesis (MC) and intrahepatic metastasis (IM) in recurrent lesions of hepatocellular carcinoma. MATERIALS AND METHODS: A total of 79 patients who underwent re-hepatectomy (2000-2013) were examined. PCR was used to analyze 13 chromosomal microsatellite loci by PCR. On the basis of this genetic analysis, the recurrent lesions were diagnosed as IM, MC or not determined (ND). Subsequently, DDx was compared with types of resection and outcome. RESULTS: The recurrent lesions were diagnosed as IM in 33 patients, MC in 44, and ND in 2. The anatomical resection group included 14 IM lesions (28%) and 36 MC lesions (72%), while the non-anatomical resection group included 19 IM lesions (70%) and 8 MC lesions (30%) (p<0.001). CONCLUSION: Anatomical resection at initial hepatectomy may reduce the likelihood of IM recurrence, leading to a better outcome for patients with HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Metástase Neoplásica/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Carcinogênese/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Diagnóstico Diferencial , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia
2.
Int J Surg Case Rep ; 55: 140-144, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30731301

RESUMO

INTRODUCTION: Acquired inhibition of coagulation factors is a rare disease, and the diagnosis is often difficult and delayed. We experienced a deficiency in all coagulation factors after hepatobiliary surgery. CASE PRESENTATION: Extended left liver resection was undertaken and hepaticojejunostomy was performed in a 70-year-old man. He had suffered from a high fever caused by cholangitis for 35 days. The major cause was a narrowing of the hepaticojejunostomy, and reconstruction was carried out. Twenty-four days later, there was a sudden massive bleed from his nose and the surgical site. Steroid pulse therapy was used as a treatment because cross mixing and some blood tests revealed the patient was experiencing an inhibition of all coagulation factors, and consequently the levels of coagulation factors dramatically recovered. DISCUSSION: We considered malignancy and surgical damages to be the underlying cause. The reported treatment and examination will help clinicians explore additional reasons for massive bleeding after a severe physical injury. CONCLUSION: We have described the first case of acquired inhibition of all coagulation factors associated with extended left lobectomy.

3.
Int J Surg Case Rep ; 52: 28-34, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30308425

RESUMO

INTRODUCTION: Cystic duct carcinoma is a rare disease, and only 33 cases reported worldwide have completely fulfilled the criteria first established by Farrar in 1951. Here we describe an extremely rare case of early cystic duct carcinoma that fulfilled the Farrar criteria, the papillary tumour protruding into the common bile duct, leading to obstructive jaundice. CASE PRESENTATION: A 76-year-old man visited a clinic with icteric conjunctivae, and was referred to our hospital for investigation of suspected obstructive jaundice. He was initially diagnosed as having a distal bile duct carcinoma on the basis of ultrasonography (US), endoscopic retrograde cholangiopancreatography (ERCP), and magnetic resonance cholangiography (MRC), and underwent pancreatoduodenectomy with regional lymphadenectomy. Macroscopic examination showed that the stalk of the papillary tumour originated from the cystic duct, and that the protruding lesion was 50 mm in size. Histopathological examination revealed the tumour to be a papillary adenocarcinoma confined within the fibromuscular layer, with no evidence of lymph node metastasis. Therefore, the final diagnosis was early cystic duct carcinoma. CONCLUSION: To our knowledge, this is the first case report of obstructive jaundice due to early carcinoma of the cystic duct protruding into the bile duct, with characteristics fulfilling the Farrar criteria.

4.
Ann Gastroenterol Surg ; 2(5): 367-375, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30238078

RESUMO

Aim: The globulin-to-albumin ratio (GAR) is useful for prognostication of patients with various cancers. However, the significance of GAR in gastric cancer (GC) remains unclear. Our purpose was to investigate the relationship between the GAR and outcome after curative resection in GC patients. Methods: Three-hundred and seventy-six patients who had undergone curative resection for GC were retrospectively reviewed. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with overall survival (OS), and their cut-off values were identified using receiver operating characteristic (ROC) curve analyses. Kaplan-Meier analysis and log-rank test were used for comparison of OS and relapse-free survival (RFS). Results: Multivariate analysis using 17 clinical characteristics selected by univariate analyses revealed that GAR (>0.80/≤0.80) was significantly associated with OS (hazard ratio [HR], 2.305; 95% CI, 1.122-4.735; P = 0.023), as well as lymph node metastasis (presence/absence) (HR, 2.417; 95% CI, 1.077-5.426; P = 0.032), neutrophil-to-lymphocyte ratio (>2.7/≤2.7) (HR, 2.368; 95% CI, 1.138-4.930; P = 0.002), and serosal invasion (presence/absence) (HR, 3.443; 95% CI, 1.048-11.31; P = 0.042). Kaplan-Meier analysis and log-rank test demonstrated that the OS and RFS of patients with a high GAR (>0.80) were significantly poorer than those with low GAR (≤0.80). Conclusions: The GAR is a useful predictor of postoperative outcome among GC patients undergoing curative resection.

5.
World J Surg ; 42(7): 2218-2226, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29288307

RESUMO

BACKGROUND: Although a recent study has shown that the C-reactive protein-to-albumin ratio (CAR) can predict the survival in patients with hepatocellular carcinoma (HCC), it is unclear whether CAR can predict the survival after surgery. OBJECTIVE: To investigate the utility of CAR for prediction of postoperative survival among HCC patients with Child-Pugh class A. METHODS: We retrospectively reviewed 239 patients with Child-Pugh class A who were newly diagnosed with HCC and received initial liver resection. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with overall survival (OS), and their cutoff values were identified using receiver operating characteristic curve analyses. The cutoff value of CAR was 0.028. Kaplan-Meier analysis and the log-rank test were used for the comparison of OS and disease-free survival (DFS) between two CAR groups (>0.028/≤0.028). RESULTS: Multivariate analysis using 16 clinical characteristics selected by univariate analyses revealed that CAR (>0.028/≤0.028) (HR, 3.211; 95% CI 1.065-9.680; P = 0.038) was significantly associated with OS, as well as anatomical resection (presence/absence) (HR, 0.275; 95% CI 0.119-0.635; P = 0.275). A significant difference in OS and DFS was observed between patients with low CAR (≤0.028) and patients with high CAR (>0.028). CONCLUSIONS: CAR is a useful predictor of postoperative survival among HCC patients with Child-Pugh class A.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Albumina Sérica/metabolismo , Idoso , Biomarcadores/sangue , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos
6.
Anim Sci J ; 89(1): 12-20, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28856828

RESUMO

Daily feed intake (DFI) is an important consideration for improving feed efficiency, but measurements using electronic feeder systems contain many missing and incorrect values. Therefore, we evaluated three methods for correcting missing DFI data (quadratic, orthogonal polynomial, and locally weighted (Loess) regression equations) and assessed the effects of these missing values on the genetic parameters and the estimated breeding values (EBV) for feeding traits. DFI records were obtained from 1622 Duroc pigs, comprising 902 individuals without missing DFI and 720 individuals with missing DFI. The Loess equation was the most suitable method for correcting the missing DFI values in 5-50% randomly deleted datasets among the three equations. Both variance components and heritability for the average DFI (ADFI) did not change because of the missing DFI proportion and Loess correction. In terms of rank correlation and information criteria, Loess correction improved the accuracy of EBV for ADFI compared to randomly deleted cases. These findings indicate that the Loess equation is useful for correcting missing DFI values for individual pigs and that the correction of missing DFI values could be effective for the estimation of breeding values and genetic improvement using EBV for feeding traits.


Assuntos
Ração Animal , Cruzamento , Ingestão de Alimentos/genética , Métodos de Alimentação , Característica Quantitativa Herdável , Suínos/genética , Suínos/fisiologia , Ração Animal/economia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Conjuntos de Dados como Assunto , Feminino , Masculino , Análise de Regressão
7.
J Surg Oncol ; 116(8): 1166-1175, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28853157

RESUMO

BACKGROUND AND OBJECTIVES: Although the globulin-to-albumin ratio (GAR) is useful for prognostication of patients with various cancers, its relationship with hepatocellular carcinoma (HCC) remains unclear. The study aims to investigate the relationship between GAR and postoperative survival among patients with HCC undergoing potentially curative liver resection (LR). METHODS: We retrospectively reviewed 368 patients with newly diagnosed HCC who underwent initial and potentially curative LR. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with overall survival (OS). Kaplan-Meier analysis and log-rank test were used to compare OS and disease-free survival (DFS). RESULTS: The result of multivariate analysis using 25 clinical characteristics selected by univariate analysis revealed that the GAR (≥0.918/<0.918) was significantly associated with OS (hazard ratio [HR], 2.398; 95% confidence interval [CI], 1.012-5.683; P = 0.047), as well as platelet count (<14/≥14, ×104 /mm3 ) and portal vein invasion (presence/absence). Kaplan-Meier analysis and log-rank test demonstrated that the OS and DFS of patients with a high GAR (>0.918) were significantly worse than that of patients with a low GAR (≤0.918). CONCLUSIONS: The GAR is a useful predictor of postoperative survival among patients with HCC undergoing potentially curative LR.


Assuntos
Carcinoma Hepatocelular/cirurgia , Globulinas/análise , Hepatectomia , Neoplasias Hepáticas/cirurgia , Albumina Sérica/análise , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
8.
Cancer Med ; 5(9): 2544-57, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27485632

RESUMO

NRF2 stabilizes redox potential through genes for glutathione and thioredoxin antioxidant systems. Whether blockade of glutathione and thioredoxin is useful in eliminating cancer stem cells remain unknown. We used xenografts derived from colorectal carcinoma patients to investigate the pharmacological inhibition of glutathione and thioredoxin systems. Higher expression of five glutathione S-transferase isoforms (GSTA1, A2, M4, O2, and P1) was observed in xenograft-derived spheroids than in fibroblasts. Piperlongumine (2.5-10 µmol/L) and auranofin (0.25-4 µmol/L) were used to inhibit glutathione S-transferase π and thioredoxin reductase, respectively. Piperlongumine or auranofin alone up-regulated the expression of NRF2 target genes, but not TP53 targets. While piperlongumine showed modest cancer-specific cell killing (IC50 difference between cancer spheroids and fibroblasts: P = 0.052), auranofin appeared more toxic to fibroblasts (IC50 difference between cancer spheroids and fibroblasts: P = 0.002). The synergism of dual inhibition was evaluated by determining the Combination Index, based on the number of surviving cells with combination treatments. Molar ratios indicated synergism in cancer spheroids, but not in fibroblasts: (auranofin:piperlongumine) = 2:5, 1:5, 1:10, and 1:20. Cancer-specific cell killing was achieved at the following drug concentrations (auranofin:piperlongumine): 0.25:2.5 µmol/L, 0.5:2.5 µmol/L, or 0.25:5 µmol/L. The dual inhibition successfully decreased CD44v9 surface presentation and delayed tumor emergence in nude mouse. However, a small subpopulation persistently survived and accumulated phosphorylated histone H2A. Such "persisters" still retained lesser but significant tumorigenicity. Thus, dual inhibition of glutathione S-transferase π and thioredoxin reductase could be a feasible option for decreasing the tumor mass and CD44v9-positive fraction by disrupting redox regulation.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/metabolismo , Glutationa/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Tiorredoxinas/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/genética , Quebras de DNA de Cadeia Dupla , Modelos Animais de Doenças , Sinergismo Farmacológico , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , Glutationa Transferase/antagonistas & inibidores , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Humanos , Isoenzimas , Camundongos , NADP/biossíntese , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Tiorredoxina Dissulfeto Redutase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Int Surg ; 100(4): 593-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25875538

RESUMO

The authors evaluated the usefulness of intraoperative photodynamic eye (PDE) observation in patients with nonocclusive mesenteric ischemia (NOMI). Between February 2012 and July 2013, 6 patients who had undergone emergency surgery for NOMI were enrolled. Intraoperative PDE observation was performed to decide the adequate length of bowel resection including all skipped dark spots, which could not be detected as ongoing mucosal ischemic changes under visible light observation. All ongoing mucosal ischemic changes were easily detected as dark spots using PDE observation in all 6 patients. The mean length of adequate ileal resection (92 ± 48 cm) was significantly longer than that of ischemic ileum (85 ± 50 cm) (mean ± SD) (P = 0.043). After resection of an adequate length of bowel, all the patients had a good course until discharge without incidents due to residual bowel ischemia, except for 1patient who died. PDE observation is useful for deciding the adequate length of bowel to resect, including ongoing mucosal ischemic changes that cannot be detected under visible light observation. In patients with NOMI, resection of an adequate length of bowel is necessary to prevent postoperative incidents due to residual bowel ischemia.


Assuntos
Diagnóstico por Imagem/instrumentação , Isquemia Mesentérica/cirurgia , Idoso , Idoso de 80 Anos ou mais , Emergências , Feminino , Fluorescência , Corantes Fluorescentes/administração & dosagem , Humanos , Verde de Indocianina/administração & dosagem , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
10.
Oncology ; 88(5): 309-19, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25591719

RESUMO

Glycolysis and the pentose phosphate pathway (PPP) are preferentially activated in cancer cells. Accumulating evidence indicated the significance of the altered glucose metabolism in cancer, but the implication for oncotherapy remains unclear. Here we report that the synthesis of glycolytic and PPP enzymes is almost ubiquitously augmented in colorectal carcinoma (CRC) specimens. The mammalian target of rapamycin (mTOR) inhibitor INK128 (300 nM) and phytochemical Avemar (1 mg/ml) inhibited the synthesis of PPP enzymes in CRC cell lines. INK128 (150-600 nM) and resveratrol (75-300 µM) inhibited aerobic glycolysis in the cell lines. INK128 (300 nM) and Avemar (1 mg/ml) decreased the NADPH/NADP(+) ratio as well as the GSH/GSSG ratio in the cell lines. Finally, per os administration of INK128 (0.8 mg/kg) or Avemar (1 g/kg) suppressed tumor growth and delayed tumor formation by transplantable CRC specimens derived from patients. Taken together, pharmacological inhibition of the mTOR-PPP axis is a promising therapeutic strategy against CRCs.


Assuntos
Antineoplásicos/farmacologia , Benzoxazóis/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Via de Pentose Fosfato/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pirimidinas/farmacologia , Estilbenos/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Benzoxazóis/administração & dosagem , Western Blotting , Linhagem Celular Tumoral , Neoplasias Colorretais/enzimologia , Feminino , Glucose/metabolismo , Dissulfeto de Glutationa/metabolismo , Glicólise/efeitos dos fármacos , Humanos , Japão , Ácido Láctico/metabolismo , Camundongos , Camundongos Nus , Extratos Vegetais/administração & dosagem , Pirimidinas/administração & dosagem , Receptores de Peptídeos/metabolismo , Resveratrol , Estilbenos/administração & dosagem , Transplante Heterólogo , Resultado do Tratamento
11.
Anticancer Res ; 34(12): 7219-26, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25503152

RESUMO

AIM: To investigate the significance of the Glasgow Prognostic Score (GPS) for predicting the postoperative survival of gastric cancer (GC) patients with a normal preoperative serum level of carcinoembryonic antigen (CEA). Because CEA is a useful marker for prognostication of several types of cancer, some patients with GC have a normal CEA level. On the other hand, the GPS has been established as a valuable inflammation-based prognostic system for cancer patients. PATIENTS AND METHODS: Among 650 patients who had undergone elective surgery for GC, 425 with a normal preoperative serum CEA level (≤5.0 ng/ml) were enrolled. Uni- and multivariate analyses were performed to evaluate the relationship of the GPS to overall survival. The Kaplan-Meier analysis and log rank test were used to compare the survival curves among patients with GPS 0, 1 and 2. RESULTS: Multivariate analysis using clinical characteristics selected from univariate analyses revealed that the GPS (0, 1/2) was associated with overall survival (hazard ratio=2.048; 95% C.I. (confidence interval)=1.002-4.185; p=0.049) along with age (≤70/>70) (years), sex, tumor type (3, 4, 5/0, 1, 2), lymph node metastasis (presence/absence) and platelet count (≤35/>35) (×10(4)/mm(3)). The Kaplan-Meier analysis and log rank test demonstrated that there were significant differences in overall survival among patients with GPS 0, 1 and 2 (p<0.001). CONCLUSION: Even if GC patients have a normal serum level of CEA, the GPS is able to predict their postoperative survival and classify such patients into three independent groups before surgery.


Assuntos
Antígeno Carcinoembrionário/sangue , Inflamação/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Idoso , Biomarcadores Tumorais/sangue , Bases de Dados Factuais , Feminino , Humanos , Inflamação/patologia , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Neoplasias Gástricas/cirurgia
12.
Anticancer Res ; 34(8): 4223-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25075051

RESUMO

AIM: To investigate the influence of clinical characteristics including nutritional markers on postoperative survival in patients undergoing total gastrectomy (TG) for gastric cancer (GC). PATIENTS AND METHODS: One hundred fifty-four patients were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to explore the most valuable clinical characteristic that was associated with postoperative survival. RESULTS: Multivariate analysis using twelve clinical characteristics selected from univariate analyses revealed that age (≤ 72/>72), carcinoembryonic antigen (≤ 20/>20) (ng/ml), white blood cell count (≤ 9.5/>9.5) (× 10(3)/mm(3)), prognostic nutritional index (PNI) (≤ 45/>45) and lymph node metastasis (negative/positive) were associated with postoperative survival. Kaplan-Meier analysis and log-rank test showed that patients with higher PNI (>45) had a higher postoperative survival rate than those with lower PNI (≤ 45) (p<0.001). CONCLUSION: PNI is associated with postoperative survival of patients undergoing TG for GC and is able to divide such patients into two independent groups before surgery.


Assuntos
Gastrectomia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
13.
Mol Cell Biol ; 31(3): 495-506, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21098121

RESUMO

Pot1 is a single-stranded telomere-binding protein that is conserved from fission yeast to mammals. Deletion of Schizosaccharomyces pombe pot1(+) causes immediate telomere loss. S. pombe Rqh1 is a homolog of the human RecQ helicase WRN, which plays essential roles in the maintenance of genomic stability. Here, we demonstrate that a pot1Δ rqh1-hd (helicase-dead) double mutant maintains telomeres that are dependent on Rad51-mediated homologous recombination. Interestingly, the pot1Δ rqh1-hd double mutant displays a "cut" (cell untimely torn) phenotype and is sensitive to the antimicrotubule drug thiabendazole (TBZ). Moreover, the chromosome ends of the double mutant do not enter the pulsed-field electrophoresis gel. These results suggest that the entangled chromosome ends in the pot1Δ rqh1-hd double mutant inhibit chromosome segregation, signifying that Pot1 and Rqh1 are required for efficient chromosome segregation. We also found that POT1 knockdown, WRN-deficient human cells are sensitive to the antimicrotubule drug vinblastine, implying that some of the functions of S. pombe Pot1 and Rqh1 may be conserved in their respective human counterparts POT1 and WRN.


Assuntos
Segregação de Cromossomos , Cromossomos Fúngicos/metabolismo , DNA Helicases/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/enzimologia , Schizosaccharomyces/genética , Proteínas de Ligação a Telômeros/metabolismo , Segregação de Cromossomos/efeitos dos fármacos , Exodesoxirribonucleases/metabolismo , Inativação Gênica/efeitos dos fármacos , Células HeLa , Humanos , Viabilidade Microbiana/efeitos dos fármacos , Mitose/efeitos dos fármacos , Mutação/genética , RecQ Helicases/metabolismo , Recombinação Genética/efeitos dos fármacos , Proteína de Replicação A/metabolismo , Schizosaccharomyces/citologia , Schizosaccharomyces/efeitos dos fármacos , Telômero/metabolismo , Tiabendazol/farmacologia , Vimblastina/farmacologia , Helicase da Síndrome de Werner
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