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1.
Int J Clin Oncol ; 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32200481

RESUMO

BACKGROUND: Fluorouracil and leucovorin combined with oxaliplatin or irinotecan plus bevacizumab (Bmab) or cetuximab (Cmab) are now widely accepted treatment options as first-line or second-line chemotherapy for metastatic colorectal cancer (mCRC). Sequential chemotherapy with oral 5-FU backbone for mCRC without using central venous ports is beneficial for both patients and physicians. We designed the SOBIC trial to validate the effectiveness of the first- and second-line oral combination chemotherapy for mCRC. PATIENTS AND METHODS: From May 2010 through March 2013, 52 patients were enrolled from 47 institutions in the Hyogo Colorectal Cancer Surgery Group. First-line chemotherapy was S-1 + oxaliplatin (SOX) plus Bmab, and second-line chemotherapy after first-line failure was irinotecan + S-1 (IRIS) + Cmab, IRIS + Bmab, or IRIS based on the KRAS status. RESULTS: The 50 finally included patients received first-line chemotherapy. Second-line therapy was administered to 20 patients (40%): 12 patients received IRIS + Cmab and 8 patients received IRIS + Bmab. The median follow-up period was 48.6 months (range 35-67 months). The median second progression-free survival was 24.2 months (95% confidence interval [CI] 17.7-35.2). The response rate after first- and second-line chemotherapy was 46.7% and 15%, respectively. The median overall survival was 35.2 months (95% CI: 27.8 to not reached). The main grade 3-4 adverse events were sensory neuropathy (18%) and fatigue (10%). There were no treatment-related deaths. CONCLUSION: Sequential S-1-based combination regimens including oxaliplatin, irinotecan, Bmab, and Cmab were beneficial for patients with mCRC.

2.
Int J Mol Sci ; 21(5)2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32164307

RESUMO

A clinical study carried out previously by our group has demonstrated that yogurt manufactured with a plant-derived lactic acid bacterium, Lactobacillus plantarum SN13T, significantly reduces the γ-glutamyl transpeptidase (γ-GTP) level as a liver-function parameter. In the present study, we show that with the oral administration of live SN13T cells, alcohol-poisoning symptoms in mice are improved, and the condition does not become fatal. However, prior to the simultaneous administration with ethanol, when the cells were heat-killed or sonicated, the improvement was not observed, and almost all of the mice died. In addition, the dysbiosis of the intestinal microbiota observed in the mice administered with ethanol was restored by simultaneous administration with live SN13T cells. Furthermore, by analyzing the metabolites detected in contents from the mouse cecum, it was demonstrated that the increase in nonvolatile putrefactive amines observed in the ethanol-administration group was reduced by simultaneous administration with live SN13T cells. Judging from these results, the lactic acid bacterial cells capable of reaching the living bowels prevent ethanol-induced poisoning and restore the intestinal microbiota.

3.
Kyobu Geka ; 72(9): 655-657, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31506404

RESUMO

A 60-year-old man consulted a clinic complains of sore throat. Squamous cell carcinoma of the hypopharynx and adenocarcinoma of the stomach were pointed out and he was refered to our hospital. As a result of detailed systemic examination, squamous cell carcinoma of the esophagus and squamous cell carcinoma of the right lung were also pointed out, which led to a diagnosis of synchronous quadruple cancer. On the basis of discussions among multiple clinical departments, systemic chemotherapy with cisplatin(CDDP), fluorouracil (5-FU) and docetaxel(DTX) was preceded locolegional therapies. After that, complete thoracoscopic right lower lobectomy and then a laparoscopic distal gastrectomy was performed. Radiation therapy was applied for hypopharyngeal cancer. Finally, endoscopic submucosal dissection for esophageal cancer was performed. Twenty months have passed since the last treatment, the patient is alive with a relapse-free condition.


Assuntos
Neoplasias Primárias Múltiplas , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Neoplasias Esofágicas , Fluoruracila , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
4.
Biol Pharm Bull ; 42(9): 1581-1589, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474718

RESUMO

As a bacterium used in industry for production of several amino acids, an endotoxin-free Corynebacterium (C.) glutamicum is well known. However, it is also true that the endotoxin-producing other Corynebacterium species is present. An aim of this study is to obtain a lactic acid bacterium (LAB) that produces ornithine and citrulline at high levels. We successfully isolated a strain, designated K-28, and identified it as Weissella (W.) confusa. The production of ornithine and citrulline by K-28 was 18 ± 1 and 10 ± 2 g/L, respectively, with a 100 ± 9% conversion rate when arginine was continuously fed into a jar fermenter. Although the ornithine high production using C. glutamicum is industrially present, the strains have been genetically modified. In that connection, the wild-type of C. glutamicum produces only 0.5 g/L ornithine, indicating that W. confusa K-28 is superior to C. glutamicum to use a probiotic microorganism. We confirmed that W. confusa K-28 harbors an arginine deiminase (ADI) gene cluster, wkaABDCR. The production of ornithine and the expression of these genes significantly decreased under the aerobic condition rather than anaerobic one. The expression level of the five genes did not differ with or without arginine, suggesting that the production of amino acids in the K-28 strain was not induced by exogenous arginine.


Assuntos
Citrulina/biossíntese , Flores/microbiologia , Ornitina/biossíntese , Senna (Planta)/microbiologia , Weissella/metabolismo , Animais , Citrulina/toxicidade , Masculino , Ornitina/toxicidade , Probióticos , Ratos Sprague-Dawley , Ratos Wistar , Testes de Toxicidade Aguda , Weissella/isolamento & purificação
5.
J Antibiot (Tokyo) ; 72(11): 834-842, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31399643

RESUMO

Lactic acid bacteria (LAB) confer health benefits to human when administered orally. We have recently isolated several species of LAB strains from plant sources, such as fruits, vegetables, flowers, and medicinal plants. Since antibiotics used to treat bacterial infection diseases induce the emergence of drug-resistant bacteria in intestinal microflora, it is important to evaluate the susceptibility of LAB strains to antibiotics to ensure the safety and security of processed foods. The aim of the present study is to determine the minimum inhibitory concentration (MIC) of antibiotics against several plant-derived LAB strains. When aminoglycoside antibiotics, such as streptomycin (SM), kanamycin (KM), and gentamicin (GM), were evaluated using LAB susceptibility test medium (LSM), the MIC was higher than when using Mueller-Hinton (MH) medium. Etest, which is an antibiotic susceptibility assay method consisting of a predefined gradient of antibiotic concentrations on a plastic strip, is used to determine the MIC of antibiotics world-wide. In the present study, we demonstrated that Etest was particularly valuable while testing LAB strains. We also show that the low susceptibility of the plant-derived LAB strains against each antibiotic tested is due to intrinsic resistance and not acquired resistance. This finding is based on the whole-genome sequence information reflecting the horizontal spread of the drug-resistance genes in the LAB strains.

6.
J Pharm Pharm Sci ; 22(1): 407-417, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31430249

RESUMO

PURPOSE: The dose of mycophenolate mofetil (MMF) used to prevent rejection after lung transplantation is often adjusted based on the 12-hour area under the concentration-time curve (AUC0-12) of mycophenolic acid (MPA). A limited sampling strategy (LSS) is useful to define the pharmacokinetic (PK) profiles of MPA and mycophenolic acid acyl glucuronide (AcMPAG). Therefore, this study aimed to design a LSS based on multiple linear regression for estimating the AUC0-12 of MPA and AcMPAG at the minimum blood sampling points in Japanese lung transplant patients with concomitant tacrolimus. METHODS: Forty-five lung transplantation recipients were enrolled in a PK study of MPA, mycophenolic acid glucuronide (MPAG), and AcMPAG. The plasma MPA, MPAG, and AcMPAG concentrations were determined just before and at 0.5, 1, 2, 4, 8, and 12 hours after dosing. The AUC0-12 of MPA and AcMPAG was calculated using a linear trapezoidal rule from the plasma concentration of each blood sampling time. LSS was used to develop models for estimated AUC in the model group (n = 23) and was evaluated in the validation group (n = 22). RESULTS: The best three time-point equation was 4.04 + 1.64·C1 + 3.08·C4 + 5.17·C8 for MPA, and -0.13 + 3.01·C1 + 3.51·C4 + 5.74·C8 for AcMPAG. The prediction errors (PE) and the absolute prediction errors (APE) were within the clinically acceptable ± 5% and 15% range, respectively (MPA: PE = 2.00%, APE = 11.66%, AcMPAG: PE = 0.98%, APE = 14.69%). The percentage of estimated AUC0-12 within ± 15% of the observed AUC0-12 was 77.27% for MPA and 81.82% for AcMPAG. CONCLUSION: LSS using three time-point (C1, C4, and C8) provides the most reliable and accurate simultaneous estimation of the AUC0-12 of MPA and AcMPAG in Japanese lung transplant patients.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31433681

RESUMO

Mechanical unloading impairs cytosolic calcium (Ca2+) homeostasis in skeletal muscles. In this study, we investigated whether sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) itself or one of the regulators of the Ca2+ SERCA pump, sarcolipin (SLN), is altered to deregulate Ca2+ homeostasis in cast-immobilized, atrophied muscles. Hindlimb muscles of 8-week-old male C57BL/6J mice were subjected to bilateral cast immobilization for 2 weeks. Two-week cast-immobilization induced both body weight and skeletal muscle loss. Highly phosphorylated CaMKII in the atrophied muscles suggested that cytosolic Ca2+ concentration was elevated. Extremely high expression levels of SLN mRNA and protein were observed in the atrophied muscles. Up-regulation of SLN at the transcriptional level was supported by low RCAN1 expression, which is a negative regulator of SLN. We treated C2C12 cells with dexamethasone to mimic muscle atrophy in vitro and showed a direct relationship between high SLN mRNA expression and low Ca2+ uptake by sarcoplasmic reticulum. Since SLN reportedly plays a role in non-shivering thermogenesis, we performed a cold tolerance test of the whole body. As a result, we found that mice with cast immobilization showed high cold tolerance, suggesting that cast-immobilization promoted whole-body thermogenesis. Although the activity level was decreased during cast-immobilization without change in food intake, adipose tissue weights also decreased significantly after cast immobilization. Concomitantly, we conclude that cast-immobilization of hindlimb increased thermogenesis in C57Bl/6J mice, probably via high expression of sarcolipin.

8.
Molecules ; 24(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426284

RESUMO

Allergic disease is one of the most important and common health problems worldwide. We have previously demonstrated that a fig leaf-derived lactic acid bacterium Lactobacillus (Lb.) paracasei IJH-SONE68 produces a novel exopolysaccharide (EPS). Furthermore, we have shown that the EPS inhibits the catalytic activity of hyaluronidase (EC 3.2.1.36) promoting inflammatory reactions. To evaluate the anti-allergy and anti-inflammatory effects of the EPS, in the present study, we employed the picryl-chloride-induced delayed-type (type IV) allergy model mice, which is used to evaluate the contact dermatitis. Oral administration of the EPS was observed to reduce the ear swelling in the model mice. We also observed that the overexpression of ear interleukin-4 (T helper (Th) 2 cytokine) mRNA and the increase in serum immunoglobulin E (IgE) are repressed. However, the expression of interferon-γ (Th1 cytokine) was not accelerated in all of the allergen-challenged model mice. The improvement may be responsible for the Th2 downregulation rather than the Th1 upregulation. In addition, the symptom of immediate-type (type I) allergy model mice was improved by oral administration of the IJH-SONE68 cell (data not shown). We can conclude that the IJH-SONE68-derived EPS is useful to improve the type I and IV allergies including atopic dermatitis.


Assuntos
Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Dermatite de Contato/prevenção & controle , Fármacos Dermatológicos/farmacologia , Lactobacillus paracasei/química , Polissacarídeos Bacterianos/farmacologia , Administração Oral , Alérgenos/imunologia , Alérgenos/metabolismo , Animais , Antialérgicos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Dermatite de Contato/etiologia , Dermatite de Contato/imunologia , Dermatite de Contato/patologia , Fármacos Dermatológicos/isolamento & purificação , Modelos Animais de Doenças , Orelha , Expressão Gênica/efeitos dos fármacos , Hialuronoglucosaminidase/antagonistas & inibidores , Hialuronoglucosaminidase/imunologia , Hialuronoglucosaminidase/metabolismo , Imunoglobulina E/sangue , Imunoglobulina E/genética , Interferon gama/genética , Interferon gama/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Lactobacillus paracasei/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Cloreto de Picrila/administração & dosagem , Polissacarídeos Bacterianos/isolamento & purificação , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
9.
Ther Drug Monit ; 41(5): 615-619, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31033859

RESUMO

BACKGROUND: Sirolimus and tacrolimus require accurate drug dosing based on their target blood levels to produce better clinical outcomes, specifically, the avoidance of drug-induced adverse effects and the maintenance of efficacy. However, because the ideal dose of sirolimus and the schedule for measuring its blood levels are unclear in lung transplant patients, an index is required for estimating sirolimus blood concentrations. The aim of this work is to study the correlation between the trough concentration/dose normalized by body weight (C0/D) ratios of sirolimus and tacrolimus in lung transplant patients. METHODS: Thirteen lymphangiomyomatosis patients who underwent lung transplantation and were treated with sirolimus and tacrolimus from February 2015 to July 2018 were divided into 2 groups, one receiving twice-daily (TD, n = 6) and the other once-daily (OD, n = 7) tacrolimus formulations. The correlation between the C0/D ratio of sirolimus and patient background was evaluated using Spearman's rank correlation coefficient. Correlations between sirolimus and tacrolimus C0/D ratios or doses were analyzed by single regression analysis. RESULTS: Significant correlations were found between the C0/D ratios of sirolimus and tacrolimus. The regression equations from the initial data of TD and OD groups at steady state were y = 1.880x + 32.636 (adjusted R = 0.743, P = 0.017) and y = 1.684x + 38.816 (adjusted R = 0.919, P < 0.001), respectively. In addition, the regression equations from all data of TD and OD groups were y = 1.883x + 4.170 (adjusted R = 0.546, P < 0.001) and y = 1.950x + 43.188 (adjusted R = 0.898, P < 0.001), respectively. A significant correlation between the dosage of sirolimus and tacrolimus was observed only in the OD group, with relatively low accuracy. CONCLUSIONS: Blood sirolimus concentrations can be estimated using the C0/D ratio of tacrolimus, suggesting that the C0/D ratio of tacrolimus is an index of required sirolimus dosage and the frequency of blood sirolimus concentration measurements.

10.
PLoS One ; 14(2): e0210975, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30742625

RESUMO

PURPOSE: Whereas native lung overinflation has been thought to happen in recipients of single lung transplantation for lymphangioleiomyomatosis because of its increased compliance, there is no study that has reported the details on the change of the native lung volume after single lung transplantation by three-dimensional computed tomography volumetry. The purpose of the present study was to evaluate the lung volume after single lung transplantation for lymphangioleiomyomatosis by three-dimensional computed tomography volumetry and investigate the correlation between the native lung volume change and postoperative pulmonary function. METHODS: We retrospectively reviewed the data of 17 patients who underwent single lung transplantation for lymphangioleiomyomatosis. We defined the ratio of the native lung volume to total lung volume (N/T ratio) as an indicator of overinflation of the native lung. In order to assess changes in the N/T ratio over time, we calculated the rate of change in the N/T ratio which is standardized by the N/T ratio at 1 year after single lung transplantation: rate of change in N/T ratio (%) = {(N/T ratio at a certain year)/(N/T ratio at 1 year)- 1}× 100. RESULTS: We investigated the correlations between the N/T ratio and the pulmonary function test parameters at 1 year and 5 years; however, there was no significant correlation between them. On the other hand, there was a significant negative correlation between the rate of change in the N/T ratio and that in forced expiratory volume in 1 second %predicted (%FEV1) at 5 years after single lung transplantation. CONCLUSION: The single lung transplantation recipients for lymphangioleiomyomatosis showed increased rate of change in the N/T ratio in the long-time course after lung transplantation with the decrease of %FEV1. We expect that these cases will probably cause the overinflation of the native lung in the future.


Assuntos
Imagem Tridimensional , Neoplasias Pulmonares , Transplante de Pulmão , Pulmão , Linfangioleiomiomatose , Tomografia Computadorizada por Raios X , Adulto , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Pulmão/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/cirurgia , Linfangioleiomiomatose/diagnóstico por imagem , Linfangioleiomiomatose/fisiopatologia , Linfangioleiomiomatose/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Gen Thorac Cardiovasc Surg ; 67(9): 788-793, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30790239

RESUMO

OBJECTIVES: Appropriate selection for surgery is particularly important in T4 non-small cell lung cancer patients. In clinical settings, patients those who are positive for T4 criteria occasionally are also positive for T3 factors which are independently defined from original T4 or even have multiple T4 factors. Significance of these factors on prognosis is still unknown. METHODS: We retrospectively reviewed clinicopathorogical data of 113 patients with T4 non-small cell lung cancer those who underwent surgery between 1990 and 2015 in Tohoku University Hospital. Significance on prognosis of single or multiple T4 factors and with or without independent T3 factors were statistically analyzed. RESULTS: No significant difference was seen in the 5-year survival rate between patients with single (35.6%) and multiple (31.4%) T4 factors (P = 0.94), but the rate was significantly lower when patients also had independent T3 factors (19.6%) compared with when they did not (42.5%) (P = 0.011). The 5-year survival rate was particularly lower among patients with invasion of the chest wall or parietal pleura (8.1%) than in those without (40.6%) (P = 0.0052). CONCLUSIONS: Invasion of the chest wall or parietal pleura is poor prognostic factors in T4 non-small cell lung cancer patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Pleura/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Hospitais Universitários , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Recidiva Local de Neoplasia , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Fumar , Taxa de Sobrevida , Parede Torácica/patologia , Parede Torácica/cirurgia
12.
Surg Today ; 49(2): 143-149, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30198048

RESUMO

PURPOSE: The purpose of this study was to assess the usefulness of positron emission tomography/computed tomography (PET/CT) in the differential diagnosis of anterior mediastinal tumors. METHODS: A total of 94 patients with anterior mediastinal masses or nodules (male, n = 41; female, n = 53; age, 17-84 years) were retrospectively evaluated. All patients were evaluated by PET/CT and the masses or nodules were histologically diagnosed in our institution. RESULTS: Anterior mediastinal masses and nodules were classified into two disease categories: Low (thymic hyperplasia, thymoma, mature teratoma, and MALT lymphoma) and High (thymic carcinoid, thymic cancer, diffuse large B-cell lymphoma, T-cell lymphoblastic lymphoma, Hodgkin's lymphoma, and malignant germ cell tumors) groups. The sensitivity and specificity of maximum standardized uptake value (SUVmax) 7.5 for the detection of High group were 77% and 100%, respectively. The SUVmax distributions of the WHO histological thymoma types and Masaoka stage thymomas extensively overlapped. Masaoka stage III thymomas had significantly higher SUVmax than Masaoka stage I thymomas. Regarding the TNM classification, the SUVmax of T3 and T1b thymomas was higher than T1a thymoma. CONCLUSION: Although the SUVmax of each disease overlapped, PET/CT findings provided useful information for the differential diagnosis of anterior mediastinal masses.


Assuntos
Neoplasias do Mediastino/diagnóstico por imagem , Mediastino/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Linfoma/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Sensibilidade e Especificidade , Teratoma/diagnóstico por imagem , Timoma/diagnóstico por imagem , Adulto Jovem
13.
Intern Med ; 58(8): 1145-1150, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30568114

RESUMO

Chronic hypersensitivity pneumonitis is an interstitial pneumonia caused by an immunological reaction to the chronic inhalation of an antigen. Little is known, however, about the pathological change of the pulmonary lesions. A 33-year-old man was diagnosed with chronic bird-related hypersensitivity pneumonitis based on the findings of a surgical lung biopsy and an inhalation provocation test. He underwent lung transplantation at 8 years after the diagnosis because of disease progression. We conclude that the analysis of the explant suggests that the presence of extensive fibrosis in the centrilobular and perilobular area with bridging fibrosis is a form of pathological progression of chronic hypersensitivity pneumonitis.


Assuntos
Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/tratamento farmacológico , Biópsia/métodos , Aves , Transplante de Pulmão/métodos , Pulmão/patologia , Pulmão/cirurgia , Adulto , Animais , Doença Crônica/terapia , Progressão da Doença , Fibrose/diagnóstico , Fibrose/cirurgia , Humanos , Masculino , Resultado do Tratamento
14.
Cancer Sci ; 109(12): 3934-3942, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30246377

RESUMO

The purpose of the present study was to assess the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan against locally advanced lower rectal cancer according to UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms. Between 2009 and 2016, 46 patients with resectable rectal cancer (T3-T4, N0-N2, M0) received preoperative chemoradiotherapy consisting of 80 mg/m2 per day tegafur/gimeracil/oteracil (S-1; days 1-5, 8-12, 22-26, and 29-33), 60 mg/m2 per day irinotecan (days 1, 8, 22, and 29), and 45 Gy radiation (1.8 Gy/day, 5 days per week for 5 weeks). Six to eight weeks after completing chemoradiotherapy, total mesorectal excision was carried out. Patients with UGT1A1 polymorphisms were divided into WT (n = 26), heterozygous (n = 15), and homozygous (n = 5) groups, the latter including double heterozygosities. We evaluated associations between clinical characteristics, including UGT1A1 polymorphisms, and chemoradiotherapy efficacy and toxicity. Incidence rates of grade 3+ neutropenia and diarrhea were 17.0% and 30.4%, respectively. Relative dose intensity was 89.3%. Pathological complete response rate (grade 3) was 26.1%, and the good response (grade 2/3) rate was 84.8%. UGT1A1 polymorphisms were significantly associated with neutropenia and pathological good responses, but not with diarrhea. UGT1A1 polymorphism was the only predictive factor for pathological good responses. Our results indicate that UGT1A1 polymorphism is a predictive factor to determine the clinical efficacy of preoperative chemoradiotherapy and hematological toxicity induced by chemoradiotherapy using irinotecan in locally advanced rectal cancer patients.


Assuntos
Quimiorradioterapia/métodos , Glucuronosiltransferase/genética , Irinotecano/administração & dosagem , Ácido Oxônico/administração & dosagem , Polimorfismo de Nucleotídeo Único , Neoplasias Retais/terapia , Tegafur/administração & dosagem , Adulto , Idoso , Quimiorradioterapia/efeitos adversos , Fracionamento da Dose de Radiação , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Irinotecano/efeitos adversos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Ácido Oxônico/efeitos adversos , Variantes Farmacogenômicos , Neoplasias Retais/genética , Neoplasias Retais/patologia , Tegafur/efeitos adversos , Resultado do Tratamento
15.
Oncol Rep ; 40(3): 1761-1768, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015929

RESUMO

The need for effective treatment of KRAS­mutant lung cancer is an emerging issue. Rho GTPase­activating protein 35 (ARHGAP35) is reported to be a possible molecular target for lung adenocarcinoma. We investigated the effect of long­term ARHGAP35 suppression on the proliferation, migration and molecular dynamics of lung adenocarcinomas harboring KRAS and EGFR gene mutations. Lung adenocarcinoma cell lines A549 (KRAS­mutant) and PC9 and H1975 (EGFR­mutants) were used, and ARHGAP35 knockdown was carried out using puromycin. Cell viability, migration and molecular dynamics were assayed 1 month after introducing small hairpin RNA. The compensatory upregulated mechanism was screened by western blotting and confirmed by a specific inhibitor. Finally, we tested the effects of cosuppression of the SRC/ARHGAP35 axis and the identified pathway in vitro. ARHGAP35 suppression was attenuated by long­term knockdown of the target genes. Compensatory mechanisms by SRC and STAT3 caused attenuation in A549 cells. After long­term ARHGAP35 knockdown, both A549 and PC9 cells were more sensitive to treatment with a STAT3 inhibitor. The suppressive effect of ARHGAP35 knockdown on migration was sustained, but only modest, in all cell lines. Synergistic and strong growth inhibition was observed with concomitant use of an SRC inhibitor and a STAT3 inhibitor in A549 cells. STAT3 activation compensated for ARHGAP35 knockdown in lung adenocarcinoma with the KRAS mutation. Moreover, cosuppression of the STAT3 pathway and SRC/ARHGAP35 axis may be an effective strategy for treating lung adenocarcinoma, especially in the presence of a KRAS mutation.


Assuntos
Receptores ErbB/genética , Fatores de Troca do Nucleotídeo Guanina/antagonistas & inibidores , Neoplasias Pulmonares/prevenção & controle , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas pp60(c-src)/antagonistas & inibidores , Proteínas Repressoras/antagonistas & inibidores , Fator de Transcrição STAT3/antagonistas & inibidores , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/prevenção & controle , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Proteínas Repressoras/genética , Fator de Transcrição STAT3/genética , Células Tumorais Cultivadas
16.
Respir Res ; 19(1): 116, 2018 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-29895305

RESUMO

Figure 2 of this original publication was incorrectly formatted. The updated Fig. 2 is published in this correction article [1].

17.
Oncotarget ; 9(39): 25474-25490, 2018 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-29876002

RESUMO

Introduction: The follow-up schedule for colorectal cancer patients after curative surgery is inconsistent among the guidelines. Evaluation of time to recurrence (TTR) and survival after recurrence (SAR) may provide evidence for appropriate follow-up. Methods: We assessed 3039 colon cancer (CC) and 1953 rectal cancer (RC) patients who underwent curative surgery between 2007 and 2008. We evaluated the pre- and post-recurrent clinicopathological factors associated with TTR and SAR in each stage of CC and RC. Results: The recurrence rates of stages I, II, and III were 1.2%, 13.1%, and 26.3%, respectively, for CC, and 8.4%, 20.0%, and 30.4%, respectively, for RC. In CC patients, high carcinoembryonic antigen (CEA) level and lymphovascular invasion were independent predictors of short TTR. In RC patients, metastatic factors (liver metastasis in stage III) and venous invasion (stage III) were independent predictors of short TTR. The prognostic factors of SAR were age (stage II CC and stage III RC), female gender (stage III RC), high CEA level (stage II RC), histological type (stage III CRC), nodal status (stage III CC), recurrence within 1 year (stage III RC), M1b recurrence (stage II CRC), local recurrence (stage II CC), and no surgical resection after recurrence (stage II and III CRC). Conclusions: The follow-up schedule for stage I should be different from that for the other stages. We recommend that intensive follow-up is appropriate in stage III CC patients with undifferentiated adenocarcinoma or N2 nodal status, stage II RC patients with high preoperative CEA level, and stage III RC patients.

18.
Pharmacol Res Perspect ; 6(3): e00405, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29850024

RESUMO

Inhaled drugs are critical for the treatment of inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD). To develop better therapeutics for pulmonary disease it is of potential importance to understand molecular mechanisms of local biotransformation in the lung. Alveolar epithelial type II (ATII) cells have a key role in homeostasis in the lung, but little is known about expression patterns of genes encoding cytochrome P450 (CYP) enzymes in ATII cells. In addition, alteration of CYP gene expression has not been fully defined in COPD. We previously established a method to purify ATII cells from the adult human lung using fluorescence-activated cell sorting. By employing this technique we determined gene expression patterns of 14 CYP enzymes in ATII cells from nonsmokers (n = 4) and smokers (n = 4), both having normal pulmonary function. Although most CYP genes are highly expressed in primary hepatocytes, we found that CYP1B1 mRNA expression was 7.2-fold higher in ATII compared to hepatocytes (P = .0275). Additionally we noted a 3.0-fold upregulation of CYP2C19 and 50% reduction in CYP2J2 mRNA expressions in ATII cells isolated from patients with COPD (n = 3) compared to smokers without COPD (n = 4). These data, for the first time, detail a comprehensive set of genes encoding CYP enzymes in human ATII cells and highlights differentially expressed CYP mRNAs of patients with COPD. Such understanding may have important implications for the development of novel inhaled drugs.


Assuntos
Células Epiteliais Alveolares/química , Sistema Enzimático do Citocromo P-450/genética , Doença Pulmonar Obstrutiva Crônica/genética , Regulação para Cima , Idoso , Idoso de 80 Anos ou mais , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP2C19/genética , Feminino , Hepatócitos/química , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/genética
19.
Surg Today ; 48(10): 951, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29948173

RESUMO

In the original publication, Fig. 3 has been incorrectly published. The correct version of Fig. 3 is given in this Correction.

20.
J Biochem ; 164(2): 87-92, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29726956

RESUMO

A lactic acid bacterium Lactobacillus paracasei IJH-SONE68, which was isolated from a fig leaf by our group, was found to produce both acidic and neutral exopolysaccharides (EPSs). The nuclear magnetic resonance analysis demonstrates that the former EPS is composed primarily of mannose, and the latter one consists of the α-1, 6-linked glycan chains made of N-acetylglucosamine (GlcNAc). The presence of α-1, 6-linked GlcNAc polysaccharide is first reported in prokaryotes. Furthermore, to reveal the EPS-biosynthetic gene organization in the IJH-SONE68 strain, in the present study, we determined the whole-genome sequence.


Assuntos
Ácido Láctico/metabolismo , Lactobacillus paracasei/metabolismo , Polissacarídeos/química , Configuração de Carboidratos , Polissacarídeos/biossíntese
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