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1.
Tohoku J Exp Med ; 263(1): 11-16, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38325831

RESUMO

Non-islet cell tumor hypoglycemia (NICTH) is one of the paraneoplastic syndromes manifesting severe hypoglycemia caused by aberrant production of high-molecular-weight insulin-like growth factor 2 (big-IGF2). Two surgical cases of extremely large thoracic solitary fibrous tumors (SFT) with unusual history of NICTH are presented. One case manifested severe hypoglycemia after four years of the first complete surgical resection of the tumor with potential malignant transformation, and the other case showed severe hypoglycemia after ten years of the first detection of the tumor. Meticulous laboratory testing, including serum endocrinological tests and western immunoblotting before and after surgery was performed, and both cases were diagnosed as NICTH. Both patients underwent open thoracic surgery. The patients showed normal glucose and hormone levels immediately after the resection of responsible tumors with elevated blood insulin concentration. SFTs are generally considered benign; however, life-threatening hypoglycemia can happen regardless of treatment. Careful follow-up of the tumor growth is warranted.


Assuntos
Hipoglicemia , Tumor Fibroso Solitário Pleural , Humanos , Hipoglicemia/etiologia , Fator de Crescimento Insulin-Like II/metabolismo , Tumor Fibroso Solitário Pleural/cirurgia , Tumor Fibroso Solitário Pleural/complicações , Tumor Fibroso Solitário Pleural/patologia , Tumor Fibroso Solitário Pleural/diagnóstico por imagem , Tomografia Computadorizada por Raios X
2.
Tohoku J Exp Med ; 263(1): 35-42, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38355111

RESUMO

Recent advancements in computed tomography (CT) scanning have improved the detection rates of peripheral pulmonary nodules, including those with ground-glass opacities (GGOs). This study focuses on part-solid pure ground-glass nodules (GGNs) and aims to identify imaging predictors that can reliably differentiate primary lung cancer from nodules with other diagnoses among part-solid GGNs on high-resolution CT (HRCT). A retrospective study was conducted on 609 patients who underwent surgical treatment or observation for lung nodules. Radiological findings from pre-operative HRCT scans were reviewed and several CT imaging features of part-solid GGNs were examined for their positive predictive value to identify primary lung cancer. The proportions of the nodules with a final diagnosis of primary lung cancer were significantly higher in part-solid GGNs (91.9%) compared with solid nodules (70.3%) or pure GGNs (66.7%). Among CT imaging features of part-solid GGNs that were evaluated, consolidation-to-tumor ratio (CTR) < 0.5 (98.1%), pleural indentation (96.4%), and clear tumor border (96.7%) had high positive predictive value to identify primary lung cancer. When two imaging features were combined, the combination of CTR < 0.5 and a clear tumor border was identified to have 100% positive predictive values with a sensitivity of 40.8%. Thus we conclude that part-solid GGNs with a CTR < 0.5 accompanied by a clear tumor border evaluated by HRCT are very likely to be primary lung cancers with an acceptable sensitivity. Preoperative diagnostic procedures to obtain a pathological diagnosis may potentially be omitted in patients harboring such part-solid GGNs.


Assuntos
Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Adulto , Curva ROC
3.
Surg Today ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709286

RESUMO

PURPOSE: Nutritional scores have been reported to be useful prognostic factors for various cancers. This study evaluated the usefulness of the preoperative controlling nutritional status (CONUT) score as a predictor of recurrence of non-small cell lung cancer (NSCLC). METHODS: The present study included 422 patients with stage I-IIIA NSCLC who underwent complete resection at Tohoku University Hospital between January 2010 and December 2016. The patients were divided into the low-CONUT and high-CONUT groups based on their CONUT scores. Overall survival (OS), recurrence-free survival (RFS), and cumulative recurrence rates in the low- and high-CONUT groups were evaluated retrospectively. RESULTS: One hundred forty-seven patients (34.8%) were assigned to the high-CONUT group. The high-CONUT group had a significantly worse performance status, pleural invasion, vascular invasion, and lung metastasis. In the whole cohort, the low-CONUT group showed better overall survival, recurrence-free survival, and a low cumulative recurrence rate in comparison to the high-CONUT group. There was no significant difference in prognosis or recurrence between the low- and high-CONUT groups after propensity score matching. CONCLUSION: Patients with a high CONUT score may be at high risk of recurrence because of the high frequency of pleural invasion, vascular invasion, and lung metastasis.

4.
Surg Today ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546861

RESUMO

PURPOSES: Delayed chest closure (DCC) is a widely accepted procedure in the context of lung transplantation (LTx); yet there are few reports detailing its long-term survival and clinical outcomes. METHODS: We reviewed the medical records of recipients who underwent deceased-donor lung transplantation (LTx) at Tohoku University Hospital. Long-term survival, including overall survival, freedom from chronic lung allograft dysfunction (CLAD), and CLAD-free survival and the clinical outcomes of graft function and physical performance and constitution were reviewed in recipients with DCC. RESULTS: Between 2009 and 2022, 116 patients underwent LTx, 33 of whom (28.4%) required DCC. The intra-and post-operative courses of the recipients who required DCC were more complicated than those of the recipients who underwent primary chest closure (PCC), with frequent volume reduction surgery and longer periods of invasive mechanical ventilation. Pulmonary vascular disease was considered a risk factor for these complications and DCC. Nonetheless, long-term survival and graft functions were comparable between the DCC and PCC groups. The physical performance and constitution of recipients who required DCC continued to improve, and by 2 years after transplantation, exhibited almost no difference from those who underwent PCC. CONCLUSIONS: In view of the profoundly complicated intra- and post-operative courses, DCC should be performed cautiously and only when clinically indicated, despite which it can result in equivalent long-term survival and acceptable outcomes to PCC.

5.
Biol Pharm Bull ; 46(10): 1451-1460, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37779047

RESUMO

Long-term and extensive exposure to UV irradiation can cause sunburn, photoaging, or skin cancer. Various studies have shown that Dendrobium officinale extract has a certain protective effect on skin-related diseases. Lactobacillus plantarum is a probiotic that has been reported to be used for co-fermentation with various plants to enhance the activity of extracts. This article discusses the effectiveness of fermentation of Dendrobium officinale extract with Lactobacillus plantarum GT-17F on protection against UV-mediated photoaging. The study found that fermented extract of Dendrobium officinale (FDO) has a stronger antioxidant effect, especially in free radical scavenging. Pretreatment with FDO enables human skin fibroblast (HSF) cells and reconstruction skin models (EpiSkin and T-Skin) to resist UV-mediated degradation of type I collagen and type III collagen, repair epidermal barrier function, and reduce the damage of barrier-related proteins, such as filaggrin (FLG) and loricrin (LOR). Those findings provide a basis for further studies to evaluate the effectiveness of fermented Dendrobium officinale in preventing UV-mediated damage and photoaging in humans.


Assuntos
Dendrobium , Lactobacillus plantarum , Envelhecimento da Pele , Dermatopatias , Humanos , Pele
6.
Biol Pharm Bull ; 46(6): 840-847, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37258150

RESUMO

In the present study, we have obtained a temperature-sensitive replication mutant in the Escherichia (E.) coli-lactic acid bacterium (LAB) shuttle vector pLES003-b carrying erythromycin-resistance gene by error-prone PCR technique. Among 858 clones obtained in the construction of the random mutation libraries of pLES003-b in the ori and repA regions, three clones could grow normally at 28 °C but not at 42 °C. One of the clones was designated as pLES003-b TS1. The sequencing analysis of pLES003-b TS1 revealed that the plasmid has four substitution mutations (376G > A, 435A > T, 914C > A, and 1996T > A) and one insertional mutation (1806_1807insA). Among those mutations, substitution mutation 914C > A, which leads to a CGC-to-AGC codon change at position 44 of the RepA protein (arginine-to-serine substitution mutation: R44S in RepA), was predicted to be a cause of temperature sensitivity. Therefore, the C-to-A substitution was introduced into the repA gene in pLES003-b using a site-directed mutagenesis method, and the resultant plasmid was electroporated into a Lactobacillus (L.) plantarum cell. The resultant transformant cannot grow at 42 °C in the presence of erythromycin, which is used as a selective marker, indicating that the R44S point mutation in the RepA protein may be crucial for temperature sensitivity. Furthermore, we have developed a new plasmid as an efficient genetic engineering tool for random insertional mutagenesis in LABs using a combination of transposon Tn10 and the temperature-sensitive replication system in pLES003-b. The resultant plasmid vector, which was designated pLES-Tn10-TS1, would be useful for genetic analysis of the functional molecule in lactic acid bacterial strains.


Assuntos
Escherichia coli , Lactobacillales , Escherichia coli/genética , Escherichia coli/metabolismo , Temperatura , Replicação do DNA , Vetores Genéticos/genética , Plasmídeos/genética , Proteínas/metabolismo , Bactérias/genética , Mutagênese , Ácido Láctico/metabolismo
7.
Appl Microbiol Biotechnol ; 106(4): 1435-1446, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35089399

RESUMO

L-alanine possesses extensive physiological functionality and tremendous pharmacological significance, therefore could be considered as potential ingredient for food, pharmaceutical, and personal care products. However, therapeutic properties of L-alanine still need to be addressed in detail to further strengthen its utilization as a viable ingredient for developing natural therapeutics with minimum side effects. Thus, the present study was aimed to explore the anticipated therapeutic potential of L-alanine, produced microbially using a lactic acid bacterial strain Pediococcus acidilactici BD16 (alaD+) expressing L-alanine dehydrogenase enzyme. The anticipated therapeutic potential of L-alanine was assessed in terms of anti-proliferative, anti-bacterial, and anti-urolithiatic properties. Anti-bacterial assays revealed that L-alanine successfully inhibited growth and in vitro proliferation of important human pathogens including Enterococcus faecalis, Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, Streptococcus mutans, and Vibrio cholerae in a concentration-dependent manner. Current investigation has also revealed its significant anti-proliferative potential against human lung adenocarcinoma (A549; IC50 7.32 µM) and mammary gland adenocarcinoma (MCF-7; IC50 8.81 µM) cells. The anti-urolithiatic potential of L-alanine was augmented over three different phases, viz., nucleation inhibition, aggregation inhibition, and oxalate depletion. Further, an in vitro cell culture-based kidney stone dissolution model using HEK293-T cells was also established to further strengthen its anti-urolithiatic potential. This is probably the first in vitro cell culture-based model which experimentally validates the immense therapeutic efficacy of L-alanine in treating urolithiasis disease. KEY POINTS: • Assessment of therapeutic potential of L-alanine produced by LAB. • L-alanine exhibited significant anti-proliferative and anti-bacterial activities. • L-alanine as potential anti-urolithiatic agent.


Assuntos
Pediococcus acidilactici , Alanina/farmacologia , Enterococcus faecalis , Células HEK293 , Humanos , Pediococcus , Staphylococcus aureus
8.
Kyobu Geka ; 75(10): 825-830, 2022 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-36155577

RESUMO

The initial treatment for the patient with primary or secondary spontaneous pneumothorax occupying less than 15% of the hemithorax is observation. And then the treatment with primary spontaneous pneumothorax greater than 15% of the volume of hemithorax is a simple thoracoscopic aspiration. However, the treatment with secondary spontaneous pneumothorax greater than 15% of the volume of hemithorax is tube thoracotomy. Conservative treatment for continuous air leakage with secondary spontaneous pneumothorax is instillation of a sclerosing agent( small amount of picibanil 3 KE). Surgical treatment for continuous air leakage with secondary spontaneous pneumothorax due to severe idiopathic pulmonary fibrosis (IPF) is intractable. We have experienced three cases in which surgical treatment is difficult in secondary spontaneous pneumothorax with underlying lung diseases. The first cases are a pneumothorax with a giant bulla or severe lung emphysema. Second cases are a pneumothorax with a fragile lung. Third cases are a pneumothorax with a hardened lung. We need devised surgical approaches to these cases.


Assuntos
Pneumotórax , Enfisema Pulmonar , Algoritmos , Humanos , Picibanil , Pneumotórax/complicações , Pneumotórax/cirurgia , Enfisema Pulmonar/cirurgia , Soluções Esclerosantes
9.
Biol Pharm Bull ; 44(12): 1886-1890, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34853272

RESUMO

A lactic acid bacterial strain, Lactobacillus plantarum SN35N, which has been isolated from the pear, secretes negatively charged acidic exopolysaccharide (EPS) to outside cells. We have previously found that the SN35N-derived acidic EPS inhibits the catalytic activity of hyaluronidase (EC 3.2.1.35) promoting inflammation. The aim of this study is to find other health benefits of EPS. EPS has been found to exhibit an inhibitory effect against the influenza virus (Alphainfluenzavirus Influenza A virus) and feline calicivirus (Vesivirus Feline calicivirus), which is recognized as a model of norovirus. Although more studies on the structure-function relationship of EPSs are needed, SN35N-derived EPS is a promising lead for developing not only anti-inflammatory agents, but also antiviral substances.


Assuntos
Antivirais/farmacologia , Lactobacillus plantarum , Polissacarídeos Bacterianos/farmacologia , Pyrus/microbiologia , Animais , Anti-Inflamatórios/farmacologia , Antivirais/isolamento & purificação , Calicivirus Felino/efeitos dos fármacos , Gatos , Cães , Hialuronoglucosaminidase , Lactobacillales , Lactobacillus plantarum/classificação , Células Madin Darby de Rim Canino , Norovirus/efeitos dos fármacos , Orthomyxoviridae/efeitos dos fármacos , Polissacarídeos Bacterianos/isolamento & purificação , Especificidade da Espécie
10.
Biomed Chromatogr ; 35(6): e5067, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33450064

RESUMO

Several drugs are administered to lung-transplanted patients, which are monitored using therapeutic drug monitoring (TDM). Therefore, we developed and validated a liquid chromatography-tandem mass spectrometry method to simultaneously analyze immunosuppressive drugs such as mycophenolic acid, antifungal drugs such as voriconazole and itraconazole, and its metabolite hydroxyitraconazole. Chromatographic separation was achieved using a C18 column and gradient flow of mobile phase comprising 20 mM aqueous ammonium formate and 20 mM ammonium formate-methanol solution. A simple protein precipitation treatment was performed using acetonitrile/methanol and mycophenolic acid-2 H3 , voriconazole-2 H3 , itraconazole-2 H4 , and hydroxyitraconazole-2 H4 as internal standards. The linearity ranges of mycophenolic acid, voriconazole, itraconazole, and hydroxyitraconazole were 100-20,000, 50-10,000, 5-1000, and 5-1000 ng/mL, respectively. The retention time of each target was less than 2 min. The relative errors in intra- and inter-day were within ±7.6%, the coefficient of variation was 8.9% or less for quality control low, medium, and high, and it was 15.8% or less for lower limit of quantitation. Moreover, the patient samples were successfully quantified, and they were within the linear range of measurements. Therefore, our new method may be useful for TDM in lung-transplanted patients.


Assuntos
Cromatografia Líquida/métodos , Monitoramento de Medicamentos/métodos , Transplante de Pulmão , Espectrometria de Massas em Tandem/métodos , Adulto , Antifúngicos/sangue , Antifúngicos/farmacocinética , Antifúngicos/uso terapêutico , Feminino , Humanos , Imunossupressores/sangue , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
Molecules ; 26(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361824

RESUMO

Functional foods or drinks prepared using lactic acid bacteria (LAB) have recently gained considerable attention because they can offer additional nutritional and health benefits. The present study aimed to develop functional drinks by the fermentation of buttermilk and soymilk preparations using the Pediococcus acidilactici BD16 (alaD+) strain expressing the L-alanine dehydrogenase enzyme. LAB fermentation was carried out for 24 h and its impact on the physicochemical and quality attributes of the fermented drinks was evaluated. Levels of total antioxidants, phenolics, flavonoids, and especially L-alanine enhanced significantly after LAB fermentation. Further, GC-MS-based metabolomic fingerprinting was performed to identify the presence of bioactive metabolites such as 1,2-benzenedicarboxylic acid, 1-dodecene, 2-aminononadecane, 3-octadecene, 4-octen-3-one, acetic acid, azanonane, benzaldehyde, benzoic acid, chloroacetic acid, colchicine, heptadecanenitrile, hexadecanal, quercetin, and triacontane, which could be accountable for the improvement of organoleptic attributes and health benefits of the drinks. Meanwhile, the levels of certain undesirable metabolites such as 1-pentadecene, 2-bromopropionic acid, 8-heptadecene, formic acid, and propionic acid, which impart bitterness, rancidity, and unpleasant odor to the fermented drinks, were reduced considerably after LAB fermentation. This study is probably the first of its kind that highlights the application of P. acidilactici BD16 (alaD+) as a starter culture candidate for the production of functional buttermilk and soymilk.


Assuntos
Leitelho/análise , Fermentação , Pediococcus acidilactici/crescimento & desenvolvimento , Leite de Soja/métodos , Leitelho/microbiologia , Pediococcus acidilactici/metabolismo , Leite de Soja/química
12.
Kyobu Geka ; 74(13): 1059-1062, 2021 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-34876533

RESUMO

The patient was a 41-year-old man. He was diagnosed with pleurisy and came to our hospital. The pleural effusion and pleurisy remained even after administration of sufficient doses of antibiotics. A thorough examination revealed an anterior mediastinal tumor. Six months later, pericarditis also developed. Autoimmune diseases, infections, and malignant diseases were suspected, but a definitive diagnosis could not be made. In order to confirm the diagnosis, anterior mediastinal tumor resection and pleural biopsy were performed. The anterior mediastinal tumor was diagnosed as cholesterin granuloma pathollogically. Cholesterin granuloma is a granuloma formed by deposition of cholesterin crystals and cholesterin granuloma occurring in the mediastinum is extremely rare.


Assuntos
Pericardite , Derrame Pleural , Pleurisia , Adulto , Granuloma/complicações , Humanos , Masculino , Mediastino , Pericardite/complicações , Pericardite/diagnóstico por imagem , Pleurisia/etiologia
13.
Kyobu Geka ; 74(3): 191-195, 2021 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-33831871

RESUMO

The incidence of postoperative pulmonary torsion is not frequent but it has a high mortality rate once it occurs, and prompt diagnosis and treatment are required. From past reports, it is considered effective to point out disruption of pulmonary blood flow by contrast-enhanced computed tomography (CT) examination for diagnosis. However, the comparison of pre- and post-operative plain CT images is considered to be useful in diagnosing lung torsion, and postoperative CT lung window setting sagittal images were examined in three cases of postoperative lung torsion. Results indicate that pulmonary torsion of the middle lobe after right lower lobectomy and the middle lobe after right upper lobectomy can be diagnosed by the present method.


Assuntos
Pneumopatias , Neoplasias Pulmonares , Diagnóstico Precoce , Humanos , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Pneumopatias/diagnóstico por imagem , Pneumopatias/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Tomografia Computadorizada por Raios X , Anormalidade Torcional/diagnóstico por imagem , Anormalidade Torcional/cirurgia
14.
Kyobu Geka ; 74(7): 533-537, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34193789

RESUMO

In recent years, with the improvement of diagnostic techniques and treatment outcomes, the number of lung cancer cases after esophageal cancer treatment has been increasing. In general, severe adhesions are expected in the right lung, during lung resection after esophageal cancer surgery. In this study, we reviewed intraoperative findings of lung resection with respect to the influence of different treatment methods for esophageal cancer, the site of adhesion formation for each lobe, and the techniques and precautions for lung resection. There were no difficulty in the left upper major segmentectomy. During the left lower lobectomy, the inflammation around the inferior pulmonary vein was noted. The adhesions between the reconstructed gastric tube and the inferior pulmonary vein were found during the right lower lobectomy. During the right upper lobectomy, severe adhesions between the lung and the superior vena cava as well as the gastric tube in the posterior mediastinum were observed, which should be paid much attention.


Assuntos
Neoplasias Esofágicas , Neoplasias Pulmonares , Neoplasias Esofágicas/cirurgia , Humanos , Pulmão , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Veia Cava Superior
15.
Clin Transplant ; 34(12): e14088, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32949050

RESUMO

BACKGROUND: The therapeutic drug monitoring of mycophenolic acid (MPA) has been investigated for renal and heart transplantations; however, its usefulness in lung transplantation is unclear. METHODS: The MPA area under the plasma concentration-time curve (AUC) was calculated in 59 adult lung transplant recipients. The MPA AUC0-12 s were compared among the three groups determined by the presence of adverse events (no events, infection, and chronic lung allograft dysfunction [CLAD]). Next, MPA AUC0-12 thresholds for the adverse events were identified by receiver operating characteristic analysis. Cumulative occurrence rate of the adverse events was compared between two groups (adequate and inadequate groups) according to the thresholds. RESULTS: The MPA AUC0-12 s in the no event, infection, and CLAD groups were 30.3 ± 6.5, 36.8 ± 10.7, and 20.6 ± 9.6 µg·h/mL, respectively (P = .0027), while the tacrolimus trough levels were similarly controlled in the groups. The thresholds of MPA AUC0-12 for the occurrence of infection and CLAD were 40.5 and 22.8 µg·h/mL, respectively. The cumulative occurrence rate of adverse events of adequate group (15.3%) was significantly lower than that of inadequate group (56.0%) (P = .0050). CONCLUSIONS: The MPA AUC0-12 may affect the occurrence of adverse events in lung transplant recipients.


Assuntos
Transplante de Rim , Transplante de Pulmão , Adulto , Área Sob a Curva , Humanos , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico , Tacrolimo
16.
Int J Clin Oncol ; 25(7): 1285-1290, 2020 Jul.
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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Bevacizumab/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Ácido Oxônico/uso terapêutico , Intervalo Livre de Progressão , Tegafur/uso terapêutico , Resultado do Tratamento
17.
Biomed Chromatogr ; 34(8): e4853, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32302012

RESUMO

Sirolimus is used on patients after solid organ transplantation and on lymphangioleiomyomatosis (LAM) patients, and therapeutic drug monitoring is required in clinical practice. We have previously reported an accurate method for quantitative determination of sirolimus, but its sample preparation step was complicated. In this study, we developed a modified liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for sirolimus quantification. A supported liquid extraction cartridge was used to purify sirolimus from whole blood and ion suppression was mostly prevented. The validation results met the acceptance criteria. This method was compared with the antigen conjugated magnetic immunoassay (ACMIA) and our previously reported method, using whole blood samples from LAM patients. Comparison of the Bland-Altman plots of the currently developed method and the previous method revealed no significant difference between the two methods (mean bias, -2.02%; 95% CI, -7.81-3.78). The values obtained using ACMIA were significantly higher than those obtained using the current method by 13.87% (95% CI, 6.49-21.25) owing to cross-reactivity. The degrees of cross reactivities in LAM patients and in organ transplant patients were similar, and our LC/ESI-MS/MS method precisely measured the blood concentrations of sirolimus.


Assuntos
Cromatografia Líquida/métodos , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/normas , Sirolimo/sangue , Espectrometria de Massas em Tandem/métodos , Humanos , Imunoensaio , Imunossupressores/sangue , Modelos Lineares , Extração Líquido-Líquido , Linfangioleiomiomatose/tratamento farmacológico , Transplante de Órgãos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray
18.
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.


Assuntos
Alcoolismo/dietoterapia , Disbiose/dietoterapia , Lactobacillus plantarum/fisiologia , Probióticos/administração & dosagem , Administração Oral , Alcoolismo/complicações , Aminas/análise , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Modelos Animais de Doenças , Disbiose/etiologia , Fezes/química , Fezes/microbiologia , Microbioma Gastrointestinal , Masculino , Camundongos , Probióticos/farmacologia , RNA Ribossômico 16S/genética
19.
Kyobu Geka ; 73(10): 845-850, 2020 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-33130777

RESUMO

Pulmonary dysfunction with lung cancer has been shown a major postoperative risk factor in patients undergoing thoracic surgery. Preoperative physiological assessment according to guideline by American College of Chest Physicians (ACCP) or European Respiratory Society( ERS)/European Society of Thoracic Surgeons (ESTS) is important to select patients due to evaluate the risk of lung resection for a lung cancer patient. Moreover, for lung cancer patients undergoing thoracic surgery with pulmonary dysfunction, circulatory function evaluation is important in addition to preoperative respiratory management and rehabilitation. Thoracic surgery for patients with pulmonary dyfunction should be selected to assess preoperative pulmonary function and to predict postoperative complications.


Assuntos
Neoplasias Pulmonares , Procedimentos Cirúrgicos Pulmonares , Cirurgia Torácica , Humanos , Pulmão , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Fatores de Risco
20.
Am J Physiol Regul Integr Comp Physiol ; 317(5): R649-R661, 2019 11 01.
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(endo)plasmic 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-wk-old male C57BL/6J mice were subjected to bilateral cast immobilization for 2 wk. Two-week-cast immobilization induced both body weight and skeletal muscle loss. Highly phosphorylated Ca2+/calmodulin-dependent protein kinase II 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. Upregulation 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 nonshivering 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 SLN.


Assuntos
Membro Posterior/metabolismo , Extremidade Inferior/fisiopatologia , Músculo Esquelético/metabolismo , Retículo Sarcoplasmático/metabolismo , Termogênese/fisiologia , Animais , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Camundongos Endogâmicos C57BL , Atrofia Muscular/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Ativação Transcricional/fisiologia
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