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1.
Adv Ther ; 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32676927

RESUMO

INTRODUCTION: Lenvatinib is approved in Japan for treating patients with all histological subtypes of unresectable thyroid cancer, including differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC), and anaplastic thyroid cancer (ATC). However, safety and effectiveness data are limited in Japanese patients. Therefore, this prospective, post-marketing observational study evaluated, in daily clinical practice, the safety and effectiveness of lenvatinib in Japanese patients with unresectable thyroid cancer. METHODS: All patients with unresectable thyroid cancer first treated with lenvatinib between May and November 2015 were registered. Patients were orally administered lenvatinib and followed up for 12 months. The endpoints included adverse drug reactions (ADRs), overall survival (OS), overall response rate (ORR), and time-to-treatment failure. Post hoc Cox multivariate analyses were performed to assess prognostic factors associated with the 12-month OS rate. RESULTS: Of 629 registered patients, 594 were included in the analysis. A total of 442 patients (74.4%) had DTC, 28 (4.7%) had MTC, and 124 (20.9%) had ATC. Hypertension, proteinuria, and palmar-plantar erythrodysesthesia syndrome were the most frequently reported ADRs across all histological subtypes. The median OS was 101.0 days in patients with ATC which was not reached in patients with DTC and patients with MTC, with 12-month OS rates of 15.6%, 75.7%, and 83.0%, respectively. The ORRs were 59.2%, 45.0%, and 43.8% among 368 patients with DTC, 20 with MTC, and 105 with ATC, respectively. Multivariate analyses revealed that Eastern Cooperative Oncology Group performance status (ECOG PS), tumor size, the presence of tumor invasion, and body weight were baseline prognostic factors affecting OS in patients with DTC, while ECOG PS and the presence of liver metastasis were prognostic factors in patients with ATC. CONCLUSION: Lenvatinib demonstrated an acceptable safety profile for patients with thyroid cancer in a real-world setting in Japan. The safety profile and effectiveness findings for lenvatinib in this study were consistent with those from previous clinical trials, irrespective of histological subtype.

2.
BMC Bioinformatics ; 21(1): 263, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32580745

RESUMO

BACKGROUND: The combination of systematic evolution of ligands by exponential enrichment (SELEX) and deep sequencing is termed high-throughput (HT)-SELEX, which enables searching aptamer candidates from a massive amount of oligonucleotide sequences. A clustering method is an important procedure to identify sequence groups including aptamer candidates for evaluation with experimental analysis. In general, aptamer includes a specific target binding region, which is necessary for binding to the target molecules. The length of the target binding region varies depending on the target molecules and/or binding styles. Currently available clustering methods for HT-SELEX only estimate clusters based on the similarity of full-length sequences or limited length of motifs as target binding regions. Hence, a clustering method considering the target binding region with different lengths is required. Moreover, to handle such huge data and to save sequencing cost, a clustering method with fast calculation from a single round of HT-SELEX data, not multiple rounds, is also preferred. RESULTS: We developed fast string-based clustering (FSBC) for HT-SELEX data. FSBC was designed to estimate clusters by searching various lengths of over-represented strings as target binding regions. FSBC was also designed for fast calculation with search space reduction from a single round, typically the final round, of HT-SELEX data considering imbalanced nucleobases of the aptamer selection process. The calculation time and clustering accuracy of FSBC were compared with those of four conventional clustering methods, FASTAptamer, AptaCluster, APTANI, and AptaTRACE, using HT-SELEX data (>15 million oligonucleotide sequences). FSBC, AptaCluster, and AptaTRACE could complete the clustering for all sequence data, and FSBC and AptaTRACE performed higher clustering accuracy. FSBC showed the highest clustering accuracy and had the second fastest calculation speed among all methods compared. CONCLUSION: FSBC is applicable to a large HT-SELEX dataset, which can facilitate the accurate identification of groups including aptamer candidates. AVAILABILITY OF DATA AND MATERIALS: FSBC is available at http://www.aoki.ecei.tohoku.ac.jp/fsbc/.

3.
ACS Synth Biol ; 9(7): 1623-1631, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32531157

RESUMO

Artificial control of gene expression is one of the core technologies for engineering biological systems. Riboswitches are cis-acting elements on mRNA that regulate gene expression in a ligand-dependent manner often seen in prokaryotes, but rarely in eukaryotes. Because of the poor variety of such elements available in eukaryotic systems, the number of artificially engineered eukaryotic riboswitches, especially of the upregulation type, is still limited. Here, we developed a design principle for upregulation-type riboswitches that utilize non-AUG initiation induced by ribosomal stalling in a ligand-dependent manner in Saccharomyces cerevisiae. Our design principle simply required the proper positioning of a near-cognate start codon relative to the RNA aptamer. Intriguingly, the CUG codon was the most preferable for non-AUG ON switches in terms of output level and switch performance. This work establishes novel choices for artificial genetic control in eukaryotes with versatile potential for industrial and biomedical applications as well as basic research.

4.
Leuk Res ; 95: 106399, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32534365

RESUMO

OBJECTIVES: MALT lymphoma occurs in various organs and has several characteristic genetic aberrations. Thyroid MALT lymphoma has been reported to include t(3;14)(p14.1;q32)/FOXP1-IGH as a specific genetic aberration, but the number of studies is limited. METHOD AND RESULTS: We examined 86 thyroid lymphoma cases using fluorescence in situ hybridization (FISH) for the detection of t(3;14)/FOXP1-IGH in formalin fixed paraffin-embedded tissue (FFPE). Histopathological diagnoses of the analyzed specimen were as follows: thyroid MALT lymphoma (n = 59), DLBCL (n = 23), follicular lymphoma (n = 4), and benign lesions (n = 14) included Hashimoto's thyroiditis (n = 13) and other (n = 1). Of the 100 analyzed cases, thirty-six (36 %) thyroid lymphoma cases were positive for t(3;14)/FOXP1-IGH. Thirty-three (55.9 %) of the 59 MALT lymphoma cases were positive for t(3;14)/FOXP1-IGH. Three (13.0 %) of the 23 DLBCL cases were positive for t(3;14)/FOXP1-IGH. All 4 follicular lymphomas examined were negative for t(3;14)/FOXP1-IGH. None of the benign cases was positive for t(3;14)/FOXP1-IGH, including Hashimoto's thyroiditis (0/13) and benign tissue (0/1). CONCLUSIONS: Our study found that t(3;14)/FOXP1-IGH was frequently found in thyroid MALT lymphoma. A detection of t(3;14)/FOXP1-IGH is extremely useful for the differential diagnosis between primary MALT lymphoma of the thyroid and other thyroid disorders.

5.
Endocr J ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32350192

RESUMO

Radioactive iodine (RAI) therapy has been the mainstay of treatment for papillary thyroid carcinoma (PTC) patients with distant metastasis (DM). Although tyrosine kinase inhibitors (TKIs) were introduced for the treatment of RAI refractory metastatic thyroid carcinoma several years ago, clinical outcomes for PTC patients with DM treated using RAI therapy remain unclear. We retrospectively examined 64 PTC patients (9 men, 55 women) with DM at diagnosis treated using RAI therapy without administration of any kind of chemotherapy or TKIs. Median age of patients was 58 years. Site of DM was the lungs (n = 59), bone (n = 3), and pleural dissemination (n = 2). No patients showed multiple-organ metastases at diagnosis. By the end of the study period, 21 patients had died of PTC. Cause-specific survival rates at 10, 15, and 20 years after initial surgery were 68.2%, 63.6% and 61.1%, respectively. Uni- and multivariate analyses identified age ≥55 years (HR 3.1, p = 0.023), site of DM other than the lungs (HR 13.4, p < 0.0001), and DM with no RAI avidity (HR 5.1, p = 0.0098) as factors independently associated with disease-related death. When analyses were restricted to patients with lung metastasis (n = 59), surgical non-curability was another independent risk factor (HR 5.2, p = 0.0047) in addition to age and RAI avidity. According to risk stratification analysis based on these risk factors, patients with site of DM other than the lungs or with lung metastasis showing ≥2 risk factors among age ≥55 years, DM with no RAI avidity, and surgical non-curability are expected to show higher mortality rates.

6.
Int J Clin Oncol ; 25(7): 1278-1284, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32347432

RESUMO

BACKGROUND: Proteinuria induced by lenvatinib is a class effect that occurs secondary to VEGFR suppression. Withholding of lenvatinib is required in cases with severe proteinuria. Urine protein-creatinine ratio (UPCR, g/gCre) has recently attracted attention as an alternative to 24-h urine collection for assessing proteinuria. The aim of this study was to examine the correlation between the results of proteinuria assessed by the dipstick test and UPCR, and to investigate the influence of proteinuria grading with UPCR on lenvatinib dose adjustment compared to that with only the dipstick test. METHOD: Three hundred and ten urine samples from 63 patients with advanced thyroid cancer under treatment with lenvatinib, which were tested by both the dipstick test and UPCR were analyzed. Lenvatinib was withheld when there was evidence of CTCAE grade 3 proteinuria, and restarted when it resolved. The frequency of proteinuria, correlation between the results of the dipstick test and UPCR test, and the effect of dose withholding in cases with results of 3 + in the dipstick test were calculated. RESULTS: Proteinuria was seen in 56 (88.9%) patients. Of the 154 dipstick 3 + samples, only 56 (36.4%) were judged as more than 3.5 g/gCre by UPCR (grade 3 proteinuria), although none of the 1 + and only 3.7% of 2 + samples were judged as grade 3 proteinuria. We were able to prevent unnecessary lenvatinib interruption due to proteinuria in 63.6% of dipstick 3 + samples by assessment of UPCR. CONCLUSIONS: Urinalysis by combination of the dipstick test and UPCR assessment might be a better strategy for preventing unnecessary interruption of lenvatinib.

7.
Endocrine ; 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32307657

RESUMO

PURPOSE: Studies have shown that inflammatory biomarkers, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), are associated with prognosis or treatment efficacy in various cancers. The present study investigated the association between the inflammatory biomarkers and dynamics of NLR, and prognosis or disease progression in anaplastic thyroid carcinoma (ATC). METHODS: This study included 55 patients with ATC who had available complete blood count (CBC) data. Overall survival based on inflammatory biomarker value, and the dynamics of NLR among patients with ATC were investigated. Change in NLR was obtained by subtracting the baseline value from the max value obtained during follow-up period, and we subclassified 51 ATC patients who had follow-up CBC data into the increased group (change of NLR > 5.5) and non-increased group (change of NLR ≤ 5.5). RESULTS: There were no significant differences in OS according to baseline NLR, PLR, and LMR values. Among the 51 patients with ATC who had follow-up CBC data, the median OS was 7.7 [95% confidence interval (CI): 5.2-12.1] months in the increased group (n = 27), versus 23.5 [95% CI: 13.9-not available] months in the non-increased (n = 24) group (p < 0.001). CONCLUSIONS: The present study found no association between baseline inflammatory biomarkers and OS among patients with ATC. However, ATC patients whose NLR increased compared with individual baseline during follow-up period had worse prognosis than non-increased patients.

8.
Medicine (Baltimore) ; 99(11): e19408, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176066

RESUMO

Some thyroid cancer patients experience a rapid disease progression after the discontinuation of tyrosine kinase inhibitors (TKIs), which is called flare phenomenon. The incidence of the flare phenomenon of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) ranged from 4% to 11.1% and the median time to occurrence of the flare phenomenon ranged from 7 to 12 days in previous reports. In this study, we investigate the timing and incidence of the flare phenomenon in thyroid cancer patients treated with lenvatinib.The records of patients treated with lenvatinib were retrospectively reviewed. The primary outcomes were the incidence rate and timing of the flare phenomenon after the discontinuation of lenvatinib. The flare phenomenon was defined as death, hospitalization attributable to tumor progression, or unexpected event (e.g., pleural drainage) within 1 month of lenvatinib cessation. We excluded patients with progression of underlying diseases other than thyroid cancer or infection, those in whom the disease progressed, or those who died without achieving a clinical response (stable disease, partial response, or complete response).In total, 8 (14.3%) of the 56 patients experienced the flare phenomenon. The median time from lenvatinib cessation to the flare phenomenon was 9 (range, 4-30) days. Three patients in the flare group died within 1 month of lenvatinib cessation without an imaging evaluation. The remaining 5 patients had dyspnea and pleural effusion, and pleural drainage was performed in 3 of the 5 patients. Lenvatinib was resumed in 4 of the 8 patients in the flare group. Median overall survival (OS) was 15.1 months in the flare group and 41.9 months in the non-flare group. The OS tended to be poor in the flare group than in the non-flare group; however, this difference was not statistically significant (P = .051).In lenvatinib treatment for thyroid cancer, the incidence and timing of the flare phenomenon were similar to those observed with other TKIs. OS tended to be poor in the flare group than in the non-flare group. Further studies are needed to determine the mechanism of the flare phenomenon and establish measures and treatment policies.


Assuntos
Antineoplásicos/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Quinolinas/administração & dosagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
JA Clin Rep ; 6(1): 13, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060808

RESUMO

The Editor-in-Chief has retracted this article [1]. The ethics committee approval was granted for an observational study and the need for patient consent was waived. However, the study design described is a randomized controlled trial and therefore patient consent should have been obtained. All authors agree with this retraction.

11.
Thyroid ; 30(3): 451-456, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31928169

RESUMO

Background: The clinical course of Graves' disease (GD) in women who switched from methimazole (MMI) to potassium iodide (KI) during the first trimester of pregnancy has never been reported in detail. Objective: To investigate the characteristics of GD patients whose thyroid hormone levels increase after substituting KI for MMI. Patients: Two hundred forty women with GD who had been treated with MMI and switched from MMI to inorganic iodide to control hyperthyroidism during the first trimester between January 1, 2005, and March 31, 2018. Results: In 133 (55.4%) of the GD patients, medication was completely tapered during pregnancy, and the other 107 (44.6%) GD patients were taking medication at delivery: 57 were taking KI alone and 50 were taking an antithyroid drug with or without KI. It was difficult to control the maternal thyrotoxicosis of 22 of the 107 patients with KI alone, and a higher dose of MMI compared with the dose at the time of conception was required (worsened group). Multivariate analysis revealed that the TRAb value at the time of switch from MMI to KI was the only factor that predicted continuation of the thyroid suppression medication, but none of the parameters was a predictor of the worsened group. Conclusions: It must be kept in mind that a certain proportion of GD patients escape from the antithyroid effect of iodide and that careful follow-up is necessary after switching a pregnant patient's medication to KI.

12.
Thyroid ; 30(4): 548-556, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31910105

RESUMO

Background: In the recent American Thyroid Association (ATA) guidelines for adult differentiated thyroid carcinoma (DTC) patients, risk stratification is clearly defined and lobectomy is acceptable for low-risk DTC. However, risk stratification for children with DTC in the ATA pediatric guidelines is rather unclear, and total thyroidectomy is recommended for all patients with any risk. The aim of this study was to attempt risk stratification based on our experience and to consider the appropriate extent of thyroidectomy, especially for low-risk DTC in the pediatric population. Patients and Methods: The subjects were 153 patients with DTC ≤18 years old, including 58 patients ≤15 years old and 136 female patients, who underwent initial curative surgery in our hospital between 1979 and 2014. Underlying pathology was papillary thyroid carcinoma in 130 patients and follicular thyroid carcinoma in 23. Risk factors related to disease-free survival (DFS) were analyzed and risk stratification was performed. Results: No patient died of the disease and 34 patients (22.2%) developed recurrences. At initial surgery, 30 patients (19.6%) had lymph node metastases diagnosed before initial surgery (cN1) and 9 (5.9%) had gross extrathyroidal extension (ETE). Significant factors related to DFS on multivariate analysis were cN1, ETE, and number of metastatic lymph nodes (NMLNs) ≥10, including microscopic MLNs. According to these factors, subjects were divided into three categories: low risk (no risk factors, n = 89); intermediate risk (1 risk factor, n = 37); and high risk (≥2 risk factors, n = 27). Ten-year DFS rates in the low-, intermediate-, and high-risk groups were 96%, 83%, and 48%, respectively. Only 12% of low-risk patients underwent total thyroidectomy. Because NMLNs become obvious only after surgery, another analysis after excluding "NMLNs" as a factor showed that cN and ETE were significant factors related to poor DFS. According to these two factors, risk stratification was attempted in the same manner. Ten-year DFS rates in the low- (no risk factor, n = 117), intermediate- (one risk factor, n = 29), and high-risk (two risk factors, n = 7) groups were 92%, 59%, and 43%, respectively. Only 12% of low-risk patients underwent total thyroidectomy. Conclusions: For low-risk pediatric patients, lobectomy may be sufficient as the initial surgical procedure.

13.
Thyroid ; 30(2): 214-221, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31854270

RESUMO

Background: The ultimate clinical goal of advanced cancer treatment is improvement of survival. Tyrosine kinase inhibitors (TKIs) were recently approved for radioiodine-refractory differentiated thyroid carcinoma (RR-DTC) that is resistant to conventional therapies since they have significant potential to improve survival in patients who previously had no more treatment strategies available. However, eligible patients are limited in clinical practice, making it difficult to accurately determine the efficacy of TKIs. Patients and Methods: We retrospectively analyzed the efficacy of lenvatinib at a single institution, enrolling 42 RR-DTC patients. Results: The best overall response was partial remission in 26 (62%) patients, stable disease in 10 (24%) patients, and progressive disease (PD) in 6 (14%) patients. The results indicated three-year overall survival (OS) and progression-free survival rates of 51.0% and 32.4%, respectively. Twenty-three (55%) patients had backgrounds that did not match the inclusion criteria of the Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. Furthermore, PD-experienced patients individually decided whether to continue lenvatinib, and 17 (41%) made the decision themselves; these patients had a three-year OS of 43.0% and postprogression survival (PPS) of 13.3 [95% confidence interval 6.1-not reached] months. Conclusions: Our real-world investigation revealed that patients have wide-ranging background characteristics, and the decision regarding continuation of therapy after PD is based on the patient's general condition. Our management protocol resulted in good PPS. Furthermore, our results indicated equivalent efficacy of lenvatinib as in the SELECT trial. In conclusion, lenvatinib proved effective for RR-DTC patients in a real-world setting.

14.
Reprod Med Biol ; 18(4): 357-361, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31607795

RESUMO

Purpose: Piezo-assisted intracytoplasmic sperm injection (Piezo-ICSI) is reported to be an effective method for inseminating fragile oocytes compared with conventional ICSI (c-ICSI). However, infertile patient groups suitable for Piezo-ICSI have not been elucidated. This study was conducted to determine age groups suitable for Piezo-ICSI using sibling egg controls inseminated by a well-trained embryologist to reduce technical inequalities. Methods: A total of 947 matured oocytes were inseminated either by Piezo-ICSI or by c-ICSI in sibling oocytes as controls. Fertilization (2 pronuclei, PN), survival, and blastocyst development rates on day (D) 5 and D6 after insemination were compared between the Piezo-ICSI and c-ICSI groups. Further analyses were applied to groups of women >35 or ≤35 years of age. Results: There were no significant differences in fertilization, survival, or blastocyst development rates between the two insemination treatment groups. However, for women >35 years of age, the fertilization (P = .008) and blastocyst development (P = .016) rates with Piezo-ICSI on D5 and D6 were significantly higher than in those subjected to c-ICSI. Conclusions: Piezo-ICSI was useful for inseminating oocytes from women >35 years of age.

15.
J Radiat Res ; 60(6): 831-836, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31423531

RESUMO

Differentiated thyroid cancer (DTC) is associated with a good long-term prognosis, but bone metastases can adversely affect patients' quality of life and survival. Stereotactic radiotherapy (SRT) can deliver high-dose irradiation to target lesions and it has been reported to be useful for various cancers. However, few studies have examined the efficacy of SRT for thyroid cancer. In the present study, the aim was to investigate the efficacy of SRT using the CyberKnife for bone metastases from DTC. From September 2013 to April 2018, SRT with the CyberKnife system was used to treat 60 bone metastases from DTC in 13 patients. The patients' medical records were retrospectively reviewed to obtain information about the adverse events associated with SRT. Of the 60 lesions, 40 could be evaluated by follow-up CT for therapeutic effectiveness, and the RECIST criteria were used to assess the response. The cancers were papillary cancer in 3 patients, follicular cancer in 9 and poorly differentiated cancer in 1. SRT was delivered in 1-10 fractions, with a median dose of 27 Gy (range, 8-48 Gy). Adverse events were infrequent and mild. The median follow-up of the 40 lesions was 11 (range, 2-56) months. The responses were partial response in 2 lesions, stable disease in 37 lesions and progressive disease in 1 lesion, with a 1-year local control rate of 97.1%. The present study showed that SRT using the CyberKnife system was a feasible and effective treatment for bone metastases of DTC.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Diferenciação Celular , Radiocirurgia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
16.
J Theor Biol ; 480: 1-12, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31323234

RESUMO

In nature, cooperation among individuals is often accompanied by competition among the same individuals for the cooperatively produced rewards. In such a situation, the evolution of cooperative and competitive investments influences each other, but previous theoretical studies mostly focused on either cooperation or competition. Here we consider a generic situation in which individuals cooperatively produce rewards according to the continuous snowdrift game, and then rewards are divided among cooperating individuals according to a generalized tug-of-war game. Using adaptive dynamics and numerical simulations, we investigated the joint evolution of two continuous traits, the investment in cooperation and in competition, respectively. We found that competition for the division of rewards promotes evolutionary branching, and hence polymorphism in both the cooperative and the competitive traits. In polymorphic populations, cooperation levels are positively correlated with competition levels among strains, so that cooperators tend to benefit disproportionately from the benefits produced. We also found that the mean cooperation level within the population is promoted by the competition. Our results show that coevolution of cooperation and competition has qualitatively different outcomes compared to the evolution of only cooperation or only competition, and suggest that it is important to simultaneously consider multiple aspects of social interactions.

17.
Radiat Prot Dosimetry ; 184(3-4): 493-495, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31323674

RESUMO

Gut microflora (GM) impacts human health in various ways, both beneficial and detrimental. Recently, it has attracted attention for its application in treatment, as protective agents, and as biomarkers in radiation exposure. In this study, we focused on organic acids that have not yet been reported to be related to radiation exposure; we measured the pH and organic acid content in the faeces of 0, 2, 4 and 8 Gy-irradiated mice. A common trend of fluctuation of some organic acids was observed in each group, suggesting a correlation between radiation exposure and organic acid fluctuation. Lactate fluctuation was similar between 0 and 2 Gy-, and 4 and 8 Gy-irradiated mice. Based on this finding, we suggest that lactate may also be an organic acid that is greatly affected by irradiation.


Assuntos
Ácidos/metabolismo , Bactérias/metabolismo , Biomarcadores/análise , Microbioma Gastrointestinal/fisiologia , Compostos Orgânicos/metabolismo , Exposição à Radiação/análise , Animais , Bactérias/efeitos da radiação , Relação Dose-Resposta à Radiação , Fezes/química , Microbioma Gastrointestinal/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Irradiação Corporal Total
18.
Kyobu Geka ; 72(8): 641-643, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31353361

RESUMO

We report a resected case of basaloid squamous cell carcinoma (BSC). BSC is a rare type of malignant lung tumor. A 79-year-old woman had a 13 mm tumor in the left upper lobe on chest computed tomography (CT). On fluorodeoxyglucose-position emission tomography (FDG-PET), the tumor showed the accumulation of FDG with an SUVmax of 14.7. A left upper lobectomy with lymph node dissection was performed by video-assisted thoracoscopic surgery. The pathological diagnosis was BSC (pT2aN0M0, stage IB). There was no recurrence following lung cancer resection for 12 months. BSC is generally poor prognosis.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Recidiva Local de Neoplasia , Tomografia Computadorizada por Raios X
19.
Brain Dev ; 41(9): 803-807, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31178082

RESUMO

An m.10158T>C mutation in MT-ND3, encoding a subunit of respiratory complex I, causes early-onset Leigh syndrome (LS), mitochondrial encephalomyopathy with lactic acid and stroke-like episodes (MELAS) syndrome, and LS and MELAS overlapping syndrome, presumably dependent on the ratio of heteroplasmy. Herein, we report a 4-year-old girl with heteroplasmic m.10158T>C mutation, showing an evolving age-dependent phenotype from LS to MELAS syndromes. She showed mild developmental delay during infancy, which was associated with magnetic resonance imaging lesions in the brain stem and basal ganglia. At the age of 4 years, she developed rapid neurological deterioration and intractable seizures, which was associated with recurrent multiple cerebral lesions as well as basal ganglia lesions. Her cerebral lesions were located predominantly in white matter and appeared at multiple areas simultaneously, unique characteristics that are distinct from typical MELAS. Two patients with LS-MELAS overlapping syndrome with m.10158T>C have been previously reported, however, this is the first patient with m.10158T>C showing significant age-dependent changes in clinical features and neuro-images, implying an age-dependent role of complex I in the developing brain.


Assuntos
Complexo I de Transporte de Elétrons/genética , Doença de Leigh/genética , Síndrome MELAS/genética , Mutação , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Doença de Leigh/diagnóstico por imagem , Doença de Leigh/fisiopatologia , Síndrome MELAS/diagnóstico por imagem , Síndrome MELAS/fisiopatologia , Fenótipo
20.
Surgery ; 166(3): 342-348, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31128851

RESUMO

BACKGROUND: Although lobectomy is considered acceptable as a primary surgical treatment for papillary thyroid carcinoma in properly selected patients, a standard treatment for postlobectomy lymph node recurrence has not been established. Here we compared the effectiveness of therapy with lymphadenectomy alone to that of treatment with completion thyroidectomy and lymphadenectomy followed by radioactive iodine. METHODS: This was a retrospective study of patients with papillary thyroid carcinoma who underwent surgery for lymph node recurrence in the period from January 2003 to December 2008, all of whom had previously undergone initial lobectomy with or without lymph node dissection. One-hundred and twenty-five patients were included in the primary analysis. RESULTS: Ninety-eight of these patients underwent lymphadenectomy alone (L group), and 27 received lymphadenectomy and completion thyroidectomy followed by radioactive iodine (LC&R group). The median follow-up time was 10.2 years. The overall survival, distant relapse-free survival, and lymph node relapse-free survival were not significantly different between the LC&R and L groups (P = .89, 0.58, and .22, respectively), whereas the LC&R group patients had significantly longer operation time, higher blood loss, and a higher rate of postoperative hypoparathyroidism compared with the L group (P < .001, respectively). CONCLUSION: Compared with completion thyroidectomy and lymphadenectomy followed by radioactive iodine, lymphadenectomy alone was considered an acceptable therapeutic option which decreased the surgical disadvantages but did not decrease survival for at least 10 years after recurrence surgery for PTC patients with only lymph node recurrence.


Assuntos
Técnicas de Ablação , Radioisótopos do Iodo/uso terapêutico , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/terapia , Tireoidectomia , Adulto , Idoso , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Retratamento , Estudos Retrospectivos , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Resultado do Tratamento
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