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1.
Jpn J Ophthalmol ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39002076

RESUMO

PURPOSE: To evaluate changes in cataract and refractive surgery practice patterns among members of the Japanese Society of Cataract and Refractive Surgery (JSCRS) over the past 20 years. STUDY DESIGN: Questionnaire survey study. SUBJECTS AND METHODS: Clinical surveys were conducted annually between February and April from 2004 to 2023. Survey questions covered various areas, including cataract surgical techniques, anesthesia, endophthalmitis prophylaxis, toric and presbyopia-correcting intraocular lenses (IOLs), complications, and refractive surgery. RESULTS: The highest (n=554 [36.8%]) and lowest (n=316 [19.1%]) numbers of responses were collected in 2012 and 2016, respectively. In perioperative management, the intraoperative use of polyvinyl alcohol-iodine solution and topical antibiotic prescription 3 days before surgery has increased. The use of intracameral injection at the end of surgery has also significantly increased, although it has not been established as common practice. In anesthesia, there is a clear polarization between the use of topical drops and tenon injection. The use of toric IOLs and presbyopia-correcting IOLs has significantly increased from 2010 to 2023. In the latter, the use of trifocal IOLs has particularly increased. Regarding IOL power calculations, the Barrett True K and the Barrett Universal II formulas are rapidly gaining popularity for application with and without post-laser vision correction, respectively. In refractive surgery, phakic IOLs and corneal refractive therapy have attracted considerable interest, followed by laser in situ keratomileusis. CONCLUSIONS: Evaluation of annual clinical survey data over the past two decades provided valuable insights into the shifting practice patterns and clinical opinions among JSCRS members.

2.
Ann Clin Lab Sci ; 54(3): 419-422, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-39048165

RESUMO

OBJECTIVE: Familial hypercholesterolemia (FH) is characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD). Although the role of LDL-C in FH has been studied, the contribution of high-density lipoproteins (HDL) to CVD in FH remains unknown. This study aimed at highlighting the role of HDL in FH. METHODS: HDL-specific phospholipid efflux (HDL-SPE) assay was developed to predict CVD risk. HDL-SPE was examined in FH patients (n=30) and compared with age- and sex-matched non-FH controls (n=60). RESULTS: FH patients had significantly lower HDL-SPE levels (0.90±0.12) than controls (1.12±0.10; p<0.05), despite similar HDL-cholesterol levels in both groups (FH: 57.9±18.7 mg/dl; controls: 57.1±13.8 mg/dl). These differences remained significant after adjusting for confounders. CONCLUSIONS: These findings suggest there may be dysfunctionality of HDL in FH.


Assuntos
Hiperlipoproteinemia Tipo II , Lipoproteínas HDL , Fosfolipídeos , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/metabolismo , Masculino , Feminino , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/sangue , Adulto , Fosfolipídeos/metabolismo , Fosfolipídeos/sangue , Pessoa de Meia-Idade , Estudos de Casos e Controles , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/sangue
3.
Cancer Chemother Pharmacol ; 93(4): 319-328, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38017207

RESUMO

PURPOSE: Acneiform rash is frequently observed in patients undergoing cancer treatment with anti-epidermal growth factor receptor (EGFR) antibody drugs and can often necessitate treatment discontinuation. However, the specific changes in skin parameters resulting from anti-EGFR antibody drug administration are poorly understood. Therefore, this study aimed to longitudinally and quantitatively evaluate the changes in skin parameters (transepidermal water loss [TEWL], hydration level, and sebum level) caused by anti-EGFR antibody drugs and investigate their potential as control markers for skin disorders. METHODS: This prospective study included 12 patients with colorectal cancer who received anti-EGFR antibody drugs for the first time. The assessment items included the grade of acneiform rash and skin parameters (TEWL, hydration level, and sebum level), which were observed for up to 6 weeks after administration of the medication. RESULTS: The enrolled patients were classified into two groups based on the grade of acneiform rash caused by anti-EGFR antibody drugs: "Grade 1 and lower," and "Grade 2 and higher." The skin parameters were compared between these groups. The results showed that in the "Grade 2 and higher" group, TEWL in the face (at week 2 of administration), chest (baseline, weeks 2 and 6 of administration), and back (at week 2 of administration) were significantly higher than those in the "Grade 1 and lower" group. However, the two groups showed no significant differences in hydration or sebum levels at any time point. CONCLUSION: TEWL can serve as a marker for acneiform rashes induced by anti-EGFR antibody drugs during cancer treatment.


Assuntos
Neoplasias Colorretais , Exantema , Humanos , Panitumumabe/efeitos adversos , Estudos Prospectivos , Receptores ErbB , Pele , Exantema/induzido quimicamente , Neoplasias Colorretais/tratamento farmacológico , Cetuximab/efeitos adversos
4.
iScience ; 26(12): 108486, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38125025

RESUMO

Oral squamous cell carcinoma (OSCC), a prevalent and aggressive neoplasm, poses a significant challenge due to poor prognosis and limited prognostic biomarkers. Leveraging highly multiplexed imaging mass cytometry, we investigated the tumor immune microenvironment (TIME) in OSCC biopsies, characterizing immune cell distribution and signaling activity at the tumor-invasive front. Our spatial subsetting approach standardized cellular populations by tissue zone, improving feature reproducibility and revealing TIME patterns accompanying loss-of-differentiation. Employing a machine-learning pipeline combining reliable feature selection with multivariable modeling, we achieved accurate histological grade classification (AUC = 0.88). Three model features correlated with clinical outcomes in an independent cohort: granulocyte MAPKAPK2 signaling at the tumor front, stromal CD4+ memory T cell size, and the distance of fibroblasts from the tumor border. This study establishes a robust modeling framework for distilling complex imaging data, uncovering sentinel characteristics of the OSCC TIME to facilitate prognostic biomarkers discovery for recurrence risk stratification and immunomodulatory therapy development.

5.
J Clin Invest ; 133(18)2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37471145

RESUMO

BACKGROUNDCellular cholesterol efflux capacity (CEC) is a better predictor of cardiovascular disease (CVD) events than HDL-cholesterol (HDL-C) but is not suitable as a routine clinical assay.METHODSWe developed an HDL-specific phospholipid efflux (HDL-SPE) assay to assess HDL functionality based on whole plasma HDL apolipoprotein-mediated solubilization of fluorescent phosphatidylethanolamine from artificial lipid donor particles. We first assessed the association of HDL-SPE with prevalent coronary artery disease (CAD): study I included NIH severe-CAD (n = 50) and non-CAD (n = 50) participants, who were frequency matched for sex, BMI, type 2 diabetes mellitus, and smoking; study II included Japanese CAD (n = 70) and non-CAD (n = 154) participants. We also examined the association of HDL-SPE with incident CVD events in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study comparing 340 patients with 340 controls individually matched for age, sex, smoking, and HDL-C levels.RESULTSReceiver operating characteristic curves revealed stronger associations of HDL-SPE with prevalent CAD. The AUCs in study I were as follows: HDL-SPE, 0.68; apolipoprotein A-I (apoA-I), 0.62; HDL-C, 0.63; and CEC, 0.52. The AUCs in study II were as follows: HDL-SPE, 0.83; apoA-I, 0.64; and HDL-C, 0.53. Also longitudinally, HDL-SPE was significantly associated with incident CVD events independent of traditional risk factors with ORs below 0.2 per SD increment in the PREVEND study (P < 0.001).CONCLUSIONHDL-SPE could serve as a routine clinical assay for improving CVD risk assessment and drug discovery.TRIAL REGISTRATIONClinicalTrials.gov NCT01621594.FUNDINGNHLBI Intramural Research Program, NIH (HL006095-06).


Assuntos
Doenças Cardiovasculares , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Humanos , Lipoproteínas HDL , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Apolipoproteína A-I , HDL-Colesterol , Fosfolipídeos
6.
Biosci Biotechnol Biochem ; 86(12): 1680-1687, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36138494

RESUMO

Ingestion of plant and fungal glucosylceramides is known to reduce colon carcinogenesis and skin barrier damage in mice and humans. However, such effects in animal experiments have not been revealed for plant and fungal ceramides because the content of ceramides contained in plants and fungi is so low that the large amount required for animal experiments is difficult to obtain. Noting that the fungus shiitake mushroom (Lentinula edodes) is rich in a glucosylceramide, (4E,8E)-N-d-2'-hydroxypalmitoyl-1-O-ß-d-glucopyranosyl-9-methyl-4,8-sphingadienine [Glc-d19:2(4E,8E,9Me)-h16:0], we developed a new method to purify this fungal glucosylceramide using ethanol precipitation and high-performance liquid chromatography. We also developed a new method to produce large amounts of a ceramide [d19:2(4E,8E,9Me)-h16:0] from this purified glucosylceramide using human glycoside hydrolase family 30 glucocerebrosidase (imiglucerase). These methods will be useful for elucidating the physiological function by ingestion of fungal ceramides in animal experiments.


Assuntos
Glucosilceramidas , Cogumelos Shiitake , Humanos , Camundongos , Animais , Glucosilceramidas/química , Ceramidas , Cromatografia Líquida de Alta Pressão
7.
Anal Biochem ; 656: 114880, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36063916

RESUMO

MicroRNAs (miRNAs) are potential clinical biomarkers for the detection of various diseases. However, their quantification has not been implemented in clinical practice given the inconsistencies in their variable recovery rate and accuracy of the results. Thus, we utilized a technique based on bioluminescent enzyme immunoassay (BLEIA) to perform fully automated miRNA quantification using magnetic particles conjugated with antibodies targeting DNA-RNA hybrids, biotinylated DNA probes specific to miRNAs, and firefly luciferase-labeled streptavidin. This method enabled direct use of diluted serum and automation of all processes within 1 hr. The results revealed a wide linear range between 10 fmol/L and 1 nmol/L, high sensitivity with a detection limit of 6.3 fmol/L or below, high specificity with a false positive rate under 2.4%, and high reproducibility in intra- and inter-experimental observations (under CV 10% and r = 0.9965, respectively). Furthermore, a significant correlation was revealed between quantitative reverse transcription-polymerase chain reaction and BLEIA assay for the quantification of synthetic miRNA (r = 0.9993) and endogenous miRNA in healthy serums (r = 0.8203), respectively. Overall, we developed a fully automated miRNA quantification method based on BLEIA, which can be adopted in a clinical setting. However, further studies are needed to assess its clinical performance.


Assuntos
MicroRNAs , Biomarcadores , DNA , Sondas de DNA , Imunoensaio/métodos , Técnicas Imunoenzimáticas , Luciferases de Vaga-Lume , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estreptavidina
8.
Br J Ophthalmol ; 106(9): 1227-1234, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108223

RESUMO

AIM: To compare the preoperative biometric data and the refractive accuracy of cataract surgery among major surgical sites in a nationwide multicentre study. METHODS: We prospectively obtained the preoperative biometric data of 2143 eyes of 2143 consecutive patients undergoing standard cataract surgery at major 12 facilities and compared the preoperative biometry as well as the postoperative refractive accuracy among them. RESULTS: We found significant differences in most preoperative variables, such as axial length (one-way analysis of variance, p=0.003), anterior chamber depth (p<0.001), lens thickness (p<0.001) and central corneal thickness (p<0.001), except for mean keratometry (p=0.587) and corneal astigmatism (p=0.304), among the 12 surgical sites. The prediction error using the Sanders-Retzlaff-Kraff/Theoretical (SRK/T formula was significantly more hyperopic than that using the Barrett Universal II formula (paired t-test, p<0.001). The absolute error using the SRK/T formula was significantly larger than that using the Barrett Universal II formula (p=0.016). The prediction error using the SRK/T formula was significantly more hyperopic than that using the Barrett Universal II formula at 10 of 12 institutions, but significantly more myopic at one institution. The absolute error using the SRK/T formula was significantly larger than that using the Barrett Universal II formula at 4 of 12 institutions but significantly smaller at two institutions. CONCLUSIONS: Regional divergences of the preoperative biometry were not necessarily negligible, and the optimised intraocular lens power calculation formula was individually different among the 12 facilities. Our findings highlight the importance of individual optimisation of these formulas at each facility, especially in consideration of these biometric variations.Trial registration numberClinical Trial Registry; 000039976.


Assuntos
Catarata , Hiperopia , Lentes Intraoculares , Facoemulsificação , Biometria , Humanos , Japão , Implante de Lente Intraocular , Óptica e Fotônica , Refração Ocular , Estudos Retrospectivos
9.
J Oral Biosci ; 63(4): 436-443, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34555528

RESUMO

OBJECTIVES: Temporomandibular joint osteoarthritis (TMJ-OA) causes degenerative changes in TMJ tissues. The inter-tissue crosstalk that exacerbates illness and organic changes in bone secondary to TMJ-OA potentially affects the muscles; therefore, patients with a muscular disease might also suffer from bone disease. However, knowledge gaps exist concerning muscle pathology at the onset of TMJ-OA. In this study, we documented the pathogeneses of the bone and muscle at the onset of TMJ-OA using a mouse model. METHODS: We performed a partial resection of the TMJ disk to establish a mouse model of TMJ-OA. After the onset of TMJ-OA, we performed various measurements at 8, 12, and 16 weeks post-surgery in the defined groups. RESULTS: The volume of the mandibular head in the TMJ-OA group was significantly greater than that in the control group. The temporal muscles in the TMJ-OA group were significantly deformed compared with those in the control group; however, between-group comparisons did not reveal significant differences in the mandibular head or temporal muscles after surgery. Therefore, we hypothesized that the degree of mandibular head hypertrophy would alter the temporal muscles. A subsequent analysis of the correlation between the bone and muscle confirmed that the deformity of the temporal muscle increased with increasing hypertrophy of the mandibular head. Temporal and masseter muscle contact was observed in 25% of surgical groups. CONCLUSIONS: This study demonstrates that TMJ-OA progressed when organic changes occurred in bones and muscles, supporting the symbiotic relationship between bones and muscles.


Assuntos
Transtornos da Articulação Temporomandibular , Discotomia , Humanos , Côndilo Mandibular/patologia , Músculos/patologia , Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/cirurgia
10.
Int J Comput Assist Radiol Surg ; 16(4): 663-671, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33709240

RESUMO

PURPOSE: In endovascular neurosurgery, the operator often acquires three-dimensional (3D) images of the cerebral vessels. Although workstation reoperation is required in some situations during treatment, it leads to time loss because a sterile condition cannot be maintained and treatment must be temporarily interrupted. Therefore, a workstation reoperating system is required while maintaining the desired sterility. METHODS: A contactless operating interface using Kinect to control 3D images was developed via gesture recognition for endovascular neurosurgery and was applied to a 3D volume rendering technique (VRT) image reconstructed at the workstation. The left-hand movement determines the assigned functions, whereas the right-hand movement is used like a computer mouse to pan and zoom in/out. In addition to the interface, voice commands were used and assigned to digital operations, such as image view changes and mode signal changes. RESULTS: This system was used for the actual endovascular treatment of cerebral aneurysms and cerebral arteriovenous malformations. The operator and gesture were recognized without any problems. Using voice operation, it was possible to expeditiously set the VRT image back to the reference angle. Furthermore, it was possible to finely adjust gesture operations, including mouse operation, and treatment was completed while maintaining sterile conditions. CONCLUSION: A contactless operating interface was developed by combining the existing workstation system with Kinect and voice recognition software, allowing surgeons to perform a series of operations, which are normally performed in a console room, while maintaining sterile conditions.


Assuntos
Gestos , Imageamento Tridimensional/métodos , Neurocirurgia/instrumentação , Neurocirurgia/métodos , Interface Usuário-Computador , Algoritmos , Simulação por Computador , Sistemas Computacionais , Computadores , Desenho de Equipamento , Mãos , Humanos , Aneurisma Intracraniano , Movimento , Procedimentos Neurocirúrgicos , Salas Cirúrgicas , Processamento de Sinais Assistido por Computador , Software
11.
Pancreatology ; 21(4): 771-778, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33707114

RESUMO

BACKGROUND: The epithelial-mesenchymal transition (EMT) in cancer cells has been shown to closely associate with the survival and drug resistance of cancer cells. We recently provided evidence that Wnt signal activator leucine-rich repeat in flightless-1-interacting protein 1 (LRRFIP1) regulates EMT in pancreatic cancer. LRRFIP1 silencing inhibits the translocation of ß-catenin to the nucleus, which led to reverse EMT in cancer cells. It was suggested that LRRFIP1 was implicated in gemcitabine sensitivity by regulating EMT signaling. METHODS: Gemcitabine chemosensitivity was investigated in LRRFIP1-knockdown pancreatic cancer cells (PANC-1 and MIA Paca-2). In addition, the effects of LRRFIP1 knockdown on JNK/SAPK (stress activated-protein kinase) signaling and apoptosis were evaluated. RESULTS: LRRFIP1 silencing accelerates gemcitabine-induced caspase activity and cell death in pancreatic cancer cells. It was also revealed that gemcitabine-induced phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun were increased in LRRFIP1 knockdown cells. The activation of JNK/c-Jun in LRRFIP1-knockdown cells was significantly diminished by the inhibition of Rac activity. It was confirmed that the acquisition of gemcitabine sensitivity by LRRFIP1 silencing largely depends on the stimulation of JNK/SAPK (stress activated-protein kinase) signaling. CONCLUSIONS: Our findings suggest that reversing EMT and transient activation of JNK might be essential for the gemcitabine sensitivity in LRRFIP1 knockdown pancreatic cancer cells. Our discoveries highlight the potential role of LRRFIP1 in the chemosensitivity related to the regulation of EMT signaling.


Assuntos
Desoxicitidina , Neoplasias Pancreáticas , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Proteínas de Ligação a RNA , Gencitabina , Neoplasias Pancreáticas
12.
Ann Anat ; 235: 151694, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33571646

RESUMO

Skeletal muscle regeneration is initiated by the activation of the transcription factor paired box 7 (Pax7), which is expressed in the satellite cells. The nuclear transcription factor T-cell factor 4 (Tcf4) is expressed in the fibroblasts and is involved in muscle tissue repair, while M2-like macrophages play an important role in skeletal muscle regeneration. However, the localization of M2-like macrophages and the expression of Tcf4 over a period of time during skeletal muscle regeneration remain unknown. Therefore, the murine masseter muscle was immunofluorescence investigated for the surface protein CD206 of M2-like macrophages and Tcf4 of fibroblasts during skeletal muscle regeneration to understand the changes in the CD206 and Tcf4 expression over time. We observed that CD206 entered the cytoplasm of some regenerating muscle fibers 5-7 days after the experimental muscle damage, that is, in the early stage of maturation of the regenerating muscle fibers with central nuclei. In addition, Tcf4 was expressed in the nuclei of the fibroblasts around the regenerating muscle fibers and in the central nuclei of the regenerating muscle fibers. Furthermore, the expression of laminin adjacent to Tcf4-positive cells was observed to partially disappear, and the shape of this missing part was observed to be identical to that of the nuclei of Tcf4-positive cells adjacent to the laminin. Clathrin was also expressed in these sites, demonstrating endocytosis. Thus, these results suggest that in the early stage of maturation of the regenerating muscle fibers, M2-like macrophages and Tcf4-positive fibroblasts enter the cytoplasm of the regenerating muscle fibers, thereby regulating the expression of various maturation factors.


Assuntos
Regeneração , Proteína 2 Semelhante ao Fator 7 de Transcrição , Animais , Fibroblastos , Macrófagos , Camundongos , Fibras Musculares Esqueléticas , Músculo Esquelético
13.
Gan To Kagaku Ryoho ; 48(1): 104-106, 2021 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-33468735

RESUMO

The number of elderly patients and colorectal cancer patients is increasing, so laparoscopic surgery for colorectal cancer in elderly patients is suspected to increase. In 456 patients who underwent laparoscopic surgery for colorectal cancer, we investigated whether laparoscopic surgery for elderly patients with colon cancer patients could be performed equally compared to non-elderly patients. Preoperative ASA-PS was slightly poorer in elderly patients. There was no significant difference in pStage. The 5-year overall survival rate was lower in the elderly, but there were no significant differences in blood loss, operation time, postoperative hospital stays and incidence of complications of Clavien-Dindo classification grade 3 or higher. It was suggested that laparoscopic surgery for elderly patients with colorectal cancer may be safely performed compared with non-elderly patients.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Laparoscopia , Idoso , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/cirurgia , Humanos , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
14.
Surg Today ; 51(1): 144-152, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32623583

RESUMO

PURPOSE: The Controlling Nutritional Status (CONUT) Score, originally developed as a nutritional screening tool, is a cumulative score calculated from the serum albumin level, total cholesterol level, and total lymphocyte count. Previous studies have demonstrated that the score has significant prognostic value in various malignancies. We investigated the relationship between the CONUT score and long-term survival in obstructive colorectal cancer (OCRC) patients who underwent self-expandable metallic colonic stent placement and subsequently received curative surgery. METHODS: We retrospectively analyzed 57 pathological stage II and III OCRC patients between 2013 and 2019. The associations between the preoperative CONUT score and clinicopathological factors and patient survival were evaluated. RESULTS: A receiver operating characteristic curve analysis revealed that the optimal cut-off value for the CONUT score was 7. A CONUT score of ≥ 7 was significantly associated with elevated CA19-9 level (p = 0.03). Multivariate analyses revealed that a CONUT score of ≥ 7 was independently associated with cancer-specific survival (hazard ratio [HR] = 10.2, 95% confidence interval [CI] 1.2-85.9, p = 0.03) and disease-free survival (HR = 7.1, 95% CI 2.3-21.7, p = 0.0006). CONCLUSION: The results demonstrated that the CONUT score was a potent prognostic indicator. Evaluating the CONUT score might result in more precise patient assessment and tailored treatment.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Estado Nutricional , Stents Metálicos Autoexpansíveis , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Prognóstico , Estudos Retrospectivos , Albumina Sérica , Taxa de Sobrevida
15.
Cells ; 9(7)2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32708195

RESUMO

Motor neuron diseases are a group of progressive neurological disorders that degenerate motor neurons. The neuroblastoma × spinal cord hybrid cell line NSC-34 is widely used as an experimental model in studies of motor neuron diseases. However, the differentiation efficiency of NSC-34 cells to neurons is not always sufficient. We have found that prostaglandin E2 (PGE2) induces morphological differentiation in NSC-34 cells. The present study investigated the functional properties of PGE2-differentiated NSC-34 cells. Retinoic acid (RA), a widely-used agent inducing cell differentiation, facilitated neuritogenesis, which peaked on day 7, whereas PGE2-induced neuritogenesis took only 2 days to reach the same level. Whole-cell patch-clamp recordings showed that the current threshold of PGE2-treated cell action potentials was lower than that of RA-treated cells. PGE2 and RA increased the protein expression levels of neuronal differentiation markers, microtubule-associated protein 2c and synaptophysin, and to the same extent, motor neuron-specific markers HB9 and Islet-1. On the other hand, protein levels of choline acetyltransferase and basal release of acetylcholine in PGE2-treated cells were higher than in RA-treated cells. These results suggest that PGE2 is a rapid and efficient differentiation-inducing factor for the preparation of functionally mature motor neurons from NSC-34 cells.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Dinoprostona/farmacologia , Neurônios Motores/citologia , Acetilcolina/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ativação do Canal Iônico/efeitos dos fármacos , Camundongos , Neurônios Motores/efeitos dos fármacos , Crescimento Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Tetrodotoxina/farmacologia , Tretinoína/farmacologia
16.
Surg Today ; 50(10): 1272-1281, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32346761

RESUMO

PURPOSE: Inflammation-based markers predict long-term outcomes of various malignancies. We investigated the relationship between these markers and the long-term survival in obstructive colorectal cancer (OCRC) patients with self-expandable metallic colonic stents (SEMSs) who subsequently received curative surgery. METHODS: We retrospectively analyzed 72 consecutive pathological stage II and III OCRC patients between 2013 and 2019. The prognostic significance of the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), and platelet-lymphocyte ratio (PLR) was evaluated. RESULTS: The overall survival (OS), cancer-specific survival, and disease-free survival (DFS) were significantly shorter in the PNI < 35 group than in the PNI ≥ 35 group (p = 0.006, p < 0.001, and p = 0.003, respectively), and multivariate analyses revealed the PNI to be the only inflammation-based marker independently associated with the survival. A PNI < 35 was significantly associated with an elevated CA 19-9 level (p = 0.04) and longer postoperative hospital stay (p = 0.03). Adjuvant chemotherapy was also significantly associated with the OS (p = 0.040) and DFS (p = 0.011) in multivariate analyses. CONCLUSION: The results showed that the PNI was a potent prognostic indicator. For OCRC patients, both systemic inflammation and the nutrition status seem to be important for predicting the prognosis, and administering adjuvant chemotherapy was very important.


Assuntos
Neoplasias Colorretais/cirurgia , Avaliação Nutricional , Estado Nutricional , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CA-19-9 , Quimioterapia Adjuvante , Neoplasias Colorretais/complicações , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Inflamação , Obstrução Intestinal/etiologia , Obstrução Intestinal/mortalidade , Obstrução Intestinal/cirurgia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Stents Metálicos Autoexpansíveis
17.
Cancer Res ; 80(6): 1279-1292, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31919242

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is among the cancers with the poorest prognoses due to its highly malignant features. BTB and CNC homology 1 (BACH1) has been implicated in RAS-driven tumor formation. We focused on the role of BACH1 in PDAC, more than 90% of which have KRAS mutation. Knockdown of BACH1 in PDAC cell lines reduced cell migration and invasion, in part, by increasing E-cadherin expression, whereas its overexpression showed opposite effects. BACH1 directly repressed the expression of FOXA1 that is known to activate the expression of CDH1 encoding E-cadherin and to inhibit epithelial-to-mesenchymal transition. BACH1 also directly repressed the expression of genes important for epithelial cell adhesion including CLDN3 and CLDN4. In a mouse orthotopic implantation model, BACH1 was required for the high metastatic ability of AsPC-1 cells. IHC analysis of clinical specimens with a newly developed anti-BACH1 mAb revealed that high expression of BACH1 is a poor prognostic factor. These results suggest that the gene regulatory network of BACH1 and downstream genes including CDH1 contribute to the malignant features of PDAC by regulating epithelial-to-mesenchymal transition. SIGNIFICANCE: Greater understanding of the gene regulatory network involved in epithelial-to-mesenchymal transition of pancreatic cancer cells will provide novel therapeutic targets and diagnostic markers.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Carcinoma Ductal Pancreático/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/genética , Animais , Antígenos CD/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Caderinas/genética , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Movimento Celular/genética , Claudina-3/genética , Claudina-4/genética , Feminino , Técnicas de Inativação de Genes , Redes Reguladoras de Genes , Fator 3-alfa Nuclear de Hepatócito/genética , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , RNA-Seq
18.
Gan To Kagaku Ryoho ; 47(13): 1957-1959, 2020 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-33468765

RESUMO

A 67-year-old man with complaints of upper abdominal pain visited a clinic and was diagnosed with type 3 gastric cancer. Contrasted-enhanced CT revealed gastric wall thickening and extensive metastatic lymph nodes particularly around the celiac artery and also invasion to pancreas. He was diagnosed with cT4b, cN2, cM0, cStage ⅢB and we treated with neoadjuvant chemotherapy(NAC)consisting of 4 courses of S-1 and cisplatin regimen. After the NAC, primary cancer and metastatic lymph nodes were reduced remarkably. A curative operation could be performed and the histopathological examination showed"Grade 3, pathological complete response".


Assuntos
Terapia Neoadjuvante , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Combinação de Medicamentos , Gastrectomia , Humanos , Masculino , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tegafur/uso terapêutico
19.
Gan To Kagaku Ryoho ; 47(13): 1795-1797, 2020 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-33468832

RESUMO

A 59-year-old man with chief complaints of right-sided rib pain and fever was admitted to our hospital. A type 2 tumor in the ascending colon was revealed by total colonoscopy. Computed tomography examination revealed multiple tumors in the liver. The white blood cell count was high as 13,740/µL. Chemotherapy was planned after treatment with antibiotics, but it was not successful. Right colectomy was performed for infection control. mFOLFOX6 therapy was performed, but liver metastases progressed rapidly, and he died on the 39th postoperative day. The immunohistochemistry revealed G-CSF producing colon cancer. G-CSF producing colon cancer progresses rapidly with poor prognosis. It is necessary to think carefully about indication of surgery and chemotherapy.


Assuntos
Colo Ascendente , Neoplasias do Colo , Colo Ascendente/cirurgia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Fator Estimulador de Colônias de Granulócitos , Granulócitos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade
20.
Surg Today ; 50(3): 232-239, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31407166

RESUMO

PURPOSE: Inflammation-based markers predict the long-term outcomes of various malignancies. We investigated the relationship between the modified Glasgow prognostic score (mGPS) and the long-term outcomes of obstructive colorectal cancer in patients who underwent self-expandable metallic colonic stent placement and subsequently received curative surgery. METHODS: We retrospectively analyzed 63 consecutive patients with pathological stage II and III obstructive colorectal cancer from 2013 to 2018. The mGPS was calculated before stenting and surgery, and the difference of the scores was defined as the d-mGPS. RESULTS: All d-mGPS = 2 patients were > 70 years of age (p = 0.01). Postoperative complications were more common in the preoperative mGPS = 2 group (p = 0.02). The postoperative hospital stay was significantly longer in the mGPS = 2 group (p = 0.007). Multivariate analyses revealed that d-mGPS was an independent prognostic factor for overall survival (OS) (hazard ratio [HR] = 9.18, p = 0.004) and cancer-specific survival (HR = 9.98, p = 0.01). Preoperative mGPS = 2 was significantly associated with poor OS (HR = 5.53, p = 0.04). CONCLUSION: The results indicated that mGPS might serve as a valuable indicator of the immunonutritional status of preoperative patients, and a preoperative change of the status might affect the long-term outcomes of patients with obstructive colorectal cancer.


Assuntos
Neoplasias Colorretais/cirurgia , Escala de Resultado de Glasgow , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Stents , Idoso , Neoplasias Colorretais/complicações , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Humanos , Estadiamento de Neoplasias , Estado Nutricional , Valor Preditivo dos Testes , Período Pré-Operatório , Fatores de Tempo
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