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1.
Chem Commun (Camb) ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622899

RESUMO

A dual-enzyme cascade, xylitol dehydrogenase and xylulose kinase, derived from the xylose metabolic pathway, was constructed on a three-dimensional DNA scaffold which exhibited a dynamic shape transition from an open state to a closed hexagonal prism. Evaluation of the cascade reaction efficiencies in the open and closed states revealed little to no inter-enzyme distance dependence, presumably due to the far larger catalytic constant of the downstream enzyme. The inter-enzyme distance was not the dominant factor for cascade efficiency when the kinetic parameters of the cascade enzymes were imbalanced with the highly efficient downstream enzyme.

2.
Work ; 70(1): 271-277, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511470

RESUMO

BACKGROUND: The identification of factors that are related to return to work after surgery for breast cancer could help healthcare professionals accurately identify patients at risk of return to work-related difficulties in order to provide them with appropriate support during breast cancer management. OBJECTIVE: The aim of this study was to identify factors related to return to work in breast cancer patients three months after axillary lymph node dissection. METHODS: Seventy-three women who were working before the surgery were evaluated. Age, body mass index, level of lymph node dissection, marital status, children, co-resident household members, preoperative chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, shoulder range of motion, upper limb function (Disabilities of the Arm, Shoulder and Hand; DASH), and work were evaluated. Patients who had returned to work constituted the return to work group, and those who had not returned to work constituted the no return to work group. RESULTS: Of the patients, 36 returned to work at three months. Logistic regression analysis including the five variables showed that shoulder flexion range of motion and DASH were significantly associated with return to work (p < 0.05). CONCLUSIONS: The observation that the symptoms and limitations of upper limb function and shoulder flexion range of motion affect return to work may indicate the importance of postoperative rehabilitation in breast cancer patients following axillary lymph node dissection.


Assuntos
Neoplasias da Mama , Axila , Neoplasias da Mama/cirurgia , Criança , Feminino , Humanos , Excisão de Linfonodo , Amplitude de Movimento Articular , Retorno ao Trabalho
3.
Nat Biomed Eng ; 5(8): 926-940, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34373601

RESUMO

Current protocols for the differentiation of human pluripotent stem cells (hPSCs) into chondrocytes do not allow for the expansion of intermediate progenitors so as to prospectively assess their chondrogenic potential. Here we report a protocol that leverages PRRX1-tdTomato reporter hPSCs for the selective induction of expandable and ontogenetically defined PRRX1+ limb-bud-like mesenchymal cells under defined xeno-free conditions, and the prospective assessment of the cells' chondrogenic potential via the cell-surface markers CD90, CD140B and CD82. The cells, which proliferated stably and exhibited the potential to undergo chondrogenic differentiation, formed hyaline cartilaginous-like tissue commensurate to their PRRX1-expression levels. Moreover, we show that limb-bud-like mesenchymal cells derived from patient-derived induced hPSCs can be used to identify therapeutic candidates for type II collagenopathy and we developed a method to generate uniformly sized hyaline cartilaginous-like particles by plating the cells on culture dishes coated with spots of a zwitterionic polymer. PRRX1+ limb-bud-like mesenchymal cells could facilitate the mass production of chondrocytes and cartilaginous tissues for applications in drug screening and tissue engineering.


Assuntos
Proteínas de Homeodomínio/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Pluripotentes/citologia , Animais , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Condrócitos/citologia , Condrócitos/metabolismo , Condrócitos/transplante , Condrogênese , Doenças do Colágeno/terapia , Meios de Cultura/química , Proteínas de Homeodomínio/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Pluripotentes/metabolismo , Polímeros/química , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Antígenos Thy-1/metabolismo , Engenharia Tecidual
4.
Nucleic Acids Res ; 49(14): 7884-7900, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34289063

RESUMO

The low thermal stability of DNA nanostructures is the major drawback in their practical applications. Most of the DNA nanotubes/tiles and the DNA origami structures melt below 60°C due to the presence of discontinuities in the phosphate backbone (i.e., nicks) of the staple strands. In molecular biology, enzymatic ligation is commonly used to seal the nicks in the duplex DNA. However, in DNA nanotechnology, the ligation procedures are neither optimized for the DNA origami nor routinely applied to link the nicks in it. Here, we report a detailed analysis and optimization of the conditions for the enzymatic ligation of the staple strands in four types of 2D square lattice DNA origami. Our results indicated that the ligation takes overnight, efficient at 37°C rather than the usual 16°C or room temperature, and typically requires much higher concentration of T4 DNA ligase. Under the optimized conditions, up to 10 staples ligation with a maximum ligation efficiency of 55% was achieved. Also, the ligation is found to increase the thermal stability of the origami as low as 5°C to as high as 20°C, depending on the structure. Further, our studies indicated that the ligation of the staple strands influences the globular structure/planarity of the DNA origami, and the origami is more compact when the staples are ligated. The globular structure of the native and ligated origami was also found to be altered dynamically and progressively upon ethidium bromide intercalation in a concentration-dependent manner.


Assuntos
DNA Ligases/metabolismo , DNA/química , Nanoestruturas/química , Conformação de Ácido Nucleico , Temperatura , DNA/genética , DNA/metabolismo , Eletroforese em Gel de Ágar/métodos , Etídio/química , Cinética , Microscopia de Força Atômica/métodos , Desnaturação de Ácido Nucleico , Fosforilação , Termodinâmica
5.
Biochem Biophys Res Commun ; 557: 199-205, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-33872989

RESUMO

Malignant peripheral nerve sheath tumor (MPNST), a highly malignant tumor that arises in peripheral nerve tissues, is known to be highly resistant to radiation and chemotherapy. Although there are several reports on genetic mutations and epigenetic changes that define the pathogenesis of MPNST, there is insufficient information regarding the microenvironment that contributes to the malignancy of MPNST. In the present study, we demonstrate that adrenaline increases the cancer stem cell population in MPNST. This effect is mediated by adrenaline stimulation of beta-2 adrenergic receptor (ADRB2), which activates the Hippo transducer, YAP/TAZ. Inhibition and RNAi experiments revealed that inhibition of ADRB2 attenuated the adrenaline-triggered activity of YAP/TAZ and subsequently attenuated MPNST cells stemness. Furthermore, ADRB2-YAP/TAZ axis was confirmed in the MPNST patients' specimens. The prognosis of patients with high levels of ADRB2 was found to be significantly worse. These data show that adrenaline exacerbates MPNST prognosis and may aid the development of new treatment strategies for MPNST.


Assuntos
Epinefrina/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Neoplasias da Bainha Neural/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias da Bainha Neural/genética , Neoplasias da Bainha Neural/patologia , Prognóstico , Interferência de RNA , Receptores Adrenérgicos beta 2/genética , Transdução de Sinais/genética , Fatores de Transcrição/metabolismo
6.
Chem Commun (Camb) ; 57(32): 3925-3928, 2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-33871490

RESUMO

The catalytic enhancements of enzymes loaded on DNA nanostructures have been attributed to the characteristics provided by highly negative charges on the surface of the DNA scaffold, such as the modulation of the local pH near enzymes. In this study, two types of enzymes with optimal activity at pH 6 and 8 equally displayed significant catalytic enhancements on the DNA scaffold surface. By using a ratiometric pH indicator, a lower local pH shift of 0.8 was observed near the DNA scaffold surface. The postulated local pH change near the DNA scaffold surface is unlikely to play a general role in enhancing the activity of the scaffolded enzymes.


Assuntos
Aldeído Redutase/química , D-Xilulose Redutase/química , DNA/química , Enzimas Imobilizadas/química , Nanoestruturas/química , Aldeído Redutase/metabolismo , Melhoramento Biomédico , Catálise , D-Xilulose Redutase/metabolismo , Enzimas Imobilizadas/metabolismo , Concentração de Íons de Hidrogênio , Conformação Molecular , Relação Estrutura-Atividade , Propriedades de Superfície
7.
Cancers (Basel) ; 13(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802565

RESUMO

Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRPα, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas.

8.
Acta Med Okayama ; 75(1): 39-44, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33649612

RESUMO

In this study, we examined whether axillary web syndrome (AWS) in patients with breast cancer following axil-lary lymph node dissection affects range of motion (ROM), upper extremity function, and quality of life (QOL). The risk factors for AWS were also evaluated in a total of 238 consecutive breast cancer patients follow-ing axillary lymph node dissection. At 1, 2, and 3 months after surgery, there were no significant differences between the AWS group and the non-AWS group in upper-limb function or QOL. At 2 months after surgery, shoulder flexion and abduction ROM were significantly higher in the AWS group than in the non-AWS group (p < 0.05). Self-training time at home was not significantly different between the groups at 1, 2, or 3 months. Only age was a significant predictor of AWS at 1 month after surgery (p < 0.05). The AWS group in the present study did not have worse results for shoulder joint ROM, upper-limb function, and QOL than the non-AWS group. Younger age should be useful for predicting the development of AWS in the early postoperative period.

9.
Healthcare (Basel) ; 9(2)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669376

RESUMO

OBJECTIVE: The purpose of this study was to investigate factors related to early quality of life (QOL) three months after surgery in breast cancer patients with axillary lymph node dissection. METHODS: The subjects of this study were 195 consecutive patients who underwent axillary lymph node dissection for breast cancer. Age, body mass index, level of lymph node dissection, marriage, children, co-resident household members, neoadjuvant chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, upper limb function (disabilities of the arm, shoulder, and hand (DASH)), and QOL (European Organization for the Treatment and Research of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)) were evaluated. For each item of the EORTC QLQ-C30, compared with preoperative status and three months after surgery, those who improved or remained unchanged in the three months after surgery were classified as the maintenance and improved groups, and those with worsening status were classified as the worsened group. RESULTS: Age, level of lymph node dissection, DASH, neoadjuvant chemotherapy, postoperative chemotherapy, and postoperative radiotherapy were significantly associated with QOL (p < 0.05). CONCLUSIONS: The early QOL of postoperative patients with breast cancer is affected by multiple factors, such as upper limb function and postoperative chemotherapy, and thus comprehensive intervention is required.

10.
Jpn J Clin Oncol ; 51(4): 523-537, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33611603

RESUMO

Sarcomas are a heterogeneous group of malignancies of mesenchymal origin; their molecular and genomic mechanisms differ with regard to histology. These characteristics lead to the presentation of varied immunological profiles based on the tumor microenvironment. Various immunotherapies are considered for the treatment of sarcoma. These treatments are performed either in isolation or in combination with other methods such as cytotoxic chemotherapy or the use of molecular target agents. Among these, two recently emerging immunotherapies include T-cell receptor gene therapy and immune checkpoint inhibitor therapy, which are expected to be effective for many types of sarcoma. A sarcoma with a disease-specific translocation and a limited number of mutations, such as synovial sarcoma, expresses high levels of self-antigens, like the New York esophageal squamous cell carcinoma 1, which has been targeted in T-cell receptor gene therapy. On the other hand, sarcomas with a greater number of mutations, such as undifferentiated pleomorphic sarcomas, myxofibrosarcoma and dedifferentiated liposarcomas, can be good candidates for immune checkpoint inhibitors. Among immune checkpoint inhibitor therapies, programmed cell death-1 blockade (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte-associated antigen 4 blockade (ipilimumab) have been investigated most often in sarcoma. Although the sole use of immune checkpoint inhibitors provides limited efficacy, combined immunotherapy with immune checkpoint inhibitors or molecular target agents, especially antiangiogenic agents, has shown moderate results against some types of sarcoma, such as the alveolar soft part sarcoma. Several clinical trials utilizing immunotherapy, including T-cell receptor gene therapy and immune checkpoint inhibitors, in sarcomas are under progress. By clarifying the tumor microenvironment and biomarker-predictive capacity of immunotherapy in sarcomas, better clinical trials can be designed; this could lead to improved outcomes for immunotherapy in sarcoma.


Assuntos
Imunoterapia , Sarcoma/imunologia , Sarcoma/terapia , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Vacinas Anticâncer/imunologia , Humanos , Sarcoma/patologia , Microambiente Tumoral
11.
Support Care Cancer ; 29(2): 771-778, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32468131

RESUMO

OBJECTIVES: Postoperative shoulder joint dysfunction has been observed at a certain rate after breast cancer surgery with axillary lymph node dissection. The purposes of this study were to verify the feasibility and effects of home-based exercise using a DVD and clarify the target of intensive intervention with physiotherapy by identifying the factors that cause postoperative shoulder dysfunction. METHODS: The study comprised 237 female patients who underwent breast cancer surgery with axillary lymph node dissection, whose data were acquired until 3 months postoperatively. All patients were instructed to exercise at home using a DVD. Range of motion (ROM) of shoulder flexion and abduction and the disability of the arm, shoulder, and hand (DASH) score were measured before surgery, 1 week and 1, 2, and 3 months after surgery. As factors influencing the recovery of shoulder ROM at 3 months after surgery, the presence or absence of radiation and factors up to 1 month after surgery (age, body mass index, the relationship between operated side and dominant side of the hand, treatment modalities, and complications). RESULTS: Shoulder ROM and DASH scores had gradually recovered from 1 week to 3 months postoperatively. As the results of the multivariate analysis, the factors that were associated with the recovery of ROM of shoulder flexion at 3 months were the side of surgery corresponding to the dominant hand (negative factor) and the presence of paresthesia at 1 week postoperatively (positive factor) (p < 0.05). Radiation therapy and the side of surgery corresponding to the dominant hand were negative factors for the recovery of shoulder abduction (p < 0.01). Regarding the feasibility of the home exercise, 214/229 (93.4%), 172/210 (81.9%), and 139/206 (67.5%) of patients performed exercise at least once a day at 1, 2, and 3 months after surgery, respectively. CONCLUSION: Our result indicated that the side of surgery corresponding to the dominant hand was the inhibiting factor for recovery for both shoulder flexion and abduction at 3 months after surgery. Home-based exercise with DVD was considered feasible. For the verification of this effectiveness, a randomized control study should be planned in the future.


Assuntos
Axila/cirurgia , Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Excisão de Linfonodo/efeitos adversos , Amplitude de Movimento Articular/fisiologia , Ombro/patologia , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Estudos Prospectivos , Fatores de Risco , Ombro/efeitos da radiação
12.
Sci Rep ; 10(1): 21578, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33299043

RESUMO

Unidirectional porous hydroxyapatite (UDPHAp) was developed as an excellent scaffold with unidirectional pores oriented in the horizontal direction with interpore connections. The purpose of this study was to assess radiographic changes and clinical outcomes and complications following UDPHAp implantation to treat benign bone tumors. We retrospectively analyzed 44 patients treated with intralesional resection and UDPHAp implantation for benign bone tumors between 2010 and 2015. Clinical and radiographic findings were evaluated postoperatively at regular follow-up visits. The mean follow-up was 49 months. Radiographic changes were classified into five stages based on bone formation in the implanted UDPHAp according to Tamai's classification. All patients showed excellent bone formation inside and around implanted UDPHAp. Absorption of UDPHAp and bone marrow cavity remodeling was identified in 20 patients at a mean of 17 months postoperatively, and was significantly more common in young patients. Preoperative cortical thinning was completely regenerated in 26 of 31 patients on average 10 months after surgery. There were no cases of delayed wound healing, postoperative infection, or allergic reaction related to implanted UDPHAp. UDPHAp is a useful bone-filling substitute for treating benign bone tumor, and the use of this material has a low complication rate.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Substitutos Ósseos/uso terapêutico , Durapatita/uso terapêutico , Fêmur/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Adolescente , Neoplasias Ósseas/diagnóstico por imagem , Substitutos Ósseos/administração & dosagem , Transplante Ósseo , Criança , Durapatita/administração & dosagem , Feminino , Fêmur/diagnóstico por imagem , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Microtomografia por Raio-X
13.
Clin Orthop Relat Res ; 478(11): 2550-2561, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33112583

RESUMO

BACKGROUND: Dedifferentiated liposarcoma (DDLPS) is a rare malignancy that transitions from an atypical lipomatous tumor to a sarcoma with a variable morphologic appearance. The behavior of this tumor in the retroperitoneum is aggressive, but the behavior of DDLPS in the extremities is less well-defined because it is rare. Few reports have assessed the imaging features and clinical outcomes of primary DDLPS in the extremities. QUESTIONS/PURPOSES: In patients with primary DDLPS of the extremity, we asked the following questions: (1) How frequently do additional primary malignancies occur in patients with DDLPS? (2) What is the rate of overall survival, metastases, and local recurrence in DDLPS? (3) What factors are associated with metastasis-free survival and local recurrence in DDLPS? METHODS: We defined DDLPS as a biphasic neoplasm that transitions from an atypical lipomatous tumor (ALT) to a sarcoma of variable morphologic appearance and histologic grades. We retrospectively evaluated the medical records of patients with DDLPS of the extremities who underwent surgery in our institution between 2003 and 2017. During that time, 16 patients were treated for this diagnosis; one was excluded from this study because the patient did not have an MRI, leaving 15 patients (nine men, six women; their median [range] age was 67 years [42 to 87]) for evaluation. All had a minimum of 2 years follow-up (median [range] 54 months [25 to 136]); 14 of 15 have been seen in the last 5 years (one patient, who was doing well at the time, was lost after 9 years of follow-up). In 11 patients, MRI demonstrated two components: an ALT component with high intensity on both T1-weighed and T2-weighted sequences and a dedifferentiated component low-to-intermediate intensity on T1-weighed and heterogeneous hyperintensity on T2-weighted sequence. Nine patients were evaluated using 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography (FDG-PET) combined with CT (PET/CT). PET/CT showed a biphasic pattern with a close relationship to MRI findings. The dedifferentiated component presented with high FDG uptake (median [range] maximum standardized uptake value 5.1 [1.9 to 22.6]), while the atypical lipomatous tumor component showed almost no FDG uptake. In all patients, immunohistochemical studies of p16 and cyclin-dependent kinase-4 (CDK4) were investigated. Positive staining for both p16 and CDK4 were seen in 13 of 15 patients.We retrospectively evaluated the electronic medical records of all patients in our institution for the presence of additional primary malignancies, local recurrence-free survival, metastasis-free survival, and overall survival. The survival rate was estimated using the Kaplan-Meier method. The Wilcoxon exact test was used to determine the prognostic importance of the following survival variables: age, sex, maximum tumor size, radiotherapy, and surgical margin. RESULTS: Seven additional primary malignancies developed in five of 15 patients (two lung cancers, two sarcomas, one renal cell cancer, one uterine cancer, and one non-Hodgkin lymphoma). The 3- and 5-year metastasis-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. With the numbers available, we found no factors associated with metastasis-free survival. The 3- and 5-year overall survival rates were 100% (95% CI 1.00 to 1.00) and 88% (95% CI 0.65 to 1.00), respectively. Three of 15 patients had local recurrence. The 3- and 5-year local recurrence-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. Large (> 15 cm) tumors were more likely to have a local recurrence (p = 0.04). CONCLUSIONS: In this small series, we found that the extremities are a favorable site for DDLPS compared with the retroperitoneum, although we did not directly compare the two sites. This rare tumor has a relatively high likelihood of being associated with other malignancies. We believe patients should be assessed and monitored carefully for this possibility. In the future, larger studies are needed to better define predictors of local recurrence, although the tumor's size may be associated with a greater propensity for local recurrence. LEVEL OF EVIDENCE: Level II, prognostic study.


Assuntos
Extremidades/patologia , Extremidades/cirurgia , Lipossarcoma/mortalidade , Lipossarcoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Extremidades/diagnóstico por imagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Lipossarcoma/diagnóstico por imagem , Lipossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Int J Mol Sci ; 21(20)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066270

RESUMO

Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of Ccn3 mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with p21 and p53 mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 in vitro, either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by H2O2 caused a dose-dependent increase in Ccn3 gene and CCN3 protein expression, along with enhanced expression of p21 and p53 mRNA and proteins, as well as SA-ß gal activity. Overexpression of CCN3 also enhanced p21 promoter activity via p53. Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of p21 and p53 mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21.


Assuntos
Cartilagem Articular/metabolismo , Proteína Sobre-Expressa em Nefroblastoma/metabolismo , Osteoartrite do Joelho/metabolismo , Animais , Cartilagem Articular/crescimento & desenvolvimento , Linhagem Celular Tumoral , Células Cultivadas , Senescência Celular , Condrócitos/metabolismo , Condrócitos/patologia , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteína Sobre-Expressa em Nefroblastoma/genética , Osteoartrite do Joelho/patologia , Ratos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
15.
Oncol Lett ; 20(3): 2977-2986, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32782615

RESUMO

The effect of nivolumab and the relation between bone response and tumor control in patients with non-small-cell lung cancer (NSCLC) with bone metastases are not clear. The outcome of nivolumab monotherapy was investigated, and whether the response of bone metastases is useful as an early predictor of tumor control in patients with NSCLC with bone metastases was examined. The participants included 15 patients who received nivolumab monotherapy for NSCLC with bone metastases in our institution between 2015 and 2017. Tumor control was defined using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST1.1). Response of bone metastases was assessed by the MD Anderson response criteria (MDA criteria). Responses according to RECIST1.1 and the MDA criteria were classified as responder (complete response or partial response) and non-responder [progressive disease (PD) or stable disease]. Progression-free survival (PFS) was investigated using the Kaplan-Meier method. With RECIST1.1, the overall response rate was 20%. Multivariate analysis showed that the MDA criteria were the only risk factor for patients with PD (RECIST1.1). Median PFS was 1.9 months, with PFS of 20% at 6 months. Univariate analysis showed that being a non-responder according to the MDA criteria was the only risk factor for PFS. In patients who were responders (MDA criteria) within 3 months, PFS was 83 and 50% at 3 and 6 months, respectively, though all non-responder (MDA criteria) patients converted to PD (RECIST1.1) within 3 months. Response according to RECIST1.1 was significantly correlated with response according to the MDA criteria (P<0.05). In patients who were both responders according to RECIST1.1 and the MDA criteria, time to response with the MDA criteria (1.4-2.0 months) was earlier than with RECIST1.1 (2.8-3.0 months) in all patients. In conclusion, application of the MDA criteria within 2 months of nivolumab monotherapy is useful for early prediction of response and prognosis in patients with NSCLC with bone metastases.

16.
J Pediatr Orthop B ; 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32804881

RESUMO

Early prediction of future acetabular development is important to determine an additional surgery for developmental dysplasia of the hip (DDH). The purpose of this study was to investigate the predictive factors of acetabular development using MRI. We retrospectively investigated dislocated 40 hips and 34 normal hips in 37 pediatric patients (9 males and 28 females) with DDH who underwent open reduction after walking age. We evaluated the cartilaginous acetabulum and labrum of the patients using coronal MRI T2*-weighted images at 5 years of age. The mean age at the time of surgery was 22 months, and the mean age at the final survey was 19 years. We divided patients into two groups in accordance with the Severin classification at the final follow-up. Groups with good outcomes (affected 26 hips and unaffected 27 hips) and poor outcomes (14 hips and 7 hips) were compared using the MRI parameters on each side. Predictive factors of acetabular development were identified using univariate and multiple logistic regression analyses. Using multiple logistic regression analysis, labral acetabular roof depth and labral hip center distance at 5 years of age represented predictors after open reduction (odds ratio 0.27, P = 0.035; odds ratio 3.4, P = 0.028, respectively) on the affected side, and bony hip center distance represented a predictor on the unaffected side (odds ratio 2.6, P = 0.049). Acetabular development in the unaffected side could be predicted by bony assessment, while acetabular development in the affected side had to be assessed by labrum using MRI.

17.
J Phys Chem B ; 124(35): 7525-7536, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32790384

RESUMO

Far-field fluorescence localization nanoscopy of individual fluorophores at a temperature of 1.8 K was demonstrated using DNA origami as a one-nanometer-accurate scaffold. Red and near-infrared fluorophores were modified to the scaffold, and the fluorophores were 11 or 77 nm apart. We performed the localization nanoscopy of these two fluorophores at 1.8 K with a far-field fluorescence microscope. Under the cryogenic conditions, the fluorophores were perfectly immobilized and their photobleaching was drastically suppressed; consequently, the lateral spatial precision (a measure of reproducibility) was increased to 1 nm. However, the lateral spatial accuracy (a measure of trueness) remained tens of nanometers. We observed that the fluorophore centroids were laterally shifted as a function of the axial position. Because the orientation of the transition dipole of the fluorophores was fixed under cryogenic conditions, the anisotropic emission from the single fixed dipole had led to the lateral shift. This systematic error due to the dipole-orientation effect could be corrected by the three-dimensional localization of the individual fluorophores with spatial precisions of (lateral) 1 nm and (axial) 17 nm. In addition, the xy-error arising from the three-dimensional (3D) orientation of the scaffold with the two fluorophores 11 nm apart was estimated to be 0.3 nm. As a result, the individual fluorophores on the DNA origami were localized at the designed position, and the lateral spatial accuracy was quantified to be 4 nm in the standard error.


Assuntos
DNA , Corantes Fluorescentes , Microscopia de Fluorescência , Fotodegradação , Reprodutibilidade dos Testes
18.
Ann Rehabil Med ; 44(1): 69-76, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32130840

RESUMO

OBJECTIVE: To investigate the factors affecting the discharge destination of patients with spinal bone metastases. METHODS: We reviewed the medical records of patients admitted to our institute with a diagnosis of skeletalrelated events secondary to malignant disease. Exclusion criteria comprised decreased cognitive function and hypercalcemia, brain metastasis, peritoneal dissemination, and pleural dissemination. The factors examined included the discharge destination, age, sex, the Barthel Index (BI) at admission and discharge, pain at admission and discharge, number of co-resident household members, length of hospital stay, treatment strategy, spinal instability neoplastic score, vertebral body collapse, spinal level of bone metastases, and motor paralysis. For the discharge destination, patients at discharge were grouped into two categories. The home group included patients discharged to their own homes, and the non-home group included patients discharged to other hospitals. RESULTS: Of 140 patients, the home group comprised 120 patients and the non-home group comprised 20 patients. Activities of daily living (ADL) and pain at rest and during motion improved significantly in the home group, whereas only pain at rest and during motion improved significantly in the non-home group. The results indicated that discharge BI and motor paralysis were the best predictors of the discharge destination; a BI cut-off value of 72.5 predicted discharge to home. CONCLUSION: This study showed that the ADL level on discharge and motor paralysis affected the discharge destination of patients with spinal bone metastases. These results are likely to be helpful in predicting the discharge destination of patients with spinal bone metastases.

19.
PLoS One ; 15(3): e0230113, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32142547

RESUMO

BACKGROUND: The drawback of the delta-shaped gastroduodenostomy (DSG) in totally laparoscopic distal gastrectomy (TLDG) is the presence of intraoperative duodenal injury and postoperative anastomotic stenosis, which can occur due to a relatively short duodenal bulb diameter. MATERIALS AND METHODS: From June 2013 to June 2019, 35 patients with gastric cancer underwent TLDG with a modified DSG consisting of linear stapling and single-layer hand suturing in our institution. All anastomotic procedures were performed by the right hand of the operator positioned between the patient's legs. Linear stapling of the posterior walls of the remnant stomach and duodenum without creating a gap was performed using a 45-mm linear stapler, considering the prevention of intraoperative duodenal injury. The stapler entry hole was closed using a single-layer full-thickness hand suturing technique with knotted sutures and a knotless barbed suture. We described the clinical data and outcomes in the present retrospective patient series. RESULTS: No intraoperative duodenal injury occurred in any of the 35 patients. The median staple length at linear stapling of the posterior walls of the remnant stomach and duodenum was 41.7 ± 4.2 (30-45) mm, and 2 patients (5.7%) had a staple length of 30 mm. There were no incidences of postoperative anastomotic stenosis. CONCLUSIONS: We suggest that a modified DSG consisting of linear stapling and single-layer hand suturing performed by an operator positioned between the patient's legs can be one option for B-Ⅰ reconstruction following TLDG because it can aid in preventing both intraoperative duodenal injury and postoperative anastomotic stenosis.


Assuntos
Constrição Patológica/prevenção & controle , Duodeno/lesões , Gastrectomia/métodos , Gastroenterostomia/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Duodeno/patologia , Feminino , Coto Gástrico/patologia , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Período Pós-Operatório , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Grampeadores Cirúrgicos , Técnicas de Sutura/instrumentação
20.
Bioorg Med Chem ; 28(8): 115430, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32197812

RESUMO

The plausible nitric oxide (NO)-sensing module of TRPC5 was incorporated in a enhanced green fluorescent protein (EGFP) to evaluate its conformational change as an optical response upon the reaction with NO. Two cysteine residues located in the NO-sensing module have been proposed to form a disulfide bond through S-nitrosylation of the thiol group by NO. Modification of the cysteine residues by NO resulted a ratiometric change of EGFP emission through transducing the conformational change of NO-sensing module to the EGFP chromophore. The oxidized form of NO-sensing module fused EGFP changed the intensity of emission spectra upon reduction of the disulfide bond at the NO-reactive module. The NO-sensing module fused EGFP in its reduced form avidly reacted with NO and realized the ratiometric fluorescence intensity changes depending on the formation of disulfide bond. These results support the notion that NO induces a conformational change at the putative NO-sensing segment of TRPC5, and provide a prototype for the genetically encoded cellular NO sensors.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Óxido Nítrico/farmacologia , Canais de Cátion TRPC/metabolismo , Escherichia coli , Proteínas de Fluorescência Verde , Humanos , Peróxido de Hidrogênio , Imagem Óptica , Relação Estrutura-Atividade , Canais de Cátion TRPC/química
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