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1.
Proc Natl Acad Sci U S A ; 120(40): e2307318120, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37748074

RESUMO

Epithelial tissue is at the forefront of innate immunity, playing a crucial role in the recognition and elimination of pathogens. Met is a receptor tyrosine kinase that is necessary for epithelial cell survival, proliferation, and regeneration. Here, we showed that Met is essential for the induction of cytokine production by cytosolic nonself double-stranded RNA through retinoic acid-inducible gene-I-like receptors (RLRs) in epithelial cells. Surprisingly, the tyrosine kinase activity of Met was dispensable for promoting cytokine production. Rather, the intracellular carboxy terminus of Met interacted with mitochondrial antiviral-signaling protein (MAVS) in RLR-mediated signaling to directly promote MAVS signalosome formation. These studies revealed a kinase activity-independent function of Met in the promotion of antiviral innate immune responses, defining dual roles of Met in both regeneration and immune responses in the epithelium.


Assuntos
Células Epiteliais , Receptores Proteína Tirosina Quinases , Imunidade Inata , Antivirais , Citocinas
2.
Neuropsychol Rehabil ; 33(3): 528-550, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35088654

RESUMO

Personal neglect is the neglect of self-body space, which often occurs in patients with unilateral spatial neglect (USN), but lacks a dedicated rehabilitation. The purpose of this study was to investigate the effects of visual-motor illusion (VMI) on two-stroke hemiplegic patients with left-side personal neglect. Case 1 was a 53-year-old man diagnosed with a right lenticulostriate artery infarction. Case 2 was a 76-year-old woman diagnosed with a right middle cerebral artery infarction. USN symptoms were not observed in either patient in the desk USN assessment, but personal neglect and USN symptoms in daily life were observed in both patients. Intervention effects were verified using an ABA design, comprising a 5-day three-phase (A1, B, A2). In phase B, VMI was performed on the paralyzed upper limb for 10 min in addition to conventional physical therapy. Outcomes measures were the Fluff test, Catherine Bergego Scale (CBS), Fugl-Meyer Assessment (FMA), and Functional Independence Measure (FIM). In both patients, no improvements were noted in FMA, but improvements were observed in the Fluff test, CBS, and FIM in phase B; these effects were retained in phase A2. Therefore, VMI may have contributed to improvements in Personal neglect and USN symptoms in daily life.


Assuntos
Ilusões , Transtornos da Percepção , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Masculino , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Hemiplegia/complicações , Acidente Vascular Cerebral/complicações , Transtornos da Percepção/reabilitação
3.
Brain Inj ; 36(1): 121-126, 2022 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-35377819

RESUMO

PURPOSE: The study aimed to clarify whether the vividness of motor imagery is related to lower limb function and walking ability in patients with hemiplegic stroke. MATERIALS AND METHODS: The study was a cross-sectional preliminary study. The subjects were 15 patients with hemiplegic stroke. The vividness of motor imagery was assessed using the kinesthetic and visual imagery questionnaire. The kinesthetic imagery (KI) involves the sensation of one's own movement, whereas the visual imagery (VI) involves the imagination of a third-person performing the self-movement. Their physical functions were assessed using the Brunnstrom recovery stage, stroke impairment assessment set, 10-m maximum walking speed test, and functional independence measure. KI and VI were compared using the t test. Correlation analysis was performed between KI or VI and various variables as well as between the motor imagery gap (difference between KI and VI) and various variables. RESULTS: KI was significantly lower than VI (p < .01). KI was correlated not only with lower limb function (r = 0.68) but also with walking speed (r = -0.64). The motor imagery gap was correlated with hip joint function (r = -0.53). CONCLUSIONS: KI and motor imagery gap were associated with lower limb function and walking ability.


Assuntos
Hemiplegia , Acidente Vascular Cerebral , Estudos Transversais , Hemiplegia/etiologia , Humanos , Imagens, Psicoterapia , Cinestesia , Desempenho Psicomotor , Acidente Vascular Cerebral/complicações
4.
J Phys Ther Sci ; 34(1): 65-70, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35035082

RESUMO

[Purpose] The purpose of this study was to investigate the effect of kinesthetic illusion induced by visual stimulation to the paralyzed side ankle joint on the sit-to-stand of a hemiparesis stroke patient. [Participant and Methods] A 33-year-old male with left hemiparesis due to a right putamen hemorrhage participated. This study used the ABA' single-case design. Phase A and A' conducted only conventional physiotherapy. Phase B conducted kinesthetic illusion induced by visual stimulation and conventional physiotherapy. To create a kinesthetic illusion, a video image of the patient's ankle joint dorsiflexion movement on the non-paralyzed side was inverted and placed on the patient's paralyzed ankle. The patient observed this display for 5 min. We evaluated weight-bearing symmetry values during sit-to-stand, duration of sit-to-stand, trunk and ankle joint movement on the paralyzed side during sit-to-stand, active ankle dorsiflexion angle on the paralyzed side, and the composite spasticity score. [Results] The weight-bearing symmetry values, movement of the ankle dorsiflexion during sit-to-stand, active ankle dorsiflexion angle, and composite spasticity score were significantly improved in phase B as compared with phase A and the effect was sustained in phase A'. [Conclusion] Kinesthetic illusion induced by visual stimulation for a hemiparesis stroke patient affected the ankle dorsiflexion function, resulting in an improved asymmetry during sit-to-stand as assessed by weight-bearing symmetry values.

5.
Nat Chem Biol ; 15(6): 598-606, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31101918

RESUMO

Activation of hepatocyte growth factor (HGF) by proteolytic processing is triggered in cancer microenvironments, and subsequent signaling through the MET receptor is involved in cancer progression. However, the structure of HGF remains elusive, and few small/medium-sized molecules can modulate HGF. Here, we identified HiP-8, a macrocyclic peptide consisting of 12 amino acids, which selectively recognizes active HGF. Biochemical analysis and real-time single-molecule imaging by high-speed atomic force microscopy demonstrated that HiP-8 restricted the dynamic domains of HGF into static closed conformations, resulting in allosteric inhibition. Positron emission tomography using HiP-8 as a radiotracer enabled noninvasive visualization and simultaneous inhibition of HGF-MET activation status in tumors in a mouse model. Our results illustrate the conformational change in proteolytic activation of HGF and its detection and inhibition by a macrocyclic peptide, which may be useful for diagnosis and treatment of cancers.


Assuntos
Fator de Crescimento de Hepatócito/análise , Compostos Macrocíclicos/química , Neoplasias Experimentais/diagnóstico por imagem , Imagem Óptica , Peptídeos/química , Animais , Fator de Crescimento de Hepatócito/antagonistas & inibidores , Fator de Crescimento de Hepatócito/metabolismo , Compostos Macrocíclicos/farmacologia , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Peptídeos/farmacologia , Tomografia por Emissão de Pósitrons
6.
Exp Brain Res ; 239(7): 2261-2271, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34081177

RESUMO

This study aimed to verify whether visual-motor illusion changes the functional connectivity during kinesthetic motor imagery and the vividness of kinesthetic motor imagery. Twelve right-handed healthy adults participated in this study. All participants randomly performed both the illusion and observation conditions in 20 min, respectively. Illusion condition was induced kinesthetic illusion by viewing own finger movement video. Observation condition was observed own finger movement video. Before and after each condition, the brain activity of kinesthetic motor imagery was measured using functional near-infrared spectroscopy. The measure of brain activity under kinesthetic motor imagery was executed in five sets using block design. Under the kinesthetic motor imagery, participants were asked to imagine the movement of their right finger. Functional connectivity was analyzed during the kinesthetic motor imagery. In addition, after performing the task under kinesthetic motor imagery, the vividness of the kinesthetic motor imagery was measured using a visual analog scale. Furthermore, after each condition, the degree of kinesthetic illusion and sense of body ownership measured based on a seven-point Likert scale. Our results indicated that the functional connectivity during kinesthetic motor imagery was changed in the frontal-parietal network of the right hemisphere. The vividness of the kinesthetic motor imagery was significantly higher with the illusion condition compared with the observation condition. The degree of kinesthetic illusion and sense of body ownership were significantly higher with the illusion condition compared with the observation condition. In conclusion, the visual-motor illusion changes the functional connectivity during kinesthetic motor imagery and influences the vividness of kinesthetic motor imagery. The visual-motor illusion provides evidence that it improves motor imagery ability. VMI may be used in patients with impaired motor imagery.


Assuntos
Ilusões , Adulto , Dedos , Humanos , Imagens, Psicoterapia , Imaginação , Cinestesia , Movimento
7.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502141

RESUMO

NK1, a splicing variant of hepatocyte growth factor (HGF), binds to and activates Met receptor by forming an NK1 dimer and 2:2 complex with Met. Although the structural mechanism underlying Met activation by HGF remains incompletely resolved, it has been proposed that the NK1 dimer structure participates in this activation. We investigated the NK1 dimer interface's role in Met activation by HGF. Because N127, V140, and K144 are closely involved in the head-to-tail NK1 dimer formation, mutant NK1 proteins with replacement of these residues by alanine were prepared. In Met tyrosine phosphorylation assays, N127-NK1, V140-NK1, and K144-NK1 showed 8.3%, 23.8%, and 52.2% activity, respectively, compared with wild-type NK1. Although wild-type NK1 promoted cell migration and scattering, N127-NK1, V140-NK1, and K144-NK1 hardly or marginally promoted them, indicating loss of activity of these mutant NK1 proteins to activate Met. In contrast, mutant HGFs (N127-HGF, V140-HGF, and K144-HGF) with the same amino acid replacements as in NK1 induced Met tyrosine phosphorylation and biological responses at levels comparable to those of wild-type HGF. These results indicate that the structural basis responsible for NK1-dependent Met dimer formation and activation differs from, or is at least distinguishable from, the structural basis responsible for HGF-dependent Met activation.


Assuntos
Fator de Crescimento de Hepatócito/química , Proteínas Proto-Oncogênicas c-met/metabolismo , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Cães , Células HEK293 , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Células Madin Darby de Rim Canino , Mutação , Ligação Proteica , Multimerização Proteica , Proteínas Proto-Oncogênicas c-met/química , Transdução de Sinais
8.
Brain Cogn ; 146: 105632, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33129054

RESUMO

Visual-motor illusion (VMI) is to evoke a kinesthetic sensation by viewing images of oneself performing physical exercise while the body is at rest. Previous studies demonstrated that VMI activates the motor association brain areas; however, it is unclear whether VMI immediately alters the resting-state functional connectivity (RSFC). This study is aimed to verify whether the VMI induction changed the RSFC using functional near-infrared spectroscopy (fNIRS). The right hands of 13 healthy adults underwent illusion and observation conditions for 20 min each. Before and after each condition, RSFC was measured using fNIRS. After each condition, degree of kinesthetic illusion and a sense of body ownership measured using the Likert scale. Our results indicated that, compared with the observation condition, the degree of kinesthetic illusion and the sense of body ownership were significantly higher after the illusion condition. Compared with the observation condition, RSFC after the illusion condition significantly increased brain areas associated with kinesthetic illusion, a sense of body ownership, and motor execution. In conclusion, RSFC has become a biomarker that shows changes in brain function occurring due to VMI. VMI may be applied to the treatment of patients with stroke or orthopedic diseases.


Assuntos
Ilusões , Córtex Motor , Adulto , Encéfalo , Mapeamento Encefálico , Humanos , Espectroscopia de Luz Próxima ao Infravermelho
9.
Int J Mol Sci ; 21(21)2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33121208

RESUMO

Using a random non-standard peptide integrated discovery system, we obtained cyclic peptides that bind to hepatocyte growth factor (HGF) or mesenchymal-epithelial transition factor. (MET) HGF-inhibitory peptide-8 (HiP-8) selectively bound to two-chain active HGF, but not to single-chain precursor HGF. HGF showed a dynamic change in its molecular shape in atomic force microscopy, but HiP-8 inhibited dynamic change in the molecular shape into a static status. The inhibition of the molecular dynamics of HGF by HiP-8 was associated with the loss of the ability to bind MET. HiP-8 could selectively detect active HGF in cancer tissues, and active HGF probed by HiP-8 showed co-localization with activated MET. Using HiP-8, cancer tissues with active HGF could be detected by positron emission tomography. HiP-8 seems to be applicable for the diagnosis and treatment of cancers. In contrast, based on the receptor dimerization as an essential process for activation, the cross-linking of the cyclic peptides that bind to the extracellular region of MET successfully generated an artificial ligand to MET. The synthetic MET agonists activated MET and exhibited biological activities which were indistinguishable from the effects of HGF. MET agonists composed of cyclic peptides can be manufactured by chemical synthesis but not recombinant protein expression, and thus are expected to be new biologics that are applicable to therapeutics and regenerative medicine.


Assuntos
Produtos Biológicos/farmacologia , Fator de Crescimento de Hepatócito/metabolismo , Neoplasias/metabolismo , Peptídeos Cíclicos/farmacologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Animais , Sítios de Ligação , Produtos Biológicos/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fator de Crescimento de Hepatócito/antagonistas & inibidores , Humanos , Neoplasias/tratamento farmacológico , Peptídeos Cíclicos/uso terapêutico , Ligação Proteica , Proteínas Proto-Oncogênicas c-met/agonistas , Proteínas Proto-Oncogênicas c-met/química , Transdução de Sinais/efeitos dos fármacos
10.
No Shinkei Geka ; 48(6): 547-552, 2020 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-32572008

RESUMO

We report a case of anterior cranial fossa dural arteriovenous fistula(ACF-DAVF)in a patient whose diagnosis was made according to characteristic findings on arterial spin labeling(ASL)MRI. CASE:A 68-year-old man was admitted to our hospital because of intractable epilepsy. Based on the initial MRI findings, an initial diagnosis of limbic encephalitis was made. Steroids and anticonvulsant drugs were administered;however, the seizures could not be controlled. A second MRI with ASL revealed abnormal vessel signals in the base segments of the left frontal and temporal lobes toward the basal vein of Rosenthal. Digital subtraction angiography(DSA)revealed an arteriovenous shunt in the left anterior cranial fossa, which drained toward the medial side of the left temporal lobe. A diagnosis of ACF-DAVF with status epilepticus was made, and the main drainer was cauterized. After the surgical procedure, the epilepsy was controlled with antiepileptic drugs, and postoperative MRI revealed obliteration of ACF-DAVF, disappearance of the high-intensity area on FLAIR sequences, and disappearance of the high-intensity signal area on ASL.


Assuntos
Fístula Arteriovenosa , Malformações Vasculares do Sistema Nervoso Central , Idoso , Angiografia Digital , Fossa Craniana Anterior/diagnóstico por imagem , Humanos , Masculino , Convulsões
11.
Cancer Sci ; 110(10): 3340-3349, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342590

RESUMO

Aberrant activation of the MET/hepatocyte growth factor (HGF) receptor participates in the malignant behavior of cancer cells, such as invasion-metastasis and resistance to molecular targeted drugs. Many mutations in the MET extracellular region have been reported, but their significance is largely unknown. Here, we report the dysregulation of mutant MET originally found in a lung cancer patient with Val370 to Asp370 (V370D) replacement located in the extracellular SEMA domain. MET-knockout cells were prepared and reconstituted with WT-MET or V370D-MET. HGF stimulation induced MET dimerization and biological responses in cells reconstituted with WT-MET, but HGF did not induce MET dimerization and failed to induce biological responses in V370D-MET cells. The V370D mutation abrogated HGF-dependent drug resistance of lung cancer cells to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI). Compared with WT-MET cells, V370D-MET cells showed different activation patterns in receptor tyrosine kinases upon exposure to survival/growth-stressed conditions. Surface plasmon resonance analysis indicated that affinity between the extracellular region of V370D-MET and HGF was reduced compared with that for WT-MET. Further analysis of the association between V370D-MET and the separate domains of HGF indicated that the SP domain of HGF was unchanged, but its association with the NK4 domain of HGF was mostly lost in V370D-MET. These results indicate that the V370D mutation in the MET receptor impairs the functional association with HGF and is therefore a loss-of-function mutation. This mutation may change the dependence of cancer cell growth/survival on signaling molecules, which may promote cancer cell characteristics under certain conditions.


Assuntos
Fator de Crescimento de Hepatócito/metabolismo , Neoplasias Pulmonares/genética , Mutação de Sentido Incorreto , Proteínas Proto-Oncogênicas c-met/química , Proteínas Proto-Oncogênicas c-met/genética , Animais , Células CHO , Linhagem Celular Tumoral , Cricetulus , Resistencia a Medicamentos Antineoplásicos , Técnicas de Inativação de Genes , Humanos , Mutação com Perda de Função , Domínios Proteicos , Inibidores de Proteínas Quinases/farmacologia , Multimerização Proteica , Proteínas Proto-Oncogênicas c-met/metabolismo , Ativação Transcricional
12.
Int J Mol Sci ; 20(12)2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31212972

RESUMO

Hepatocyte growth factor (HGF) is secreted as an inactive single-chain HGF (scHGF); however, only proteolytically processed two-chain HGF (tcHGF) can activate the MET receptor. We investigated the localization of tcHGF and activated/phosphorylated MET (pMET) using a tcHGF-specific antibody. In day 16.5 mouse embryos, total HGF (scHGF + tcHGF) was mainly localized in smooth muscle cells close to, but separate from, MET-positive epithelial cells in endodermal organs, including the stomach. In the adult stomach, total HGF was localized in smooth muscle cells, and tcHGF was mainly localized in the glandular base region. Immunostaining for pMET and Lgr5-driven green fluorescent protein (GFP) indicated that pMET localization overlapped with Lgr5+ gastric stem cells. HGF promoted organoid formation similar to EGF, indicating the potential for HGF to promote the survival and growth of gastric stem cells. pMET and tcHGF localizations changed during regeneration following gastric injury. These results indicate that MET is constantly activated in gastric stem cells and that the localization of pMET differs from the primary localization of precursor HGF but has a close relationship to tcHGF. Our results suggest the importance of the microenvironmental generation of tcHGF in the regulation of development, regeneration, and stem cell behavior.


Assuntos
Fator de Crescimento de Hepatócito/metabolismo , Organogênese , Cicatrização , Animais , Biomarcadores , Fator de Crescimento de Hepatócito/genética , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Organogênese/genética , Fosforilação , Transporte Proteico , Proteínas Proto-Oncogênicas c-met/metabolismo , Regeneração , Células-Tronco/citologia , Células-Tronco/metabolismo , Cicatrização/genética
13.
J Phys Ther Sci ; 31(12): 992-996, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32038070

RESUMO

[Purpose] The aim of this study was to clarify whether the motor imagery of walking and physical function are related in mild hemiplegic stroke patients. [Participants and Methods] Sixteen mild hemiplegic stroke patients were included in this study. We evaluated motor imagery with a 10-m walking, the estimation error and the kinesthetic and visual imagery questionnaire. Physical function was evaluated with the actual 10-m walk test time, Brunnstrom recovery stage, stroke impairment assessment set, and functional independent measure. The correlation coefficient was calculated using Spearman's correlation coefficient for all evaluation methods. [Results] The 10-m walking motor imagery took an average of 23.36 ± 22.14 s. The actual 10-m walk test averaged 24.87 ± 21.41 s. The 10-m walking motor imagery and the 10-m walking speed were significantly correlated. There was a significant correlation between the 10-m walking motor imagery and the Brunnstrom recovery stage, stroke impairment assessment set, and functional independent measure. There were no significant correlations between the estimation error and all the assessments. [Conclusion] These results show that the motor imagery of walking is related to physical function in mild hemiplegic stroke patients.

14.
Neurocase ; 24(5-6): 245-249, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30657014

RESUMO

The purpose of this study was to investigate the effect of simultaneous intervention with the kinesthetic illusion induced by visual stimulation (KiNvis) and voluntary exercise on ankle dorsiflexion dysfunction in a patient with right-sided stroke hemiparesis. Within an ABAB single-case design, we conducted two phases each lasting five days. Phase A represented the baseline during which only voluntary ankle dorsiflexion (VAD) was performed. Phase B involved simultaneous performance of VAD and KiNvis. We measured the angle of ankle joint dorsiflexion (AJD), and the 10 m maximum walking speed (10MWS). AJD and 10MWS were significantly improved in phase B.


Assuntos
Tornozelo/fisiopatologia , Ilusões/fisiologia , Cinestesia/fisiologia , Reabilitação Neurológica/métodos , Paresia/fisiopatologia , Paresia/terapia , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Estimulação Física , Projetos de Pesquisa , Acidente Vascular Cerebral/complicações
15.
Int J Mol Sci ; 19(10)2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30322054

RESUMO

Non-native ligands for growth factor receptors with distinct chemical properties and different biological activities have the potential to become therapeutic applications. We previously generated MET/hepatocyte growth factor (HGF) receptor agonists using bivalent macrocyclic peptides. The highest MET-activating agonists exhibited biological activity that was indistinguishable from the effects of HGF. In this study, we investigated MET activation, signal characteristics, and biological responses induced by a macrocyclic peptide partial agonist known as aML5-PEG11. aML5-PEG11 induced weak tyrosine phosphorylation of MET while enhancing cell migration with potency comparable to HGF. aML5-PEG11 induced marked AKT (protein kinase B) and ERK (extracellular signal-regulated kinase) activation at a comparable potency and time-dependency to HGF, which suggests that enhancement of cell motility is attributable to activation of these molecules. In a 3-D culture of bile duct cancer cells in collagen gel, HGF induced robust activation of MET, ERK, and AKT, which was associated with enhanced expression of genes involved in bile duct development and subsequent branching of tubulogenesis. In contrast, aML5-PEG11 induced marginal activation of MET, ERK, and AKT (levels near the detection limits), which was associated with failure to enhance the expression of genes involved in bile duct development and a lack of tubulogenic response. Thus, MET activation by aML5-PEG11 couples to biological responses differently from HGF in an extracellular context-dependent manner.


Assuntos
Fator de Crescimento de Hepatócito/metabolismo , Peptídeos/farmacologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Ativação Transcricional , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Compostos Macrocíclicos/química , Compostos Macrocíclicos/farmacologia , Peptídeos/química , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-met/agonistas
16.
J Obstet Gynaecol Res ; 43(4): 718-722, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28127834

RESUMO

AIM: The aim of this study was to evaluate the outcomes of uterine cervical cancer patients with pelvic lymph node (PLN) metastases after radiotherapy without boost irradiation of the metastases and to clarify the necessity of the boost irradiation of metastatic lesions. METHODS: Thirty-two patients with uterine cervical cancer metastasizing only to the PLN were treated with definitive radiotherapy without boost irradiation of the metastases between 2008 and 2012 at our institution and were selected for this study. The pattern of progression, overall survival, and progression-free survival were analyzed. RESULTS: Ninety percent of the PLN metastases were controlled by radiotherapy. Twenty-two of 32 patients (69%) experienced progression. Distant metastases as initial progression were observed in 21 of these 22 patients (95%). Only two patients experienced failures in pre-treatment metastatic PLN as initial progression, along with other failures. Severe late lower gastrointestinal toxicities were not observed in any patients. Two-year cumulative overall survival and progression-free survival were 74% and 31%, respectively. CONCLUSION: Boost irradiation of PLN metastases is not necessarily indispensable. Further studies to examine the necessity of boost irradiation of PLN metastases in radiotherapy for uterine cervical cancer patients with metastases are required.


Assuntos
Progressão da Doença , Metástase Linfática/radioterapia , Avaliação de Processos e Resultados em Cuidados de Saúde , Pelve/patologia , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Neoplasias do Colo do Útero/patologia
17.
Exp Cell Res ; 326(2): 267-79, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24780821

RESUMO

Interaction between tumor cells and stromal fibroblasts plays essential roles in tumor progression. However, its detailed molecular mechanism remains unclear. To understand the mechanism, we investigated molecules mediating this interaction using the three-dimensional (3D) co-culture system of Panc-1 pancreatic carcinoma cells with normal fibroblasts. When the two kinds of cells were placed on the top of collagen gel, the tumor cells scattered into the fibroblast layer, apparently undergoing epithelial-mesenchymal transition. When fibroblasts were placed within collagen gel, Panc-1 cells actively invaded into the collagen gel, extending a microtubule-based long protrusion. Although transforming growth factor-ß (TGF-ß) and hepatocyte growth factor (HGF) individually stimulated the tumor cell invasion into collagen gel without fibroblasts, TGF-ß signaling inhibitors (SB431542 and LY2157299) significantly enhanced the Panc-1 cell invasion in the 3D co-culture with fibroblasts. Experiments with HGF/Met signaling inhibitors or with the fibroblast conditioned medium revealed that HGF was a major invasion-promoting factor secreted from fibroblasts and SB431542 increased the HGF secretion by blocking the HGF-suppressing activity of cancer cell-derived TGF-ß. These results indicate that HGF and TGF-ß are critical regulators for both tumor-stroma interaction and tumor invasion. The results also suggest that TGF-ß signaling inhibitors may promote tumor progression under some pathological conditions.


Assuntos
Fator de Crescimento de Hepatócito/metabolismo , Invasividade Neoplásica/fisiopatologia , Neoplasias Pancreáticas/metabolismo , Fator de Crescimento Transformador beta/antagonistas & inibidores , Benzamidas/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Técnicas de Cocultura , Colágeno/metabolismo , Dioxóis/farmacologia , Transição Epitelial-Mesenquimal , Fibroblastos/metabolismo , Fator de Crescimento de Hepatócito/antagonistas & inibidores , Humanos , Modelos Estatísticos , Invasividade Neoplásica/patologia , Neoplasias Pancreáticas/patologia , Transdução de Sinais , Células Estromais/metabolismo , Fator de Crescimento Transformador beta/metabolismo
18.
PLoS One ; 19(2): e0298000, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38319926

RESUMO

Rehabilitation methods for executive dysfunction were focused on cognitive rehabilitation in patients with stroke and traumatic brain injury. However, no reviews have focused on the various rehabilitation methods and assessment of executive function in patients with only stroke and included various study designs. This study aimed to identify various interventions and assessments in patients with stroke and executive dysfunction via a scoping review. We searched for articles using the PubMed, Web of Science, and CINAHL databases. Two reviewers independently screened the articles based on the inclusion and exclusion criteria using the title, abstract, and full text. We subsequently determined the study design, sample size, time since stroke, intervention, and assessment. We extracted 1131 articles, of which 27 articles were selected. The study designs were randomized controlled trials (81.5%), pilot studies (11.1%), and feasibility studies (7.4%), with a total of 599 participants. Interventions varied from cognitive training (22.2%), virtual reality (22.2%), noninvasive brain stimulation (14.8%), and dual-task training (11.1%), with consistent results. The assessments used were the Trail Making Test Part B (70.4%), Stroop Color and Word Test (44.4%), Digit Symbol Test, Frontal Assessment Battery, and Tower of London test (11.1%). In conclusion, this scoping review provided various interventions and assessments in patients with stroke with executive dysfunction.


Assuntos
Disfunção Cognitiva , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Função Executiva , Reabilitação do Acidente Vascular Cerebral/métodos , Atividades Cotidianas , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Motor Control ; 28(4): 442-463, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39069292

RESUMO

Over the past two decades, motor imagery (MI) has been used as a supplementary treatment approach to regain physical function in patients with stroke. However, the baseline treatment and the quality of study methodology for new treatment approaches have improved. This systematic review examined the evidence published in the past few decades on the effectiveness of MI on upper- and lower-extremity function and functional performance in patients with stroke. A total of 29 randomized controlled and crossover trials that compared MI with other interventions were analyzed. In addition, the outcomes were grouped into upper-, lower-extremity function, and functional performance for data analysis. More than half of the upper-extremity function studies reported improved performance in Fugl-Meyer assessment, Wolf motor function test, and box and block test in both acute and chronic stages. Lower-extremity function and functional performance were primarily investigated using Fugl-Meyer assessment, gait speed and parameters, activities of daily living, and balance ability. When considering only high-quality studies, six of 15 on upper extremity reported significant effects, whereas five of 15 reported nonsignificant effects. In addition, six of 14 studies on gait and balance reported significant effects. This systematic review suggests that both MI training and conventional rehabilitation programs effectively enhance upper limb functional abilities, including improvements in gait speed and balance, in individuals with acute and chronic stroke. Although the studies published during the past few decades showed heterogeneity in onset after stroke, research protocol, training intensity, and research methodology quality, none of them reported the long-term effects.


Assuntos
Imagens, Psicoterapia , Reabilitação do Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Imagens, Psicoterapia/métodos , Extremidade Superior/fisiopatologia , Extremidade Superior/fisiologia , Extremidade Inferior/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Equilíbrio Postural/fisiologia
20.
Cureus ; 16(7): e65786, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39219877

RESUMO

Background Visual-motor illusion (VMI) is a cognitive approach used to evoke kinesthetic sensations. Research suggests that VMI can modulate brain activity depending on the specific joint movement observed. This study aimed to identify differences in brain activity when observing video images of joint movements at different intensities of movement in VMI. Methodology The study included 14 healthy adult participants. Two types of video images were used: pure ankle dorsiflexion movements (Standard-VMI) and ankle dorsiflexion movements with added resistance (Power-VMI). The brain activity measurement protocol employed a block design with one set of 15 seconds rest, 30 seconds VMI task, and 30 seconds follow-up. Each participant performed the VMI task twice, alternating between Standard-VMI and Power-VMI. Brain activity was measured using functional near-infrared spectroscopy, focusing on motor-related regions. Subjective impressions were assessed using visual analog scales (VAS) for kinesthetic illusions. Results The results revealed that Power-VMI stimulated significantly greater brain activity in the premotor and supplementary motor cortex, supramarginal gyrus, and superior parietal lobule compared with Standard-VMI. Power-VMI resulted in higher VAS values for kinesthetic illusion than Standard-VMI. Additionally, a positive correlation was observed between brain activity in the superior parietal lobule and the degree of kinesthetic illusion. Conclusions These findings indicate that Power-VMI enhances both motor-related brain areas and motor-sensory illusions, potentially having a greater impact on improving motor function. This study provides valuable insights for developing VMI interventions for rehabilitation, particularly for individuals with paralysis or movement impairments.

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