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1.
No Shinkei Geka ; 52(1): 22-28, 2024 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-38246666

RESUMO

Neurosurgeons must have knowledge about the epidemiology of trigeminal neuralgia and facial spasm. The annual incidence of trigeminal neuralgia is 4.3-28.9 per 100,000 persons, with a prevalence of 76.8 per 100,000 persons, increasing with age. It is more common in women and on the right side, with SCA being the most common causative vessel. The long-term efficacy of MVD for trigeminal neuralgia is 80% with complete resolution of pain and 5.2% with complications, which is safe and highly effective when performed by an expert surgeon. Hemifacial spasm has an annual incidence of 0.78/100,000 with a prevalence of approximately 10 per 100,000, increasing with age. It is more common in women and on the left side. AICA alone is the most common causative vessel. The long-term efficacy of MVD for facial spasms is 87.1% with complete resolution of facial spasms and 3.0% with complications. As with trigeminal neuralgia, safe and highly effective treatment can be expected when treated by an expert surgeon.


Assuntos
Espasmo Hemifacial , Neuralgia do Trigêmeo , Feminino , Humanos , Espasmo Hemifacial/cirurgia , Neuralgia do Trigêmeo/cirurgia , Prevalência , Dor , Neurocirurgiões
2.
J Med Invest ; 69(1.2): 117-119, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35466132

RESUMO

BACKGROUND: Navigation system devices have been developed to allow precise resection of brain tumor. The fence-post catheter techniques that use a navigation system have been used in many neurosurgery centers. However, an exclusive catheter for the fence-post catheter techniques have not been made, and substituted silicon tube of the cerebral ventricle drainage or a Nelaton catheter is widely used. OBJECTIVE: In this brief technical note, we describe a new fence-post catheter with steel tip device that was designed for more precise tissue resection and is useful in tumor resection. METHODS: The newly designed fence-post catheter helps to visually gauge the accurate depth from the tumor bottom during tumor resection. Furthermore, the catheter tip has moderate weight and is made of a non-magnetic material. RESULTS: Using our fence-post catheter, which has a metal part at the tip of the tube (length, 13 mm), operators can clearly notice that they are getting closer to base of the tumor by checking the metal part during the resection of deep tumors. CONCLUSION: Our newly developed fence-post tube enables easy confirmation of the distance to deep-tissue regions and improves the degree of safety during tumor removal. J. Med. Invest. 69 : 117-119, February, 2022.


Assuntos
Neoplasias Encefálicas , Glioma , Encéfalo/patologia , Neoplasias Encefálicas/cirurgia , Catéteres , Glioma/patologia , Glioma/cirurgia , Humanos , Procedimentos Neurocirúrgicos/métodos
3.
Oper Neurosurg (Hagerstown) ; 23(1): e16-e22, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35486878

RESUMO

BACKGROUND: Microvascular decompression (MVD) is the only potential cure for hemifacial spasm (HFS). However, traditional techniques such as the interposition method may have limited effect in some cases. Alternative techniques have been proposed; however, they can be more complex or difficult to perform than the standard approach. OBJECTIVE: To describe a safe decompression technique-the "shelter method"-which involves creating a shelter-like space around the facial nerve root exit zone and present associated outcomes. METHODS: Medical records and intraoperative findings of 92 patients with HFS who underwent MVD using the shelter method between April 1997 and March 2017 were retrospectively reviewed. As a historical control group, we included 53 patients who had undergone MVD by the traditional interposition method before March 1989. The patients were divided into 3 subgroups according to the arteries involved and degree or direction of arterial compression to the seventh nerve. Patient outcomes were assessed as excellent, good, fair, and poor according to the MVD scoring system of the Japan Society for MVD Surgery. RESULTS: In the shelter method group, complete disappearance of HFS was achieved in 87 patients (94.6%). The curative rate of the shelter method group was significantly higher than that of the interposition method group. The overall complication rates were significantly lower in the shelter method group than in the interposition method group. CONCLUSION: Our findings indicate high curative and low complication rates of the shelter method, suggesting that it helps treat HFS caused by various types of arterial compression.


Assuntos
Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Nervo Facial/cirurgia , Espasmo Hemifacial/cirurgia , Humanos , Cirurgia de Descompressão Microvascular/métodos , Estudos Retrospectivos , Resultado do Tratamento
5.
J Clin Neurosci ; 94: 244-249, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34863446

RESUMO

The prevalence of chronic subdural hematoma (CSDH) associated with dural metastasis is uncertain, and appropriate treatment strategies have not been established. This study aimed to investigate the characteristics of and appropriate treatment strategies for CSDH associated with dural metastasis. We retrospectively reviewed the charts of 214 patients who underwent surgery for CSDH. The patients were divided into the dural metastasis group (DMG; n = 5, 2.3%) and no dural metastasis group (No-DMG; n = 209, 97.3%). Patient characteristics, treatment, and outcomes were compared between the two groups. Active cancer was detected in 31 out of 214 patients, 5 of whom (16.1%) had dural metastasis. In-hospital death (80.0% vs. 0%; p < 0.001) and recurrence within 14 days (80.0% vs. 2.9%; p < 0.001) and 60 days (80.0% vs. 13.9%; p = 0.002) were significantly prevalent in the DMG. All patients in the DMG developed subdural hematoma re-accumulation requiring emergent surgery because of brain herniation, and patients in the DMG had significantly worse recurrence-free survival (p < 0.001). This relationship remained significant (p < 0.001) even when the analysis was limited to the active cancer cohort (n = 31). CSDH associated with dural metastasis leads to early recurrence and death because of the difficulty in controlling subdural hematoma re-accumulation by common drainage procedures. Depending on the primary cancer status, withdrawal of active treatment and change to palliative care should be discussed after diagnosing CSDH associated with dural metastasis.


Assuntos
Hematoma Subdural Crônico , Neoplasias , Estudos de Coortes , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/etiologia , Hematoma Subdural Crônico/cirurgia , Mortalidade Hospitalar , Humanos , Recidiva , Estudos Retrospectivos
6.
J Med Invest ; 68(3.4): 286-291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759146

RESUMO

BACKGROUND: PCNSL is mainly treated with HD-MTX-based chemotherapy with or without WBRT. However, As WBRT is associated with delayed neurotoxicity leading to dementia in the elderly, many institutes reported benefits of intensive chemotherapy or high-dose chemotherapy with ASCT. We investigated whether treatment with HD-MTX and rituximab, followed by continued-maintenance HD-MTX monotherapy (3.5g / m2), improves overall survival (OS). METHODS: In this retrospective, single-center trial 52 immunocompetent patients with newly diagnosed PCNSL were included. All were treated between January 2005 and December 2017. The controls were 18 patients who, between 2005 and 2011, had received 3 cycles of HD-MTX and then adjuvant treatment with WBRT. In 2011 we started HD-MTX continued-maintenance therapy to treat 34 PCNSL patients. In the induction phase, these patients received HD-MTX every 14 days until a complete response (CR) was observed. When CR was obtained, maintenance therapy with HD-MTX (3.5g / m2) was delivered every three months. RESULTS: In 3-year overall survival (OS) there was a statistically significant difference between the two groups [controls : 33.1% (95%, CI 12.4 - 55.7%) ; maintenance group : 74.9% (95%, CI 55.6 - 86.7%) (p < 0.02)]. Conclusion : The induction of HD-MTX based chemotherapy followed by continued-maintenance HD-MTX monotherapy improved OS compared with chemoradiotherapy consisting of HD-MTX followed by WBRT. J. Med. Invest. 68 : 286-291, August, 2021.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma não Hodgkin , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Metotrexato/uso terapêutico , Estudos Retrospectivos
7.
Sci Rep ; 11(1): 15105, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301977

RESUMO

Glioblastoma (GBM) has high mortality rates because of extreme therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) combined with low-intensity ultrasonication (US) and PpIX, as a sonosensitizer, is an emerging and promising approach, although its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented the anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, an MDR1 inhibitor, and augmented anti-tumor effects of SDT. MDR1 down-regulation via the Akt/NF-κB pathway by celecoxib was confirmed, using an NF-κB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via the Akt/NF-κB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Glioma/metabolismo , NF-kappa B/metabolismo , Células-Tronco Neoplásicas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Protoporfirinas/metabolismo , Ácido Aminolevulínico/farmacologia , Animais , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Glioblastoma/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neoplásicas/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Terapia por Ultrassom/métodos
8.
Neurosurgery ; 89(4): 557-564, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34325470

RESUMO

BACKGROUND: Microvascular decompression (MVD) is the most effective procedure for the long-term management of trigeminal neuralgia (TGN). However, retrospective and single-center studies are inherently biased, and there are currently no prospective, multicenter studies. OBJECTIVE: To evaluate the short- and long-term outcomes and complications in patients with TGN who underwent MVD at specialized Japanese institutions. METHODS: We enrolled patients with TGN who underwent MVD between April 2012 and March 2015. We recorded their facial pain grade and complications at 7 d (short term), 1 yr (mid-term), and 3 yr (long term) postoperatively. RESULTS: There were 166 patients, comprising 60 men and 106 women (mean age 62.7 yr). Furthermore, 105 patients were aged over 60 yr. We conducted neuromonitoring in 84.3% of the cases. The complete pain relief, mortality, and complication rates at the short-term follow-up were 78.9%, 0%, and 16.3%, respectively. Overall, 155 patients (93.4%) completed the long-term follow-up, with the complete pain relief and complication rates of 80.0% and 5.2%, respectively. CONCLUSION: In the hands of experienced neurosurgeons, MVD for TGN can achieve high long-term curative effects. In addition, complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with TGN, including elderly patients.


Assuntos
Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Neuralgia do Trigêmeo/cirurgia
9.
NMC Case Rep J ; 8(1): 79-84, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34012754

RESUMO

Pineal glial cysts associated with bilateral hearing impairment are very rare. Here, we present the case of a 13-year-old boy with a pineal cyst, which caused severe bilateral hearing impairment persisting from 6 years of age. When the patient was 6 years old, the bilateral hearing acuity was about 40 dB on audiometry. Upon admission to our otolaryngology department, his audiogram revealed a bilateral worsening of the hearing acuity (80 dB). Magnetic resonance imaging (MRI) revealed an abnormal pineal cyst with tectal compression from the left with hardly normal bilateral brainstem auditory evoked potentials (BAEPs). We obtained informed consent for exploratory surgery and employed the right occipital transtentorial approach for pineal cyst removal. Based on histological examination, we diagnosed a glial cyst of the pineal gland. At 12 months postoperatively, the patient's hearing improved, showing a bilateral hearing acuity of 40 dB on audiometry. Since the auditory pathway has both crossed and uncrossed fibers at the upper pons and midbrain level, compression at the lateral lemniscus or inferior colliculus level can cause bilateral hearing impairment. In the present case, there was a possible slow pineal cyst growth that eventually compressed the upper pons to the midbrain, lateral lemniscuses, or inferior colliculi from the left side, this eventually led to bilateral hearing impairment. These findings indicate that surgery can improve hearing acuity in patients with a pineal cyst associated with progressive hearing impairment.

10.
Neurosurgery ; 88(4): 846-854, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33469667

RESUMO

BACKGROUND: Microvascular decompression (MVD) is the most effective procedure for hemifacial spasm (HFS). MVD results from nonspecialized or low-volume institutes are not always reliable. Most studies on MVD for HFS are retrospective and single centered; to the best of our knowledge, no prospective, multicenter studies exist. OBJECTIVE: To evaluate short- and long-term outcomes and complications in patients who underwent MVD for HFS in specialized Japanese institutions, in this multicenter, prospective, cohort study. METHODS: Included patients had undergone MVD for HFS in study centers between April 2012 and March 2015. Patients' postoperative grade of involuntary movements and complications were recorded postoperatively at 7 d (short-term) and at 1 (mid-term) and 3 (long-term) yr. RESULTS: A total of 486 patients (150 men, 336 women; mean age 53.9 yr with 181 patients over 60 yr) were enrolled during the study period. Neuromonitoring was used in 96.3% of the cases. The complete cure rate of symptom relief, mortality rate, and complication rate at short-term follow-up were 70.6%, 0%, and 15%, respectively. The long-term follow-up was completed by 463 patients (95.3%); the complete cure rate of symptom relief and complication rate were 87.1% and 3.0%, respectively. CONCLUSION: Our study revealed that under expert guidance and intraoperative neuromonitoring, the long-term curative effect rate of MVD for HFS is high, while complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with HFS, including elderly patients.


Assuntos
Espasmo Hemifacial/diagnóstico , Espasmo Hemifacial/cirurgia , Cirurgia de Descompressão Microvascular/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Espasmo Hemifacial/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Estudos Prospectivos , Resultado do Tratamento
11.
Sci Rep ; 10(1): 15286, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943658

RESUMO

Glioblastoma multiforme involves glioma stem cells (GSCs) that are resistant to various therapeutic approaches. Here, we studied the importance of paracrine signaling in the glioma microenvironment by focusing on the celecoxib-mediated role of chemokines C-C motif ligand 2 (CCL2), C-X-C ligand 10 (CXCL10), and their receptors, CCR2 and CXCR3, in GSCs and a GSC-bearing malignant glioma model. C57BL/6 mice were injected with orthotopic GSCs intracranially and divided into groups administered either 10 or 30 mg/kg celecoxib, or saline to examine the antitumor effects associated with chemokine expression. In GSCs, we analyzed cell viability and expression of chemokines and their receptors in the presence/absence of celecoxib. In the malignant glioma model, celecoxib exhibited antitumor effects in a dose dependent manner and decreased protein and mRNA levels of Ccl2 and CxcL10 and Cxcr3 but not of Ccr2. CCL2 and CXCL10 co-localized with Nestin+ stem cells, CD16+ or CD163+ macrophages and Iba-1+ microglia. In GSCs, celecoxib inhibited Ccl2 and Cxcr3 expression in a nuclear factor-kappa B-dependent manner but not Ccr2 and CxcL10. Moreover, Ccl2 silencing resulted in decreased GSC viability. These results suggest that celecoxib-mediated regulation of the CCL2/CCR2 and CXCL10/ CXCR3 axes may partially contribute to glioma-specific antitumor effects.


Assuntos
Quimiocina CCL2/genética , Quimiocina CXCL10/genética , Regulação para Baixo/genética , Glioma/genética , Receptores CCR2/genética , Receptores CXCR3/genética , Animais , Antineoplásicos/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Glioma/tratamento farmacológico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética
12.
Neurooncol Adv ; 2(1): vdz058, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32642723

RESUMO

BACKGROUND: Antitumor therapies targeting programmed cell death-1 (PD-1) or its ligand-1 (PD-L1) are used in various cancers. However, in glioblastoma (GBM), the expression of PD-L1 varies between patients, and the relationship between this variation and the efficacy of anti-PD-1 antibody therapy remains unclear. High expression levels of PD-L1 affect the proliferation and invasiveness of GBM cells. As COX-2 modulates PD-L1 expression in cancer cells, we tested the hypothesis that the COX-2 inhibitor celecoxib potentiates anti-PD-1 antibody treatment via the downregulation of PD-L1. METHODS: Six-week-old male C57BL/6 mice injected with murine glioma stem cells (GSCs) were randomly divided into four groups treated with vehicle, celecoxib, anti-PD-1 antibody, or celecoxib plus anti-PD-1 antibody and the antitumor effects of these treatments were assessed. To verify the mechanisms underlying these effects, murine GSCs and human GBM cells were studied in vitro. RESULTS: Compared with that with each single treatment, the combination of celecoxib and anti-PD-1 antibody treatment significantly decreased tumor volume and prolonged survival. The high expression of PD-L1 was decreased by celecoxib in the glioma model injected with murine GSCs, cultured murine GSCs, and cultured human GBM cells. This reduction was associated with post-transcriptional regulation of the co-chaperone FK506-binding protein 5 (FKBP5). CONCLUSIONS: Combination therapy with anti-PD-1 antibody plus celecoxib might be a promising therapeutic strategy to target PD-L1 in glioblastoma. The downregulation of highly-expressed PD-L1 via FKBP5, induced by celecoxib, could play a role in its antitumor effects.

13.
J Med Invest ; 66(3.4): 308-313, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31656295

RESUMO

Purpose : To compare data on brain tumors derived from intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) imaging with multiple parameters obtained on dynamic susceptibility contrast (DSC) perfusion MRI and to clarify the characteristics of IVIM and ASL perfusion data from the viewpoint of cerebral blood flow (CBF) analysis. Methods : ASL-CBF and IVIM techniques as well as DSC examination were performed in 24 patients with brain tumors. The IVIM data were analyzed with the two models. The relative blood flow (rBF), relative blood volume (rBV) corrected relative blood volume (crBV), mean transit time (MTT), and leakage coefficient (K2) were obtained from the DSC MRI data. Results : The ASL-CBF had the same tendency as the perfusion parameters derived from the DSC data, but the permeability from the vessels had less of an effect on the ASL-CBF. The diffusion coefficient of the fast component on IVIM contained more information on permeability than the f value. Conclusion : ASL-CBF is more suitable for the evaluation of perfusion in brain tumors than IVIM parameters. ASL-CBF and IVIM techniques should be carefully selected and the biological significance of each parameter should be understood for the correct comprehension of the pathological status of brain tumors. J. Med. Invest. 66 : 308-313, August, 2019.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/fisiopatologia , Circulação Cerebrovascular , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Marcadores de Spin
14.
J Med Invest ; 66(3.4): 314-318, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31656296

RESUMO

Objective : One major complication associated with STB is intratumoral hematoma, which is also the most common cause of morbidity related to permanent paralysis and mortality in STB. The risk of perioperative hemorrhage is generally between 1% and 10%, but this could be an underestimation since it is not common for many neurosurgeons to perform CT scans after uncomplicated STBs. In this study, we describe the incidence of cerebral hemorrhage, including asymptomatic cerebral hemorrhage. Methods : We recently reviewed data on the diagnosis rate and occurrence of complications, including symptomatic and asymptomatic cerebral hemorrhage, in 80 patients who underwent STB at our facility between 2005 and 2014. Results : Histological diagnosis was established for 75 cases (93.8%), glioma was the most frequently encountered tumor. Symptomatic hemorrhage was observed in two cases (2.6%), with the symptoms subsiding within two days. The morbidity and mortality rate was 0%. However, asymptomatic hemorrhages were observed in 23 cases (28.8%). Conclusion : Stereotactic biopsy is a less invasive procedure for obtaining samples of brain tumors for diagnosis. The bleeding of the tissue-resection cavity that includes asymptomatic hemorrhage occurs at a constant rate. It is important to reduce the symptomatic bleeding associated with stereotactic biopsy. J. Med. Invest. 66 : 314-318, August, 2019.


Assuntos
Biópsia/efeitos adversos , Neoplasias Encefálicas/diagnóstico , Encéfalo/patologia , Hemorragia Cerebral/etiologia , Técnicas Estereotáxicas/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
J Med Invest ; 66(3.4): 355-357, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31656305

RESUMO

Metastatic tumors to the orbit of the eye, especially from primary carcinomas of the uterine cervix are very rare. A 64-year-old woman with a history of carcinoma of the uterine cervix presented with right eye pain and blepharoptosis for 2 weeks. Magnetic resonance imaging revealed a mass at the right orbital apex. Surgical extirpation was performed due to severe pain. Postoperative pathology demonstrated a poorly differentiated squamous cell carcinoma. The origin was ultimately considered to be the carcinoma of the uterine cervix. In conclusion, this report describes a rare case of a metastatic tumor at the orbital apex derived from the cervix of the uterus. J. Med. Invest. 66 : 355-357, August, 2019.


Assuntos
Carcinoma de Células Escamosas/secundário , Neoplasias Orbitárias/secundário , Neoplasias do Colo do Útero/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias do Colo do Útero/diagnóstico por imagem
16.
J Neurooncol ; 139(2): 323-332, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29779087

RESUMO

BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1. METHODS: GBM cells (U87MG and U251MG), primary TGB105 cells, and mice xenografted with U87MG cells were treated with Ad-DKK3 or TMZ alone or in combination. RESULTS: Ad-DKK3 augmentation of the anti-tumor effects of TMZ was associated with reduced MDR1 expression in both in vivo and in vitro studies. The survival of Ad-DKK3-treated U87MG cells was inhibited and the expression of MDR1 was reduced. This was associated with the inhibition of Akt/NFκB but not of YB-1 via the JNK/c-Jun- or Akt pathway. CONCLUSIONS: Our results suggest that Ad-DKK3 regulates the expression of MDR1 via Akt/NFκB pathways and that it augments the anti-tumor effects of TMZ in GBM cells.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Temozolomida/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Neurol Med Chir (Tokyo) ; 58(1): 10-16, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29093308

RESUMO

Microvascular decompression (MVD) is a widely used, safe, and effective treatment for trigeminal neuralgia (TGN). However, the extent of application of this therapeutic method and its outcomes in Japan are currently unclear. To address these questions, the authors analyzed the use of MVD for the treatment of TGN during the 33-month period from July 2010 to March 2013, using data contained in the Diagnosis Procedure Combination database. The analysis revealed that MVD was used for the treatment of TGN in 1619 cases (608 men, 1011 women), with approximately 1.66 times more women treated than men. MVD for TGN was most frequently performed in individuals 60 to 79 years of age; of particular note was the remarkable increase in the number of women in this particular category. The overall number of procedures performed per 100,000 population/year in Japan was 0.46. The number of procedures was larger in prefectures with higher populations, with a tendency toward a higher number of MVD procedures performed in the area designated West than in the East. Discharge outcomes indicated that cure and improvement were achieved in 97.6% of cases, with a mortality rate of 0.2%, and no differences in discharge outcomes between men and women. The mean length of hospital stay in patients undergoing MVD for TGN was 14.8 days. This analysis revealed discernable trends in the use of MVD for the treatment of TGN in Japan.


Assuntos
Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Japão , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento , Neuralgia do Trigêmeo/diagnóstico , Neuralgia do Trigêmeo/mortalidade , Adulto Jovem
18.
Intern Med ; 56(18): 2455-2461, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28824054

RESUMO

Acromegaly is caused by excessive growth hormone secretion, usually from pituitary adenomas. Somoatostatin analogues are widely used as primary or adjunctive therapy in the management of acromegaly. In this report, we present a case with remarkable shrinkage of a tumor after relatively short-term octreotide long-acting release (LAR) administration. During the 30-month follow-up after starting octreotide LAR, there was no recurrence of acromegaly with remarkable shrinkage of the tumor on pituitary magnetic resonance imaging. A literature review of the predictors for tumor shrinkage after the administration of somatostatin analogues in patients with acromegaly is also discussed in relation to this case.


Assuntos
Acromegalia/tratamento farmacológico , Adenoma/tratamento farmacológico , Antineoplásicos Hormonais/farmacologia , Octreotida/farmacologia , Neoplasias Hipofisárias/tratamento farmacológico , Adenoma/diagnóstico por imagem , Adenoma/metabolismo , Antineoplásicos Hormonais/administração & dosagem , Hormônio do Crescimento/biossíntese , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Octreotida/administração & dosagem , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/metabolismo , Somatostatina/análogos & derivados
19.
Oper Neurosurg (Hagerstown) ; 13(3): 392-397, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28521349

RESUMO

BACKGROUND: The reported 30-day mortality rate after brain tumor surgery is 2.2% to 2.9%, with a postoperative hematoma (POH) as the most frequent cause of death. OBJECTIVE: To investigate the risk factors for a POH requiring a recraniotomy after brain tumor surgery in a large, contemporary, single-institution consecutive series. METHODS: We included 1149 patients who underwent surgery for intracranial tumors at the Tokushima University Hospital from 1997 to 2014. The patient charts were retrospectively studied from our prospectively collected database. We analyzed the risk factors, type of hemorrhage, time to reoperation, and outcomes. RESULTS: The incidence of a POH requiring a recraniotomy was 2.09%. Among the patients with a POH requiring a recraniotomy, 12.5% died within 30 days of the first surgery. The incidence of a POH requiring a recraniotomy significantly correlated with the incidence of a hemangioblastoma, infratentorial tumors, and a prolonged operative time (>10 h), but not with the patient age or sex, surgical procedure (biopsy or craniotomy), surgical type (primary or secondary), bleeding volume, or intraoperative blood transfusion requirement. A recraniotomy for a POH was performed in 54% of the patients just after the first operation, and within 24 h for 79% of the patients. The clinical status at the time of discharge deteriorated in 52% of the patients. CONCLUSION: Hemangioblastomas, infratentorial tumors, and an operative time exceeding 10 h were significantly correlated with an increased risk of a POH; these factors were responsible for 12.5% of the 30-day surgical mortality rate.


Assuntos
Neoplasias Encefálicas/cirurgia , Craniotomia/efeitos adversos , Hematoma/epidemiologia , Hematoma/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Criança , Pré-Escolar , Feminino , Hematoma/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Reoperação/métodos , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
20.
J Neurooncol ; 132(2): 231-238, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28283800

RESUMO

Approximately half of surgically-treated patients with low-grade-glioma (LGG) suffer recurrence or metastasis. Currently there is no effective drug treatment. While the selective COX-2 inhibitor celecoxib showed anti-neoplastic activity against several malignant tumors, its effects against LGG remain to be elucidated. Ours is the first report that the expression level of COX-2 in brain tissue samples from patients with LGG and in LGG cell lines is higher than in the non-neoplastic region and in normal brain cells. We found that celecoxib attenuated LGG cell proliferation in a dose-dependent manner. It inhibited the generation of prostaglandin E2 and induced apoptosis and cell-cycle arrest. We also show that celecoxib hampered the activation of the Akt/survivin- and the Akt/ID3 pathway in LGGs. These findings suggest that celecoxib may have a promising therapeutic potential and that the early treatment of LGG patients with the drug may be beneficial.


Assuntos
Apoptose/fisiologia , Neoplasias Encefálicas/patologia , Encéfalo/patologia , Proliferação de Células/fisiologia , Ciclo-Oxigenase 2/metabolismo , Glioma/patologia , Transdução de Sinais/fisiologia , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Celecoxib/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas Inibidoras de Apoptose/farmacologia , Proteínas Inibidoras de Diferenciação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Survivina
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