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1.
J Neurosurg Case Lessons ; 3(7)2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36130551

RESUMO

BACKGROUND: The authors' previous cadaveric study reported a new surgical approach that can expose the deep cerebellar hemisphere, cerebellopontine angle, and upper fourth ventricle through dissection of the horizontal fissure of the suboccipital cerebellar hemisphere. Here, the authors present their experience with the first clinical use of the suboccipital trans-horizontal fissure (SOTHF) approach requiring access to the third and upper fourth ventricle lesions, a challenging compartment to access by traditional approaches. OBSERVATIONS: In cases 1 and 2, computed tomography demonstrated large hematomas in the left cerebellar hemisphere with extension into the third ventricle and/or the upper fourth ventricle, resulting in obstructive hydrocephalus. Large hematomas in both the cerebellar hemisphere and the upper fourth ventricle were successfully removed via an SOTHF approach alone without external ventricular drainage. Furthermore, the hematoma in the third ventricle was removed through the aqueduct in case 2. Access to the upper fourth ventricle and the third ventricle were intraoperatively verified using a neuronavigation system. The patients immediately regained consciousness, and the result of cerebellar function testing was almost normal after the operation. LESSONS: An SOTHF approach can achieve the removal of cerebellar and intraventricular hematomas simultaneously, is a faster and potentially safer method than others, and subsequently allows rapid clinical improvement.

2.
Medicines (Basel) ; 9(7)2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35877817

RESUMO

Complication of leptomeningeal carcinomatosis (LMC) is critical. It causes rapid neurological deterioration, and subsequently, discontinuation of the ineffective treatment even in body tumor dormancy. Large molecular chemotherapeutic agents that are unlikely to penetrate the CSF space, are more likely to not treat LMC, typically in chemo-sensitive tumors. With the introduction of novel regimens, significant advances in overall survival have been observed even in formerly chemo-resistant tumors, such as pancreatic cancer. Although such cases are still rare, the number of pancreatic cancer patients complicated with LMC are increasing, and this therefore needs more recognition. A 49-year-old woman was diagnosed with stage IVa pancreatic cancer. She underwent surgery, and subsequent adjuvant chemotherapy. After three lines of chemotherapy over a 3-year period, where the body disease remained dormant, the patient was complicated by LMC. The diagnosis was made 4 months after the onset of headache. The patient received intrathecal methotrexate treatment but succumbed shortly after treatment induction. Pancreatic cancer is still relatively chemo-resistant and is one of the least likely types of tumor to be complicated by LMC due to patients dying of the primary tumor. Advancements in treatments have led to a prolonged period of primary tumor control, but not in the CNS due to the poor penetration of chemo-agents to this site. The present case seems to be a typical result of modern era anti-cancer therapy. Therefore, we emphasize the necessity of earlier recognition of this complication so that we can initiate specific treatment targeting the CSF space, especially in this formerly chemo-resistant tumor in order to improve its prognosis.

3.
Brain Sci ; 12(6)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35741633

RESUMO

Leptomeningeal carcinomatosis (LMC) is a rare but devastating complication of advanced cancer. Breast cancer, lung cancer, and melanoma are the three most common causes of LMC, whereas it is rare in ovarian cancer. Here, we report the case of a 59-year-old woman who was diagnosed with LMC from ovarian cancer and was successfully treated with intrathecal chemotherapy via Ommaya reservoir and radiation therapy. The patient had an amelioration of symptoms and prolonged survival. Though LMC from ovarian cancer is thought to be rare, it is not going to remain a rare entity because the incidence of LMC in general is thought to be increasing, which is also the case with ovarian cancer. According to 31 cases whose treatment course is reported in literature, despite the absence of an established treatment for LMC, intrathecal (IT) chemotherapy whose survival benefit has been suggested in past studies might also prolong survival in patients with LMC from ovarian cancer. IT chemotherapy via Ommaya reservoir may be preferred to the lumbar puncture route. The presentation of non-specific symptoms of LMC in patients may hinder its diagnosis; however, early diagnosis and treatment induction is the key for patients' prolonged survival and restored useful life.

4.
Medicines (Basel) ; 9(4)2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35447878

RESUMO

Background: Dura mater infiltration is the main growth pattern of meningiomas. Local recurrence may occur in any type of meningioma, but it is more likely so in atypical meningiomas. Therefore, a wide resection of tumor cell-invaded dura mater is necessary to avoid recurrence. DuraGen® (an artificial dural substitute) can be used for dural reconstruction in meningiomas. Here, we report a rare case of a patient with atypical meningioma that invaded into the DuraGen®-derived mature dura mater. Case presentation: A 66-year-old female showed a three-time recurrence of atypical meningioma. Simpson grade I resection (en bloc tumor with autologous dura mater and DuraGen®-derived dura mater resection) was achieved at the 3rd recurrence. Collagen fibers running regularly and transversely were observed in the DuraGen®-derived dura mater resembling the autologous meningeal layer. Meningioma cell invasion, displayed by occasional EMA immunostaining, was observed in the DuraGen®-derived dura mater. Conclusions: This case indicates that meningioma cells may invade and survive in the DuraGen®-derived dura mater. Whether or not DuraGen® is not appropriate as a dural substitute remains unanswered. Further experiences are needed to validate these findings in large sample sizes.

5.
Front Surg ; 9: 866476, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360435

RESUMO

Background: Advances in digital imaging including evolving of 3-dimensional (3D) exoscope has allowed its use as an alternative to microscopes in neurosurgery. The exoscope can concede wide space around the operating table and patient. Here, we show a three-surgeon-six-hand operative approach using a 4K-3D exoscope. Practical advantages and disadvantages of this approach are discussed. Clinical Presentation: A 58-year-old male was refered with a 60 mm diameter meningioma in the right frontal convexity. The tumor removal was done by an operator and two assistants with a scrub nurse while viewing images displayed on a 55-inch monitor with integrated 4K and 3D visualization technology retrieved by KINEVO®. Meaningful communication between the operator and two assistants allowed for simultaneous, and precise surgical procedures. Gross total removal was achieved without damaging the brain. Conclusion: The ocular-free, openness of 4K-3D exoscope allows for a three-surgeon-six-handed operation, which leads to simultaneous surgical maneuvers by multiple hands, shorter operative time, flexible/intermittent brain retraction made by two assistants, and educational benefits owing to the surgical procedure being visually shared.

6.
Oper Neurosurg (Hagerstown) ; 21(6): E479-E487, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34624893

RESUMO

BACKGROUND: Surgical treatment of pathological lesions in the deep cerebellar hemisphere, cerebellopontine angle (CPA), and fourth ventricle of the posterior cranial fossa (PCF) is challenging. Conventional neurosurgical approaches to these lesions are associated with risk of various complications. Mastery of efficient fissure dissection is imperative when approaching deep-seated lesions. The horizontal fissure (HF) is the largest and deepest fissure of the cerebellum. OBJECTIVE: To conduct an anatomical study and introduce a novel suboccipital trans-HF (SOTHF) approach to access lesions of the deep cerebellar hemispheres, CPA, and upper fourth ventricle of the PCF. METHODS: We performed a cadaveric dissection study focusing on anatomical landmarks and surgical feasibility of the SOTHF approach then implemented it in 2 patients with a deep cerebellar hemispheric tumor. RESULTS: Anatomical feasibility of the SOTHF approach was demonstrated and compared with conventional approaches in the cadaveric study. Opening the suboccipital surface of the HF to create medial, intermediate, and lateral surgical corridors provided optimal viewing angles and wide access to the deep cerebellar hemispheres, CPA, and upper fourth ventricle without heavy cerebellar retraction. Sacrificing cerebellar neural structures and complex skull base techniques were not required to obtain adequate exposure. The SOTHF approach was successfully applied without complication in 2 patients with a deep cerebellar hemispheric tumor. CONCLUSION: The HF is an important cerebellar fissure that provides a gateway to deep areas of the PCF. Further studies are needed to define and expand applications of the SOTHF approach.


Assuntos
Fossa Craniana Posterior , Procedimentos Neurocirúrgicos , Cadáver , Ângulo Cerebelopontino/cirurgia , Fossa Craniana Posterior/cirurgia , Quarto Ventrículo/diagnóstico por imagem , Quarto Ventrículo/cirurgia , Humanos , Procedimentos Neurocirúrgicos/métodos
7.
J Infect Chemother ; 27(3): 486-491, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33214071

RESUMO

INTRODUCTION: Leptomeningeal metastases (LM) from solid tumors have poor prognosis. Intrathecal chemotherapy through the Ommaya reservoir (OR) is one of the options for treating LM; however, OR-related bacterial meningitis (ORRBM) is a severe complication in patients who underwent OR placement. Little is known about the incidence rate and prognosis of ORRBM among patients with LM from solid tumors. METHODS: We retrospectively reviewed the records of patients who underwent OR placement to treat LM from solid tumors at Kawasaki Municipal Kawasaki Hospital between January 2009, and December 2018. RESULTS: Among 136 patients with OR placement (median age of 64.5 years) including 30,320 Ommaya-days, 18 (13.2%) developed ORRBM (5.9 infections per 10,000 Ommaya-days). The major primary diseases were lung cancer (65.4%). The median times from OR placement and from last OR puncture to ORRBM onset were 20 days and 4.5 days, respectively. Major clinical symptoms were fever (83.3%), headache (50.0%), disturbance of consciousness (50.0%), and nausea (38.9%). Seventeen of 18 patients underwent an OR removal operation. One patient died from ORRBM, and another patient died from heart failure during ORRBM treatment. The median duration of treatment with antibiotics was 16.5 days. The median survival period from the day of OR placement was 146.5 days among patients who developed ORRBM and 142.5 days among patients who did not develop ORRBM. CONCLUSIONS: The rate of ORRBM among patients with LM from solid tumors in our hospital was 13.2%. ORRBM may not shorten the patients' survival period with adequate management including removal of the device.


Assuntos
Neoplasias Pulmonares , Meningites Bacterianas , Adulto , Humanos , Japão/epidemiologia , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
8.
Int J Oncol ; 47(1): 61-70, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25963555

RESUMO

Viable and stable human cancer cell lines and animal models combined with adequate clinical information are essential for future advances in cancer research and patient care. Conventional in vitro cancer cell lines are commonly available; however, they lack detailed information on the patient from which they originate, including disease phenotype and drug sensitivity. Patient-derived xenografts (PDX) with clinical information (so-called 'cancer xenopatients') are a promising advance that may accelerate the development of anticancer therapies. We established 61 PDX lines from 116 surgically removed tumor tissues inoculated subcutaneously into NOG mice (53% success rate). PDX lines were established from various types of epithelial tumors and also from sarcomas, including gastrointestinal stromal tumors and Ewing/PNET sarcomas. The metastatic tumors yielded PDX lines more effectively (65%) than the primary tumors (27%, P<0.001). In our PDX models, morphological characteristics, gene expression profiles, and genetic alteration patterns were all well preserved. In eight cases (7%), the transplantable xenografts for several generations were composed of large monotonous nonepithelial cells of human origin, revealed to be Epstein-Barr virus infection-associated lympho-proliferative lesions. Despite this, PDX linked with clinical information offer many advantages for preclinical studies investigating new anticancer drugs. The fast and efficient establishment of individual PDX may also contribute to future personalized anticancer therapies.


Assuntos
Transplante de Neoplasias/métodos , Neoplasias/patologia , Transplante Heterólogo/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Medicina de Precisão , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
9.
J Neurooncol ; 124(1): 127-35, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26007163

RESUMO

Functional preservation is critical in glioma surgery, and the extent of resection influences survival outcome. Neoadjuvant chemotherapy is a promising option because of its potential to facilitate tumor shrinkage and maximum tumor resection. The object of this study was to assess the utility of the neoadjuvant strategy in a prospective series of gliomas with favorable molecular status. Twenty-six consecutive cases of diffuse gliomas of WHO grade II or III with either 1p19q codeletion or MGMT methylation were treated with upfront chemotherapy following maximal safe removal. In cases of incomplete initial surgery, second-look resection was intended after tumor volume decrease by chemotherapy. Among 22 evaluable cases, chemotherapy led to a median change in the sum of the product of perpendicular diameters of -35 %, and 14 out of the 22 cases (64 %) showed objective response. Second-look resection after tumor volume decrease was performed in 12 out of 19 cases of incomplete initial surgery (GTR/STR 9, removal of residual methionine PET uptake 3). The median progression-free survival among the 22 patients with grade II tumors was 57 months, with some cases showing durable progression-free survival after second-look resection. MIB-1 indices of the second-look resected tumors were lower than those of the initial tumors, and the methylation status of the MGMT gene was unchanged. Neoadjuvant chemotherapy based on molecular guidance often produces significant volume decrease of incompletely resected gliomas. Radical second-look resection is an optional advantage of upfront chemotherapy for chemosensitive gliomas compared with initial radiotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Glioma/tratamento farmacológico , Glioma/genética , Glioma/cirurgia , Adulto , Neoplasias Encefálicas/diagnóstico , Deleção Cromossômica , Cromossomos Humanos Par 1 , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Feminino , Glioma/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Nitrosoureia/uso terapêutico , Estudos Prospectivos , Temozolomida , Resultado do Tratamento , Proteínas Supressoras de Tumor/genética
10.
Surg Neurol Int ; 3: 1, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22347671

RESUMO

BACKGROUND: Rosai-Dorfman disease (RDD) was first described in 1969 as an idiopathic histiocytic proliferative disorder. It commonly presents as a massive and painless adenopathy. Until 1990, extranodal involvement of the central nervous system (CNS) was rare and reported in less than 5% of the total number of patients with extranodal RDD. Complete removal of CNS RDD has been achieved in many cases. CASE DESCRIPTION: We report a case of an isolated intracranial RDD in a 53-year-old man. The patient had an episode of generalized seizures. Imaging studies of the brain were compatible with a meningioma en plaque. The mass was exposed by a right frontotemporal craniotomy. The tumor was adhered tightly to the adjacent cerebral cortex and was permeated by pial arteries of the brain surface. The sacrificing of these arteries was inevitable in order to achieve the total removal of the tumor. The patient had incomplete left hemiparesis after the surgery. Brain computed tomography (CT) imaging revealed a postoperative hemorrhage and a low-density lesion in the right frontal lobe. The patient was postoperatively diagnosed with isolated central nervous system RDD. CONCLUSION: Although the complete removal of dural-based lesions without any neurological deficits has been performed in many cases, the treatment of cases with high risks, such as the present case, indicates conservative excisions and adjuvant radiotherapy with or without chemotherapy.

11.
J Chromatogr A ; 1206(1): 41-4, 2008 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-18692851

RESUMO

In order to develop a high-throughput assay for nitric oxide metabolites, nitrite (NO2-) and nitrate (NO3-), in biological fluids, we have investigated the simultaneous determination of them using an electrophoretic lab-on-a-chip (microchip capillary electrophoresis, MCE) technique. In this study, in order to establish an MCE assay process without deproteinization, the addition of a zwitterionic additive into the running buffer to reduce the adsorption of protein onto the surface of channel was investigated. Initially, some zwitterionic additives were investigated by making a comparison of relative standard deviations (RSDs) of the migration times for NO2(-) and NO3(-) on capillary electrophoresis. From the results of our comparison of the RSD values, 2% (w/w) N-cyclohexyl-2-aminoethanesulfonic acid (CHES) was selected. As a result of the application of the running buffer with CHES to the MCE process, the complete separation of NO2(-) and NO3(-) in human plasma without deproteinization was achieved within 1 min. Since the RSD values of the positions of the peaks were less than 2.3%, beneficial reduction effects on MCE were suggested. When we used an internal standard method in order to correct the injection volume, the RSDs of the peak heights and areas were less than 10%, and the correlation coefficients of spiked calibration curves ranging from 0 to 350 microM were 0.999 and 0.997 for NO2(-) and NO3(-), respectively. The limits of detection (S/N=3) were 53 microM for NO2(-) and 41 microM for NO3(-). Moreover, the correlation coefficients in excess of 0.99 between the MCE method and a conventional Griess method were achieved for both NO2(-) and NO3(-). Consequently, the possibility of establishing a high-throughput assay process was obtained by utilizing 2% (w/w) CHES to reduce protein adsorption.


Assuntos
Eletroforese em Microchip/métodos , Procedimentos Analíticos em Microchip/métodos , Nitratos/sangue , Óxido Nítrico/metabolismo , Nitritos/sangue , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Taurina/análogos & derivados
12.
Surg Today ; 36(6): 554-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16715429

RESUMO

We report a case of metachronous bilateral adrenal metastases from mucinous adenocarcinoma of the stomach. A 68-year-old man who had undergone surgery for advanced gastric cancer 5 months earlier had a follow-up computed tomography (CT) scan, which showed a right adrenal tumor. We performed a right adrenalectomy, and histopathological examination revealed a mucinous adenocarcinoma with features consistent with those of gastric cancer. A routine follow-up CT scan done 41 months after the right adrenalectomy showed a left adrenal mass. Chemotherapy had no apparent effect, and left adrenalectomy was performed 65 months after the right adrenalectomy. Histopathological examination also revealed a metastasis from gastric cancer. The patient was alive without recurrence 40 months after the left adrenalectomy. This case suggests that resection of adrenal metastasis from gastric cancer is an effective treatment option that may prolong survival in selected patients.


Assuntos
Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/secundário , Neoplasias das Glândulas Suprarrenais/secundário , Neoplasias Gástricas/patologia , Adenocarcinoma Mucinoso/cirurgia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Idoso , Humanos , Masculino , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/cirurgia , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios X
13.
Cancer Res ; 65(11): 4861-9, 2005 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-15930307

RESUMO

Pharmacologic inhibition of the DNA signal transducers Chk1 and p38 blocks G2 arrest and sensitizes glioblastoma cells to chemotherapeutic methylating agent-induced cytotoxicity. Because Akt pathway activation has been suggested to also block G2 arrest induced by DNA-damaging agents and because glioma cells frequently have high levels of Akt activation, we examined the contribution of the Akt pathway to methylating agent-induced G2 arrest and toxicity. U87MG human glioma cells containing an inducible Akt expression construct were incubated with inducing agent or vehicle, after which the cells were exposed to temozolomide and assayed for activation of the components of the G2 arrest pathway and survival. Temozolomide-treated control cells activated the DNA damage signal transducers Chk1, Chk2, and p38, leading to Cdc25C and Cdc2 inactivation, prolonged G2 arrest, and loss of clonagenicity by a combination of senescence and mitotic catastrophe. Temozolomide-treated cells induced to overexpress Akt, however, exhibited significantly less drug-induced Cdc25C/Cdc2 inactivation and less G2 arrest. Akt-mediated suppression of G2 arrest was associated not with alterations in Chk1 or p38 activation but rather with suppression of Chk2 activation and reduced recruitment of Chk2 to sites of damage in chromatin. Unlike bypass of the G2 checkpoint induced by pharmacologic inhibitors of Chk1 or p38, however, Akt-induced bypass of G2 arrest suppressed, rather than enhanced, temozolomide-induced senescence and mitotic catastrophe. These results show that whereas Akt activation suppresses temozolomide-induced Chk2 activation and G2 arrest, the overriding effect is protection from temozolomide-induced cytotoxicity. The Akt pathway therefore represents a new target for the sensitization of gliomas to chemotherapeutic methylating agents such as temozolomide.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Dacarbazina/análogos & derivados , Dacarbazina/farmacologia , Fase G2/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Astrócitos/enzimologia , Linhagem Celular Transformada , Linhagem Celular Tumoral , Quinase do Ponto de Checagem 2 , Dacarbazina/antagonistas & inibidores , Ativação Enzimática/efeitos dos fármacos , Fase G2/fisiologia , Glioblastoma/tratamento farmacológico , Glioblastoma/enzimologia , Glioblastoma/patologia , Humanos , Metilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt , Temozolomida
14.
J Neurosurg ; 100(6): 1060-5, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15200121

RESUMO

OBJECT: The Chk1 and p38 mitogen-activated protein kinase (MAPK) pathways play key roles in the G2 arrest caused by exposing glioma cells to temozolomide (TMZ). Although inhibition of either pathway sensitizes glioma cells to TMZ-induced cytotoxicity, the relative contributions of these pathways to TMZ-induced G2 arrest and to TMZ resistance conferred by G2 arrest have not been defined. METHODS: The authors pharmacologically inhibited the Chk1 and/or p38 pathways in U87MG human glioma cells prior to and/or after exposure to TMZ; thereafter, effects on the TMZ-induced G2 arrest pathway and toxicity were monitored. The p38 inhibitor SB203580 or the Chk1 inhibitor UCN-01 or their combination blocked TMZ-mediated inactivation of cdc25C and cdc2, suggesting that p38 and Chk1 pathways work cooperatively and are both necessary to inactivate cdc25C and cdc2. Consistent with this idea, the inhibition of both Chk1 and p38 pathways did not lead to greater bypass of TMZ-induced G2 arrest or greater cytotoxicity than inhibition of either pathway alone. Inhibition of p38 did not alter TMZ-induced Chk1 activation/phosphorylation and vice versa, suggesting that p38 and Chk1 do not cooperatively bring about G2 arrest by reciprocal activation/phosphorylation. The two pathways, however, are not functionally identical; the Chk1 pathway was required for both the initiation and maintenance of TMZ-induced G2 arrest, whereas the p38 pathway played a role only in the initiation. CONCLUSIONS: The Chk1 and p38 pathways cooperate to bring about TMZ-induced G2 arrest, and the inhibition of either pathway alone is sufficient to sensitize U87MG glioma cells to TMZ-induced cytotoxicity.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/patologia , Dacarbazina/análogos & derivados , Dacarbazina/farmacologia , Fase G2/efeitos dos fármacos , Glioma/patologia , Proteínas Quinases Ativadas por Mitógeno/farmacologia , Proteínas Quinases/farmacologia , Antineoplásicos Alquilantes/metabolismo , Quinase 1 do Ponto de Checagem , Dacarbazina/metabolismo , Resistencia a Medicamentos Antineoplásicos , Humanos , Fosforilação , Temozolomida , Células Tumorais Cultivadas , Proteínas Quinases p38 Ativadas por Mitógeno
15.
Mol Cell Biol ; 23(22): 8306-15, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14585987

RESUMO

Although human cells exposed to DNA-methylating agents undergo mismatch repair (MMR)-dependent G(2) arrest, the basis for the linkage between MMR and the G(2) checkpoint is unclear. We noted that mitogen-activated protein kinase p38alpha was activated in MMR-proficient human glioma cells exposed to the chemotherapeutic methylating agent temozolomide (TMZ) but not in paired cells made MMR deficient by expression of a short inhibitory RNA (siRNA) targeted to the MMR protein Mlh1. Furthermore, activation of p38alpha in MMR-proficient cells was associated with nuclear inactivation of the cell cycle regulator Cdc25C phosphatase and its downstream target Cdc2 and with activation of the G(2) checkpoint, actions which were suppressed by the p38alpha/beta inhibitors SB203580 and SB202590 or by expression of a p38alpha siRNA. Finally, pharmacologic or genetic inhibition of p38alpha increased the sensitivity of MMR-proficient cells to the cytotoxic actions of TMZ by increasing the percentage of cells that underwent mitotic catastrophe as a consequence of G(2) checkpoint bypass. These results suggest that p38alpha links DNA MMR to the G(2) checkpoint and to resistance to chemotherapeutic DNA-methylating agents. The p38 pathway may therefore represent a new target for the development of agents to sensitize tumor cells to chemotherapeutic methylating agents.


Assuntos
Reparo do DNA/fisiologia , Dacarbazina/análogos & derivados , Fase G2/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Antineoplásicos Alquilantes/farmacologia , Pareamento Incorreto de Bases , Sequência de Bases , Linhagem Celular Tumoral , Metilação de DNA , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Dacarbazina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Humanos , Imidazóis/farmacologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/genética , Piridinas/farmacologia , Temozolomida , Proteínas Quinases p38 Ativadas por Mitógeno
16.
Neurol Med Chir (Tokyo) ; 43(1): 51-4, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12568324

RESUMO

A 21-year-old man presented with bitemporal hemianopia and hyperprolactinemia. Magnetic resonance (MR) imaging showed a suprasellar cystic tumor in contact with the pituitary stalk. The diagnosis was craniopharyngioma. Intraoperatively, there was no clear continuity between the tumor and the tissue of the anterior lobe of the pituitary gland. The pituitary stalk and the diaphragma sellae were intact, and their morphology remained almost completely normal after the tumor was removed. The histological diagnosis was prolactin-producing pituitary adenoma. Postoperatively, the bitemporal hemianopia improved, and the serum prolactin levels returned to normal. The final diagnosis was suprasellar ectopic pituitary adenoma arising in the peri-infundibular region. Follow-up MR imaging at 1 year showed a normal pituitary stalk and pituitary gland, with no evidence of residual tumor.


Assuntos
Cistos do Sistema Nervoso Central/patologia , Neuro-Hipófise/patologia , Neoplasias Hipofisárias/patologia , Prolactinoma/patologia , Adulto , Humanos , Masculino
17.
Brain Res ; 962(1-2): 105-10, 2003 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-12543460

RESUMO

We investigated c-Met expression in cultured astrocytes and their regulation by cytokines. Immunocytochemistry revealed that c-Met was expressed in cultured astrocytes. Western blotting revealed that acidic and basic fibroblast growth factor (FGF) enhanced and hepatocyte growth factor (HGF) reduced c-Met expression. Reverse transcription-polymerase chain reaction revealed that FGFs and HGF enhanced c-met expression. These findings suggest that c-Met expressed in astrocytes may have important roles during the nervous system regeneration.


Assuntos
Astrócitos/fisiologia , Citocinas/farmacologia , Proteínas Proto-Oncogênicas c-met/genética , Animais , Animais Recém-Nascidos , Células Cultivadas , Fator de Crescimento Epidérmico/farmacologia , Fator 1 de Crescimento de Fibroblastos/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fator de Crescimento de Hepatócito/farmacologia , Interleucina-1/farmacologia , Regeneração Nervosa , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/farmacologia
18.
Neurol Med Chir (Tokyo) ; 42(11): 521-5, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12472219

RESUMO

Two patients with vagal schwannoma manifesting as deafness with no lower cranial nerve paresis were treated surgically. A 42-year-old male underwent partial resection of the tumor, which was tightly adhered to the cranial nerves, to prevent lower cranial nerve paresis. A 29-year-old female underwent total removal of the tumor without complications. The patients recovered useful audition with no postoperative deficit.


Assuntos
Neoplasias dos Nervos Cranianos/complicações , Neoplasias dos Nervos Cranianos/cirurgia , Transtornos da Audição/etiologia , Neurilemoma/complicações , Neurilemoma/cirurgia , Nervo Vago/cirurgia , Adulto , Neoplasias dos Nervos Cranianos/patologia , Transtornos da Audição/diagnóstico , Humanos , Masculino , Neurilemoma/patologia , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Nervo Vago/patologia
19.
J Neurooncol ; 59(2): 107-15, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12241103

RESUMO

Patched (Ptc) is a transmembrane receptor for sonic hedgehog (Shh) and functionally associated with another transmembrane protein, smoothened (Smo). Ptc is a tumor suppressor gene whereas Smo serves as a proto-oncogene of neuroectodermal tumors. Their downstream molecules, Gli1, Gli2, and Gli3, are oncogenes of glioblastomas. We have analyzed mRNA expression of Ptc, Smo, and Gli family members in human astrocytic tumors. The mRNA expression was quantified by real-time polymerase chain reactions in 40 tumors (diffuse astrocytomas; 6 cases: anaplastic astrocytomas; 12 cases: glioblastomas; 22 cases) and four cell lines derived from astrocytic tumors. The MIB-1 proliferating cell indices (PCIs) of these tumors were analyzed by immunohistochemistry. In comparison with the World Health Organization (WHO) classification, the amount of Ptc and Smo mRNAs decreased in proportion to the progression of histological maliganancy, and similar results were obtained with astrocytic tumor-derived cell lines. However, there was no remarkable correlation between the mRNA expression level of each gene and the MIB-1 PCIs. The mRNA expression level of Gli1 was variable and highly elevated in two cases. No remarkable features were found clinically or histologically in these two cases. In summary, our results indicate that Ptc and Smo mRNA levels have an inverse correlation with histological malignancy and suggest that these gene products are implicated in the suppression of astrocytic tumors. In contrast, there was no significant correlation between the mRNA levels of the Gli family members and histological malignancy, suggesting that Gli proteins are not associated with the progression of astrocytic tumors.


Assuntos
Astrocitoma/genética , Astrocitoma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proteínas de Membrana/biossíntese , Proteínas Oncogênicas/biossíntese , Receptores de Superfície Celular/biossíntese , Receptores Acoplados a Proteínas G , Fatores de Transcrição/biossíntese , Adulto , Astrocitoma/metabolismo , Biomarcadores Tumorais , Neoplasias Encefálicas/metabolismo , Criança , Feminino , Proteínas Hedgehog , Humanos , Imuno-Histoquímica , Lactente , Antígeno Ki-67/metabolismo , Masculino , Invasividade Neoplásica , Receptores Patched , Reação em Cadeia da Polimerase , Proto-Oncogene Mas , RNA Mensageiro/análise , Transdução de Sinais , Receptor Smoothened , Transativadores/metabolismo , Proteína GLI1 em Dedos de Zinco
20.
Neuropathology ; 22(4): 290-3, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12564769

RESUMO

An extra-axial nodule in the cerebello-medullary fissure is described, occurring in a 27-year-old-woman. MRI and CT scans revealed the lesion was a non-enhanced round mass, which was associated with mild atrophy of the surrounding cerebellum, but with no perifocal edema. In the surgical observation, the mass was white, elastic and hard, well demarcated and localized in the cerebello-medullary fissure. Histologically, the lesion was composed of astrocytes and collagen-producing fibroblasts with no anaplasia. These findings suggested that the lesion was hamartomatous, but not neoplastic. This type of gliofibrous nodule has not been previously reported.


Assuntos
Encefalopatias/patologia , Hamartoma/patologia , Adulto , Astrócitos/patologia , Encefalopatias/diagnóstico por imagem , Encefalopatias/metabolismo , Encefalopatias/cirurgia , Neoplasias Encefálicas/patologia , Cerebelo/patologia , Diagnóstico Diferencial , Feminino , Fibroblastos/patologia , Hamartoma/diagnóstico por imagem , Hamartoma/metabolismo , Hamartoma/cirurgia , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Bulbo/patologia , Tomografia Computadorizada por Raios X
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