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1.
J Craniovertebr Junction Spine ; 14(1): 50-54, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37213584

RESUMO

Aim: We aimed to examine the safety and effectiveness of a posterior approach alone in the surgical treatment of sacral-presacral tumors. In addition, we investigate factors that determine the selection of a posterior approach alone. Materials and Methods: Patients with sacral-presacral tumors who underwent surgery in our institution between 2007 and 2019 were examined in this study. Data regarding patient age, gender, tumor size (>6 cm and <6 cm), tumor localization (below or above S1), tumor pathology (benign or malignant), surgical approach (anterior alone, posterior alone, or combined), and extent of resection were recorded. The Spearman's correlation analyses were conducted between surgical approach and tumor size, localization, and pathology. Factors influencing the extent of resection were also examined. Results: Complete tumor resection was achieved in 18 of 20 patients. A posterior approach alone was used in 16. No strong or significant relation was detected between surgical approach and tumor size (r = 0.218; P = 0.355). There was no strong or significant relationship between surgical approach and tumor localization (r = 0.145; P = 0.541) or tumor pathology (r = 0.250; P = 0.288). Tumor size, localization, and pathology were not independent factors that determined surgical approach. The only significant independent determining factor for incomplete resection was tumor pathology (r = 0.688; P = 0.001). Conclusion: A posterior approach is safe and effective in the surgical treatment of sacral-presacral tumors independent of tumor localization, size, or pathology and is a feasible first-line treatment option.

3.
Nat Commun ; 13(1): 6041, 2022 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-36253360

RESUMO

Tumors exhibit enhancer reprogramming compared to normal tissue. The etiology is largely attributed to cell-intrinsic genomic alterations. Here, using freshly resected primary CRC tumors and patient-matched adjacent normal colon, we find divergent epigenetic landscapes between CRC tumors and cell lines. Intriguingly, this phenomenon extends to highly recurrent aberrant super-enhancers gained in CRC over normal. We find one such super-enhancer activated in epithelial cancer cells due to surrounding inflammation in the tumor microenvironment. We restore this super-enhancer and its expressed gene, PDZK1IP1, following treatment with cytokines or xenotransplantation into nude mice, thus demonstrating cell-extrinsic etiology. We demonstrate mechanistically that PDZK1IP1 enhances the reductive capacity CRC cancer cells via the pentose phosphate pathway. We show this activation enables efficient growth under oxidative conditions, challenging the previous notion that PDZK1IP1 acts as a tumor suppressor in CRC. Collectively, these observations highlight the significance of epigenomic profiling on primary specimens.


Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Citocinas/metabolismo , Elementos Facilitadores Genéticos/genética , Regulação Neoplásica da Expressão Gênica , Camundongos , Camundongos Nus , Microambiente Tumoral/genética
4.
Turk Neurosurg ; 32(5): 764-772, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35416268

RESUMO

AIM: To investigate the effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on acoustic characteristics of voice production in Turkish patients with Parkinson's disease (PD). MATERIAL AND METHODS: This study recruited 20 patients diagnosed with PD. Voice samples were recorded under the "stimulation on" and "stimulation off" conditions of STN-DBS. Acoustic recordings of the patients were made during the production of vowels /a/, /o/, and /i/ and repetition of the syllables /pa/-/ta/-/ka/. Acoustic analyses were performed using Praat. RESULTS: A significant difference in the parameters was observed among groups for vowels. A positive significant difference was observed between preoperative med-on and postoperative med-on/stim-on groups for /a/ and the postoperative med-on/ stim-on and postoperative med-on/stim-off groups for /o/ and /i/ for frequency perturbation (jitter) and noise-to-harmonics ratio. No significant difference was noted between the preoperative med-on and postoperative med-on/stim-off groups for any vowels. CONCLUSION: STN-DBS surgery has an acute positive effect on voice. Studies on formant frequency analysis in STN-DBS may be expanded with both articulation and intelligibility tests to enable us to combine patient abilities in various perspectives and to obtain precise results.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Estimulação Encefálica Profunda/métodos , Humanos , Idioma , Doença de Parkinson/cirurgia , Núcleo Subtalâmico/fisiologia , Núcleo Subtalâmico/cirurgia
5.
Turk Neurosurg ; 32(3): 449-458, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35147967

RESUMO

AIM: To examine the postoperative outcomes of electrode fixation using bone cement and Stimloc® in patients with Parkinson?s disease (PD) who underwent subthalamic nucleus (STN) deep brain stimulation (DBS). MATERIAL AND METHODS: Between 2016 and 2018, permanent electrode fixation was performed in 30 patients with PD, of which 15 received bone cement and the remaining 15 received Stimloc®. Data regarding preoperative Unified Parkinson?s Disease Rating Scale (UPDRS) III scores, levodopa equivalent daily dose (LEDD) values, surgery duration, and the fixation technique used were recorded. Brain computed tomography was performed for early postoperative evaluation of pneumocephalus and possible hematoma as well as for the determination of migration 1 year postoperatively. UPDRS III scores and LEDD values were re-evaluated 1 year postoperatively; surgery duration, clinical effectiveness, and complication rates were compared between the two fixation techniques. RESULTS: A statistically significant difference in application time was observed between the two techniques (bone cement: 21 min, Stimloc®: 6 min). After 1 year from surgery, 0.92- and 0.88-mm migrations were observed in the bone cement and Stimloc® groups, respectively. A significant correlation between migration and the pneumocephalus volume was observed in both groups. No differences were observed between the groups regarding infection, migration, pneumocephalus volume, wound erosion, and clinical outcomes. CONCLUSION: Stimloc® is preferred over bone cement for electrode fixation in DBS surgeries as it is associated with shorter application duration; this increases patient comfort and tolerance during awake surgery. Clinical efficacy and complication rates associated with both techniques are similar.


Assuntos
Neoplasias Encefálicas , Estimulação Encefálica Profunda , Doença de Parkinson , Pneumocefalia , Cimentos Ósseos/uso terapêutico , Neoplasias Encefálicas/complicações , Estimulação Encefálica Profunda/métodos , Eletrodos , Humanos , Levodopa , Doença de Parkinson/cirurgia , Pneumocefalia/complicações , Resultado do Tratamento , Vigília
6.
Childs Nerv Syst ; 38(6): 1201-1204, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34368893

RESUMO

Lipoblastoma is a rare benign tumor originating from adipose tissue, usually seen in infancy and early childhood. Here, we present a case of scalp lipoblastoma in a 4-month-old that we treated surgically and review the literature. Although lipoblastomas may be seen in various locations during infancy and early childhood, rarely, they can also develop in the scalp.


Assuntos
Lipoblastoma , Lipoma , Pré-Escolar , Humanos , Lactente , Lipoblastoma/diagnóstico por imagem , Lipoblastoma/patologia , Lipoblastoma/cirurgia , Lipoma/diagnóstico por imagem , Lipoma/patologia , Lipoma/cirurgia , Couro Cabeludo/patologia , Couro Cabeludo/cirurgia
7.
World Neurosurg ; 154: e495-e508, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34303854

RESUMO

OBJECTIVE: Deep brain stimulation (DBS) is a frequently applied therapy in primary dystonia. For secondary dystonia, the effects can be less favorable. We share our long-term findings in 9 patients with severe secondary dystonia and discuss these findings in the light of the literature. METHODS: Patients who had undergone globus pallidus internus (GPi)-DBS for secondary dystonia were included. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores, clinical improvement rates, follow-up periods, stimulation parameters and the need for internal pulse generator replacements were analyzed. The PubMed and Google Scholar databases were searched for articles describing GPi-DBS and subthalamic nucleus (STN)-DBS only for secondary dystonia cases. Keywords were "dystonia," "deep brain stimulation," "GPi," "dystonia," "deep brain stimulation," and "STN." RESULTS: A total of 9 secondary dystonia patients (5 male, 4 female) had undergone GPi-DBS with microelectrode recording in our units. The mean follow-up period was 29 months. The average BFMDRS score was 58.2 before the surgery, whereas the mean value was 36.5 at the last follow-up of the patients (mean improvement, 39%; minimum, 9%; maximum, 63%). In the literature review, we identified 264 GPi-DBS cases (mean follow-up, 19 months) in 72 different articles about secondary dystonia. The mean BFMDRS improvement rate was 52%. In 146 secondary dystonia cases, reported in 19 articles, STN-DBS was performed. The average follow-up period was 20 months and the improvement in BFMDRS score was 66%. CONCLUSIONS: Although GPi-DBS has favorable long-term efficacy and safety in the treatment of patients with secondary dystonia, STN seems a promising target for stimulation in patients with secondary dystonia. Further studies including a large number of patients, longer follow-up periods, and more homogenous patients are necessary to establish the optimal target for DBS in the management of secondary dystonias.


Assuntos
Estimulação Encefálica Profunda/métodos , Distonia/terapia , Globo Pálido , Núcleo Subtalâmico , Humanos , Resultado do Tratamento
8.
Pediatr Neurosurg ; 56(4): 357-360, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34034264

RESUMO

PURPOSE: Hydrocephalus is a common comorbidity among the newborns, with myelomeningocele (MMC) and ventriculoperitoneal (VP) shunts being frequently used for the treatment of such patients. In this study, we aimed to compare the effectiveness of antibiotic-free and antibiotic-coated shunts to reduce the rate of shunt infection in patients with hydrocephalus and accompanying MMC. METHODS: 116 patients with hydrocephalus and MMC who were treated with VP shunts were included in the study. Shunt infection rates among antibiotic-free and antibiotic-coated shunts were compared. RESULTS: Of the 116 patients included in the study, 39 had antibiotic-coated shunts and 77 had antibiotic-free shunts. Shunt infection developed in 4 of the 39 cases treated with antibiotic-coated shunts and in 5 of the 77 cases treated with shunts without antibiotics. No significant statistical difference was found between antibiotic-coated and antibiotic-free VP shunts in terms of shunt infection (p = 0.450, p > 0.05). CONCLUSION: In patients with MMC, using VP shunts containing antibiotics was found not to have a protective effect in preventing shunt infection. Whether the sac is intact or ruptured does not affect this result.


Assuntos
Hidrocefalia , Meningomielocele , Antibacterianos , Humanos , Hidrocefalia/cirurgia , Recém-Nascido , Meningomielocele/complicações , Meningomielocele/cirurgia , Estudos Retrospectivos , Derivação Ventriculoperitoneal/efeitos adversos
9.
Acta Medica (Hradec Kralove) ; 64(1): 29-35, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33855956

RESUMO

OBJECTIVE: To evaluate and discuss the outcomes of a combination of ventriculocystostomy (VC) and endoscopic third ventriculostomy (ETV) for obstructive hydrocephalus (HCP) due to ventricular/cisternal arachnoid cysts, and only ETV for obstructive HCP due to different etiologies. METHODS: We retrospectively reviewed all 40 symptomatic patients (aged 4 months - 61 years) of obstructive HCP treated by ETV or VC+ETV during October 2014 - April 2019. VC+ETV was performed in 7 patients with intraventricular/cisternal arachnoid cyst and obstructive HCP. Only ETV was performed in 33 patients with obstructive HCP due to other etiologies. RESULTS: Successful ETV or VC+ETV surgery was performed in 35 patients. The procedure failed in 5 patients aged 90 percentile at the time of surgery. Another 5 patients aged 90 percentile).


Assuntos
Cistos Aracnóideos/cirurgia , Endoscopia/métodos , Hidrocefalia/cirurgia , Ventriculostomia/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Surg Obes Relat Dis ; 16(11): 1684-1691, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32800521

RESUMO

BACKGROUND: The loss of the fat pad surrounding the fibular head after rapid and excessive weight loss after bariatric surgery can lead to foot drop symptoms due to peroneal nerve entrapment (PNE). Conservative and surgical approaches have been described for the treatment of this condition, but there is some controversy over the effectiveness of the treatment modalities. OBJECTIVE: We aimed to investigate the causes and frequency of foot drop due to PNE after bariatric surgery and to investigate the effects of peroneal nerve decompression (PND) as a surgical treatment for PNE. SETTING: Single center, university surgical department. METHODS: We retrospectively evaluated a series of 2607 patients in terms of neurologic complications after bariatric surgery. Patients' age, sex, co-morbid diseases, vitamin and electrolyte levels, body mass index and postoperative excess weight loss, affected limb, duration of symptoms, and muscle strength scores (according to the Medical Research Council scale) were recorded. RESULTS: A total of 14 (.5%) patients had foot drop symptoms due to PNE. Of these patients, 9 underwent PND. The mean excess weight loss of PND patients at postoperative months 6 and 12 were 68.8 ± 13.5 and 100.9 ± 10.8, respectively. Foot drop symptoms became evident 5 to 11 months after bariatric surgery, affecting only a unilateral lower extremity in all patients. In laboratory analysis, there were no signs of nutritional and vitamin deficiency or insufficiency in any of the PND cases. Muscular strength was Medical Research Council grade 0 in all patients. The median duration of symptoms was 9 days, and the median complete recovery time was 40 days after PND. Patients who had a duration of symptoms for a maximum of 12 days were completely healed 30 days after PND. CONCLUSION: PND should be the first-choice treatment procedure for acute foot drop due to PNE after bariatric surgery.


Assuntos
Cirurgia Bariátrica , Neuropatias Fibulares , Cirurgia Bariátrica/efeitos adversos , Descompressão Cirúrgica , Humanos , Nervo Fibular/cirurgia , Neuropatias Fibulares/etiologia , Neuropatias Fibulares/cirurgia , Estudos Retrospectivos
11.
Prostate Cancer Prostatic Dis ; 23(4): 718-723, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32661432

RESUMO

BACKGROUND: The loss of PTEN function presents in up to 50% of late-stage prostate cancers, and is therefore a potential target for therapeutics. PTEN-deficient cells depend on de novo pyrimidine synthesis, a feature that can present a vulnerability. METHODS: We utilized in vitro growth assays and in vivo xenograft models to test the effect of de novo pyrimidine synthesis inhibition on prostate cell lines. RESULTS: Here, we demonstrate that PTEN-deficient prostate cancer cell lines are susceptible to inhibition of de novo pyrimidine synthesis by leflunomide. Tumor growth inhibition was observed in vitro and in vivo following leflunomide treatment, and is likely due to an overwhelming accumulation of DNA damage. CONCLUSIONS: Our work highlights that synthetic lethality arises upon the combination of PTEN loss and leflunomide treatment in prostate cancer, and may present a therapeutic opportunity for this patient population.


Assuntos
Leflunomida/toxicidade , PTEN Fosfo-Hidrolase/deficiência , Neoplasias da Próstata/patologia , Pirimidinas/metabolismo , Mutações Sintéticas Letais , Animais , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Imunossupressores/toxicidade , Masculino , Camundongos , Camundongos Nus , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Mol Cancer Res ; 18(3): 414-423, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31932471

RESUMO

Deciphering molecular targets to enhance sensitivity to chemotherapy is becoming a priority for effectively treating cancers. Loss of function mutations of SMAD4 in colon cancer are associated with metastatic progression and resistance to 5-fluorouracil (5-FU), the most extensively used drug of almost all chemotherapy combinations used in the treatment of metastatic colon cancer. Here, we report that SMAD4 deficiency also confers resistance to irinotecan, another common chemotherapeutic frequently used alone or in combination with 5-FU against colon cancer. Mechanistically, we find that SMAD4 interacts with and inhibits RICTOR, a component of the mTORC2 complex, resulting in suppression of downstream effector phosphorylation of AKT at Serine 473. In silico meta-analysis of publicly available gene expression datasets derived from tumors indicates that lower levels of SMAD4 or higher levels of RICTOR/AKT, irrespective of the SMAD4 status, correlate with poor survival, suggesting them as strong prognostic biomarkers and targets for therapeutic intervention. Moreover, we find that overexpression of SMAD4 or depletion of RICTOR suppresses AKT signaling and increases sensitivity to irinotecan in SMAD4-deficient colon cancer cells. Consistent with these observations, pharmacologic inhibition of AKT sensitizes SMAD4-negative colon cancer cells to irinotecan in vitro and in vivo. Overall, our study suggests that hyperactivation of the mTORC2 pathway is a therapeutic vulnerability that could be exploited to sensitize SMAD4-negative colon cancer to irinotecan. IMPLICATIONS: Hyperactivation of the mTORC2 pathway in SMAD4-negative colon cancer provides a mechanistic rationale for targeted inhibition of mTORC2 or AKT as a distinctive combinatorial therapeutic opportunity with chemotherapy for colon cancer.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Irinotecano/uso terapêutico , Proteína Companheira de mTOR Insensível à Rapamicina/efeitos dos fármacos , Proteína Smad4/metabolismo , Animais , Neoplasias do Colo/mortalidade , Feminino , Humanos , Irinotecano/farmacologia , Camundongos , Camundongos Nus , Análise de Sobrevida
13.
J Craniovertebr Junction Spine ; 10(1): 57-63, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31000983

RESUMO

OBJECTIVE: Risk factors of cranial migration were investigated in patients with lumbar disc herniation (LDH) that migrated in the cranial direction and the long-term outcomes are discussed in this study. MATERIALS AND METHODS: Patients who underwent surgery for LDH at four different centers between 2012 and 2017 were studied. Extraligamentous discs were located in the lateral part of the posterior longitudinal ligament (PLL) within the spinal canal of the axial plane, and subligamentous discs were located under the PLL. The extent of cranial migration was calculated as a percentage of the height of the migrated corpus. Based on the extent of cranial migration, partial hemilaminectomy or hemilaminectomy was performed at different rates in each patient and the amount of laminectomy performed was recorded. During surgery, all free fragments were attempted to be removed. The appropriate technique was decided intraoperatively, and the surgery was performed on an individual patient basis. RESULTS: Of 1289 patients who underwent surgery for LDH, 654 (50.73%) had caudal migration, 576 (44.68%) had migration at the level of the disc, and 59 (4.57%) had cranial migration. Analysis of 59 patients with cranial migration according to the localization of the disc fragment revealed that 31 had extraligamentous and 28 had subligamentous fragments (P = 0.024). CONCLUSIONS: Extraligamentous intervertebral disc fragments migrate more cranially than subligamentous intervertebral fragments. The anatomy of the PLL that varies along the corpus is the main reason for the weakness of the resistance of the disc material to the dorsolateral region, direction of discrete force vectors, and orientation of the disc fragment due to torsional vertebral movements.

14.
Cancer Biol Ther ; 20(8): 1113-1120, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30922194

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer with poor prognosis due to lack of druggable targets such as hormone and growth factor receptors. Therefore, identification of targetable regulators such as miRNAs could provide new avenues for therapeutic applications. Here, we report that the expression of miR-4417 is suppressed during the progression of TNBC cells from non-malignant to the malignant stage. MiR-4417 is localized to chromosome 1p36, a region with high frequency of loss of heterozygosity in multiple cancers, and its biogenesis is DICER-dependent. Low expression of miR-4417 is significantly associated with worse prognosis in TNBC patients, while overexpression of miR-4417 is sufficient to inhibit migration and mammosphere formation of TNBC cells in vitro. Overall, our findings suggest miR-4417 exerts a tumor suppressive effect and thereby could serve as a prognostic biomarker and therapeutic tool against TNBC.


Assuntos
Biomarcadores Tumorais , Genes Supressores de Tumor , MicroRNAs/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Interferência de RNA , Neoplasias de Mama Triplo Negativas/diagnóstico
15.
World Neurosurg ; 126: e835-e841, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30862597

RESUMO

OBJECTIVE: Subthalamic nucleus (STN) is the most targeted localization in the treatment of Parkinson disease (PD) with deep brain stimulation. However, no studies have been found in the literature about possible shape changes of STN in the literature. We aimed to investigate possible shape changes in the STN and the relationship between shape changes and disease duration in PD patients by using statistical analysis. METHODS: Patients who were diagnosed with idiopathic PD and controls were enrolled in this study. Age, sex, and disease duration of all cases were recorded. Turbo-spin-echo T2-weighted axial series parallel to the skull base in each case containing midbrain images were obtained, including the whole STN. Standard anatomic landmarks were selected and marked on each digital image using a special software in all cases. Statistical geometric shape and deformation analysis of STN was performed in 2 groups. RESULTS: Forty-three patients with PD and 50 age/sex-matched controls were enrolled in this study. There were statistically significant left and right STN shape differences between the groups. Maximum deformation was seen in the dorsolateral parts of both STNs. General shape variability of the STNs was found on the left (0.096) and right (0.049). CONCLUSIONS: Significant shape differences and remarkable deformation of STN are seen in patients with PD compared with controls. Maximum deformation was observed in the dorsolateral part of the STN, and with the increase in the duration of the PD, shape differences and deformations became more prominent.


Assuntos
Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico por imagem , Núcleo Subtalâmico/diagnóstico por imagem , Idoso , Mapeamento Encefálico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão
16.
Front Oncol ; 9: 32, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30805303

RESUMO

Metastatic dissemination of cancer cells to distal organs is the major cause of death for patients suffering from the aggressive basal-like breast cancer (BLBC) subtype. Recently, we have shown that interleukin 13 receptor alpha 2 (IL13Rα2) is a critical gene that is overexpressed in a subset of BLBC primary tumors associated with poor distant metastasis-free survival (DMFS) and can promote extravasation and metastasis of breast cancer cells to the lungs. However, the upstream signaling mechanisms that promote aberrant IL13Rα2 expression during tumor progression remain unknown. Driven by our previously published gene expression microarray data derived from a well-characterized cell line model for BLBC progression, we show that both Inhibin ßA (INHBA) and IL13Rα2 genes exhibit similarly higher expression levels in metastatic compared to non-metastatic cells and that overexpression of both genes predicts worse metastasis-free survival of patients with high grade tumors. Activin A, a member of the TGFß superfamily comprising two INHBA subunits, has been shown to play context-depended roles in cancer progression. Here, we demonstrate that INHBA depletion downregulates IL13Rα2 expression in metastatic breast cancer cells, whereas treatment with Activin A in non-metastatic cells increases its expression levels. We also find that Activin A predominantly induces Smad2 phosphorylation and to a lesser extent activates Smad3 and Akt. Interestingly, we also show that Activin A-mediated upregulation of IL13Rα2 is Smad2-dependent since knocking down Smad2 or using the ALK4/ALK5 inhibitors EW-7197 and SB-505124 abolishes this effect. Most importantly, our data indicate that knocking down INHBA levels in breast cancer cells delays primary tumor growth, suppresses migration in vitro and inhibits the formation of lung metastases in vivo. Conclusively, our findings presented here suggest that the development of therapeutic interventions employing small molecule inhibitors against Activin receptors or neutralizing antibodies targeting Activin A ligand, could serve as alternative approaches against breast tumors overexpressing INHBA and/or IL13Rα2.

17.
Turk Neurosurg ; 28(4): 625-629, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30192364

RESUMO

AIM: To investigate the effects of intrathecal caffeic acid phenethyl ester (CAPE) on tissue and serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-?) levels following spinal cord injury (SCI) as well as its effects on edema and microhemorrhage. MATERIAL AND METHODS: Forty rats were divided into four groups. The sham group underwent single-level laminectomy and then received an intrathecal injection of isotonic saline. The control group received an intrathecal injection of isotonic saline following SCI induction. The methylprednisolone (MP) group received a single dose of MP intrathecally following SCI. The CAPE group received a single dose of CAPE intrathecally following SCI. IL-6 and TNF-? levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. Spinal cord samples were evaluated histopathologically. RESULTS: The decrease in IL-6 levels in the CAPE group was significantly higher than that in the sham and control groups. However, this decrease was not as significant as that in the MP group. No significant decrease was identified in TNF-? levels. A significant decrease was observed in spinal cord edema and microhemorrhage in the CAPE group. A decrease in edema was observed in the MP group, but no effect was observed on microhemorrhage. CONCLUSION: Intrathecal CAPE administration following SCI decreases tissue and serum IL-6 levels as well as decreases spinal cord edema and microhemorrhage.


Assuntos
Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/uso terapêutico , Interleucina-6/metabolismo , Álcool Feniletílico/análogos & derivados , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Animais , Ácidos Cafeicos/administração & dosagem , Edema/complicações , Edema/tratamento farmacológico , Feminino , Hemorragia/complicações , Hemorragia/tratamento farmacológico , Injeções Espinhais , Interleucina-6/sangue , Metilprednisolona/uso terapêutico , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Ratos , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue
18.
Turk Neurosurg ; 28(6): 989-994, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29694663

RESUMO

AIM: To investigate the possible role of ELABELA (ELA) in the histopathological grading of gliomas. MATERIAL AND METHODS: We retrospectively assessed pathological specimens of patients who underwent surgery for intracranial space-occupying lesions. Only primary glioma specimens were included in this study. We enrolled 11 patients histologically diagnosed with low-grade glioma and 22 patients with high-grade glioma. The ELA antibody was applied to 4?6-?m-thick sections obtained from paraffin blocks. Histoscores were calculated using the distribution and intensity of staining immunoreactivity. An independent sample t-test was used for two-point inter-group assessments, whereas one-way analysis of variance was used for the other assessments. p < 0.05 was considered statistically significant. RESULTS: The histoscores of the control brain, low-grade glioma, and high-grade glioma tissues were found to be 0.08, 0.37, and 0.92, respectively. The difference in ELA immunoreactivity between the control brain tissue and glioma tissue was statistically significant (p < 0.05). In addition, a statistically significant increase was observed in ELA immunoreactivity in high-grade glioma tissues compared with that in low-grade glioma tissues (p < 0.05). CONCLUSION: ELA has an angiogenetic role in the progression of glial tumors. ELA, which is an endogenous ligand of the apelin receptor, activates the apelinergic system and causes the progression of glial tumors. Further studies with a large number of patients are necessary to investigate the angiogenetic role of ELA in glial tumors.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Encefálicas/patologia , Glioma/patologia , Hormônios Peptídicos/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos
19.
Turk Neurosurg ; 28(6): 979-982, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29634080

RESUMO

AIM: To evaluate postoperative clinical outcome and recurrence rates in cases with ventrally located spinal meningiomas who underwent Simpson grade 2 resection. MATERIAL AND METHODS: We evaluated eight cases (six females and two males; age, 28?86 years; mean age, 60 years) with ventrally located spinal meningioma that underwent surgical treatment in our clinic. The tumors were located in the thoracic region in seven cases and in the cervical region in one case. All cases underwent surgery, which was performed using a traditional posterior midline approach. Laminectomy was unilaterally extended. The case with cervically located tumor differed from the other cases in that a skull clamp was used and laminoplasty was performed. RESULTS: The tumor was completely resected in all cases. Furthermore, in all cases, the tumor nidus that caused the thickening of the dura was cauterized using bipolar cautery and peeled off (Simpson grade 2). The pathological examination of the tumor specimens revealed typical grade 1 meningioma in all cases (fibropsammomatous type, n=1; meningothelial type, n=3; and psammomatous type, n=4). Recurrence was not observed in any of the cases during the follow-up. None of the cases demonstrated postoperative neurological deterioration. At 1 month postoperatively, pain and motor deficit completely improved in all cases, with remarkable improvements of motor deficits in the early postoperative period. CONCLUSION: Simpson grade 2 resection in ventrally located spinal meningiomas results in low complication rates and is satisfactory in terms of recurrence.


Assuntos
Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Medula Espinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório
20.
Turk Neurosurg ; 28(2): 263-269, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28094428

RESUMO

AIM: To describe the intra- and postoperative results of patients who received a transforaminal anterior epidural steroid injection (TAESI) prior to lumbar microdiscectomy. MATERIAL AND METHODS: Sixty-four patients who did not improve after minimally invasive techniques (MIT) for lumbar radiculopathy were evaluated. Thirty-two of them treated with techniques other than TAESI and those receiving thrombolytic or anticoagulant drugs before microdiscectomy were excluded. We recorded the type of MIT, numbers of levels and injections, time interval between the last MIT and microdiscectomy, duration of surgery, amount of intraoperative blood loss, rate of incidental durotomy, postoperative infection, and visual analogue scale (VAS) scores for leg pain before and after microdiscectomy at 24 hours, and the 1st and 3rd months (Group 1). A total of 35 patients with no history of MIT or lumbar surgery who had undergone unilateral, single-level lumbar microdiscectomy at our clinic were randomly selected to be included in the control group (Group 2) and same parameters were recorded for the comparison of both groups. RESULTS: The mean duration of lumbar discectomy was 140 minutes, and the amount of average intraoperative blood loss was 227 cc in the study group (Group 1), and 65 minutes and 73 cc, respectively in the control group (Group 2)(p > 0.05). The comparison of VAS scores revealed that lumbar discectomy was still effective after TAESI (p=0.00). CONCLUSION: Although epidural steroid injection is an effective modality for the management of chronic pain, these patients should be informed preoperatively about the relatively long duration of surgery and the possible requirement for blood transfusion.


Assuntos
Discotomia/métodos , Radiculopatia/cirurgia , Adulto , Idoso , Discotomia/efeitos adversos , Feminino , Humanos , Injeções Epidurais/métodos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Radiculopatia/tratamento farmacológico , Recidiva , Retratamento , Fatores de Tempo , Resultado do Tratamento
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