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1.
Medicine (Baltimore) ; 102(28): e34196, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37443509

RESUMO

RATIONALE: Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is considered a reliable and indispensable imaging method when evaluating distant metastases and clinical staging of angiosarcomas. Here, we report 2 cases of angiosarcoma with bone metastases with "false negative" findings on 18F-FDG PET/CT. PATIENT CONCERNS: Case 1, a 39-year-old woman, who had undergone mastectomy for primary angiosarcoma 2 years prior, presented with a 5-month history of right coxalgia. Case 2 was a 37-year-old woman, who had undergone mastectomy for primary angiosarcoma 4 months prior. During postoperative follow-up, multiple bone lesions were detected on magnetic resonance imaging (MRI). DIAGNOSES: Based on the histopathological findings, both cases were diagnosed with bone metastases of angiosarcoma. Although MRI showed multiple bone metastatic lesions, 18F-FDG PET/CT showed no uptake or osteolytic destruction in both cases. INTERVENTIONS: Weekly paclitaxel was initiated as a salvage chemotherapy in both cases. OUTCOMES: No uptake or osteolytic lesions were observed on 18F-FDG PET/CT, despite multiple bone metastases detected on MRI. LESSONS: False-negative findings on 18F-FDG PET/CT should be considered when evaluating bone metastases of angiosarcoma. Even with negative findings on 18F-FDG PET/CT, open biopsy should be performed if MRI indicates bone metastases.


Assuntos
Doenças da Medula Óssea , Neoplasias Ósseas , Neoplasias da Mama , Hemangiossarcoma , Feminino , Humanos , Adulto , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Hemangiossarcoma/diagnóstico por imagem , Compostos Radiofarmacêuticos , Neoplasias da Mama/diagnóstico por imagem , Mastectomia , Tomografia por Emissão de Pósitrons , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Sensibilidade e Especificidade
2.
Clin Orthop Relat Res ; 481(12): 2406-2416, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37184605

RESUMO

BACKGROUND: Reconstruction after periacetabular bone tumor resection involves important tradeoffs; large bone grafts or endoprostheses are reported to offer fair walking function in general but can be technically demanding and carry a high risk of severe complications. Conversely, hip transposition avoids implant-related risks, but stability and functional return may be less consistent. Fewer studies are available on hip transposition, which is also appealing in more resource-constrained environments, and little is known about the time course from surgery to functional return after hip transposition. QUESTIONS/PURPOSES: (1) What is the time course of recovery of walking function after hip transposition, especially in the first 6 months? (2) What factors are associated with a greater likelihood of early functional recovery? (3) Is early (2-month) functional recovery associated with a greater likelihood of walking ability and higher Musculoskeletal Tumor Society (MSTS) scores? METHODS: Between 2009 and 2019, six tertiary care centers in Japan treated 48 patients with internal hemipelvectomy for malignant tumors. During that time, the preferred reconstructive approach was hip transposition, and 92% (44 of 48) of our patients were treated with this procedure. Among them, 86% (38 of 44) had follow-up of at least 6 months, had no local recurrence during that time, and were included in our retrospective study. We chose 6 months as the minimum follow-up duration because the endpoints in this study pertained to early recovery rather than reconstructive durability. Hip transposition involved moving the proximal end of the femur (femoral head, resection end of the trochanteric area, and spacers such as prostheses) upward to the underside of the resected ilium or the lateral side of the sacrum if sacroiliac joint resection was performed. The end of the proximal femur was stabilized to the remaining ilium or sacrum using polyethylene tape, polyethylene terephthalate mesh, an iliotibial tract graft, or an external fixator, according to the surgeon's preference. The median age at surgery was 46 years (range 9 to 76 years), there were 23 women and 15 men, and the median follow-up duration was 17 months (range 6 to 110 months). The postoperative time course of functional recovery was assessed with a record review, the timing of functional milestones was identified (wheelchair, walker, bilateral crutches, single crutch or cane, and walking without an aid), and the MSTS score at the final follow-up was assessed. Additionally, demographic and surgical factors were reviewed, and their association with short-term functional recovery and the final functional outcome was analyzed. RESULTS: Patients started using a walker at median postoperative day (POD) 20 (IQR 14 to 36) and with bilateral crutches at median POD 35 (IQR 20 to 57). At POD 60, which was the approximate median date of discharge, 76% (29 of 38) of patients were able to walk using bilateral crutches (the early recovery group) and 24% (nine of 38) of patients were not able to do so (the delayed recovery group). No baseline factors were different between the two groups. The early recovery group had a higher median MSTS score than the delayed recovery group: 57% (range 17% to 90%) versus 45% (13% to 57%) (p = 0.047). Moreover, more patients acquired better function (a single crutch or cane or more) in the early recovery group, with a median of 5 months (95% CI 4 to 11) than did those in the delayed recovery group (median not reached) (p = 0.0006). The HR was 15.2 (95% CI 2.5 to 93). Forty-two percent (16 of 38) underwent additional surgery for wound management. CONCLUSION: It took patients a fair amount of time to recover walking function after hip transposition, and patients who could not walk on bilateral crutches at POD 60 seemed less likely to regain walking function and were likely to have lower MSTS scores thereafter. Wound-related complications were frequent. This method may be a realistic alternative for younger patients who have the strength for a long rehabilitation period or those who want to minimize prosthesis-related complications. Future studies with more patients are necessary to understand the risk factors associated with delayed recovery.Level of Evidence Level III, therapeutic study.


Assuntos
Artroplastia de Quadril , Neoplasias Ósseas , Masculino , Humanos , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Ósseas/patologia , Artroplastia de Quadril/efeitos adversos , Caminhada
3.
Brain Nerve ; 75(4): 317-321, 2023 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-37037501

RESUMO

The notion of symptomatic epilepsy was historically reviewed. The structural etiologies of epilepsy include cerebrovascular diseases, neurodegenerative diseases, neoplasms, and traumatic brain injuries. Infections are the most common etiology worldwide. Metabolic epilepsy directly results from a known or presumed metabolic disorder. Immune epilepsy occurs because of autoimmune-mediated central nervous system inflammation.


Assuntos
Lesões Encefálicas Traumáticas , Transtornos Cerebrovasculares , Epilepsia , Humanos , Epilepsia/etiologia , Sistema Nervoso Central , Lesões Encefálicas Traumáticas/complicações
5.
PLoS One ; 18(3): e0280508, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36857355

RESUMO

Trabectedin is a therapeutic option for patients with advanced sarcoma. While a randomized trial demonstrated its prolonged progression-free survival (PFS), the reported PFS was <6 months. Some patients can achieve long-term disease control with this treatment. However, the reference information is insufficient. Herein, we retrospectively reviewed 51 sarcoma patients who received trabectedin. We analyzed the clinicopathological features, trabectedin dose, administration schedule, and clinical outcomes, including the overall response rate (ORR) and PFS. Among them, we assessed the detailed data of patients who achieved long-term disease control (PFS >1 year). The ORR in the 49 evaluable patients was 8%, and the median PFS in 51 patients was 7.5 months. Six patients (12%) achieved PFS of >1 year. Five of the six patients had metastatic lesions at trabectedin initiation. The pathological subtypes were myxoid liposarcoma (n = 2), leiomyosarcoma (n = 2), synovial sarcoma (n = 1), and Ewing sarcoma (n = 1). The final administration dose was the minimum dose (0.8 mg/m2) in two patients who continued the treatment over 20 cycles. The best radiological response was partial response (PR) in two myxoid liposarcoma patients and stable disease in four. The durations from trabectedin initiation to the first response in the two PR cases were 163 and 176 days, respectively. Our results support the validity of continuing trabectedin at a sustainable dose and interval in patients who can tolerate it. These results may be useful when considering the clinical application of trabectedin.


Assuntos
Leiomiossarcoma , Lipossarcoma Mixoide , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Adulto , Trabectedina , Estudos Retrospectivos
6.
Ann Surg Oncol ; 30(7): 4475-4484, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36853566

RESUMO

BACKGROUND: Carbon ion radiotherapy (CIRT) is an evolving treatment option for malignant pelvic tumors in patients with poor surgical indications. However, the difference in complications and functional outcomes between CIRT and surgery is poorly understood. This study compares the complications and functional outcomes of CIRT and surgery to facilitate treatment selection. METHODS: A total of 28 patients who underwent CIRT for pelvic bone tumors while theoretically meeting the surgical resection criteria were included. Sixty-nine patients who underwent surgery for pelvic bone tumors were included as controls. Major complication rates and functional outcomes (ambulatory, pain, urination, constipation) were evaluated and compared at several time points (pretreatment, discharge, and final follow-up) between the groups. RESULTS: Early (within 90 days) major complications were not observed in the CIRT group but occurred in 30% of the surgery group, which was statistically significant (P < 0.001). In contrast, late (after 90 days) major complications occurred more often in the CIRT group than in the surgery group (18% and 4%, respectively; P = 0.042). From pretreatment until discharge, all functional outcomes in the surgery group deteriorated (P < 0.001 for all) but did not change in the CIRT group (P = 0.77-1.00). At the final follow-up, all functional outcomes showed no significant intergroup difference (P = 0.28-0.92) due to the recovery trend in the surgery group and the deterioration trend in the CIRT group. CONCLUSIONS: Compared with surgery, CIRT may have favorable safety and stable functional outcomes in the short-term but more late complications. Mid-term functional outcomes were similar between the groups.


Assuntos
Neoplasias Ósseas , Radioterapia com Íons Pesados , Neoplasias Pélvicas , Humanos , Estudos de Coortes , Neoplasias Pélvicas/radioterapia , Neoplasias Pélvicas/cirurgia , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Radioterapia com Íons Pesados/efeitos adversos , Pelve
7.
Nagoya J Med Sci ; 84(2): 311-318, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35967934

RESUMO

Falls (including fall on same level and fall to a lower level) are frequent medical accidents among hospitalized patients. We investigated the status of falls in our hospital, aiming to verify the usefulness of a fall risk assessment sheet and identify the risk factors of falls. 5219 patients who were admitted to the general wards of our hospital between April 2016 and March 2019 were studied. Patient background data and the result of risk assessment based on a fall risk assessment score sheet at admission were registered. The frequency and location of falls during hospitalization, and the impact on patients were investigated. Risk factors for falls were analyzed based on the assessment results at admission. 218 falls occurred during hospitalization in 152 of 5219 patients (2.9%). The most common location of falls was bedside (68%). Falls occurred at night in 28%. The impact of falls was level 1 in 18 patients, level 2 in 117, level 3a in 11, and level 3b in 6 (all had head injuries, and one had concurrent fracture). Fall rate was 1.1% (41/3791 patients) at risk level I, 6.8% (91/1335 patients) at level II, and 21.5% (20/93 patients) at level III. Multiple logistic regression analysis identified age, history of fall, tendency to act without pressing nurse call button, unstable gait, unstable when standing, and use of narcotic as risk factors of falls. The incidence of falls at our hospital was lower compared to previous reports, and fall risk assessment was useful overall.


Assuntos
Pacientes Internados , Quartos de Pacientes , Acidentes por Quedas , Hospitalização , Humanos , Medição de Risco/métodos
8.
Int J Clin Oncol ; 27(11): 1758-1766, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35932377

RESUMO

BACKGROUND: Low-grade osteosarcomas, namely parosteal osteosarcoma (POS) and low-grade central osteosarcoma (LGCOS), occasionally dedifferentiate into high-grade malignancy, referred to as dedifferentiation in low-grade osteosarcoma (DLOS). This study aimed to elucidate the clinicopathologic features of DLOS, which are poorly described to date due to the extreme rarity of the disease. METHODS: A total of 33 patients with DLOS were included. Clinical characteristics, including the diagnostic accuracy of tumor biopsy, multimodal treatments, and clinical course, were retrospectively reviewed. Univariate analysis was performed to identify prognostic factors associated with overall survival (OS) and metastasis-free survival (MFS). RESULTS: The tumor subtypes comprised 10 cases (30.3%) of LGCOS and 23 cases (69.7%) of POS. The timing of dedifferentiation was synchronous in 25 (75.8%) and metachronous in 8 (24.2%) patients. The rates of preoperative diagnosis of DLOS were 40.0% and 65.4% for core needle biopsy and incisional biopsy, respectively. All patients underwent surgery and 25 patients received perioperative chemotherapy. Of the 13 patients who received neoadjuvant chemotherapy, 11 exhibited a poor histological response. The 5-year OS and MFS rates were 88.1% and 77.7%, respectively. Univariate analysis revealed that local recurrence was associated with poor OS (P < 0.01) and MFS (P < 0.01). Perioperative chemotherapy did not affect OS or MFS. CONCLUSIONS: The diagnostic accuracy of tumor biopsy for DLOS was lower than that for bone sarcomas, as reported previously. In contrast to conventional osteosarcomas with high chemosensitivity, both histological responses and survival analysis revealed low efficacy of chemotherapy for DLOS.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/diagnóstico , Estudos Retrospectivos , Japão , Osteossarcoma/tratamento farmacológico , Osteossarcoma/diagnóstico , Terapia Neoadjuvante/efeitos adversos , Prognóstico
9.
iScience ; 25(7): 104636, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35800760

RESUMO

Microbial inoculants containing arbuscular mycorrhizal (AM) fungi are potential tools in increasing the sustainability of our food production systems. Given the demand for sustainable agriculture, the production of such inoculants has potential economic value and has resulted in a variety of commercial inoculants currently being advertised. However, their use is limited by inconsistent product efficacy and lack of consumer confidence. Here, we propose a framework that can be used to assess the quality and reliability of AM inoculants. First, we set out a range of basic quality criteria which are required to achieve reliable inoculants. This is followed by a standardized bioassay which can be used to test inoculum viability and efficacy under controlled conditions. Implementation of these measurements would contribute to the adoption of AM inoculants by producers with the potential to increase sustainability in food production systems.

10.
Cancers (Basel) ; 14(12)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35740688

RESUMO

This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan.

11.
Exp Mol Med ; 54(6): 753-764, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668101

RESUMO

Differentiation of mesenchymal stem cells (MSCs) into osteoblasts is a critical process for proper skeletal development and acquisition/maintenance of bone mass. However, since this regulatory mechanism has not yet been fully elucidated, the treatment of severe osteoporosis and fractures is a challenge. Here, through a comprehensive analysis of gene expression during the differentiation of MSCs into osteoblasts, we show that the forkhead transcription factor Foxf2 is a crucial regulator of this process. Foxf2 expression transiently increased during MSC osteoblastic differentiation. Overexpression of Foxf2 in MSCs inhibited osteoblastic differentiation, and conversely, knockdown of Foxf2 expression promoted this process. Osteoprogenitor-specific Foxf2 knockout mice developed a high bone mass phenotype due to increased bone formation. RNA-seq analysis and molecular experiments revealed that Foxf2 regulation of bone formation is mediated by Wnt2b. Knockdown of Foxf2 in mouse femurs enhanced bone regeneration in vivo. FOXF2 expression was correlated with hip bone mineral density in postmenopausal women with low bone mass. Finally, inhibition of FOXF2 promoted osteoblastic differentiation of human MSCs. This study uncovers a critical role of Foxf2 in the differentiation of MSCs into osteoblasts and provides insight into the pathogenesis associated with bone-related diseases such as osteoporosis and nonunion after fracture.


Assuntos
Osteoporose , Via de Sinalização Wnt , Animais , Diferenciação Celular/genética , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Glicoproteínas/metabolismo , Camundongos , Camundongos Knockout , Osteoblastos/metabolismo , Osteogênese/genética , Osteoporose/genética , Proteínas Wnt/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
12.
Prog Rehabil Med ; 7: 20220018, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35434403

RESUMO

Objectives: We investigated the clinical situation of fractures that occurred in patients in the severely disabled patients' ward of our hospital. The study aimed to identify risk factors for the occurrence of long bone fractures in the extremities, which pose problems in nursing care. Methods: We retrospectively studied fractures that occurred between April 2015 and March 2021 among a total of 126 patients in the severely disabled patients' ward of our hospital. The fracture site, frequency of occurrence, cause of injury, and other parameters were investigated. We statistically compared the fracture group and non-fracture group with respect to age, sex, body position before fracture, motor function, food intake status, body mass index, use of anti-epileptic drugs, hip dislocation, and maximum extension angle and range of motion of elbow/knee joints. Results: Among 126 patients, a total of 35 fractures occurred in 28 patients (22%). There were 19 long bone fractures of the extremities in 17 patients. Multiple logistic regression analysis using the occurrence of long bone fractures of the extremities as the objective variable identified the following significant independent variables: age [odds ratio (OR)=1.087, P=0.008], maximum extension angle of the elbow joint (OR=1.039, P=0.023), range of motion of the elbow joint (OR=0.940, P=0.003), and range of motion of the knee joint (OR=0.972, P=0.034). Conclusions: This study reveals that older age and flexion contracture of elbow and knee joints are risk factors for the occurrence of long bone fractures in severely disabled patients.

14.
Cancers (Basel) ; 13(24)2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34944888

RESUMO

Pazopanib with trabectedin and eribulin is widely used to treat soft-tissue sarcoma (STS). We have shown that baseline neutrophil-to-lymphocyte ratio (NLR) may predict the efficacy and patient prognosis of eribulin. Changes in NLR, but not baseline NLR, can predict patient prognosis of trabectedin. However, prognostic factors of pazopanib for STS have not been identified. We present a retrospective analysis of 141 patients treated with pazopanib for recurrent or metastatic non-round cell STS. Univariate and multivariate analyses were performed to determine the predictive factors of durable clinical benefit (DCB), overall survival (OS), and progression-free survival. L-sarcoma histology (odds ratio [OR] = 0.31, 95% CI = 0.12-0.79; p = 0.014) and pre-treatment NLR < 3.0 (OR = 2.03, 95% CI = 1.02-6.67; p = 0.045) were independent predictive factors of DCB. Pre-treatment NLR < 3.0 (hazard ratio [HR] = 0.55, 95% CI = 0.36-0.84; p = 0.0057), liposarcoma histology (HR = 1.78, 95% CI = 1.09-2.91; p = 0.022), primary extremity site (HR = 0.48, 95% CI = 0.31-0.75; p = 0.0010), ECOG PS ≥ 1 (HR = 1.62, 95% CI = 1.08-2.42; p = 0.019), and CRP < 0.3 (HR = 0.52, 95% CI = 0.33-0.82; p = 0.0050) were independent predictive factors of OS. These findings indicate that baseline NLR predicts the efficacy and patient prognosis of pazopanib for STS.

15.
Microbiol Immunol ; 65(12): 559-565, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34536031

RESUMO

A novel Gram-positive, facultatively anaerobic, rod-shaped, nonspore forming, nonmotile organism was isolated from a Japanese serow oral cavity. Designated strain MAS-1T , it is most closely related to Actinomyces bowdenii DSM 15435T , with which it shares 98.07% sequence homology in the 16S ribosomal RNA gene. The primarily detected cellular fatty acids in strain MAS-1T were C16:0 and C18:1 w9c. The predominant respiratory quinone was MK-9 (H4 ). The major polar lipids were phosphatidylcholines, phosphatidylinositols, and glycophospholipids. The genomic DNA GC content of the isolate was 71.3 mol%. The digital DNA-DNA hybridization and average nucleotide identity values between MAS-1T and its related species were 23.5%-39.5% and 82.11%-91.01%, respectively, which were below the threshold (70% and 95%, respectively) for species delineation, indicating that strain MAS-1T represents a novel species. Strain MAS-1T can be differentiated from A. bowdenii by their reactions to naphthol-AS-BI-phosphohydrolase, α-galactosidase, ß-galactosidase, and N-acetyl-ß-glucosaminidase, as well as differing acid production from glycogen. Based on the results of genotypic, phenotypic, and biochemical analyses, herein it is proposed that the identified bacteria can be classified as a novel species, Actinomyces capricornis sp. nov., strain MAS-1T (=JCM 34236T = DSM 111732T ).


Assuntos
Actinomyces , Fosfolipídeos , Actinomyces/genética , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos , Japão , Boca , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
16.
Indian J Orthop ; 55(4): 892-897, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34194644

RESUMO

PURPOSE: Intramuscular myxoma (IM) is a rare benign myxoid tumor that may be challenging to differentiate from sarcoma in small amounts of biopsied material. Although IM appears to be well-circumscribed macroscopically, it infiltrates the adjacent edematous muscle microscopically. The recommended treatment is resection, but there is controversy with regard to the appropriate surgical margin. This study aimed to clarify which surgical procedure that should be applied when the preoperative diagnosis is IM and how to manage treatment if the postoperative diagnosis turns out to be a sarcoma. METHODS: We retrospectively examined 55 IM patients treated from January 1982 to December 2014. Patient characteristics, tumor location, tumor size, radiograph, preoperative and postoperative pathological reports, surgical techniques, treatment outcome, and complications were reviewed. The patients were followed up on for at least 5 years. All patients were confirmed not to have Mazabraud syndrome. RESULTS: In the 55 IM patients examined, the mean patient age was 48 years and most were female. The most common tumor locations were in the muscles of the thighs (47%) and buttocks (20%). The mean tumor diameter was 5 cm. Wide resection and marginal resection were performed in 24 and 31 patients, respectively. The mean follow-up duration was 19 years. No local recurrence, malignant transformation, or complications were observed. CONCLUSIONS: Marginal resection is suitable in patients whose preoperative diagnosis is IM, as it is able to prevent local recurrence and allows for the preservation of muscle and muscle fascia. If the postoperative diagnosis turns out to be myxoid sarcoma, minimum surgical contamination makes additional wide resection less invasive.

17.
Oncogene ; 40(36): 5548-5558, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34302117

RESUMO

Osteosarcoma is the most common primary malignant bone cancer, with high rates of pulmonary metastasis. Osteosarcoma patients with pulmonary metastasis have worse prognosis than those with localized disease, leading to dramatically reduced survival rates. Therefore, understanding the biological characteristics of metastatic osteosarcoma and the molecular mechanisms of invasion and metastasis of osteosarcoma cells will lead to the development of innovative therapeutic intervention for advanced osteosarcoma. Here, we identified that osteosarcoma cells commonly exhibit high platelet activation-inducing characteristics, and molecules released from activated platelets promote the invasiveness of osteosarcoma cells. Given that heat-denatured platelet releasate maintained the ability to promote osteosarcoma invasion, we focused on heat-tolerant molecules, such as lipid mediators in the platelet releasate. Osteosarcoma-induced platelet activation leads to abundant lysophosphatidic acid (LPA) release. Exposure to LPA or platelet releasate induced morphological changes and increased invasiveness of osteosarcoma cells. By analyzing publicly available transcriptome datasets and our in-house osteosarcoma patient-derived xenograft tumors, we found that LPA receptor 1 (LPAR1) is notably upregulated in osteosarcoma. LPAR1 gene KO in osteosarcoma cells abolished the platelet-mediated osteosarcoma invasion in vitro and the formation of early pulmonary metastatic foci in experimental pulmonary metastasis models. Of note, the pharmacological inhibition of LPAR1 by the orally available LPAR1 antagonist, ONO-7300243, prevented pulmonary metastasis of osteosarcoma in the mouse models. These results indicate that the LPA-LPAR1 axis is essential for the osteosarcoma invasion and metastasis, and targeting LPAR1 would be a promising therapeutic intervention for advanced osteosarcoma.


Assuntos
Lisofosfolipídeos , Osteossarcoma , Plaquetas , Humanos , Neoplasias Pulmonares , Ativação Transcricional
18.
Epilepsy Res ; 175: 106697, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34175794

RESUMO

AIMS: Valproic acid (VPA) is a widely used antiepileptic drug for the treatment of epilepsy, seizures, and bipolar and psychiatric disorders. A deficiency of carnitine, a compound involved in energy production, is associated with chronic VPA use. However, the clinical factors affecting blood carnitine levels and their pathophysiology remain unclear. Hence, we aimed to identify the factors that correlated with serum carnitine levels in epilepsy patients receiving chronic VPA therapy. METHODS: This observational study included 138 epilepsy patients receiving chronic VPA therapy. Serum total and free carnitine levels, routine blood tests and drug concentrations were assessed. The correlation between carnitine levels and other factors were calculated using Spearman's rank correlation coefficients, and a principal component analysis (PCA) and a multiple linear regression analysis were performed. RESULTS: Overall, serum free carnitine levels showed significant negative correlations with epilepsy duration, VPA treatment duration, daily VPA dose, and blood VPA concentration. A significant positive correlation was observed with erythrocyte count, hemoglobin levels, and creatinine levels. Of the 138 patients, 21 (15.2 %) with serum free carnitine levels of <20 µmol/L had significantly longer disease duration, a higher daily VPA dose, and lower blood clobazam concentrations. In the 48 VPA monotherapy patients, serum free carnitine levels showed a significant negative correlation with disease duration and duration of VPA therapy. Furthermore, in the 2.1 % patients receiving VPA monotherapy, serum free carnitine levels were <20 µmol/L. PCA resulted in seven factor solution (eigenvalue >1; 71.67 % explained variance). Component 1 clearly revealed the maximal loading for serum free carnitine level (.792) and the most negative loading for disease duration of epilepsy (-.595). A linear regression analysis revealed that the duration of epilepsy, serum creatinine level, and daily dose of VPA were significant (p < .01) factors that affected serum free carnitine levels. CONCLUSIONS: The effects of combination therapy with VPA and other anti-epileptic drug(s) on carnitine levels are higher than that of VPA monotherapy. Additionally, epilepsy duration may affect serum free carnitine level.


Assuntos
Epilepsia , Ácido Valproico , Adulto , Aminoácidos , Anticonvulsivantes/uso terapêutico , Carnitina , Humanos , Ácido Valproico/efeitos adversos
19.
Cancer Diagn Progn ; 1(4): 339-343, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35403151

RESUMO

Background: Extra-abdominal desmoid tumors often occur in the necks, shoulder, chest wall, back, arm, buttock, thigh and leg. Multicentric extra-abdominal desmoids are rather rare and seem to have other clinical features. The aim of our study was to investigate clinical features, especially multicentric occurrence of extra-abdominal desmoid tumors. Patients and Methods: A total of 135 patients diagnosed with extra-abdominal desmoid were enrolled in this study from January 2005 to December 2019 at the Cancer Institute Hospital of The Japanese Foundation for Cancer Research. The operative procedure was principally wide excision. The clinicopathological factors [e.g., age, gender, pain, restriction of range of motion (ROM), tumor site, tumor size, surgical margin, multicentric occurrence, local recurrence, tumoral regression] were collected and assessed by univariate analysis. We assessed how multicentric occurrence influenced clinicopathological factors of desmoid tumors. Results: The median follow-up was 39.9 months (range=0.29-259 months). Among 135 patients, 20 had multicentric occurrence. Multicentric extra-abdominal desmoids occurred in the neck in six cases, shoulder in four, chest wall in three, back in three, thigh in two and leg in two. In the case of multicentric occurrence on thighs and legs, tumors arose not in the anterior compartment but in the posterior compartment. Univariate analysis showed association of multicentric extra-abdominal desmoids with high local recurrence (p=0.0003), restriction of ROM (p=0.0012) and tumor size larger than 5 cm (p=0.04) but surgical margins were not correlated with local recurrence (p=0.37). Conclusion: Surgery should be performed in those who have severe pain or restriction of ROM. A 'Wait and see' policy is a first-line management, especially for those with multicentric extra-abdominal desmoids.

20.
Proc Natl Acad Sci U S A ; 117(41): 25779-25788, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-32999061

RESUMO

Arbuscular mycorrhizal (AM) fungi, forming symbiotic associations with land plants, are obligate symbionts that cannot complete their natural life cycle without a host. The fatty acid auxotrophy of AM fungi is supported by recent studies showing that lipids synthesized by the host plants are transferred to the fungi, and that the latter lack genes encoding cytosolic fatty acid synthases. Therefore, to establish an asymbiotic cultivation system for AM fungi, we tried to identify the fatty acids that could promote biomass production. To determine whether AM fungi can grow on medium supplied with fatty acids or lipids under asymbiotic conditions, we tested eight saturated or unsaturated fatty acids (C12 to C18) and two ß-monoacylglycerols. Only myristate (C14:0) led to an increase in the biomass of Rhizophagus irregularis, inducing extensive hyphal growth and formation of infection-competent secondary spores. However, such spores were smaller than those generated symbiotically. Furthermore, we demonstrated that R. irregularis can take up fatty acids in its branched hyphae and use myristate as a carbon and energy source. Myristate also promoted the growth of Rhizophagus clarus and Gigaspora margarita Finally, mixtures of myristate and palmitate accelerated fungal growth and induced a substantial change in fatty acid composition of triacylglycerol compared with single myristate application, although palmitate was not used as a carbon source for cell wall biosynthesis in this culture system. Our findings demonstrate that myristate boosts the asymbiotic growth of AM fungi and can also serve as a carbon and energy source.


Assuntos
Glomeromycota/metabolismo , Micorrizas/metabolismo , Miristatos/metabolismo , Carbono/metabolismo , Parede Celular/metabolismo , Metabolismo Energético , Glomeromycota/crescimento & desenvolvimento , Hifas/crescimento & desenvolvimento , Hifas/metabolismo , Micorrizas/crescimento & desenvolvimento
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