Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 94
Filtrar
1.
Acta Neurochir (Wien) ; 166(1): 408, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39404864

RESUMO

PURPOSE: Growth hormone (GH)-secreting pituitary neuroendocrine tumors (PitNETs) are the most common cause of acromegaly. The endoscopic endonasal transsphenoidal approach (EEA) is commonly employed to remove them. Although morphological differences in the nasal cavity exist between acromegaly patients and those with other types of PitNET, few quantitative studies have been performed. This study aimed to evaluate the anatomical features of the nasal cavity and paranasal sinuses in patients with acromegaly. METHODS: Preoperative computed tomography images of the nasal cavity and paranasal sinuses were compared between 20 patients with a GH-secreting PitNET (acromegaly group) and 22 with a non-functioning PitNET (control group). In the acromegaly group, the relationships between preoperative GH and/or insulin-like growth factor 1 (IGF-1) levels and anatomical characteristics were assessed. RESULTS: In the acromegaly group, the distance between the nostril and dorsum sellae was significantly longer and the distance between the parasellar internal carotid arteries was significantly shorter (p = 0.0022 and 0.0092, respectively). Pneumatization volume in the nasal cavity did not differ between the groups. Nasal mucosa and bony hypertrophy were observed in the acromegaly group. Preoperative GH level was correlated with the width of the piriform aperture (p = 0.0171). CONCLUSION: The nasal and paranasal changes associated with acromegaly can make EEA challenging to perform. Widening the surgical corridor anterior to the sphenoid sinus is important in these patients.


Assuntos
Acromegalia , Cavidade Nasal , Seios Paranasais , Humanos , Acromegalia/cirurgia , Acromegalia/diagnóstico por imagem , Cavidade Nasal/cirurgia , Cavidade Nasal/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Seios Paranasais/cirurgia , Seios Paranasais/diagnóstico por imagem , Idoso , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Tomografia Computadorizada por Raios X , Endoscopia/métodos , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Seio Esfenoidal/cirurgia , Seio Esfenoidal/diagnóstico por imagem , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/diagnóstico por imagem
2.
Anticancer Res ; 44(10): 4609-4615, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39348985

RESUMO

BACKGROUND/AIM: Many glioma patients struggle to return to work after surgery because of higher brain dysfunction. Although the right frontal lobe has historically been considered functionally silent, reports of performing awake surgery to evaluate higher brain functions in patients with tumors in this area have increased. We present two cases of patients who underwent awake surgery for malignant glioma in the right frontal lobe to preserve emotional recognition and facilitate an early return to work. CASE REPORT: Case 1 was a 48-year-old right-handed woman employed as a nursery school teacher and case 2 was a 21-year-old right-handed man employed in sales. Both had contrast-enhancing right frontal lobe tumors exhibiting high signal intensity on fluid attenuated inversion recovery imaging and underwent awake surgery. During the operation, cortical mapping was performed using the Reading the Mind in the Eyes, calculation, and motor tasks. Resection of sites involved in motor and emotional recognition functions was avoided. In case 1, all regions of high signal intensity were completely resected; in case 2, all regions exhibiting enhancement were resected. Both patients were discharged home without neurological deficits and returned to work within 21 days after surgery. CONCLUSION: It may be important to focus not only on overall survival and progression-free survival in glioma patients, but also on factors associated with life satisfaction, such as time to return to work after surgery and time until work becomes difficult. Awake surgery aimed at preserving higher brain functions is useful and may also improve life satisfaction.


Assuntos
Neoplasias Encefálicas , Emoções , Lobo Frontal , Glioma , Retorno ao Trabalho , Vigília , Humanos , Glioma/cirurgia , Glioma/psicologia , Glioma/patologia , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/psicologia , Neoplasias Encefálicas/patologia , Lobo Frontal/cirurgia , Lobo Frontal/diagnóstico por imagem , Vigília/fisiologia , Adulto Jovem , Procedimentos Neurocirúrgicos/métodos
3.
Sci Rep ; 14(1): 21430, 2024 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271763

RESUMO

The stiffness of human cancers may be correlated with their pathology, and can be used as a biomarker for diagnosis, malignancy prediction, molecular expression, and postoperative complications. Neurosurgeons perform tumor resection based on tactile sensations. However, it takes years of surgical experience to appropriately distinguish brain tumors from surrounding parenchymal tissue. Haptics is a technology related to the touch sensation. Haptic technology can amplify, transmit, record, and reproduce real sensations, and the physical properties (e.g., stiffness) of an object can be quantified. In the present study, glioblastoma (SF126-firefly luciferase-mCherry [FmC], U87-FmC, U251-FmC) and malignant meningioma (IOMM-Lee-FmC, HKBMM-FmC) cell lines were transplanted into nude mice, and the stiffness of tumors and normal brain tissues were measured using our newly developed surgical forceps equipped with haptic technology. We found that all five brain tumor tissues were stiffer than normal brain tissue (p < 0.001), and that brain tumor pathology (three types of glioblastomas, two types of malignant meningioma) was significantly stiffer than normal brain tissue (p < 0.001 for all). Our findings suggest that tissue stiffness may be a useful marker to distinguish brain tumors from surrounding parenchymal tissue during microsurgery, and that haptic forceps may help neurosurgeons to sense minute changes in tissue stiffness.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Meningioma , Camundongos Nus , Microcirurgia , Animais , Humanos , Microcirurgia/métodos , Microcirurgia/instrumentação , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Glioblastoma/cirurgia , Glioblastoma/patologia , Camundongos , Meningioma/cirurgia , Meningioma/patologia , Linhagem Celular Tumoral , Instrumentos Cirúrgicos
4.
Br J Nutr ; 132(3): 351-358, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-38826083

RESUMO

Many improvements have been made to bring infant formula (IF) closer to human milk (HM) regarding its nutritional and biological properties. Nevertheless, the protein components of HM and IF are still different, which may affect their digestibility. This study aimed to evaluate and compare the protein digestibility of HM and IF using the infant INFOGEST digestion method. Pooled HM and a commercial IF were subjected to the infant INFOGEST method, which simulates the physiological digestion conditions of infants, with multiple directions, i.e. the curd state, gel images of SDS-PAGE, molecular weight distribution, free amino acid concentrations and in vitro protein digestion rate. HM underwent proteolysis before digestion and tended to have a higher protein digestion rate with finer curds during gastric digestion, than the IF. However, multifaceted analyses showed that the protein digestibility of HM and IF was not significantly different after gastrointestinal digestion. In conclusion, the infant INFOGEST method showed that the digestibility of HM and IF proteins differed to some extent before digestion and after gastric digestion, but not at the end of gastrointestinal digestion. The findings of this study will contribute to the refinement of IF with better protein digestibility in infant stomach.


Assuntos
Digestão , Fórmulas Infantis , Leite Humano , Humanos , Digestão/fisiologia , Fórmulas Infantis/química , Leite Humano/química , Leite Humano/metabolismo , Lactente , Aminoácidos/metabolismo , Aminoácidos/análise , Proteínas Alimentares/metabolismo , Proteínas Alimentares/análise , Proteólise , Proteínas do Leite/metabolismo , Fenômenos Fisiológicos da Nutrição do Lactente
5.
J Med Case Rep ; 18(1): 269, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38835078

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is the second most common type of leukemia in children. Although prognostic and diagnostic tests of AML patients have improved, there is still a great demand for new reliable clinical biomarkers for AML. Read-through fusion transcripts (RTFTs) are complex transcripts of adjacent genes whose molecular mechanisms are poorly understood. This is the first report of the presence of the PPP1R1B::STARD3 fusion transcript in an AML patient. Here, we investigated the presence of PPP1R1B::STARD3 RTFT in a case of AML using paired-end RNA sequencing (RNA-seq). CASE PRESENTATION: A Persian 12-year-old male was admitted to Dr. Sheikh Hospital of Mashhad, Iran, in September 2019 with the following symptoms, including fever, convulsions, hemorrhage, and bone pain. The patient was diagnosed with AML (non-M3-FAB subtype) based on cell morphologies and immunophenotypical features. Chromosomal analysis using the G-banding technique revealed t (9;22) (q34;q13). CONCLUSIONS: Single-cell RNA sequencing (scRNA-seq) analysis suggested that the PPP1R1B promoter may be responsible for the PPP1R1B::STARD3 expression. Alterations in the level of lipid metabolites implicate cancer development, and this fusion can play a crucial role in the cholesterol movement in cancer cells. PPP1R1B::STARD3 may be considered a candidate for targeted therapies of the cholesterol metabolic and the PI3K/AKT signaling pathways involved in cancer development and progression.


Assuntos
Leucemia Mieloide Aguda , Humanos , Masculino , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Criança , Proteína Fosfatase 1/genética , Proteínas de Fusão Oncogênica/genética
6.
Brain Tumor Pathol ; 41(2): 43-49, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38564040

RESUMO

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted is known for their relative chemosensitivity and indolent clinical course among diffuse gliomas of adult type. Based on the data from phase 3 clinical trials, the standard of post-surgical care for those tumors is considered to be initial chemoradiotherapy regardless of histopathological grade, particularly with PCV. However, partly due to its renewed definition in late years, prognostic factors in patients with those tumors are not well established. Moreover, the survival rate declines over 15 years, with only a 37% OS rate at 20 years for grade 3 tumors, even with the current standard of care. Given that most of this disease occurs in young or middle-aged adults, further improvements in treatment and management are necessary. Here, we discuss prognostic factors, standard of care and chemotherapy, and future perspectives with neoadjuvant strategy in those tumors.


Assuntos
Neoplasias Encefálicas , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 1 , Isocitrato Desidrogenase , Mutação , Terapia Neoadjuvante , Oligodendroglioma , Padrão de Cuidado , Humanos , Oligodendroglioma/genética , Oligodendroglioma/terapia , Oligodendroglioma/patologia , Isocitrato Desidrogenase/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Prognóstico , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 19/genética , Adulto , Deleção Cromossômica , Taxa de Sobrevida , Pessoa de Meia-Idade
7.
Case Rep Oncol ; 17(1): 113-121, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38260034

RESUMO

Introduction: Glioblastomas can manifest as multiple, simultaneous, noncontiguous lesions. We genetically analyzed multiple glioblastomas and discuss their etiological origins in this report. Case Presentation: We present the case of a 47-year-old woman who presented with memory impairment and left partial paralysis. Radiographic imaging revealed three apparently noncontiguous lesions in the right temporal and parietal lobes extending into the corpus callosum, leading to diagnosis of multicentric glioblastomas. All three lesions were excised. Genetic analysis of the lesions revealed a TERT promoter C228T mutation, a roughly equivalent amplification of EGFR, and homozygous deletion of CDKN2A/B exclusively in the two contrast-enhanced lesions. Additionally, the contrast-enhanced lesions exhibited the same two-base pair mutations of PTEN, whereas the non-enhanced lesion showed a partially distinct 13-base pair mutation. The other genetic characteristics were consistent. Rather than each having arisen de novo, we believe that they had developed by infiltration and are therefore best classified as multifocal glioblastomas. Conclusion: Our findings underscore anew the possibility of infiltration by glioblastomas, even within regions devoid of signal alterations on T2-weighted images or fluid-attenuated inversion recovery images. Genetic analysis can play a crucial role in differentiating whether multiple glioblastomas are multifocal or multicentric.

8.
Stem Cells Transl Med ; 12(7): 444-458, 2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37311043

RESUMO

Primary and metastatic lung cancer is a leading cause of cancer-related death and novel therapies are urgently needed. Epidermal growth factor receptor (EGFR) and death receptor (DR) 4/5 are both highly expressed in primary and metastatic non-small cell lung cancer (NSCLC); however, targeting these receptors individually has demonstrated limited therapeutic benefit in patients. In this study, we created and characterized diagnostic and therapeutic stem cells (SC), expressing EGFR-targeted nanobody (EV) fused to the extracellular domain of death DR4/5 ligand (DRL) (EVDRL) that simultaneously targets EGFR and DR4/5, in primary and metastatic NSCLC tumor models. We show that EVDRL targets both cell surface receptors, and induces caspase-mediated apoptosis in a broad spectrum of NSCLC cell lines. Utilizing real-time dual imaging and correlative immunohistochemistry, we show that allogeneic SCs home to tumors and when engineered to express EVDRL, alleviate tumor burden and significantly increase survival in primary and brain metastatic NSCLC. This study reports mechanistic insights into simultaneous targeting of EGFR- and DR4/5 in lung tumors and presents a promising approach for translation into the clinical setting.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Transplante de Células-Tronco Hematopoéticas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Receptores ErbB/uso terapêutico , Morte Celular , Neoplasias Encefálicas/terapia , Proliferação de Células , Encéfalo/patologia
9.
Brain Nerve ; 75(5): 561-566, 2023 May.
Artigo em Japonês | MEDLINE | ID: mdl-37194532

RESUMO

Treatment of brain tumors, particularly malignant gliomas, is challenging using only surgical resection and radiation therapy, and medical treatment plays an important role in the management of these malignancies. Temozolomide has been mainly used for the treatment of malignant gliomas over a decade. However, novel therapeutic options, such as molecular-targeted drugs and oncolytic virus therapeutic agents have been introduced in recent years. Classical anticancer medications, such as nitrosoureas and platinum-based drugs, continue to be administered for treatment of some types of malignant brain tumors.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Glioma/tratamento farmacológico , Temozolomida/uso terapêutico , Compostos de Nitrosoureia/uso terapêutico
10.
Sci Transl Med ; 15(698): eade8732, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37256936

RESUMO

Oncolytic virus therapy has shown activity against primary melanomas; however, its efficacy in brain metastases remains challenging, mainly because of the delivery and immunosuppressive nature of tumors in the brain. To address this challenge, we first established PTEN-deficient melanoma brain metastasis mouse models and characterized them to be more immunosuppressive compared with primary melanoma, mimicking the clinical settings. Next, we developed an allogeneic twin stem cell (TSC) system composed of two tumor-targeting stem cell (SC) populations. One SC was loaded with oncolytic herpes simplex virus (oHSV), and the other SC was CRISPR-Cas9 gene-edited to knock out nectin 1 (N1) receptor (N1KO) to acquire resistance to oHSV and release immunomodulators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF). Using mouse models of brain metastatic BRAFV600E/PTEN-/- and BRAFV600E/wt/PTEN-/- mutant melanomas, we show that locoregional delivery of TSCs releasing oHSV and GM-CSF (TSC-G) activated dendritic cell- and T cell-mediated immune responses. In addition, our strategy exhibited greater therapeutic efficacy when compared with the existing oncolytic viral therapeutic approaches. Moreover, the TSCs composed of SC-oHSV and SCN1KO-releasing GM-CSF and single-chain variable fragment anti-PD-1 (TSC-G/P) had therapeutic efficacy in both syngeneic and patient-derived humanized mouse models of leptomeningeal metastasis. Our findings provide a promising allogeneic SC-based immunotherapeutic strategy against melanomas in the CNS and a road map toward clinical translation.


Assuntos
Neoplasias Encefálicas , Melanoma , Terapia Viral Oncolítica , Vírus Oncolíticos , Animais , Camundongos , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Edição de Genes , Proteínas Proto-Oncogênicas B-raf , Melanoma/terapia , Melanoma/patologia , Simplexvirus/genética , Vírus Oncolíticos/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Encéfalo/patologia , Imunoterapia , Células-Tronco , Melanoma Maligno Cutâneo
11.
Front Neurol ; 14: 1162733, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37064182

RESUMO

Objective: Endoscopic endonasal surgery (EES) for deep intracranial lesions has gained popularity following recent developments in endoscopic technology. The operability of invasive pituitary neuroendocrine tumors (PitNETs) depends on the anatomy of the nasal cavity and paranasal sinus. This study aimed to establish a simple volume reconstruction algorithm of the nasal cavity and paranasal sinus. Additionally, this is the first study to demonstrate the relationship between the segmentation method and the clinical significance in patients with PitNET. Methods: Pre-and postoperative tumor volumes were analyzed in 106 patients with primary (new-onset) PitNETs (80 nonfunctioning and 26 functioning) who underwent EES. The efficiency and accuracy of the semiautomatic segmentation with manual adjustments (SSMA) method was compared with other established segmentation methods for volumetric analysis in the nasal cavity and paranasal sinuses. Correlations between the measured nasal cavity and paranasal sinus volumes and the extent of tumor removal were evaluated. Results: The SSMA method yielded accurate and time-saving results following the volumetric analyses of nasal cavity and paranasal sinuses with complex structures. Alternatively, the manual and semiautomatic segmentation methods proved time-consuming and inaccurate, respectively. The sphenoid sinus volume measured by SSMA was significantly correlated with the extent of tumor removal in patients with nonfunctioning Knosp grade 3 and 4 PitNET (r = 0.318; p = 0.015). Conclusion: The volume of sphenoid sinus potentially could predict the extent of resection due to better visualization of the tumor for PitNETs with CS invasion.

12.
Geriatr Gerontol Int ; 22(4): 271-277, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35118789

RESUMO

AIM: Super-elderly patients are often frail and the decision on surgical indications remains a difficult issue. The purpose of this study was to provide a certain preoperative surgical risk assessment tool for super-elderly people. METHODS: We selected 112 individuals who were super-elderly patients aged >90 years who had surgeries under general anesthesia in our department. Based on the quality of the postoperative outcome of each case, we categorized these patients into two groups: good and poor groups. We evaluated the fundamental examination items, such as American Society of Anesthesiologists physical status, skeletal muscle mass index and so on, and a couple of the well-known risk score systems represented by Estimation of Physiology Ability and Surgical Stress. RESULTS: A total of 85 of the 112 patients belonged to the good group and the rest belonged to the poor group. The quality of postoperative outcome is well characterized by Estimation of Physiology Ability and Surgical Stress (P = 0.001). Receiver operating characteristic analysis of Estimation of Physiology Ability and Surgical Stress for the quality of postoperative outcome shows sensitivity of 0.83 and specificity of 0.61. Multivariate logistic regression analysis showed that skeletal muscle mass index and American Society of Anesthesiologists physical status are prominent as the risk determinants affecting the quality of postoperative outcome. A scoring system based on the skeletal muscle mass index, which is a good index of sarcopenia, and American Society of Anesthesiologists physical status, named the "SAP score" has the following characteristics. P-value <0.001, sensitivity 0.76 and specificity 0.91. CONCLUSIONS: Informed consent based on the risk score might be able to reduce the regrettable situation where it would have been better to have had surgery or not to have had surgery. Geriatr Gerontol Int 2022; 22: 271-277.


Assuntos
Complicações Pós-Operatórias , Sarcopenia , Idoso , Idoso de 80 Anos ou mais , Humanos , Complicações Pós-Operatórias/epidemiologia , Curva ROC , Medição de Risco , Fatores de Risco , Sarcopenia/diagnóstico
13.
J Neurooncol ; 155(3): 235-246, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34718935

RESUMO

PURPOSE: Lower grade gliomas with 1p/19q codeletion are often responsive to chemotherapy, and several of these have been treated using upfront chemotherapy and subsequent resection following tumor volume decrease. This study aimed to elucidate the histological changes and the mechanism of recurrence after alkylating agent chemotherapy in 1p/19-codeleted gliomas. METHODS: Fourteen 1p/19q-codeleted gliomas resected following tumor volume decrease after alkylating agent chemotherapy were included and compared with their pre-chemotherapy specimens. Histological changes were investigated using hematoxylin-eosin staining, and changes in proliferative activity, status of glioma stem cells (GSCs), and tumor-infiltrating macrophages were assessed using immunohistochemistry for Ki-67/MIB-1, CD68 as a pan-macrophage/monocyte marker, CD163 as a presumed marker of M2 polarity, and nestin and CD133 as markers of GSCs. RESULTS: The most frequent histological findings following chemotherapy included a sparse glial background and abundant foamy cell infiltration. The Ki-67/MIB-1 index decreased and the number of CD68 + cells increased after chemotherapy. The increasing rate of CD68 + cells in the post-/pre-chemotherapy specimens was inversely correlated with patient prognosis but not tumor response. The number of CD163 + cells, M2/M1 + M2 ratio, and the ratio of GSCs to total tumor cells increased after chemotherapy, and those in the post-chemotherapy specimens were negatively correlated with patient prognosis. There was a correlation between the M2/M1 + M2 ratio and the ratio of GSCs in both pre- and post-chemotherapy specimens. CONCLUSION: GSCs in conjunction with M2 macrophages constitute the mechanism of resistance to and recurrence after alkylating agent chemotherapy in 1p/19q-codeleted gliomas.


Assuntos
Neoplasias Encefálicas , Glioma , Alquilantes , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Glioma/tratamento farmacológico , Glioma/genética , Glioma/cirurgia , Humanos , Isocitrato Desidrogenase/genética , Antígeno Ki-67 , Mutação
14.
Clin Neurol Neurosurg ; 207: 106720, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34102420

RESUMO

OBJECTIVE: Brain tumors often become clinically evident during pregnancy; however, the mechanism has not been well elucidated. Purpose of this study is to investigate the influence of molecular genetic factors on the progression of brain tumors during pregnancy or the postpartum period. METHODS: Twelve cases of brain tumors that presented during pregnancy or postpartum period were included: five gliomas, three meningiomas, two vestibular schwannomas, and two chordomas. Tumor samples were investigated by metaphase comparative genomic hybridization and immunohistochemistry, for chromosomal copy number aberration (CNA) and receptor expression of sex hormones and growth factors. RESULTS: The results were correlated with the timing of tumor presentation in relation to the stage of pregnancy. EGFR, VEGFR-1/2, AR, and c-Myc were expressed in gliomas, PgR, ER, HER-2, VEGFR-1, EGF and VEGFR2 in meningiomas, VEGFR-1 in vestibular schwannomas, and EGFR, VEGFR-1/2, and c-Myc in chordomas. The CNAs of the tumors varied. Four of the five gliomas presented in the 2nd trimester, all three meningiomas in the 3rd trimester or postpartum period, and both of the two schwannomas in the late 2nd trimester. Expression of VEGFR-1/2 and EGFR was observed regardless of the timing of tumor presentation, whereas female hormone receptors and HER-2 were exclusively found in meningiomas. Interestingly, one anaplastic astrocytoma (IDH mut, non-codeleted) that progressed from precedent grade 2 tumor harbored amplification of the MYC locus. CONCLUSION: Progression of brain tumors during pregnancy is associated with various growth factors as well as sex hormones. The timing of presentation is likely dependent on molecular receptors specific to each tumor type.


Assuntos
Neoplasias Encefálicas/patologia , Complicações Neoplásicas na Gravidez/patologia , Adulto , Progressão da Doença , Feminino , Humanos , Período Pós-Parto , Gravidez
15.
Sci Adv ; 7(10)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658202

RESUMO

Basal-like breast cancer (BLBC) shows brain metastatic (BM) capability and overexpresses EGFR and death-receptors 4/5 (DR4/5); however, the anatomical location of BM prohibits efficient drug-delivery to these targetable markers. In this study, we developed BLBC-BM mouse models featuring different patterns of BMs and explored the versatility of estem cell (SC)-mediated bi-functional EGFR and DR4/5-targeted treatment in these models. Most BLBC lines demonstrated a high sensitivity to EGFR and DR4/5 bi-targeting therapeutic protein, EVDRL [anti-EGFR VHH (EV) fused to DR ligand (DRL)]. Functional analyses using inhibitors and CRISPR-Cas9 knockouts revealed that the EV domain facilitated in augmenting DR4/5-DRL binding and enhancing DRL-induced apoptosis. EVDRL secreting stem cells alleviated tumor-burden and significantly increased survival in mouse models of residual-tumor after macrometastasis resection, perivascular niche micrometastasis, and leptomeningeal metastasis. This study reports mechanism based simultaneous targeting of EGFR and DR4/5 in BLBC and defines a new treatment paradigm for treatment of BM.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Transplante de Células-Tronco Hematopoéticas , Animais , Encéfalo/metabolismo , Neoplasias Encefálicas/terapia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Receptores ErbB/genética , Feminino , Humanos , Ligantes , Camundongos , Receptores de Morte Celular/metabolismo
16.
Trends Cancer ; 7(9): 809-822, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33722479

RESUMO

Patients with extracranial tumors, like lung, breast, and skin cancers, often develop brain metastases (BM) during the course of their diseases and BM commonly represent the terminal stage of cancer progression. Recent insights in the immune biology of BM and the increasing focus of immunotherapy as a therapeutic option for cancer has prompted testing of promising biological immunotherapies, including immune cell-targeting, virotherapy, vaccines, and different cell-based therapies. Here, we review the pathobiology of BM progression and evaluate the potential of next-generation immunotherapies for BM tumors. We also provide future perspectives on the development and implementation of such therapies for brain metastatic cancer patients.


Assuntos
Neoplasias Encefálicas , Terapia Viral Oncolítica , Encéfalo , Neoplasias Encefálicas/terapia , Humanos , Imunoterapia
17.
Int J Hematol ; 111(6): 803-811, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32020505

RESUMO

The prognosis of cardiac light-chain (AL) amyloidosis is considered to be very poor. We studied the treatment efficacy and outcomes by retrospectively analyzing the clinical results of 45 patients with cardiac AL amyloidosis treated at our hospital between September 2008 and March 2016. The group of patients analyzed included 29 males and 16 females with a median age of 68 years. Their baseline median NT-proBNP, cTnT, and dFLC were 3167 pg/ml, 0.080 ng/ml, and 286.17 mg/l, respectively. Twenty-eight patients were in Cardiac Stage (CS) III and 17 patients were in Revised Prognostic Stage (RPS) IV. At the median follow-up of 10 months, the median overall survival (OS) was 16 months and 3-year OS was 35.9%. The patients in CS III showed significantly poorer survival rate than those in CS I or II (3-year OS: 12.2% vs. 65.8%, p = 0.0115) and the patients in RPS IV showed significantly poorer survival rate than those in RPS I, II, or III (3-year OS: 11.0% vs. 53.3%, p = 0.000914). Regardless of the therapeutic approaches, patients who achieved hematological CR or cardiac organ response demonstrated significantly improved prognosis. Therefore, achievement of hematological and organ responses is important in the treatment of cardiac AL amyloidosis.


Assuntos
Bortezomib/administração & dosagem , Cardiomiopatias/terapia , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Melfalan/administração & dosagem , Transplante de Células-Tronco de Sangue Periférico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Cardiomiopatias/diagnóstico , Cardiomiopatias/mortalidade , Quimioterapia Combinada , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Japão , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Prognóstico , Estudos Retrospectivos , Proteínas Oncogênicas de Retroviridae , Índice de Gravidade de Doença
18.
Artigo em Inglês | MEDLINE | ID: mdl-31744651

RESUMO

We previously reported that triglyceride (TG) levels in small-for-gestational age (SGA) newborns were significantly higher than those in appropriate-for-gestational age (AGA) newborns. Stearoyl-CoA desaturase (SCD) activity is required for TG synthesis, while lipoprotein lipase mass (LPLm) facilitates TG clearance. The purpose of this study is to reveal whether SCD activity or LPLm is the cause of high TG levels in SGA newborns. Fifty-five newborns were classified as AGA (n = 42) and SGA (n = 13). Serum LPLm, TG and fatty acids in umbilical cord blood were analyzed. Then, [16:1 (n-7)]/ [16:0] and [18:1 (n-9)]/ [18:0] were calculated as SCD16 and SCD18 activities, respectively. The SGA group showed significantly higher TG levels and significantly lower LPLm levels than the AGA group. However, SCD16 and 18 activities were lower in SGA newborns than in AGA newborns. In conclusion, LPLm, rather than SCD activity may be involved in the increased TG levels in SGA newborns.


Assuntos
Sangue Fetal/enzimologia , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Lipase Lipoproteica/sangue , Estearoil-CoA Dessaturase/sangue , Adulto , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino
19.
Front Nutr ; 6: 12, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30828577

RESUMO

We recently reported that plasma albumin redox state, which correlates with albumin synthesis rate, could be associated with the quality of dietary protein. Aiming to elucidate the association between them, plasma albumin redox state was investigated in rats fed various kinds of AIN-93G-based low protein diets. Plasma albumin redox state was shifted to a more oxidized state in rats fed 3% casein (CN) diet than those fed 3% whey protein or 3% wheat gluten diet, while supplementing 3% CN diet with cystine reversed it to a more reduced state, indicating that cystine would complement the shortage of cysteine in CN, thereby increasing albumin synthesis rate. Supplementation with glutathione, a cysteine-containing antioxidative tripeptide, normalized hepatic glutathione redox state modulated by ingestion of 3% CN diet, but it only reversed the oxidized shift of plasma albumin redox state to an extent similar to cystine alone or the constituting amino acid mixture of glutathione (i.e., glutamic acid, cystine, and glycine), indicating that glutathione would primarily serve as a source of cysteine rather than exert its antioxidative activity. Plasma albumin would thus be influenced by amino acid balance in dietary proteins, and it could be useful as a biomarker that contributes to prevention of protein under-nutriton, caused by not only insufficient protein intake but also ingestion of poor-quality protein.

20.
Ann Nutr Metab ; 73(4): 335-343, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30428475

RESUMO

BACKGROUND: Term infants can be categorized into 3 sub-groups: early term (37w0d to 38w6d), full term (39w0d to 40w6d), and late term (41w0d and beyond). However, the fatty acid composition among the 3 groups of term infants has not been investigated. The association between fatty acid composition and gestational period of term infants in Japan is unclear. METHODS: We assessed the fatty acid composition of maternal erythrocyte membranes in the third trimester and of cord erythrocyte membranes at birth in 212 healthy term Japanese infants using data from a prospective hospital-based cohort study. RESULTS: In maternal erythrocyte membranes, docosahexaenoic acid (DHA) levels and omega-3 index were significantly higher in the late-term group than in the early-term group. In cord erythrocyte membranes, DHA levels were not significantly different between the 3 groups; late-term infants showed significantly higher DHA/arachidonic acid (ARA) and lower 20: 3n-6 and ARA levels compared to early-term infants. Gestational period positively correlated with the DHA status in maternal and cord erythrocyte membranes. CONCLUSIONS: Fatty acid composition in maternal and cord erythrocyte membranes varies between early-, full-, and late-term infants, and the greater gestational period may contribute to the relatively high n-3 polyunsaturated fatty acids status in term infants. Furthermore, maternal DHA status in the third semester directly correlates with gestational period in pregnant Japanese women.


Assuntos
Membrana Eritrocítica/química , Ácidos Graxos/análise , Idade Gestacional , Adulto , Ácido Araquidônico/sangue , Estudos de Coortes , Dieta , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Graxos/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Feminino , Sangue Fetal , Humanos , Recém-Nascido , Recém-Nascido Prematuro/sangue , Japão , Gravidez , Terceiro Trimestre da Gravidez/sangue , Estudos Prospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA