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1.
Brain Tumor Pathol ; 41(2): 61-72, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38619734

RESUMEN

Glioblastoma multiforme (GBM) acquires resistance to bevacizumab (Bev) treatment. Bev affects angiogenic factors other than vascular endothelial growth factor (VEGF), which are poorly understood. We investigated changes in angiogenic factors under and after Bev therapy, including angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), placental growth factor (PLGF), fibroblast growth factor 2, and ephrin A2 (EphA2). Fifty-four GBM tissues, including 28 specimens from 14 cases as paired specimens from the same patient obtained in three settings: initial tumor resection (naïve Bev), tumors resected following Bev therapy (effective Bev), and recurrent tumors after Bev therapy (refractory Bev). Immunohistochemistry assessed their expressions in tumor vessels and its correlation with recurrent MRI patterns. PLGF expression was higher in the effective Bev group than in the naïve Bev group (p = 0.024) and remained high in the refractory Bev group. ANGPT2 and EphA2 expressions were higher in the refractory Bev group than in the naïve Bev group (p = 0.047 and 0.028, respectively). PLGF expression was higher in the refractory Bev group compared with the naïve Bev group for paired specimens (p = 0.036). PLGF was more abundant in T2 diffuse/circumscribe patterns (p = 0.046). This is the first study to evaluate angiogenic factors other than VEGF during effective and refractory Bev therapy in patient-derived specimens.


Asunto(s)
Inhibidores de la Angiogénesis , Angiopoyetina 2 , Bevacizumab , Neoplasias Encefálicas , Glioblastoma , Neovascularización Patológica , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/cirugía , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neovascularización Patológica/tratamiento farmacológico , Adulto , Angiopoyetina 2/metabolismo , Inhibidores de la Angiogénesis/uso terapéutico , Factor de Crecimiento Placentario/metabolismo , Antineoplásicos Inmunológicos/uso terapéutico , Angiopoyetina 1/metabolismo , Recurrencia Local de Neoplasia
2.
Cureus ; 16(3): e56435, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38638739

RESUMEN

Metastatic pelvic tumors pose a significant challenge in oncologic orthopedics due to their complex management and the high potential for postoperative complications. This case study discusses a 75-year-old male with a sacral stress fracture following a type 3 internal hemipelvectomy for a metastatic lesion from gastric cancer in the left pubic bone. Initial conservative treatments failed to yield satisfactory improvement, leading to surgical intervention. Open reduction and internal fixation with an iliosacral screw, despite complications, significantly alleviated pain and improved mobility. This case underscores the difficulty in diagnosing sacral stress fractures versus metastatic lesions and highlights the effectiveness of iliosacral screw fixation in managing postoperative sacral stress fractures. It emphasizes the procedure's role in providing early pain relief and enhancing daily activity levels. Additionally, it points out the importance of addressing altered bone metabolism in the postoperative care of patients with metastatic pelvic tumors. This contributes to the literature by stressing the incidence of sacral stress fractures as a critical, though often overlooked, complication and demonstrating the benefits of iliosacral screw fixation in such scenarios for better recovery and quality of life.

3.
Int J Artif Organs ; 47(4): 290-298, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38584296

RESUMEN

BACKGROUND: Dislocation is a major complication of total hip arthroplasty (THA). The modular femoral neck system provides practical advantages by allowing adjustment of neck version and length in the presence of intraoperative instability. Anatomical studies have identified morphological differences in the hip joint between men and women. Despite sex-based differences in hip morphology, it remains unclear whether such differences affect neck selectivity in THA using a modular neck system and whether this approach achieves anatomical reconstruction, thereby reducing complications such as dislocation. This study aimed to investigate gender differences in neck selectivity in THA with the modular neck system and assess the clinical impact of the modular neck system. METHODS: A total of 163 THAs using a modular neck system were included in this study. Data on the type of modular neck and intraoperative range of motion (ROM) were retrieved from patient records. Pre- and post-operative leg length differences (LLD) were examined as part of the radiographic assessment. Dislocation was investigated as a postoperative complication. RESULTS: Neck selectivity did not significantly differ between men and women. The comparison of pre- and post-operative LLD revealed a tendency for varus necks to improve LLD more than version-controlled necks. Furthermore, no significant correlation was found between intraoperative ROM and neck selectivity, or postoperative dislocation and neck selectivity. CONCLUSIONS: This study on THA with a modular neck system provided valuable insights into sex-based differences in neck selectivity and highlighted the potential benefits of the modular neck system in addressing LLD and preventing postoperative dislocation.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Diseño de Prótesis , Rango del Movimiento Articular , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Artroplastia de Reemplazo de Cadera/instrumentación , Femenino , Masculino , Anciano , Persona de Mediana Edad , Factores Sexuales , Cuello Femoral/cirugía , Anciano de 80 o más Años , Articulación de la Cadera/cirugía , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/fisiopatología , Estudios Retrospectivos , Adulto , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento
4.
Int J Artif Organs ; 47(4): 299-302, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38515386

RESUMEN

This article describes three cases in which a dislocated hip prosthesis was reduced by a new reduction technique - that we previously described - using traction table. The dissociation of a prosthesis is a rare but serious complication of closed reduction manoeuvre. The new reduction manoeuvre using a traction table may be a good option to avoid dissociation of the prosthesis during closed reduction for treatment of dislocation after total hip arthroplasty.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Luxación de la Cadera , Prótesis de Cadera , Tracción , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/instrumentación , Anciano , Femenino , Masculino , Luxación de la Cadera/cirugía , Luxación de la Cadera/etiología , Luxación de la Cadera/diagnóstico por imagen , Falla de Prótesis , Persona de Mediana Edad , Resultado del Tratamiento
5.
Blood ; 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38513239

RESUMEN

Transient abnormal myelopoiesis (TAM) is a common complication in newborns with Down syndrome (DS). It commonly progresses to myeloid leukemia (ML-DS) after spontaneous regression. In contrast to the favorable prognosis of primary ML-DS, patients with refractory/relapsed ML-DS have poor outcomes. However, the molecular basis for refractoriness and relapse, and the full spectrum of driver mutations in ML-DS remain largely unknown. We conducted a genomic profiling study of 143 TAM, 204 ML-DS, and 34 non-DS acute megakaryoblastic leukemia cases, including 39 ML-DS cases analyzed by exome sequencing. Sixteen novel mutational targets were identified in ML-DS samples. Of these, inactivations of IRX1 (16.2%) and ZBTB7A (13.2%) were commonly implicated in the upregulation of the MYC pathway and were potential targets for ML-DS treatment with bromodomain-containing protein 4 inhibitors. Partial tandem duplications of RUNX1 on chromosome 21 were also found, specifically in ML-DS samples (13.7%), presenting its essential role in DS leukemia progression. Finally, in 177 patients with ML-DS treated following the same ML-DS protocol (the Japanese Pediatric Leukemia and Lymphoma Study Group AML-D05/D11), CDKN2A, TP53, ZBTB7A, and JAK2 alterations were associated with a poor prognosis. Patients with CDKN2A deletions (n = 7) or TP53 mutations (n = 4) had substantially lower 3-year event-free survival [28.6% vs. 90.5%, P < 0.001; 25.0% vs. 89.5%, P < 0.001] than those without these mutations. These findings considerably change the mutational landscape of ML-DS, provide new insights into the mechanisms of progression from TAM to ML-DS, and help identify new therapeutic targets and strategies for ML-DS.

6.
ACS Appl Bio Mater ; 7(3): 1513-1525, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38354359

RESUMEN

Skin is the body barrier that constrains the infiltration of particles and exogenous aggression, in which the hair follicle plays an important role. Recent studies have shown that small particles can penetrate the skin barrier and reach the hair follicle, making them a potential avenue for delivering hair growth-related substances. Interestingly, keratin-based microspheres are widely used as drug delivery carriers in various fields. In this current study, we pursue the effect of newly synthesized 3D spherical keratin particles on inducing hair growth in C57BL/6 male mice and in human hair follicle dermal papilla cells. The microspheres were created from partially sulfonated, water-soluble keratin. The keratin microspheres swelled in water to form spherical gels, which were used for further experiments. Following topical application for a period of 20 days, we observed a regrowth of hair in the previously depleted area on the dorsal part of the mice in the keratin microsphere group. This observation was accompanied by the regulation of hair-growth-related pathways as well as changes in markers associated with epidermal cells, keratin, and collagen. Interestingly, microsphere keratin treatment enhanced the cell proliferation and the expression of hair growth markers in dermal papilla cells. Based on our data, we propose that 3D spherical keratin has the potential to specifically target hair follicle growth and can be employed as a carrier for promoting hair growth-related agents.


Asunto(s)
Cabello , Queratinas , Masculino , Ratones , Humanos , Animales , Queratinas/metabolismo , Queratinas/farmacología , Microesferas , Ratones Endogámicos C57BL , Cabello/metabolismo , Agua
7.
J Neurooncol ; 166(3): 557-567, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38291182

RESUMEN

PURPOSE: This multi-institutional phase I/II study was conducted to confirm the safety and explore the clinical utility of preoperative Bevacizumab (Bev) for newly diagnosed glioblastoma (GB). METHODS: Patients were enrolled based on magnetic resonance imaging (MRI) findings typically suggestive of GB. Preoperative Bev and temozolomide (TMZ) were administered at doses of 10 mg/kg on day 0 and 150 mg/m2 on days 1-5, respectively. Surgical resection was performed between days 21 and 30, inclusive. The safety and efficacy were evaluated in a total of 15 cases by progression-free survival (PFS), changes in tumor volume, Karnofsky Performance Scale (KPS) and Mini-Mental State Examination (MMSE) scores after preoperative therapy. RESULTS: Tumor resection was performed on a mean of day 23.7. Pathological diagnosis was GB, isocitrate dehydrogenase (IDH)-wildtype in 14 cases and GB, IDH-mutant in 1 case. Severe adverse events possibly related to preoperative Bev and TMZ were observed in 2 of the 15 patients, as wound infection and postoperative hematoma and thrombocytopenia. KPS and MMSE scores were significantly improved with preoperative therapy. Tumor volume was decreased in all but one case on T1-weighted imaging with contrast-enhancement (T1CE) and in all cases on fluid-attenuated inversion recovery, with mean volume decrease rates of 36.2% and 54.0%, respectively. Median PFS and overall survival were 9.5 months and 16.5 months, respectively. CONCLUSION: Preoperative Bev and TMZ is safe as long as the instructions are followed. The strategy might be useful for GB in some patients, not only reducing tumor burden, but also improving patient KPS preoperatively. TRIAL REGISTRATION NUMBER: UMIN000025579, jRCT1031180233 https://jrct.niph.go.jp/latest-detail/jRCT1031180233 . Registration Date: Jan. 16, 2017.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Terapia Neoadyuvante , Estudios Prospectivos , Temozolomida/uso terapéutico
8.
Ann N Y Acad Sci ; 1531(1): 69-83, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38051498

RESUMEN

We consider issues related to the effect of climate change on the persistence of (trend-corrected) temperatures using global gridded data for both land and oceans. We first discuss how the presence of trends and additive noise affects inference about persistence. Ignoring a trend induces an upward bias, while not accounting for noise induces a downward bias. We show that the increase in persistence in the commonly used Warm Spell Duration Index is simply an artifact of increasing temperatures. To purge the impact of both trends and noise, we adopt a simple state-space model. Of separate interest, we document a much larger noise component for land than for oceans. The estimates of the persistence are much larger for oceans than for land. Inspection of the estimates across various subsamples and the application of tests for structural changes suggest the same pattern of persistence for both land and oceans across time, with few minor exceptions. Hence, our results show that surface temperature persistence has remained constant during the observed period.


Asunto(s)
Cambio Climático , Calentamiento Global , Humanos , Temperatura , Océanos y Mares
9.
Gan To Kagaku Ryoho ; 50(11): 1211-1213, 2023 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-38056877

RESUMEN

Many clinical trials have been conducted in which hyperthermia has been used in conjunction with chemotherapy in the management of unresectable solid tumors. In this regard, promising Phase Ⅱ trial results have been reported. We experienced three cases of unresectable colorectal cancer in which the use of hyperthermia sensitized the effects of anticancer drugs and enabled cancer control. It is considered that systemic chemotherapy with the use of hyperthermia, at the right time, will lead to better treatment outcomes.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Hipertermia Inducida , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento
10.
Nanoscale ; 15(47): 19062-19068, 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-37987533

RESUMEN

Thermally tolerant polymer optical resonators are fabricated from a stereocomplex of poly(L-lactic acid) and poly(D-lactic acid) through the oil-in-water miniemulsion method. The thermal stability of the microspheres of the stereocomplex poly(lactic acid) (SC-PLA) is superior to that of the homochiral poly(lactic acid) (HC-PLA). As a result of the high thermal stability, the optical resonator properties of the SC-PLA microspheres are preserved at an elevated temperature of up to 230 °C, which is 70 °C higher than that of microspheres formed from HC-PLA.

11.
Ann Vasc Dis ; 16(3): 210-213, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37779649

RESUMEN

We herein present a case involving an 86-year-old man with abdominal aortic aneurysm complicated by symptomatic disseminated intravascular coagulation (DIC). The patient received preoperative treatment for DIC using recombinant human soluble thrombomodulin (rTM) followed by open surgical repair of the aneurysm. The patient's coagulopathy cleared quickly after the start of rTM, and the intraoperative and postoperative course went smoothly. The patient was followed without anticoagulant medication, and there was no recurrence of DIC during 14 months of follow-up. The preoperative administration of rTM can be a useful choice to assist safe treatment of aortic aneurysm complicated by aneurysm-related DIC.

12.
Artículo en Inglés | MEDLINE | ID: mdl-37739810

RESUMEN

BACKGROUND AND OBJECTIVES: To elucidate current epidemiologic, clinical, and immunologic profiles and treatments of stiff-person syndrome (SPS) in Japan. METHODS: A nationwide mail survey was conducted using an established method. Data processing sheets were sent to randomly selected departments of internal medicine, neurology, pediatrics, psychiatry, and neurosurgery in hospitals and clinics throughout Japan to identify patients with SPS who were seen between January 2015 and December 2017. RESULTS: Thirty cases were identified as glutamic acid decarboxylase 65 (GAD65)-positive SPS cases on the basis of detailed clinical data of 55 cases. Four patients had α1 subunit of glycine receptor (GlyR) antibodies, and 1 patient had both GAD65 and GlyR antibodies. The total estimated number of patients with GAD65-positive SPS was 140, and the estimated prevalence was 0.11 per 100,000 population. The median age at onset was 51 years (range, 26-83 years), and 23 (76%) were female. Of these, 70% had classic SPS, and 30% had stiff-limb syndrome. The median time from symptom onset to diagnosis was significantly longer in the high-titer GAD65 antibody group than in the low-titer group (13 months vs 2.5 months, p = 0.01). The median modified Rankin Scale (mRS) at baseline was 4, and the median mRS at the last follow-up was 2. Among the 29 GAD65-positive patients with ≥1 year follow-up, 7 received only symptomatic treatment, 9 underwent immunotherapy without long-term immunotherapy, and 13 received long-term immunotherapy such as oral prednisolone. The coexistence of type 1 diabetes mellitus and the lack of long-term immunotherapy were independent risk factors for poor outcome (mRS ≥3) in the GAD65-positive patients (odds ratio, 15.0; 95% CI 2.6-131.6; p = 0.001; odds ratio, 19.8; 95% CI 3.2-191.5; p = 0.001, respectively). DISCUSSION: This study provides the current epidemiologic and clinical status of SPS in Japan. The symptom onset to the diagnosis of SPS was longer in patients with high-titer GAD65 antibodies than in those with low-titer GAD65 antibodies. The outcome of patients with SPS was generally favorable, but more aggressive immunotherapies are necessary for GAD65-positive patients with SPS.


Asunto(s)
Síndrome de la Persona Rígida , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos , Pueblos del Este de Asia , Glutamato Descarboxilasa , Inmunoterapia , Prevalencia , Pronóstico , Síndrome de la Persona Rígida/diagnóstico , Síndrome de la Persona Rígida/epidemiología , Síndrome de la Persona Rígida/terapia
13.
Cureus ; 15(6): e40079, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37425534

RESUMEN

The incidence of lymphoproliferative disorders associated with methotrexate is rising in patients with rheumatoid arthritis. These disorders typically exhibit spontaneous tumor regression upon discontinuation of methotrexate therapy. Spinal lesions associated with these diseases are extremely rare. We present a case of systemic lupus erythematosus in which the patient developed lumbar spine lymphoproliferative disorders secondary to methotrexate therapy, which failed to regress despite discontinuation of the drug, ultimately leading to pathological fracture necessitating posterior spinal fixation. A 60-year-old woman had been diagnosed with systemic lupus erythematosus at the age of 55 years and had been taking prednisolone, hydroxychloroquine, and methotrexate. Throughout the course of her treatment, she experienced recurrent tumefaction and lymph node swelling in various locations. These masses and lymphadenopathy were believed to be potential complications of methotrexate-associated lymphoproliferative disorders, leading to the discontinuation of methotrexate. One month prior to cessation of methotrexate therapy, the patient presented to an orthopedic clinic with lower back pain, and T2-weighted magnetic resonance imaging revealed low signal intensity in the Th10 and L2 vertebrae, initially misdiagnosed as lumbar spinal stenosis. The patient was eventually referred to our department under suspicion of malignant pathology. Computed tomography identified a vertical fracture of the L2 vertebra, which, in conjunction with the imaging results, led to the diagnosis of pathological fracture secondary to methotrexate-associated lymphoproliferative disorder. Following admission to our department, bone biopsy and percutaneous pedicle screw fixation were performed one week later. Pathological examination confirmed the diagnosis of methotrexate-associated lymphoproliferative disorder. Given the possibility of pathological fracture in patients on methotrexate therapy experiencing severe back pain, additional imaging studies should be considered.

14.
Nano Lett ; 23(14): 6512-6519, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37405910

RESUMEN

In this work, the impact of metallic and dielectric conducting substrates, gold and indium tin oxide (ITO)-coated glass, on the whispering gallery modes (WGMs) of semiconductor π-conjugated polymer microspheres is investigated. Hyperspectral mapping was performed to obtain the excitation-position-dependent emission spectra of the microspheres. Substrate-dependent quenching of WGMs sensitive to mode polarization was observed and explained. On a glass substrate, both transverse-electric (TE) and transverse-magnetic (TM) WGMs are quenched due to frustrated total internal reflection. On a gold substrate, however, only the TM WGMs are allowed in symmetry to leak into surface plasmons. An atomically flat gold substrate with subwavelength slits was used to experimentally verify the leakage of WGMs into the surface plasmon polaritons (SPPs). This work provides insight into the damping mechanisms of WGMs in microspheres on metallic and dielectric substrates.

15.
Cancer Immunol Immunother ; 72(10): 3175-3189, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37382632

RESUMEN

Dendritic cell (DC)-based immunotherapy has been applied to glioblastoma (GBM); however, biomarkers informing response remain poorly understood. We conducted a phase I/IIa clinical trial investigating tumor-fused DC (TFDC) immunotherapy following temozolomide-based chemoradiotherapy in patients with newly diagnosed GBM and determined prognostic factors in patients receiving TFDC immunotherapy. Twenty-eight adult patients with GBM isocitrate dehydrogenase (IDH) wild-type (IDH-WT) were enrolled; 127 TFDC vaccine injections (4.5 ± 2.6 times/patient) were administered. Patients with GBM IDH-WT had a respectable 5-year survival rate (24%), verifying the clinical activity of TFDC immunotherapy, particularly against O6-methylguanine-DNA methyltransferase (MGMT) unmethylated GBM (5-year survival rate: 33%). To identify novel factors influencing overall survival (OS) in GBM IDH-WT treated with TFDC immunotherapy, clinical parameters were assessed and comprehensive molecular profiling involving transcriptome and exome analyses was performed. MGMT promoter methylation status, extent of tumor resection, and vaccine parameters (administration frequency, DC and tumor cell numbers, and fusion ratio) were not associated with survival following TFDC immunotherapy. Old age and pre- and post-operative Karnofsky performance status were significantly correlated with OS. Low HLA-A expression and lack of CCDC88A, KRT4, TACC2, and TONSL mutations in tumor cells were correlated with better prognosis. We validated the activity of TFDC immunotherapy against GBM IDH-WT, including chemoresistant, MGMT promoter unmethylated cases. The identification of molecular biomarkers predictive of TFDC immunotherapy efficacy in GBM IDH-WT will facilitate the design of and patient stratification in a phase-3 trial to maximize treatment benefits.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Adulto , Humanos , Glioblastoma/terapia , Glioblastoma/tratamiento farmacológico , Pronóstico , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/uso terapéutico , Células Dendríticas , Inmunoterapia Activa , Metilación de ADN , FN-kappa B/genética
17.
World Neurosurg ; 175: e1364-e1374, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37187346

RESUMEN

BACKGROUND: Cancer stemness and immunosuppressive tumor microenvironment (TME) in accordance with tumor oxygenation are variable during bevacizumab (Bev) therapy for glioblastoma (GBM). Positron emission tomography (PET) using 18F-fluoromisonidazole (FMISO) reflects hypoxic TME. The aim of this study was to compare FMISO-PET and immunohistochemical findings of tumor oxygenation in the TME of GBM during Bev treatment. METHODS: Seven patients with newly diagnosed IDH-wildtype GBM underwent FMISO-PET during follow-up. Three patients received preoperative neoadjuvant Bev (neo-Bev) and subsequently underwent surgical resection. Reoperation was performed at the recurrence. FMISO-PET was performed before and after neo-Bev. Four patients who underwent tumor resection without neo-Bev were included as the control group. Expressions of hypoxic markers (carbonic anhydrase; CA9), stem cell markers (nestin, FOXM1), and immunoregulatory molecules (CD163, FOXP3, PD-L1) in tumor tissues were analyzed by immunohistochemistry (IHC). RESULTS: All 3 patients treated with neo-Bev showed decrease in FMISO accumulation in accordance with expressions of CA9 and FOXM1 compared with the control group. Two of these 3 patients at the recurrence showed increase in FMISO accumulation. IHC showed increased CA9-and FOXM1-positive cells in recurrent tumors. Expression of PD-L1 tended to be lower after neo-Bev compared with the control group. CONCLUSIONS: FMISO-PET effectively visualized TME oxygenation after neo-Bev. Increased FMISO accumulation at the time of recurrence, even under Bev treatment, suggests that FMISO-PET might be useful for monitoring the duration of Bev efficacy by reflecting tumor oxygenation.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/tratamiento farmacológico , Glioblastoma/cirugía , Bevacizumab/uso terapéutico , Antígeno B7-H1 , Terapia Neoadyuvante , Inmunohistoquímica , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/cirugía , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/tratamiento farmacológico , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Microambiente Tumoral
18.
Acc Chem Res ; 56(12): 1469-1481, 2023 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-37219046

RESUMEN

ConspectusFor optical and electronic applications of supramolecular assemblies, control of the hierarchical structure from nano- to micro- and millimeter scale is crucial. Supramolecular chemistry controls intermolecular interactions to build up molecular components with sizes ranging from several to several hundreds of nanometers using bottom-up self-assembly process. However, extending the supramolecular approach up to a scale of several tens of micrometers to construct objects with precisely controlled size, morphology, and orientation is challenging. Especially for microphotonics applications such as optical resonators and lasers, integrated optical devices, and sensors, a precise design of a micrometer-scale object is required. In this Account, we review the recent progress on precise control of microstructures from π-conjugated organic molecules and polymers, which work as micro-photoemitters and are suitable for optical applications.After the introduction on the importance of the control of the hierarchical structures from molecular assembly, we review supramolecular methodology for assembling molecules and supramolecules to form microstructures such as spheres and polygons with precisely controlled morphology and molecular orientations. The resultant microstructures act as anisotropic emitters of circularly polarized luminescence. We report that synchronous crystallization of π-conjugated chiral cyclophanes forms concave hexagonal pyramidal microcrystals with homogeneous size, morphology, and orientation, which clearly paves the way for the precise control of skeletal crystallization under kinetic control. Furthermore, we show microcavity functions of the self-assembled micro-objects. The self-assembled π-conjugated polymer microspheres work as whispering gallery mode (WGM) optical resonators, where the photoluminescence exhibits sharp and periodic emission lines. The spherical resonators with molecular functions act as long-distance photon energy transporters, convertors, and full-color microlasers. Fabrication of microarrays with photoswitchable WGM microresonators by the surface self-assembly technique realizes optical memory with physically unclonable functions of WGM fingerprints. All-optical logic operations are demonstrated by arranging the WGM microresonators on synthetic and natural optical fibers, where the photoswitchable WGM microresonators act as a gate for light propagation via a cavity-mediated energy transfer cascade. Meanwhile, the sharp WGM emission line is appropriate for utilization as optical sensors for monitoring the mode shift and mode splitting. The resonant peaks sensitively respond to humidity change, absorption of volatile organic compounds, microairflow, and polymer decomposition by utilizing structurally flexible polymers, microporous polymers, nonvolatile liquid droplets, and natural biopolymers as media of the resonators. We further construct microcrystals from π-conjugated molecules with rods and rhombic plates, which act as WGM laser resonators with light-harvesting function. Our developments, precise design and control of organic/polymeric microstructures, form a bridge between nanometer-scale supramolecular chemistry and bulk materials and pave the way toward flexible micro-optics applications.

19.
Acta Otolaryngol ; 143(2): 113-120, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36722024

RESUMEN

BACKGROUND: The prevalence of hearing impairment in patients with diabetes was significantly higher, and the development of preventive methods is desirable. AIMS/OBJECTIVES: This study examined the effects of eicosapentaenoic acid (EPA) administration on the prevention of early hearing loss in diabetic mice. MATERIALS AND METHODS: Tsumura, Suzuki, Obese Diabetes (TSOD) mice were used as a model of diabetes and Tsumura, Suzuki, Non Obesity (TSNO) mice were used as controls. The animals were divided into three groups: the TSNO group and the TSOD (EPA-) group (provided sunflower oil), and the TSOD (EPA+) group (provided EPA). Auditory brainstem responses (ABRs) were measured and the cochlea was evaluated histologically. RESULTS: The TSOD (EPA+) group showed a lower tendency to increase thresholds than the TSOD (EPA-) group. The TSOD (EPA+) group had a significantly lower ABR threshold than the TSOD (EPA-) group from 11 to 14 months of age at 4 kHz. Narrowing of the capillary lumens in the stria vascularis and thickening of the vessel wall in the modiolus were observed in the TSOD (EPA-) group. CONCLUSIONS AND SIGNIFICANCE: It was suggested that the suppression of cochlear vascular atherosclerosis by EPA administration in TSOD mice suppressed early age-related hearing loss.


Asunto(s)
Sordera , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Pérdida Auditiva , Ratones , Animales , Ácido Eicosapentaenoico/farmacología , Ácido Eicosapentaenoico/uso terapéutico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Pérdida Auditiva/etiología , Pérdida Auditiva/prevención & control , Modelos Animales de Enfermedad , Obesidad , Cóclea/patología , Ratones Obesos
20.
FEBS Open Bio ; 13(3): 434-446, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36648092

RESUMEN

Cancer stem cells (CSCs) are proposed to be involved in tumor initiation and play important roles in cancer relapse, metastasis, and drug resistance. Therefore, the targeting of CSCs has potential for effective anticancer therapies. Curcumin is one of the most widely characterized phytochemicals with tumor-suppressive potential. GO-Y030 is a novel curcumin analogue exhibiting a much stronger growth-inhibitory effect than curcumin. In the present study, we verified the potency of GO-Y030 against a CSC population. We observed that GO-Y030 suppressed CSC sphere-forming ability in several cancer cell lines. Interestingly, a specific inhibitor of heat shock protein (HSP) 70 also exhibited effects similar to GO-Y030 (i.e. inhibition of CSC sphere formation and upregulation of HSP70 and HSP40 protein expression), suggesting that HSP70 and/or HSP40 might be target molecules of GO-Y030. We then performed an in vitro HSP70/HSP40-mediated refolding activity assay and observed that chaperone activity was efficiently inhibited by GO-Y030. Finally, we performed a substrate-binding assay to show that GO-Y030 reduced the binding of both HSP70 and HSP40 with their substrates. HSPs prevent denaturation or unfolding of client proteins under stressful conditions such as high temperature. Because CSCs by nature adapt to various stresses by reinforcing protein-folding activity, the function of HSP70/HSP40 is important for the maintenance of CSC population. Our data suggest that GO-Y030 may impair stress tolerance in CSCs by inhibiting the interaction of HSP70/HSP40 with their substrate proteins and disrupting the function of HSP70/HSP40, thereby contributing to a reduction of the CSC population.


Asunto(s)
Curcumina , Humanos , Curcumina/farmacología , Proteínas del Choque Térmico HSP40/metabolismo , Línea Celular Tumoral , Recurrencia Local de Neoplasia , Proteínas HSP70 de Choque Térmico/metabolismo , Células Madre Neoplásicas/metabolismo
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