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1.
J Clin Med ; 13(18)2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39337019

RESUMEN

Background: Cardiac neoplasms may cause life-threatening symptoms associated with cerebral infarction, ventricular arrhythmias, and heart failure. Emergency surgery or preoperative treatment may be required for these patients. However, no study has reported the surgical outcomes in cases involving cardiac neoplasms with life-threatening complications. The current study investigated the mid- to long-term outcomes of surgery in patients with cardiac neoplasms in life-threatening conditions. Methods: This study retrospectively analyzed 36 consecutive patients who underwent resection for cardiac neoplasms with life-threatening cardiovascular, respiratory, and cerebral nervous system complications from January 2000 to December 2022. Their mean age at surgery was 54.9 years. In terms of fatal events, one patient who experienced a ventricular tachycardia storm caused by a left ventricular neoplasm was placed under deep sedation and managed with a ventilator preoperatively. Seven patients who presented with limb motor paralysis and visual defects had cerebral infarction. Two of the seven patients with cerebral infarction received cerebrovascular treatment before cardiac surgery. Results: During the follow-up period, cerebral- and cardiovascular-related deaths were not recorded. All postoperative cerebral and cardiovascular complications were new-onset cerebral infarction (n = 2) (with symptoms that improved during the long term). The mean follow-up period was 6.2 years. The 5- and 10-year survival rates of all patients were 89.8% and 78.7%, respectively. There were no significant differences in postoperative prognosis between patients with preoperative cerebral infarctions and those without. Conclusions: The long-term surgical outcome of patients with life-threatening symptomatic cardiac neoplasm was good. Thus, preoperative complications did not affect prognosis.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39302664

RESUMEN

OBJECTIVES: Endoscopic evaluation of anastomosis is effective for the early detection of anastomotic complications after a bronchoplastic procedure. Herein, we aimed to clarify important findings for predicting anastomotic complications. METHODS: This single-centre retrospective study included patients who underwent bronchoplastic surgery between April 2013 and September 2023. Only cases in which bronchoscopy was performed both 1 and 2 weeks after surgery were included. Endoscopic findings (classification by Ludwig and Stoelben, mucosa colour, oedema, slough area and colour, and depression) were reviewed for all cases. The accuracy of these findings for predicting anastomotic complications was evaluated. RESULTS: Of the 190 patients included in this study, 14 (7.4%) experienced anastomotic abnormalities, 11 had fistulas (5.8%), and 7 had stenosis (3.7%). The onsets of fistula and stenosis were 20-28 and 20-44 days after surgery, respectively. In 102 patients (53.7%), the slough worsened from the first to the second week post-surgery. Therefore, it was easier to evaluate slough 2 weeks post-surgery rather than 1-week post-surgery. The positive/negative predicted values of anastomotic complications in endoscopic findings 2 weeks post-surgery were circular slough, 34.2%/99.3%; slough with dark colour, 39.3%/98.1%; and depression, 54.2%/99.4%. The incidence of anastomotic abnormalities was 0% in cases without the three findings, 10% in cases with at least one finding, and 67% in cases with all three findings. CONCLUSIONS: The endoscopic findings of slough on the anastomosis 2 weeks after bronchoplasty can be easily evaluated and accurately predict complications. Three important endoscopic findings were circular slough, dark colour, and depression.

3.
Radiol Case Rep ; 19(11): 4818-4823, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39228956

RESUMEN

A 29-year-old man with diabetic nephropathy presented with fever and chills 4 days postdischarge following hospitalization for hyperglycemia. Abdominal computed tomography revealed a splenic abscess. Percutaneous drainage was performed, and intravenous meropenem was administered. Subsequent culture of the drained abscess identified Lancefieldella rimae. Based on the antimicrobial susceptibility results, the patient was switched to oral levofloxacin. This combined treatment led to the resolution of the abscess, with no recurrence after 6 months. This is the first case of a splenic abscess caused by L. rimae successfully managed by prompt percutaneous drainage and appropriate antibiotics.

4.
Biol Pharm Bull ; 47(9): 1504-1510, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39284734

RESUMEN

Signal transducer and activator of transcription 3 (STAT3) is a pleiotropic factor involved in multiple vital biological processes and a key mediator of gene transcription in response to cytokines, growth factors and aberrant activation of oncogenic signaling. STAT3 has two splicing isoforms, STAT3α and STAT3ß, derived from alternative splicing of exon 23 within pre-mRNA. STAT3ß differs from STAT3α by replacement of 55 amino-acid residues in the C-terminal transactivation domain with 7 specific amino acids. Thus, a shorter STAT3ß was originally regarded as a dominant negative isoform of STAT3α. Recently accumulating evidence from independent studies have shown STAT3 splicing isoforms confer distinct and overlapping functions in many fundamental cellular regulatory steps such as cell differentiation, inflammatory responses, and cancer progression. However, relatively little is known about the mechanisms of STAT3 pre-mRNA splicing, and it remains undiscovered which chemical compounds or bioactive substances can induce the STAT3ß expression. In this study, we generated a potent reporter for detection of alternative splicing of STAT3 pre-mRNA optimized for the screening of function-known chemical library, and successfully identified entinostat, a histone deacetylase inhibitor, as a novel inducer of STAT3ß through modulating mRNA splicing. Our findings demonstrate that alternative splicing of STAT3 can be regulated by a compound, providing an important clue for understanding the regulation mechanisms of the expression balance of STAT3 isoforms in a chemical biology approach. Entinostat is likely to be a promising seed compound for elucidating how the higher ratio of STAT3ß expression impacts on biological responses associated with Janus kinase (JAK)/STAT3 signaling pathway.


Asunto(s)
Empalme Alternativo , Benzamidas , Piridinas , Precursores del ARN , Factor de Transcripción STAT3 , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Empalme Alternativo/efectos de los fármacos , Humanos , Precursores del ARN/genética , Precursores del ARN/metabolismo , Piridinas/farmacología , Benzamidas/farmacología , Inhibidores de Histona Desacetilasas/farmacología , Células HEK293 , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo
5.
Thorac Cancer ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39230026

RESUMEN

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide despite advances in cancer therapeutics. In several gynecological cancers, anti-Müllerian hormone receptor type 2 (AMHR2) mediates AMH-induced growth inhibition and is expressed at high levels. Furthermore, 5%-8% of NSCLCs exhibit high AMHR2 expression, suggesting that AMH may inhibit the progression of some lung cancers. However, the clinical relevance of AMHR2 expression and its role in lung cancer is not fully clarified. METHODS: Immunostaining was performed on 79 surgical specimens of NSCLC. The Cancer Genome Atlas RNA-seq data for lung adenocarcinoma were analyzed, and gene ontology and gene set enrichment analyses were performed. In cellular experiments, AMHR2-overexpressing NSCLC cell lines were established, and the role of the AMH-AMHR2 pathway in cell proliferation with recombinant human AMH protein treatment was examined. RESULTS: A total of 13 cases (16.5%) were positive for immunostaining in lung adenocarcinoma tissues; no positive signals were detected in lung squamous carcinoma tissues. Gene expression variation analysis using The Cancer Genome Atlas data showed that the expression of genes related to the cell cycle was downregulated in the AMHR2-high group. Cellular experiments showed that activation of the AMH-AMHR2 pathway suppressed cell proliferation. CONCLUSION: In lung adenocarcinoma tissues with high expression of AMHR2, activation of the AMH-AMHR2 pathway may suppress cell proliferation.

6.
Surg Today ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39245749

RESUMEN

PURPOSE: We assessed the safety of general thoracic surgery in patients with prior coronary stents undergoing lung resection, based on differences in perioperative antiplatelet therapy management. METHODS: We retrospectively examined 150 patients with coronary artery stents who underwent pulmonary resection between July 2009 and July 2018. The impact of the antiplatelet agent on thoracic surgery safety was assessed by comparing perioperative outcomes, including major adverse cardiac and cerebrovascular events, among the discontinued antiplatelet therapy (group D), heparin bridging (group H), and continuous antiplatelet therapy (group C) groups. RESULTS: Groups D, H, and C included twenty-four, eighty-four, and forty-two patients, respectively. Second-generation drug-eluting stents were used in > 50% of the patients. No significant differences were found in the estimated blood loss, transfusion rate, or operative duration. Major adverse cardiac and cerebrovascular events occurred in four (2.7%) patients, which was comparable among the groups. In group H, postoperative heart failure and transient ischemic attack with stroke occurred in one patient each. Major bleeding occurred in two (4.7%) patients in group C. CONCLUSIONS: Pulmonary resection surgical outcomes in patients with coronary artery stents were feasible regardless of antiplatelet therapy continuation. However, discontinuing dual-antiplatelet or single-antiplatelet therapy in such patients may be reasonable because this generation of drug-eluting stents has a higher safety profile than bare-metal and first-generation drug-eluting stents.

8.
J Med Imaging (Bellingham) ; 11(4): 047501, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39087085

RESUMEN

Purpose: Endometrial cancer (EC) is one of the most common types of cancer affecting women. While the hematoxylin-and-eosin (H&E) staining remains the standard for histological analysis, the immunohistochemistry (IHC) method provides molecular-level visualizations. Our study proposes a digital staining method to generate the hematoxylin-3,3'-diaminobenzidine (H-DAB) IHC stain of Ki-67 for the whole slide image of the EC tumor from its H&E stain counterpart. Approach: We employed a color unmixing technique to yield stain density maps from the optical density (OD) of the stains and utilized the U-Net for end-to-end inference. The effectiveness of the proposed method was evaluated using the Pearson correlation between the digital and physical stain's labeling index (LI), a key metric indicating tumor proliferation. Two different cross-validation schemes were designed in our study: intraslide validation and cross-case validation (CCV). In the widely used intraslide scheme, the training and validation sets might include different regions from the same slide. The rigorous CCV validation scheme strictly prohibited any validation slide from contributing to training. Results: The proposed method yielded a high-resolution digital stain with preserved histological features, indicating a reliable correlation with the physical stain in terms of the Ki-67 LI. In the intraslide scheme, using intraslide patches resulted in a biased accuracy (e.g., R = 0.98 ) significantly higher than that of CCV. The CCV scheme retained a fair correlation (e.g., R = 0.66 ) between the LIs calculated from the digital stain and its physical IHC counterpart. Inferring the OD of the IHC stain from that of the H&E stain enhanced the correlation metric, outperforming that of the baseline model using the RGB space. Conclusions: Our study revealed that molecule-level insights could be obtained from H&E images using deep learning. Furthermore, the improvement brought via OD inference indicated a possible method for creating more generalizable models for digital staining via per-stain analysis.

9.
Sensors (Basel) ; 24(15)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39123875

RESUMEN

We propose a hands-free control system for a human-guided smart stroller. The proposed method uses real-time peer-to-peer localization technology of the human and stroller to realize an intuitive hands-free control system based on the relative position between the human and the stroller. The control method is also based on functional and mechanical safety to ensure the safety of the stroller's occupant (child) and the pilot (parent) during locomotion. In this paper, first, we present a preliminary investigation of the humans' preference for the relative position in the context of hands-free guided strollers. Then, we present the control method and a prototype implemented with an electric wheelchair and UWB sensors for localization. We present an experimental evaluation of the proposed method with 14 persons walking with the developed prototype to investigate the usability and soundness of the proposed method compared to a remote joystick and manual operation. The evaluation experiments were conducted in an indoor environment and revealed that the proposed method matches the performance of joystick control but does not perform as well as manual operation. Notably, for female participants, the proposed method significantly surpasses joystick performance and achieves parity with manual operation, which shows its efficacy and potential for a smart stroller. Also, the results revealed that the proposed method significantly decreased the user's physical load compared to the manual operation. We present discussions on the controllability, usability, task load, and safety features of the proposed method, and conclude this work with a summary assessment.


Asunto(s)
Silla de Ruedas , Humanos , Femenino , Masculino , Caminata/fisiología , Adulto , Diseño de Equipo , Interfaz Usuario-Computador
10.
JACC Cardiovasc Interv ; 17(16): 1891-1901, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39197987

RESUMEN

BACKGROUND: The introduction of radial-specific equipment has made transradial (TR) aortoiliac (AI) endovascular therapy (EVT) more convenient. OBJECTIVES: The authors aimed to investigate the perioperative outcomes of the TR approach in patients undergoing AI EVT for symptomatic peripheral artery disease. METHODS: The COMFORT (Contemporary Strategy for Aortoiliac Intervention) registry was a prospective, multicenter, observational study enrolling patients with symptomatic peripheral artery disease undergoing AI EVT between January 2021 and June 2023. The primary outcome was perioperative complications, whereas the secondary outcomes included core laboratory-evaluated residual stenosis >30%, time to hemostasis, time to ambulation, 30-day patency, and 30-day limb symptoms. These outcomes were compared between TR and non-TR AI EVT after propensity score matching. RESULTS: The TR approach was selected for 231 of the 947 patients (24.3%). The TR approach was chosen more in patients with a higher ankle-brachial index, chronic total occlusion, aortic lesion, bare nitinol stent implantation, and plain angioplasty, whereas it was chosen less in patients with dialysis, a history of AI EVT, chronic limb-threatening ischemia, bilateral calcification, and simultaneous infrainguinal EVT (all P < 0.05). After propensity score matching, the incidence of perioperative complications did not differ significantly between the groups (TR group: 6.0% vs non-TR group: 5.1%; P = 0.69). The proportions of residual stenosis, 30-day patency, and 30-day limb symptoms were not significantly different (all P > 0.05); however, the time to hemostasis and the time to ambulation were shorter in the TR group (both P < 0.05). CONCLUSIONS: Non-TR AI EVT and TR AI EVT using radial-specific equipment were associated with a similar risk of perioperative complications. The TR approach helps shorten the time required for hemostasis and ambulation.


Asunto(s)
Procedimientos Endovasculares , Arteria Ilíaca , Enfermedad Arterial Periférica , Arteria Radial , Sistema de Registros , Grado de Desobstrucción Vascular , Humanos , Femenino , Masculino , Anciano , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Estudios Prospectivos , Arteria Radial/fisiopatología , Resultado del Tratamiento , Factores de Tiempo , Arteria Ilíaca/diagnóstico por imagen , Arteria Ilíaca/fisiopatología , Arteria Ilíaca/cirugía , Persona de Mediana Edad , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/diagnóstico por imagen , Factores de Riesgo , Medición de Riesgo , Anciano de 80 o más Años , Cateterismo Periférico/efectos adversos , Stents , Punciones
11.
Respir Investig ; 62(5): 901-909, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39116798

RESUMEN

BACKGROUND: Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. The overall survival has not improved significantly over the last decades because no major therapeutic breakthroughs have been achieved for over 15 years. METHODS: We analyzed a genome-wide loss-of-function screening database to identify vulnerabilities in SCLC for the development of urgently needed novel therapies. RESULTS: We identified SKP2 (encoding S-phase kinase-associated protein 2) and CKS1B (encoding CDC28 protein kinase regulatory subunit 1B) as the two most essential genes in that order in SCLC. Notably, SKP2 and CKS1B comprise the p27 binding pocket of the E3 ubiquitin ligase SCFSKP2 complex. Immunohistochemistry on tissue microarrays revealed that SKP2 was expressed in >95% of samples at substantially higher levels than that observed for commonly used neuroendocrine markers. As expected, SCLC cell lines were sensitive to SKP2 inhibition. Furthermore, SKP2 or CKS1B knockdown induced apoptosis in RB1 mutant cells, whereas it induced senescence in RB1 wild-type cells. CONCLUSION: Although the mechanism underlying SKP2 knockdown-induced growth inhibition differs between RB1-wild-type and -mutant SCLC, SKP2 can be considered a novel therapeutic target for patients with SCLC regardless of the RB1 mutation status. Our findings indicate that SKP2 is a potential novel clinical diagnostic marker and therapeutic target in SCLC.


Asunto(s)
Biomarcadores de Tumor , Quinasas CDC2-CDC28 , Neoplasias Pulmonares , Proteínas Quinasas Asociadas a Fase-S , Carcinoma Pulmonar de Células Pequeñas , Proteínas Quinasas Asociadas a Fase-S/genética , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Humanos , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/terapia , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Quinasas CDC2-CDC28/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Mutación , Terapia Molecular Dirigida , Apoptosis/genética , Línea Celular Tumoral , Proteínas de Unión a Retinoblastoma/genética , Proteínas de Unión a Retinoblastoma/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
12.
Artículo en Inglés | MEDLINE | ID: mdl-39189053

RESUMEN

BACKGROUND: Endovascular therapy (EVT) is often performed for diffuse femoropopliteal lesions. This study investigated 3-year patency and clinical outcomes in patients with EVT-treated femoropopliteal lesions >25 cm. METHODS: This retrospective multicenter registry analyzed patients who presented with lower extremity artery disease having femoropopliteal lesions >25 cm who underwent EVT between 2017 and 2021. The primary outcome was restenosis 3 years after EVT. RESULTS: Overall, 504 patients with 614 lesions undergoing EVT for diffuse femoropopliteal lesions were enrolled. The prevalence of restenosis was 184.3 per 1000 lesion-years. Kaplan-Meier estimate of freedom from restenosis was 58.6% at 3 years. In the multivariate Poisson regression model, female sex (adjusted incidence risk ratio: 1.54; p = 0.003), cilostazol use (0.44; p < 0.001), revascularization history (1.87; p = 0.001), P3 involvement (2.09; p < 0.001), and reference vessel diameter <5 mm (1.88; p < 0.001) were associated independently with restenosis risk. The accumulation of these factors was associated with a lower rate of freedom from restenosis; the Kaplan-Meier estimates of the rates were 49.3% and 22.4% in the subgroups with two and more risk factors, respectively, while they were 81.1% in patients without any risk factors and 70.3% in those with one risk factor. CONCLUSIONS: Female sex, nonuse of cilostazol, revascularization history, P3 involvement, and small vessels were associated with high restenosis risk after EVT for diffuse femoropopliteal lesions. Although patients with multiple risk factors have a low patency rate, EVT offers an acceptable patency rate for those with fewer risk factors.

13.
Surg Today ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39190110

RESUMEN

PURPOSE: We aimed to identify preoperative risk factors for secondary spontaneous pneumothorax surgery. METHODS: The National Clinical Database of Japan, with six annual datasets from 2014 to 2019, was used. All patients who underwent surgery for secondary spontaneous pneumothorax were included, excluding those < 15 years old and those with incomplete data. The effects of preoperative risk factors were analyzed for operative mortality (mortality during hospitalization or within 30 days, regardless of hospitalization status), 30-day mortality, and postoperative respiratory morbidities. RESULTS: Of the 18,309 patients enrolled in the study, operative mortality, 30-day mortality, and postoperative respiratory morbidities were observed in 654 (3.6%), 343 (1.9%), and 2258 (12.3%) patients, respectively. Increasing age, male sex, body mass index < 18.5 or > 30, performance status > 2, emergent surgery, interstitial pneumonia, and diabetes in preoperative co-morbidity, tumors, and other diseases in underlying lung disease were significant risk factors for operative mortality. Those for 30-day mortality included autoimmune disease instead of male sex and diabetes, while those for postoperative respiratory morbidities included lymphangiomyomatosis instead of a body mass index > 30. CONCLUSION: We identified many preoperative risk factors for operative mortality, 30-day mortality, and postoperative respiratory morbidities in secondary spontaneous pneumothorax surgery. These findings will assist in selecting appropriate surgical candidates.

14.
J Endovasc Ther ; : 15266028241271725, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39183676

RESUMEN

BACKGROUND: Previous reports have shown comparable outcomes between drug-eluting stents (DESs) and drug-coated balloons (DCBs) for treating femoropopliteal artery (FPA) lesions; however, DCB outcomes include approximately 10% to 50% bailout stents. Therefore, comparing DESs and DCBs is not simple. The aim of this study was to compare the clinical outcomes of DESs and DCBs in patients with symptomatic FPA disease. MATERIALS AND METHODS: Using the registries of 7 institutions, we retrospectively reviewed the records of 1356 patients who underwent endovascular therapy for FPA with DESs (n=333; Eluvia, 74.0%; Zilver PTX stent, 26.0%) or DCBs without bailout stents (n=1023; IN.PACT, 67.6%; Lutonix, 32.4%). The primary outcome was the 1-year primary patency comparison between DESs and DCBs, using propensity score matching. The severity of the dissection pattern after predilatation (none or grades A-C) was included as an explanatory variable for matching. Patients with grade D dissections were excluded from the main analysis and assessed independently. RESULTS: After matching, the 1-year primary patency between DESs and DCBs was similar (88.8% vs 85.2%, p=0.31). By contrast, perioperative complications were frequent with DES, compared with DCB (5.1% vs 2.2%, p=0.005), and the intravascular ultrasound-evaluated minimum luminal area was significantly larger with DES than with DCB (19 mm2 vs 14 mm2, p<0.001). In the supplemental analysis of lesions with grade D dissection, the 1-year primary patency was significantly higher with DES than with DCB (86.1% vs 55.1%, p=0.014). CONCLUSION: In FPA lesions without severe dissection (ie, no dissection or grade A-C dissection), DESs and DCBs showed comparable 1-year primary patency in matched populations. However, DCBs did not perform well with severe dissection (ie, grade D or more). CLINICAL IMPACT: The results of this study clearly define the appropriate boundaries for the "leaving nothing behind" strategy. Clinicians can now more clearly differentiate between the use of DES and DCB, based on the results of lesion preparation. Further prospective investigations with well-designed trials and larger populations are necessary to confirm these findings.

15.
J Pharmacol Sci ; 156(2): 102-114, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39179329

RESUMEN

Synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are neurodegenerative disorders characterized by the aberrant accumulation of α-synuclein (α-syn). Although no treatment is effective for synucleinopathies, the suppression of α-syn aggregation may contribute to the development of numerous novel therapeutic targets. Recent research revealed that nicotinic acetylcholine (nACh) receptor activation has neuroprotective effects and promotes the degradation of amyloid protein by activating autophagy. In an in vitro human-derived cell line model, we demonstrated that galantamine, the nAChR allosteric potentiating ligand, significantly reduced the cell number of SH-SY5Y cells with intracellular Lewy body-like aggregates by enhancing the sensitivity of α7-nAChR. In addition, galantamine promoted autophagic flux, and prevented the formation of Lewy body-resembled aggregates. In an in vivo synucleinopathy mouse model, the propagation of α-syn aggregation in the cerebral cortex was inhibited by galantamine administration for 90 days. These results suggest that α7-nAChR is expected to be a novel therapeutic target, and galantamine is a potential agent for synucleinopathies.


Asunto(s)
Autofagia , Galantamina , alfa-Sinucleína , Receptor Nicotínico de Acetilcolina alfa 7 , Galantamina/farmacología , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , alfa-Sinucleína/metabolismo , Humanos , Autofagia/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Sinucleinopatías/tratamiento farmacológico , Sinucleinopatías/metabolismo , Fármacos Neuroprotectores/farmacología , Masculino , Ratones , Agregado de Proteínas/efectos de los fármacos , Agregación Patológica de Proteínas/tratamiento farmacológico , Ratones Endogámicos C57BL
16.
Oncogene ; 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39095584

RESUMEN

Identifying the mechanisms of action of anticancer drugs is an important step in the development of new drugs. In this study, we established a comprehensive screening platform consisting of 68 oncogenes (MANO panel), encompassing 243 genetic variants, to identify predictive markers for drug efficacy. Validation was performed using drugs that targeted EGFR, BRAF, and MAP2K1, which confirmed the utility of this functional screening panel. Screening of a BRCA2-knockout DLD1 cell line (DLD1-KO) revealed that cells expressing SMO and GLI1 were resistant to olaparib. Gene set enrichment analysis identified genes associated with DNA damage repair that were enriched in cells overexpressing SMO and GLI1. The expression of genes associated with homologous recombination repair (HR), such as the FANC family and BRCA1/2, was significantly upregulated by GLI1 expression, which is indicative of PARP inhibitor resistance. Although not all representative genes of the nucleotide excision repair (NER) pathway were upregulated, NER activity was enhanced by GLI1. The GLI1 inhibitor was effective against DLD1-KO cells overexpressing GLI1 both in vitro and in vivo. Furthermore, the combination therapy of olaparib and GLI1 inhibitor exhibited a synergistic effect on DLD1-KO, suggesting the possible clinical application of GLI1 inhibitor targeting cancer with defective DNA damage repair. This platform enables the identification of biomarkers associated with drug sensitivity, and is a useful tool for drug development.

17.
J Vasc Surg Cases Innov Tech ; 10(4): 101543, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38994221

RESUMEN

Anastomosis of the prosthetic graft to the double-barreled aorta with intimal flap fenestration is a useful technique in surgery for chronic aortic dissection. Conversely, anastomosis to the false lumen's outer wall is prone to complications such as pseudoaneurysms, but little is known about the technique of reinforcing the double-barreled aorta. In this report, we describe a surgical case of chronic aortic dissection in which an H-shaped prosthetic graft was sutured to both aortic lumens, including the intimal flap, to prevent complications at the anastomosis site.

18.
Cancers (Basel) ; 16(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39001425

RESUMEN

The objective of this study was to evaluate the relationship between pathologic response and survival in patients with clinical stage II/IIIA nonsquamous non-small-cell lung cancer (NSCLC) who intended to undergo neoadjuvant chemotherapy with bevacizumab, followed by surgery. In this phase II NAVAL study evaluating the feasibility of neoadjuvant chemotherapy with cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg), followed by surgery, progression-free survival (PFS) and overall survival (OS) were assessed as the secondary endpoints. Patients were categorized based on the proportion of residual viable primary tumor in the resected specimen after neoadjuvant chemotherapy: those with residual tumor in less than one-third were classified as pathologic responders, the rest as nonresponders. Of the 30 patients, 25 underwent surgical resection after three cycles of neoadjuvant chemotherapy with bevacizumab; 5 did not undergo surgery. Among all 30 patients, the rates of 2- and 5-year PFS were 41.5% and 34.6%, respectively, and the rates of 2- and 5-year OS were 70.0% and 60.0%, respectively. A total of 6 patients (20%) were classified as pathologic responders; the other 24 (80%), as nonresponders. The five-year PFS differed significantly between pathologic responders (100%) and nonresponders (17.5%; p = 0.002). The five-year OS also differed significantly between pathologic responders (100%) and nonresponders (43.5%; p = 0.006). Pathologic response seems to be a predictor of survival. Long-term survival after surgery is expected for pathologic responders, whereas additional therapy is needed for nonresponders.

19.
JTO Clin Res Rep ; 5(7): 100693, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39034967

RESUMEN

Introduction: Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein overexpressed in various cancer types. Although TROP2-targeting therapy is currently attracting attention, little is known about TROP2 expression in thymic carcinoma. Methods: TROP2 gene expression in thymic epithelial tumors was analyzed using RNA-sequencing (RNA-seq) data for 122 cases obtained from The Cancer Genome Atlas. Immunohistochemistry (IHC) staining with anti-TROP2 antibody (SP295) was performed in 26 cases of thymic carcinoma tissues surgically resected at Juntendo University. Results: RNA-seq data analysis from The Cancer Genome Atlas revealed that TACSTD2 (gene encoding TROP2) expression was significantly higher in thymic carcinoma than in thymoma (adjusted p = 6.64e-05). There was also a trend of increasing expression in the order of thymoma type B1, B2, B3, and thymic carcinoma. As for IHC in thymic carcinoma, TROP2 expression was localized to the membrane of cancer cells. Intensity 0, 1, and 2 was observed in six (23.1%), 11 (42.3%), and nine (34.6%) cases, respectively, leading to TROP2 positivity in 20 cases (76.9%). The median proportion of TROP2-positive tumor cells and the median H-score were 25.0% (range: 0%-100%) and 25.0 (range: 0-200), respectively. No relevant factors were identified in the analysis of TROP2 expression and patient background. Although not significant, high TROP2 expression (H-score ≥ 50) tended to be associated with shorter survival. Conclusions: TROP2 expression in thymic carcinoma was confirmed by both RNA-seq and IHC, with high expression observed in IHC for intensity (76.9%) and proportion. TROP2 could be a potential target in thymic carcinoma.

20.
Artículo en Inglés | MEDLINE | ID: mdl-38950179

RESUMEN

OBJECTIVES: The long-term oncological outcomes and risk factors for recurrence after lung segmentectomy are unclear. The aims of this study were to investigate the long-term prognosis and to evaluate risk factors for recurrence after segmentectomy. METHODS: Between January 2008 and December 2012, a total of 177 patients underwent segmentectomy for clinical stage I non-small cell lung cancer. The median follow-up period was 120.1 months. The overall survival (OS) and recurrence-free survival curves were analysed using the Kaplan-Meier method with a log-rank test. Univariable and multivariable analyses were used to identify significant factors that predicted recurrence. RESULTS: The study included 177 patients with a median age of 67 years. The median operative time was 155 min. No 30-day deaths were observed. Nine patients (5.1%) had recurrences: loco-regional in 3, distant in 3 and both in 3. The 5-year and 10-year recurrence-free survival rates were 89.7% and 79.8%, and the OS rates were 90.9% and 80.4%, respectively. On multivariable analysis, the risk factor associated with recurrence was a pure solid tumour [hazard ratio, 23.151; 95% confidence interval 2.575-208.178; P = 0.005]. The non-pure solid tumour group had a significantly better probability of survival (5-year OS: 95.4% vs 77.2%; 10-year OS: 86.5% vs 61.8%; P < 0.0001). A total of 113 patients received preoperative positron emission tomography/computed tomography. Patients with a higher maximum standardized uptake value had a significantly higher recurrence rate. CONCLUSIONS: Segmentectomy for clinical stage I non-small cell lung cancer produced acceptable long-term outcomes. Pure solid radiographic appearance was associated with recurrence and decreased survival.

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