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1.
J Cardiol Cases ; 29(4): 193-196, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38646080

RESUMO

Acute limb ischemia (ALI) related to total knee arthroplasty (TKA) is rare. Most occlusions are caused by thrombus formation in the popliteal artery (PA). Currently such cases are revascularized using less invasive approaches such as endovascular therapy or Fogarty thrombectomy. We report a case of ALI in a 65-year-old woman with complete rupture of the PA due to a TKA procedure. She had resting pain and motor paralysis in her right lower extremity after TKA. Contrast-enhanced computed tomography showed occlusion of the right femoropopliteal artery. Subsequently, she was referred to our hospital with a diagnosis of ALI. Initially, a less invasive revascularization procedure was unsuccessfully attempted. Therefore, we performed an emergency distal bypass and succeeded in revascularization. Intraoperative examination revealed a complete rupture of the PA. Postoperatively, the patient exhibited no signs of myonephropathic metabolic syndrome. Although there was significant motor impairment, the affected limbs were successfully salvaged. ALI with complete rupture of the PA associated with TKA has not been reported previously. In cases of iatrogenic ALI after TKA, it would be essential to consider diagnostic and revascularization methods that account for the possibility of severe injury to the PA. Learning objective: Acute limb ischemia after total knee arthroplasty is a rare and life- and limb-threatening condition. The underlying pathological mechanism is often thrombus occlusion due to mechanical stimuli of the popliteal artery (PA). There are no established treatments for this condition, and less invasive approaches such as endovascular procedures and Fogarty thrombectomy are often used. However, in cases involving severe damage to the PA, bypass surgery may be necessary, and revascularization procedures should be considered accordingly.

2.
Gastroenterology ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583723

RESUMO

BACKGROUND: Gastric cancer is often accompanied by a loss of MUC6, but its pathogenic role in gastric carcinogenesis remains unclear. METHOD: Muc6 knockout (Muc6-/-) mice and Muc6-dsRED mice were newly generated. Tff1Cre, Golph3-/-, R26-Golgi-mCherry, Hes1flox/flox, Cosmcflox/flox, A4gnt-/- mice were also used. Histology, DNAs and RNAs, proteins, and sugar chains were analyzed by whole exon DNA sequence, RNA sequence, immunohistochemistry, lectin-binding assays, and LC-MS analysis. Gastric organoids and cell lines were used for in vitro assays and xenograft experiments. RESULT: Deletion of Muc6 in mice spontaneously causes pan-gastritis and invasive gastric cancers. Muc6-deficient tumor growth was dependent on MAPK activation, mediated by Golgi stress-induced upregulation of GOLPH3. Glycomic profiling revealed aberrant expression of mannose-rich N-linked glycans in gastric tumors, detected with Banana lectin in association with lack of MUC6 expression. We identified a precursor of clusterin as a binding partner of mannose glycans. MAPK activation, Golgi stress responses, aberrant mannose expression are found in a separate Cosmc- and A4gnt-deficient mouse models which lack normal O-glycosylation. Banana lectin-drug conjugates proved an effective treatment for mannose-rich murine and human gastric cancer. CONCLUSION: We propose that Golgi stress responses and aberrant glycans are important drivers of, and promising new therapeutic targets for gastric cancer.

3.
Cell Mol Gastroenterol Hepatol ; 17(5): 745-767, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38309455

RESUMO

BACKGROUND & AIMS: Colorectal cancer (CRC) is the third most common cancer in the world. Gut microbiota has recently been implicated in the development of CRC. Actinomyces odontolyticus is one of the most abundant bacteria in the gut of patients with very early stages of CRC. A odontolyticus is an anaerobic bacterium existing principally in the oral cavity, similar to Fusobacterium nucleatum, which is known as a colon carcinogenic bacterium. Here we newly determined the biological functions of A odontolyticus on colonic oncogenesis. METHODS: We examined the induction of intracellular signaling by A odontolyticus in human colonic epithelial cells (CECs). DNA damage levels in CECs were confirmed using the human induced pluripotent stem cell-derived gut organoid model and mouse colon tissues in vivo. RESULTS: A odontolyticus secretes membrane vesicles (MVs), which induce nuclear factor kappa B signaling and also produce excessive reactive oxygen species (ROS) in colon epithelial cells. We found that A odontolyticus secretes lipoteichoic acid-rich MVs, promoting inflammatory signaling via TLR2. Simultaneously, those MVs are internalized into the colon epithelial cells, co-localize with the mitochondria, and cause mitochondrial dysfunction, resulting in excessive ROS production and DNA damage. Induction of excessive DNA damage in colonic cells by A odontolyticus-derived MVs was confirmed in the gut organoid model and also in mouse colon tissues. CONCLUSIONS: A odontolyticus secretes MVs, which cause chronic inflammation and ROS production in colonic epithelial cells, leading to the initiation of CRC.


Assuntos
Colo , Células-Tronco Pluripotentes Induzidas , Camundongos , Animais , Humanos , Colo/microbiologia , Espécies Reativas de Oxigênio , Composição de Bases , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Células Epiteliais , Bactérias/genética
4.
BMC Cancer ; 24(1): 218, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360579

RESUMO

BACKGROUND: Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr < 30 mL/min), but it is not completely known whether denosumab can be used in them. We aimed to determine the association between renal function and hypocalcemia development during denosumab treatment. METHODS: We included patients with solid cancer and bone metastases who started denosumab treatment between April 2017 and March 2019. They were classified into four groups based on creatinine clearance (Ccr; mL/min): normal (Ccr ≥ 80), mild (50 ≤ Ccr ˂80), moderate (30 ≤ Ccr ˂50), and severe (Ccr ˂30). Hypocalcemia was evaluated using the Common Terminology Criteria for Adverse Events (v5.0) based on the albumin-adjusted serum calcium levels; its incidence (stratified by renal function) and risk factors were investigated using a Chi-square test and logistic regression analysis. RESULTS: Of 524 patients (age: 69 ± 11 years; 303 men), 153 had a normal renal function and 222, 117, and 32 had mild, moderate, and severe renal dysfunction. The albumin-adjusted serum calcium level was higher than the measured (total) calcium level in most patients. The incidence of grade ≥ 1 hypocalcemia was 32.0% in the normal group and 37.4%, 29.9%, and 62.5% in the mild, moderate, and severe renal dysfunction groups, respectively. It was, therefore, higher in the severe renal dysfunction groups than in the normal group (P = 0.002). The incidence of grade ≥ 3 hypocalcemia did not differ significantly among the groups. Pre-treatment low serum calcium levels and severe renal dysfunction were risk factors for hypocalcemia. CONCLUSIONS: Evaluating denosumab-induced hypocalcemia required albumin adjustment, and its incidence was high among patients with severe renal dysfunction. Reduced serum calcium levels and severely impaired renal function were associated with an elevated hypocalcemia risk.


Assuntos
Conservadores da Densidade Óssea , Neoplasias Ósseas , Hipocalcemia , Nefropatias , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Hipocalcemia/induzido quimicamente , Hipocalcemia/prevenção & controle , Denosumab/efeitos adversos , Cálcio/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Estudos Retrospectivos , Neoplasias Ósseas/tratamento farmacológico , Albuminas/efeitos adversos , Nefropatias/induzido quimicamente
5.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 80(3): 279-286, 2024 Mar 20.
Artigo em Japonês | MEDLINE | ID: mdl-38311432

RESUMO

PURPOSE: The objective of this study was to compare the temperature dependence of a scintillation survey meter with and without the temperature compensation function. Investigation of temperature dependence is important to make precise measurements in various environments. METHOD: The experiment was conducted using the NaI (Tl) scintillation survey meter with the temperature compensation function (TCS-1172) and the NaI (Tl) and CsI (Tl) scintillation survey meters without the temperature compensation function (TCS-171, PDR-111). In all, 1 cm dose equivalent rate (µSv/h) was measured by changing the room temperature from 10 to 40 degree Celsius. RESULT: The results showed that the scintillation survey meter with the temperature compensation function had almost no change in the measured values with changes in room temperature, whereas the 1 cm dose equivalent rate of the scintillation survey meter without the temperature compensation function changed by a maximum of -7.2 (%/10°C) as temperature increased. CONCLUSION: This study confirms that the scintillation survey meter with the temperature compensation function was less dependent on temperature, and stable measurement was possible. However, it was suggested that the scintillation survey meter without the temperature compensation function might cause a drop in the measured value as the temperature rises.


Assuntos
Temperatura , Inquéritos e Questionários
6.
Biomed Rep ; 20(3): 51, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38357232

RESUMO

Serum microRNAs (miRNAs) are considered useful as non-invasive biomarkers for different diseases. However, the optimal method for extracting RNAs from serum is currently unknown. In the present study, several RNA extraction kits were used to examine the optimal kit. RNAs were extracted from the serum of 8-week-old C57BL/6NJcl male mice following the protocol of each RNA extraction kit. The yield of the extracted RNA samples was calculated, and an Agilent Bioanalyzer was used to assess the electrophoretic patterns. An Agilent mouse miRNA microarray was utilized to confirm the expression patterns of the extracted RNA samples. The results revealed significant differences in RNA yields from the miRNeasy Serum/Plasma Advanced kit and mirVana™ PARIS™ RNA and Native Protein Purification Kit compared with almost all other samples. Further, two peaks were determined in the miRNeasy Serum/Plasma Advanced kit using a small RNAs kit of Agilent Bioanalyzer, including one at 20-40 nucleotides (nt) and another at ~40-100 nt, whereas the other reagents had a single peak. This revealed that the extracted RNAs may differ in composition based on the RNA extraction method. Some types of miRNAs were only detected with certain RNA extraction reagents. This suggested that different RNA extraction reagents may cause differences in the types of miRNAs detected. On the other hand, the miRNAs commonly expressed by the three RNA extraction reagents are highly correlated in expression levels.

7.
Exp Ther Med ; 27(3): 120, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38361521

RESUMO

Mild cognitive impairment (MCI) is an early stage that can result in dementia. MCI can be reversed, and diagnosis at an early stage is crucial to control the progression to dementia. Dementia is currently diagnosed based on interviews and screening tests; however, novel biomarkers must be identified to allow early MCI detection. Therefore, the present study aimed to identify novel biomarkers in the form of blood microRNAs (miRNAs/miRs) for the diagnosis of MCI or early dementia. Blood samples were collected from C57BL/6NJcl male mice at four time points, including 4-week-old (4W), 8-week-old (8W), 36-week-old (36W) and 58-week-old (58W), and serum was isolated. Body weight and blood total cholesterol levels were increased, and blood alkaline phosphatase was decreased with aging. The 8W mice exhibited the highest cognitive ability in the Morris water maze test, whereas the 58W mice demonstrated decreased cognitive ability. The serum RNA concentrations of the 4W, 8W, 36W and 58W mice demonstrated no significant differences. Furthermore, small RNA levels were detected in the serum of all mice. miRNA microarray analysis revealed a >1.5-fold increase in the serum expression of two miRNAs (miR-21a-5p and miR-92a-3p) and a >1.5-fold decrease in the serum expression of two other miRNAs (miR-6769b-5p and miR-709) in 58W mice compared with those in 8W mice. In the future, we aim to further analyze aged mice to discover novel MCI biomarkers.

8.
Circ J ; 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38233147

RESUMO

BACKGROUND: The efficacy of guideline-directed medical therapy (GDMT) in the elderly remains unclear. This study evaluated the impact of GDMT (aspirin or a P2Y12inhibitor, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, ß-blocker, and statin) at discharge on long-term mortality in elderly patients with acute myocardial infarction (AMI) who had undergone percutaneous coronary intervention (PCI).Methods and Results: Of 2,547 consecutive patients with AMI undergoing PCI in 2009-2020, we retrospectively analyzed 573 patients aged ≥80 years. The median follow-up period was 1,140 days. GDMT was prescribed to 192 (33.5%) patients at discharge. Compared with patients without GDMT, those with GDMT were younger and had higher rates of ST-segment elevation myocardial infarction and left anterior descending artery culprit lesion, higher peak creatine phosphokinase concentration, and lower left ventricular ejection fraction (LVEF). After adjusting for confounders, GDMT was independently associated with a lower cardiovascular death rate (hazard ratio [HR] 0.35; 95% confidence interval [CI] 0.16-0.81), but not with all-cause mortality (HR 0.77; 95% CI 0.50-1.18). In the subgroup analysis, the favorable impact of GDMT on cardiovascular death was significant in patients aged 80-89 years, with LVEF <50%, or with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2. CONCLUSIONS: GDMT in patients with AMI aged ≥80 years undergoing PCI was associated with a lower cardiovascular death rate but not all-cause mortality.

9.
Invest New Drugs ; 42(1): 44-52, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38055127

RESUMO

Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application.


Assuntos
Antieméticos , Humanos , Antieméticos/uso terapêutico , Aprepitanto , Palonossetrom , Olanzapina/uso terapêutico , Cisplatino/efeitos adversos , Dexametasona/uso terapêutico
10.
Chembiochem ; 25(2): e202300760, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38063314

RESUMO

The bioproduction of valuable materials using biomass sugars is attracting attention as an environmentally friendly technology. However, its ability to fulfil the enormous demand to produce fuels and chemical products is limited. With a view towards the future development of a novel bioproduction process that addresses these concerns, this study investigated the feasibility of bioproduction of valuable substances using Corynebacterium glutamicum (C. glutamicum) with a chemically synthesized non-natural sugar solution. Cells were grown using the synthesized sugar solution as the sole carbon source and they produced lactate under oxygen-limited conditions. It was also found that some of the sugars produced by the series of chemical reactions inhibited cell growth since prior removal of these sugars increased the cell growth rate. The results obtained in this study indicate that chemically synthesized sugars have the potential to resolve the concerns regarding future biomass sugar supply in microbial biomanufacturing.


Assuntos
Corynebacterium glutamicum , Açúcares , Ácido Láctico , Corynebacterium glutamicum/genética , Biomassa , Engenharia Metabólica/métodos , Fermentação
11.
Front Immunol ; 14: 1284205, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38111589

RESUMO

The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving antigen immunotherapy (AIT) have not been fully clarified. Therefore, we started to perform house dust mite sublingual immunotherapy (HDM-SLIT) for 20 patients with atopic asthma comorbid with allergic rhinitis (AA+AR) who were already receiving ordinary treatments including inhaled corticosteroid (ICS). We examined percentages of circulating T follicular helper (cTfh) and regulatory (cTfr) cells and percentages of circulating regulatory T (cTreg) and B (cBreg) cells by FACS and we examined levels of Der-p/f sIgs by ELISA. Based on the symptom score (asthma control questionnaire: ACQ) and medication score ((global initiative for asthma: GINA) treatment step score) in patients with AA, the patients were divided into responders and non-responders. The percentage of cTfh2 cells significantly decreased and the percentage of cTfh1 cells significantly increased within the first year. Der-p/f sIgEs decreased after a transient elevation at 3 months in both groups. Notably, the percentage of cTfh2 cells and the ratio of cTfh2/cBreg cells and Der-p/f sIgEs greatly decreased in responders from 6 months to 12 months. The percentages of cTfr and cTreg cells showed significant negative correlations with the percentage of cTfh2 cells. The percentage of IL-4+ cTfh cells were significantly decreased and the percentage of IFN-γ+ cTfh cells were increased before treatment to 24 months in 6 patients examined (4 responders and 2 non-responders). We performed multi plelogistic regression analysis based on these results, the ratios of cTfh2/cTfr cells and cTfh2/cBreg cells at the start of therapy were statistically effective biomarkers for predicting the response to HDM-SLIT in patients with AA+AR.


Assuntos
Asma , Linfócitos B Reguladores , Transtornos Respiratórios , Imunoterapia Sublingual , Animais , Humanos , Pyroglyphidae , Dermatophagoides pteronyssinus , Linfócitos T Reguladores , Biomarcadores , Células T Auxiliares Foliculares
12.
Auris Nasus Larynx ; 51(2): 356-360, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37973437

RESUMO

IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder characterized by elevated IgG4 serum levels, abundant IgG4-positive plasmacyte infiltration, and fibrosis of various organs, including the head and neck. We aimed to provide an overall review of IgG4-RD in the sinonasal region and propose a novel entity and criteria of chronic rhinosinusitis (CRS) associated with IgG4-RD as "IgG4-CRS," a distinct manifestation of IgG4-RD in the sinonasal region. Sinonasal involvement has been increasingly recognized; however, this region is not included in the classic IgG4-RD-affected organs. The clinical features of IgG4-CRS, including its prevalence and relationship with allergies and olfactory disturbances, have also been explored. Serum IgG4 levels and IgG4-positive plasma cell infiltrations, crucial diagnostic factors, have been discussed in association with IgG4-CRS pathogenesis. Fibrosis, a hallmark of IgG4-RD, is observed in sinonasal tissues; however, typical fibrosis, such as storiform fibrosis, is not usually found. Mimics or complications in eosinophilic CRS (ECRS) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are highlighted. Treatment often involves typically effective glucocorticoids. Organ-specific diagnostic criteria for the sinonasal region have not currently been established. Hence, this review aims to foster awareness and understanding of IgG4-CRS among ENT physicians and to provide a basis for future research and diagnostic refinement.

13.
Case Rep Vasc Med ; 2023: 6730220, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034082

RESUMO

Background: Previous reports have revealed various endovascular intervention techniques for prosthetic femoropopliteal bypass occlusion (PFPBO); however, treatment for PFPBO remains challenging for most interventionalists and vascular surgeons because the procedure is complicated. Most of the reported techniques involve device implantation. In the present study, we performed a combination of surgical graft thrombectomy and drug-coated balloon angioplasty for PFPBO without implanting any additional devices. Furthermore, we determined the favorable long-term results of this treatment using follow-up angiography. Case Presentation. A 77-year-old man with a history of chronic kidney disease and coronary artery disease presented to our clinic with rest pain on his left leg. Seven years prior to the current consult, he underwent femoropopliteal bypass (FPB) surgery using a prosthetic graft due to in-stent occlusion of the left superficial femoral artery (SFA). Four years after surgery, a duplex ultrasound scan revealed stenosis of the proximal anastomosis site; hence, medical therapy was continued. On the current consult, diagnostic angiography revealed occlusion of the FPB and infrapopliteal vessels. In the first attempt at recanalization, the guidewire was unable to pass through the occluded SFA. Therefore, another technique was performed to revascularize the FPBO and infrapopliteal vessels. We obtained an angiography of the left leg after inserting the guiding sheath via the right common femoral artery (CFA). First, surgical thrombectomy using a Fogarty catheter via the exposed left CFA was performed. Following endovascular therapy via the right CFA, we performed drug-coated balloon angioplasty for anastomotic stenosis and recanalized occlusive infrapopliteal vessels. Restenosis was not observed on follow-up angiograms. On further follow-up angiography, there was notable regression of the residual stenosis at the proximal anastomosis of the prosthetic graft. Conclusion: This novel revascularization strategy may be a viable treatment option for PFPBO.

14.
Front Pediatr ; 11: 1289554, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027262

RESUMO

Introduction: Recent studies have suggested associations between RNF213 variants and the formation of periventricular anastomosis among patients with moyamoya disease, leading to early onset of cerebral hemorrhage and rebleeding. Case description: We report herein the case of a boy with Down syndrome and moyamoya syndrome. Exome sequencing identified a heterozygous RNF213 R4810K variant. After ischemic stroke occurred at 9 years old, indirect surgical revascularization was performed for the left cerebral hemisphere and improved ischemic symptoms and cerebral hypoperfusion, while the left choroidal anastomosis remained. At 13 years old, he presented with left thalamic hemorrhage attributed to the anterior choroidal artery, with rebleeding observed four days after the initial hemorrhage under strict blood pressure control. The patient was discharged without neurological deficits 20 days after the hemorrhagic stroke. Conclusion: Presence of an RNF213 variant and choroidal anastomosis may represent risk factors for cerebral hemorrhage in patients with Down syndrome and moyamoya syndrome, as well as in patients with moyamoya disease.

16.
PLoS Pathog ; 19(3): e1011282, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36976812

RESUMO

In the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects surfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy. Less is known about the impacts of gestational African-lineage ZIKV infections. Given high human immunodeficiency virus (HIV) burdens in regions where African-lineage ZIKV circulates, we evaluated whether pregnant rhesus macaques infected with simian immunodeficiency virus (SIV) have a higher risk of African-lineage ZIKV-associated birth defects. Remarkably, in both SIV+ and SIV- animals, ZIKV infection early in the first trimester caused a high incidence (78%) of spontaneous pregnancy loss within 20 days. These findings suggest a significant risk for early pregnancy loss associated with African-lineage ZIKV infection and provide the first consistent ZIKV-associated phenotype in macaques for testing medical countermeasures.


Assuntos
Aborto Espontâneo , Complicações Infecciosas na Gravidez , Vírus da Imunodeficiência Símia , Infecção por Zika virus , Zika virus , Gravidez , Feminino , Animais , Humanos , Zika virus/genética , Macaca mulatta , Primeiro Trimestre da Gravidez
18.
Eur J Clin Pharmacol ; 79(3): 407-414, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36645467

RESUMO

PURPOSE: Chemotherapy-induced neutropenia (CIN) is a dose-limiting factor for cytotoxic chemotherapy, but recently, it was suggested that CIN contributes to prolonged survival. In this study, we examined the association between severe CIN and survival and determined whether CIN affected survival in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: The medical records from 214 patients with ES-SCLC treated with etoposide or irinotecan in combination with cisplatin (EP/IP) between 2012 and 2016 were collected and retrospectively analyzed. Landmark analysis was performed at the end of cycle 4, and the relationship between severe CIN and survival was determined by a log-rank test. In addition, a multivariate analysis using the COX proportional hazard model was performed to identify independent predictive factors. The Landmark analysis included 102 patients in the IP group and 47 patients in the EP group. RESULTS: No significant difference was found between grades 0-3 and grade 4 neutropenia and overall survival (OS) in the EP group (P = 0.57). Contrariwise, for the IP patients, the median OS was 444 days for grades 0-3 and 633 days for grade 4 neutropenia, which was significantly longer for patients who developed grade 4 neutropenia (P = 0.03). Multivariate analysis adjusted for potential factors revealed that the development of grade 4 CIN was identified as a significant predictor of longer OS (hazard ratio [HR], 0.50; 95% confidence interval (CI), 0.28-0.87, P = 0.015). CONCLUSION: The results indicated that the development of severe CIN with IP therapy is associated with prolonged OS.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Neutropenia , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neutropenia/induzido quimicamente , Cisplatino/efeitos adversos , Antineoplásicos/uso terapêutico
19.
Cancer Sci ; 114(4): 1672-1685, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36511816

RESUMO

The molecular subtypes of pancreatic cancer (PC), either classical/progenitor-like or basal/squamous-like, are currently a major topic of research because of their direct association with clinical outcomes. Some transcription factors (TFs) have been reported to be associated with these subtypes. However, the mechanisms by which these molecular signatures of PCs are established remain unknown. Epigenetic regulatory processes, supported by dynamic changes in the chromatin structure, are essential for transcriptional profiles. Previously, we reported the importance of open chromatin profiles in the biological features and transcriptional status of PCs. Here, we aimed to analyze the relationships between three-dimensional (3D) genome structures and the molecular subtypes of human PCs using Hi-C analysis. We observed a correlation of the specific elements of 3D genome modules, including compartments, topologically associating domains, and enhancer-promoter loops, with the expression of related genes. We focused on HNF1B, a TF that is implicated in the progenitor subtype. Forced expression of HNF1B in squamous-type PC organoids induced the upregulation and downregulation of genes associated with progenitor and squamous subtypes, respectively. Long-range genomic interactions induced by HNF1B were accompanied by compartment modulation and H3K27ac redistribution. We also found that these HNF1B-induced changes in subtype-related gene expression required an intrinsically disordered region, suggesting a possible involvement of phase separation in compartment modulation. Thus, mapping of 3D structural changes induced by TFs, such as HNF1B, may become a useful resource for further understanding the molecular features of PCs.


Assuntos
Carcinoma de Células Escamosas , Genoma , Humanos , Cromatina/genética , Fatores de Transcrição/genética , Epigênese Genética , Carcinoma de Células Escamosas/genética , Fator 1-beta Nuclear de Hepatócito/genética , Fator 1-beta Nuclear de Hepatócito/metabolismo
20.
Circ Rep ; 4(10): 474-481, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36304433

RESUMO

Background: As life expectancy rises, percutaneous coronary intervention (PCI) is being performed more frequently, even in elderly patients with acute myocardial infarction (AMI). This study evaluated outcomes of elderly patients with AMI complicated by heart failure (AMIHF), as defined by Killip Class ≥2 at admission, who undergo PCI. Methods and Results: We retrospectively analyzed 185 patients with AMIHF aged ≥80 years (median age 85 years) who underwent PCI between 2009 and 2019. The median follow-up period was 572 days. The rates of in-hospital major bleeding (Bleeding Academic Research Consortium Type 3 or 5) and in-hospital all-cause mortality were 20.5% and 25.9%, respectively. The proportion of frail patients increased during hospitalization, from 40.6% at admission to 59.2% at discharge (P<0.01). The cumulative incidence of all-cause mortality was 36.3% at 1 year and 44.1% at 2 years. After adjusting for confounders, advanced age, Killip Class 4, final Thrombolysis in Myocardial Infarction flow grade <3, and longer door-to-balloon time were associated with higher mortality, whereas higher left ventricular ejection fraction and cardiac rehabilitation were associated with lower mortality (all P<0.05). Progression of frailty during hospitalization was an independent risk factor for long-term mortality in hospital survivors (P<0.01). Conclusions: The management of patients with AMIHF aged ≥80 years who undergo PCI remains challenging, with high rates of in-hospital major bleeding, frailty progression, and mortality.

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