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1.
Front Oncol ; 14: 1395130, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38800402

RESUMO

Lipomas, benign tumors originating from the anomalous proliferation of adipocytes, predominantly emerge in regions rich in adipose tissue. However, their presence in the head and neck areas remains rare, constituting approximately 13% of all diagnosed lipoma cases. This study presents a case involving a substantial subcutaneous lipoma located at the posterior neck, measuring about 20 cm × 19 cm × 10 cm. The patient presented with swelling and pain in the back of the neck. And the considerable dimensions of this lipoma significantly impacted the patient's quality of life and aesthetic appearance. Concurrently, the patient exhibited symptoms indicative of degenerative cervical spine disease and cervical disc herniation. After admission, a comprehensive examination, including ultrasound, CT scan, and MRI, was conducted. Given the clinical complexity, the decision for surgical intervention was deemed essential. The surgical strategy entailed a meticulous total excision of the tumor through an incision made in the posterior cross-neck, coupled with the strategic removal of excess skin. To facilitate wound healing, postoperative management included the use of negative pressure drainage. Pathological examination conclusively identified the mass as a lipoma. Postoperative follow-ups indicated successful recovery, as evidenced by the restoration of the neck's aesthetic contour and the complete resolution of the previously observed restrictions in sagittal neck movement.

2.
Cell Commun Signal ; 22(1): 272, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750472

RESUMO

BACKGROUND: In the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive. METHODS: Lentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model. RESULTS: Trem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1ß, and caused further DNA damage and promoted the apoptosis rate of tumor cells. CONCLUSIONS: Our findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.


Assuntos
Glioma , Janus Quinase 2 , Glicoproteínas de Membrana , Microglia , NF-kappa B , Receptores Imunológicos , Fator de Transcrição STAT3 , Transdução de Sinais , Glioma/genética , Glioma/patologia , Glioma/metabolismo , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Microglia/metabolismo , Microglia/patologia , Animais , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Camundongos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Transdução de Sinais/genética , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Técnicas de Silenciamento de Genes , Proliferação de Células/genética , Humanos , Inflamação/genética , Inflamação/patologia , Apoptose/genética , Progressão da Doença , Movimento Celular/genética
3.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473752

RESUMO

Gliomas represent the most common and lethal category of primary brain tumors. Bisphenol A (BPA), a widely recognized endocrine disruptor, has been implicated in the progression of cancer. Despite its established links to various cancers, the association between BPA and glioma progression remains to be clearly defined. This study aimed to shed light on the impact of BPA on glioma cell proliferation and overall tumor progression. Our results demonstrate that BPA significantly accelerates glioma cell proliferation in a time- and dose-dependent manner. Furthermore, BPA has been found to enhance the invasive and migratory capabilities of glioma cells, potentially promoting epithelial-mesenchymal transition (EMT) characteristics within these tumors. Employing bioinformatics approaches, we devised a risk assessment model to gauge the potential glioma hazards associated with BPA exposure. Our comprehensive analysis revealed that BPA not only facilitates glioma invasion and migration but also inhibits apoptotic processes. In summary, our study offers valuable insights into the mechanisms by which BPA may promote tumorigenesis in gliomas, contributing to the understanding of its broader implications in oncology.


Assuntos
Glioma , Humanos , Linhagem Celular Tumoral , Compostos Benzidrílicos/farmacologia , Fenóis/farmacologia
4.
Nat Commun ; 15(1): 1533, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378868

RESUMO

CAMILLA is a basket trial (NCT03539822) evaluating cabozantinib plus the ICI durvalumab in chemorefractory gastrointestinal cancer. Herein, are the phase II colorectal cohort results. 29 patients were evaluable. 100% had confirmed pMMR/MSS tumors. Primary endpoint was met with ORR of 27.6% (95% CI 12.7-47.2%). Secondary endpoints of 4-month PFS rate was 44.83% (95% CI 26.5-64.3%); and median OS was 9.1 months (95% CI 5.8-20.2). Grade≥3 TRAE occurred in 39%. In post-hoc analysis of patients with RAS wild type tumors, ORR was 50% and median PFS and OS were 6.3 and 21.5 months respectively. Exploratory spatial transcriptomic profiling of pretreatment tumors showed upregulation of VEGF and MET signaling, increased extracellular matrix activity and preexisting anti-tumor immune responses coexisting with immune suppressive features like T cell migration barriers in responders versus non-responders. Cabozantinib plus durvalumab demonstrated anti-tumor activity, manageable toxicity, and have led to the activation of the phase III STELLAR-303 trial.


Assuntos
Anilidas , Anticorpos Monoclonais , Neoplasias Colorretais , Piridinas , Humanos , Anticorpos Monoclonais/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Biomarcadores , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
Mol Carcinog ; 62(11): 1731-1744, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37589446

RESUMO

The cell cycle, a pivotal regulator of cell proliferation, can be significantly influenced by the phosphatase and tensin homolog (PTEN)/AKT signaling pathway's modulation of cyclin-related proteins. In our study, we discovered the crucial role of EEF1E1 in this process, as it appears to downregulate PTEN expression. Furthermore, our findings affirmed that EEF1E1 modulates downstream cell cycle-related proteins by suppressing the PTEN/AKT pathway. Cell cycle assay results revealed that EEF1E1 downregulation stunted the advancement of glioma cells in both the G1 and S phases. A suite of assays-Cell Counting Kit-8, colony formation, and ethyl-2'-deoxyuridine-substantiated that the EEF1E1 downregulation markedly curtailed glioma proliferation. We further validated this phenomenon through animal studies and coculture experiments on brain slices. Our comprehensive investigation indicates that EEF1E1 knockdown can effectively inhibit the glioma cell proliferation by regulating the cell cycle via the PTEN/AKT signaling pathway. Consequently, EEF1E1 emerges as a potential therapeutic target for glioma treatment, signifying critical clinical implications.

6.
Cancer Med ; 12(15): 16098-16107, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37326317

RESUMO

BACKGROUND: Perioperative chemotherapy/chemoradiation is standard in esophageal/gastric/gastroesophageal junction (GEJ) adenocarcinoma, immune checkpoint inhibitors (ICI) effect in setting of metastatic and postoperatively. This study is to assess ICI + chemotherapy perioperatively. METHODS: Patients with locally advanced (T1N1-3M0 or T2-3NanyM0) potentially resectable esophageal/gastric/GEJ adenocarcinoma by PET/EUS/CT and staging-laparoscopy, were treated preoperative 4 cycles mFOLFOX6 (Oxaliplatin 85 mg/m2 /Leucovorin 400 mg/m2 /5-FU bolus 400 mg/m2 then infusion 2400 mg/m2 for 46 h q2weeks) and 3 cycles pembrolizumab (200 mg q3week). Those without distal disease post-neoadjuvant and eligible for resection underwent surgery. Postoperative treatment was initiated at 4-8 weeks with 4 cycles mFOLFOX and 12 cycles pembrolizumab. The primary objective is pathological response (ypRR with tumor regression score, TRS ≤2). The expression of ICI-related markers PD-L1 (CPS), CD8, and CD20 were analyzed before and after preoperative therapy. RESULTS: Thirty-seven patients completed the preoperative treatment. Twenty-nine patients had curative R0 resection. 6/29 (21%; 95% CI: 0.08-0.40) achieved ypCR with TRS 0 in resected patients. 26/29 (90%; 95% CI: 0.73-0.98) had ypRR with TRS ≤2. Twenty-six patients finished adjuvant therapy with a median 36.3-month follow-up. Three patients had recurrence/metastatic disease (at 9-, 10-, 22 months enrollment) with one dead at 23 months, and two are still alive at 28 and 36.5 months. The remaining (23/26) are free of disease with 3 years DFS of 88.5% and 3 years OS of 92.3%. There were no unexpected toxicities. Preoperative ICI + chemotherapy enhanced immune responses significantly with increasing expression of PD-L1 (CPS ≥10, p = 0.0078) and CD8 (>5%, p = 0.0059). CONCLUSIONS: The perioperative pembrolizumab and mFOLFOX combination in resectable esophageal/gastric/GEJ adenocarcinoma is very effective with 90% ypRR, 21% ypCR, and impressive long-time survival benefits.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Antígeno B7-H1 , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/cirurgia , Junção Esofagogástrica/patologia , Terapia Neoadjuvante , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia
7.
Vascul Pharmacol ; 148: 107143, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36682595

RESUMO

BACKGROUND: No study has compared pharmacologic properties of ticagrelor and clopidogrel in non-dialysis patients with stage 4-5 chronic kidney disease (CKD). METHODS: We conducted a double-blind RCT to compare effects of ticagrelor and clopidogrel in 48 CKD, with the primary outcome of ADP-induced platelet aggregation (WBPA) after 2 weeks of DAPT. In a parallel arm, we compared effects of 2 weeks of ticagrelor plus aspirin on mean changes in WBPA and markers of thromboinflammation among non-CKD controls (n = 26) with that of CKD in the ticagrelor-arm. RESULTS: Average age of CKD was 53.7 years, with 62% women, 54% African American, and 42% with stage 5 CKD. Ticagrelor generated statistically lower WBPA values post treatment [median 0 Ω (IQR 0, 2)] vs. clopidogrel [median 0 Ω (IQR 0, 5)] (P = 0.002); percent inhibition of WBPA was greater (87 ± 22% vs. 63 ± 50%; P = 0.04; and plasma IL-6 levels were much lower (8.42 ± 1.73 pg/ml vs. 18.48 ± 26.56 pg/ml; P = 0.04). No differences in mean changes in WBPA between CKD-ticagrelor and control groups were observed. Ticagrelor- DAPT reduced levels of IL-1α and IL-1ß in CKD-ticagrelor and control groups, attenuated lowering of TNFα and TRAIL levels in CKD-ticagrelor (vs controls), and had global changes in correlation between various cytokines in a subgroup of CKD-ticagrelor subjects not on statins (n = 10). Peak/trough levels of ticagrelor/metabolite were not different between CKD-ticagrelor and control groups. CONCLUSIONS: We report significant differences in platelet aggregation and anti-inflammatory properties between ticagrelor- and clopidogrel-based DAPT in non-dialysis people with stage 4-5 CKD. These notable inflammatory responses suggest ticagrelor-based DAPT might lower inflammatory burden of asymptomatic patients with stage 4 or 5 CKD. (clinicaltrials.gov # NCT03649711).


Assuntos
Insuficiência Renal Crônica , Trombose , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Clopidogrel/efeitos adversos , Ticagrelor/efeitos adversos , Agregação Plaquetária , Inibidores da Agregação Plaquetária/uso terapêutico , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Ticlopidina/efeitos adversos , Adenosina , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Resultado do Tratamento
8.
Cell Rep Med ; 4(2): 100916, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36702123

RESUMO

This is the phase Ib part of the phase I/II CAMILLA trial evaluating cabozantinib plus durvalumab in advanced chemo-refractory proficient mismatch repair or microsatellite stable (pMMR/MSS) gastrointestinal malignancies including gastric/gastroesophageal junction/esophageal (G/GEJ/E) adenocarcinoma, colorectal cancer (CRC), and hepatocellular carcinoma (HCC). Thirty-five patients are enrolled. There are no observed dose-limiting toxicities during dose escalation. The overall grade 3/4 treatment-related adverse event rate is 34%. Among evaluable patients (n = 30), the objective response rate (ORR) is 30%, disease control rate (DCR) 83.3%, 6-month progression-free survival (PFS) 36.7%, median PFS 4.5 months, and median overall survival (OS) 8.7 months. Responses are seen in 4 of 17, 3 of 10, and 2 of 3 patients with CRC, G/GEJ/E adenocarcinoma, and HCC, respectively. Participants with a PD-L1 combined positive score (CPS) ≥5 have numerically higher ORR, PFS, and OS. Cabozantinib plus durvalumab demonstrates a tolerable safety profile and potential efficacy in previously treated advanced pMMR/MSS gastrointestinal malignancies.


Assuntos
Adenocarcinoma , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Gástricas/patologia , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia
9.
Chest ; 163(4): 861-869, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36470416

RESUMO

BACKGROUND: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. No randomized, placebo-controlled data are available that support the role of immunosuppression to treat RA-associated ILD, despite being widely used in clinical practice. RESEARCH QUESTION: How does immunosuppression impact pulmonary function trajectory in a multisite retrospective cohort of patients with RA-associated ILD? STUDY DESIGN AND METHODS: Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were identified retrospectively from five ILD centers. Change in lung function before and after treatment was analyzed using a linear spline mixed-effect model with random intercept. Prespecified secondary analyses examined the impact of radiologic pattern of ILD (ie, usual interstitial pneumonia [UIP] vs non-UIP) on treatment trajectory. RESULTS: Two hundred twelve patients were included in the analysis: 92 patients (43.4%) were treated with azathioprine, 77 patients (36.3%) were treated with mycophenolate mofetil, and 43 patients (20.3%) were treated with rituximab. In the combined analysis of all three agents, an improvement in FVC % predicted was found after 12 months of treatment compared with the potential 12-month response without treatment (+3.90%; P ≤ .001; 95% CI, 1.95-5.84). Diffusing capacity of the lungs for carbon monoxide (Dlco) % predicted also improved at 12 months (+4.53%; P ≤ .001; 95% CI, 2.12-6.94). Neither the UIP pattern of ILD nor choice of immunosuppressive agent significantly impacted the pulmonary function trajectory on immunosuppression. INTERPRETATION: Immunosuppression was associated with an improved trajectory in FVC and Dlco compared with the pretreatment pulmonary function trajectory. Prospective, randomized trials are required to validate these findings.


Assuntos
Artrite Reumatoide , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Humanos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Azatioprina/uso terapêutico , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento , Capacidade Vital
10.
Kidney360 ; 3(8): 1374-1383, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-36176642

RESUMO

Background: Individuals aged ≥75 years are the fastest-growing population starting dialysis for end-stage kidney disease (ESKD) due to living longer with coronary artery disease. ESKD alone can increase bleeding risk, but P2Y12 inhibitor (P2Y12-I) antiplatelet medications prescribed for cardiovascular treatment can exacerbate this risk in patients with ESKD. The age-specific rates of bleeding complications in dialysis patients with ESKD on P2Y12-I remain unclear, as does how age modifies the bleeding risk from P2Y12-I use in these patients. Methods: In a retrospective cohort study, we collected data on 40,972 patients receiving maintenance hemo- or peritoneal dialysis who were newly prescribed P2Y12-I therapy between 2011 and 2015 from the USRDS registry. We analyzed the effect of age on the time to first bleed and the interactions between age and P2Y12-I type on modifying the effects of a bleed. Results: Twenty percent of the cohort were aged ≥75 years. There were 3096 (8%) gastrointestinal (GI) and 1298 (3%) intracranial (IC) bleeding events during a median follow-up of 1 year. Annual incidence rates for IC bleeds were 2% in those aged <55 years and 3% in those aged ≥75 years. Rates for GI bleeds were 4% in those aged <55 years and 9% in those aged ≥75 years. On clopidogrel, prasugrel, and ticagrelor, for every decade increase in age of the cohort members, the risk of IC bleed increased by 9%, 55%, and 59%, and the risk of GI bleed increased by 21%, 28%, and 39%, respectively. At age ≥75 years, prasugrel was associated with a greater risk of IC bleed than clopidogrel. At age ≥60 years, ticagrelor was associated with a greater risk of GI bleed than clopidogrel. Conclusions: More potent P2Y12-Is (prasugrel and ticagrelor) were associated with a disproportionately higher risk of IC bleed with increasing age compared with that of clopidogrel-prasugrel was much worse than clopidogrel at age ≥75 years. All three drugs were associated with only modest increase in the risk of GI bleed with every decade increase in age-ticagrelor was much worse than clopidogrel at ≥60 years of age. These results highlight the need for head-to-head clinical trials for the use of P2Y12-Is in patients with ESKD to determine age cutoffs where the risk of bleeding outweighs the benefits of thrombosis prevention.


Assuntos
Falência Renal Crônica , Antagonistas do Receptor Purinérgico P2Y , Idoso , Clopidogrel/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Falência Renal Crônica/induzido quimicamente , Pessoa de Meia-Idade , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Ticagrelor
11.
Kidney360 ; 3(12): 2036-2047, 2022 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-36591354

RESUMO

Background: Chronic kidney disease (CKD) is characterized by dysregulated inflammation that worsens with CKD severity. The role of platelets in modulating inflammation in stage 4 or 5 CKD remains unexplored. We investigated whether there are changes in platelet-derived thromboinflammatory markers in CKD with dual antiplatelet therapy (DAPT; aspirin 81 mg/d plus P2Y12 inhibitor). Methods: In a mechanistic clinical trial, we compared platelet activation markers (aggregation and surface receptor expression), circulating platelet-leukocyte aggregates, leukocyte composition (monocyte subtypes and CD11b surface expression), and plasma cytokine profile (45 analytes) of non-CKD controls (n=26) and CKD outpatients (n=48) with a glomerular filtration rate (GFR) <30 ml/min per 1.73 m2 on 2 weeks of DAPT. Results: Patients with CKD demonstrated a reduced mean platelet count, elevated mean platelet volume, reduced platelet-leukocyte aggregates, reduced platelet-bound monocytes, higher total non-classic monocytes in the circulation, and higher levels of IL-1RA, VEGF, and fractalkine (all P<0.05). There were no differences in platelet activation markers between CKD and controls. Although DAPT reduced platelet aggregation in both groups, it had multifaceted effects on thromboinflammatory markers in CKD, including a reduction in PDGF levels in all CKD individuals, reductions in IL-1ß and TNF-α levels in select CKD individuals, and no change in a number of other cytokines. Significant positive correlations existed for baseline IL-1ß, PDGF, and TNF-α levels with older age, and for baseline TNF-α levels with presence of diabetes mellitus and worse albuminuria. Mean change in IL-1ß and PDGF levels on DAPT positively correlated with younger age, mean change in TNF-α levels with higher GFR, and mean changes in PDGF, and TRAIL levels correlated with worse albuminuria. Minimum spanning trees plot of cytokines showed platelet-derived CD40L had a large reduction in weight factor after DAPT in CKD. Additionally, platelet-derived IL-1ß and PDGF were tightly correlated with other cytokines, with IL-1ß as the hub cytokine. Conclusions: Attenuated interactions between platelets and leukocytes in the CKD state coincided with no change in platelet activation status, an altered differentiation state of monocytes, and heightened inflammatory markers. Platelet-derived cytokines were one of the central cytokines in patients with CKD that were tightly correlated with others. DAPT had multifaceted effects on thromboinflammation, suggesting that there is platelet-dependent and -independent inflammation in stage 4 or 5 CKD.


Assuntos
Insuficiência Renal Crônica , Trombose , Humanos , Albuminúria/tratamento farmacológico , Citocinas , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inibidores da Agregação Plaquetária/uso terapêutico , Trombose/tratamento farmacológico , Fator de Necrose Tumoral alfa
12.
Oncol Nurs Forum ; 47(2): 203-212, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32078618

RESUMO

OBJECTIVES: To test the feasibility of adding driving simulation tasks to measure visuospatial ability and processing speed to an existing neurocognitive battery for breast cancer survivors (BCSs). SAMPLE & SETTING: 38 BCSs and 17 healthy controls from a cross-sectional pilot study conducted at the University of Kansas Medical Center. METHODS & VARIABLES: Exploratory substudy measuring pupillary response, visuospatial ability, and processing speed during two 10-minute driving simulations (with or without n-back testing) in a sample of BCSs with self-reported cognitive complaints and healthy controls. RESULTS: Feasibility of measurement of pupillary response during driving simulation was demonstrated. No between-group differences were noted for pupillary response during driving simulation. BCSs had greater visuospatial ability and processing speed performance difficulties than healthy controls during driving simulation without n-back testing and slower n-back response time. IMPLICATIONS FOR NURSING: Preliminary evidence showed a possible link between cancer/treatment on visuospatial ability and processing speed in BCSs.


Assuntos
Condução de Veículo , Neoplasias da Mama/complicações , Sobreviventes de Câncer , Cognição/fisiologia , Distúrbios Pupilares/diagnóstico , Distúrbios Pupilares/etiologia , Navegação Espacial/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Estudos de Viabilidade , Feminino , Humanos , Kansas , Pessoa de Meia-Idade , Projetos Piloto
13.
Cardiovasc Drugs Ther ; 33(5): 511-521, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31729588

RESUMO

BACKGROUND: Trends and clinical factors associated with prescribing choices for oral P2Y12 inhibitors (P2Y12-I) remain unknown for patients on chronic dialysis, i.e., with end-stage renal disease (ESRD). METHODS: From 2011-2014 U.S. Renal Data System registry, we identified 36,542 ESRD patients who received new prescriptions for P2Y12-I (median age 64.0 years and 54% males). Of the cohort, 93% were receiving hemodialysis and 7% on peritoneal dialysis. We analyzed trends and investigated clinical factors associated with specific P2Y12-I prescribed. RESULTS: Clopidogrel was prescribed for 95%, prasugrel for 3%, and ticagrelor for 2%. Clopidogrel was favored for those ≥75 years (18% of cohort). Compared to Caucasians, African Americans (36% of cohort) and Hispanics (19% of cohort) were less likely to receive prasugrel and ticagrelor (P<0.05). Patients receiving hemodialysis versus peritoneal dialysis were less likely to receive prasugrel over clopidogrel, adjusted odds ratio (aOR) 0.67 (0.55-0.82). Each additional year of dialysis decreased the odds of receiving prasugrel over clopidogrel, aOR 0.91 (0.85-0.98). History of atrial fibrillation reduced the odds of receiving ticagrelor or prasugrel over clopidogrel, aOR 0.69 (0.54-0.89) and 0.73 (0.60-0.89), respectively. Concomitant oral anticoagulant use was not associated with choice of P2Y12-I. Occurrence of non-ST segment elevation myocardial infarction or percutaneous coronary intervention within the 6-month period prior to the index date favored ticagrelor over prasugrel, aOR 1.31 (1.06-1.62) and 1.29 (1.01-1.66), respectively. However, prescribing trends favoring ticagrelor over prasugrel were not observed for deployment of drug-eluting, or multiple coronary stents. CONCLUSION: Between 2011 and 2014, clopidogrel remained the most common P2Y12-I whereas ticagrelor and prasugrel remained underutilized in ESRD patients. Prescribing practices for these drugs were based upon clinically approved indication for their use in the general population as well as perceived complexity of an ESRD patient including demographics, dialysis-related factors and comorbidities. Comparative effectiveness studies involving ESRD patients are needed to prove that ticagrelor and prasugrel are just as safe and effective as clopidogrel before clinicians can make informed decisions for choice of P2Y12-I in this patient population.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Clopidogrel/administração & dosagem , Falência Renal Crônica/terapia , Inibidores da Agregação Plaquetária/administração & dosagem , Padrões de Prática Médica/tendências , Cloridrato de Prasugrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Diálise Renal , Ticagrelor/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Tomada de Decisão Clínica , Clopidogrel/efeitos adversos , Prescrições de Medicamentos , Uso de Medicamentos/tendências , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Diálise Peritoneal , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Prevalência , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Sistema de Registros , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto Jovem
14.
Oncol Lett ; 18(4): 3698-3704, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31516582

RESUMO

CD44 is involved in malignant processes including cell motility, tumor growth and angiogenesis. To explore the potential role of CD44 as a prognostic biomarker in low grade gliomas (LGG), the mRNA expression levels of CD44 in tissues from 12 patients with glioma were evaluated by microarray analysis. The mRNA level of CD44 in LGG and glioblastoma multiforme (GBM) were analyzed using datasets downloaded from the publicly available Oncomine database. Reverse transcription-quantitative PCR and western blotting were used to further analyze the CD44 expression level in a set of 53 patients. Kaplan-Meier analysis was performed to identify the prognostic roles of CD44 mRNA in LGG and GBM, with data obtained from the OncoLnc and Gene Expression Profiling Interactive Analysis databases and clinical follow-ups. The present results revealed that CD44 mRNA expression levels were elevated in LGG and GBM compared with normal brain tissues. Furthermore, increased CD44 expression was associated with poor survival rates in LGG. The present study suggested that CD44 may act as an independent prognostic factor for LGG, and may be a potential therapeutic target for gliomas.

15.
Support Care Cancer ; 27(3): 1121-1128, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30097791

RESUMO

PURPOSE: The purpose of this cross-sectional comparative pilot study was to evaluate cognitive effort, indexed by pupillary response (PR), for breast cancer survivors (BCS) with complaints of cognitive dysfunction following chemotherapy. STUDY AIMS: Compare the cognitive effort employed by BCS to healthy controls (HC) during neuropsychological tests (NPT) for memory, sustained attention, verbal fluency, visuospatial ability, processing speed and executive function; and Investigate the relationship between PR-indexed cognitive effort and participants' self-report of cognitive function. METHODS: Self-report of cognitive function was collected from 23 BCS and 23 HC. PR was measured during NPT. Independent two-sample t tests or Wilcoxon rank sum tests were used to compare group scores. Between-group effect size (Cohen's d) was calculated for each outcome. Correlation between mean self-report scores and PR values, as well as 95% confidence intervals, was calculated. RESULTS: No group differences were demonstrated for NPT performance. BCS reported more issues with cognitive function than HC (p < .0001). A group effect for BCS was seen with PR-indexed cognitive effort for components of most NPT (p < .05). PR was correlated with most self-report measures of cognitive function (r = 0.33-0.45). CONCLUSIONS: PR sensitivity to cognitive effort across a variety of NPT and correlation with self-report of cognitive function was demonstrated. The portability, affordability, and "real-time" aspects of PR are attractive for potential use in the clinic setting to assess cognitive function. A larger study is needed to confirm these results. Prospective investigation of PR in BCS is needed to demonstrate sensitivity to cognitive function changes over time.


Assuntos
Sobreviventes de Câncer/psicologia , Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Testes Neuropsicológicos , Pupila/fisiologia , Adulto , Antineoplásicos/efeitos adversos , Atenção , Neoplasias da Mama/tratamento farmacológico , Estudos de Casos e Controles , Transtornos Cognitivos/psicologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Estudos Transversais , Feminino , Humanos , Memória , Pessoa de Meia-Idade , Projetos Piloto , Autorrelato , Sobreviventes/psicologia
16.
Support Care Cancer ; 27(4): 1395-1403, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30128855

RESUMO

PURPOSE: The purpose of this pilot study was to evaluate the feasibility of an 8-week Qigong intervention to improve objectively and subjectively assessed cognitive function in breast cancer survivors who were 2 months to 8 years post completion of chemotherapy and radiation therapy. METHODS: A randomized, single-blind, three-arm intervention pilot was conducted to compare Qigong to gentle exercise and survivorship support. Feasibility was measured by recruitment, group session attendance, and adherence to home practice for the two exercise groups. Changes in self-report and objectively measured cognitive function were compared between the three groups from baseline (T1) to completion of the intervention (T2) and 4 weeks post intervention (T3). RESULTS: Fifty participants consented (83% of desired sample) with an overall attrition rate of 28%. Attrition was highest for the gentle exercise group (50%). Group attendance adherence ranged from 44 to 67%. The a priori established rate of 75% weekly attendance was not achieved, nor was the goal of 75% adherence to home practice for the two exercise groups (7 to 41%). Self-report of cognitive function improved most for the Qigong group (p = .01). Improvement was demonstrated for the Trail Making A (gentle exercise, p = .007) and F-A-S verbal fluency (support group, p = .02) tests. Qigong participants reported the most reduction of distress (p = .02). CONCLUSIONS: The study results suggest that mindfulness-based exercise may be superior to gentle exercise alone or survivorship support for improving self-report of cognitive function and distress after treatment for breast cancer. The mindfulness component may enhance the positive impact of exercise on cognitive function.


Assuntos
Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Transtornos Cognitivos/fisiopatologia , Cognição , Qigong , Adulto , Idoso , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/reabilitação , Transtornos Cognitivos/reabilitação , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida , Resultado do Tratamento
17.
Clin Neurol Neurosurg ; 172: 87-89, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29986201

RESUMO

BACKGROUND: Subdural osteomas are benign neoplasms that are rarely encountered. We report the case of a 64­year­old female patient with a left temporal subdural osteoma. CASE DESCRIPTION: The patient presented with intermittent dizziness that first began two years earlier. Non-contrast computed tomography revealed a densely calcified left temporal extra-axial mass. Magnetic resonance imaging of the lesion revealed signal loss on T1-weighted and T2-weighted images and non-enhancement on Gadolinium enhanced T1-weighted images, and diffusion-weighted and ADC images demonstrated reduced values attributed to calcium-induced signal loss. Histologically, the lesion predominantly consisted of lamellar bone without bone marrow elements. The patient underwent stereotactic magnetic resonance imaging-guided neurosurgical resection and recovered without complication. CONCLUSIONS: Subdural osteomas may not be enhanced on magnetic resonance imaging. Surgical tumourectomy can be considered for symptomatic patients with subdural osteomas.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Osteoma/diagnóstico por imagem , Osteoma/cirurgia , Espaço Subdural/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Feminino , Gadolínio , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Espaço Subdural/cirurgia , Tomografia Computadorizada por Raios X/métodos
18.
Cancer Epidemiol Biomarkers Prev ; 27(9): 1101-1109, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29967001

RESUMO

Background: Endometrioid carcinoma (EC) and clear cell carcinoma (CC) histotypes of epithelial ovarian cancer are understudied compared with the more common high-grade serous carcinomas (HGSC). We therefore sought to characterize EC and CC transcriptomes in relation to HGSC.Methods: Following bioinformatics processing and gene abundance normalization, differential expression analysis of RNA sequence data collected on fresh-frozen tumors was completed with nonparametric statistical analysis methods (55 ECs, 19 CCs, 112 HGSCs). Association of gene expression with progression-free survival (PFS) was completed with Cox proportional hazards models. Eight additional multi-histotype expression array datasets (N = 852 patients) were used for replication.Results: In the discovery set, tumors generally clustered together by histotype. Thirty-two protein-coding genes were differentially expressed across histotype (P < 1 × 10-10) and showed similar associations in replication datasets, including MAP2K6, KIAA1324, CDH1, ENTPD5, LAMB1, and DRAM1 Nine genes associated with PFS (P < 0.0001) showed similar associations in replication datasets. In particular, we observed shorter PFS time for CC and EC patients with high gene expression for CCNB2, CORO2A, CSNK1G1, FRMD8, LIN54, LINC00664, PDK1, and PEX6, whereas, the converse was observed for HGSC patients.Conclusions: The results suggest important histotype differences that may aid in the development of treatment options, particularly those for patients with EC or CC.Impact: We present replicated findings on transcriptomic differences and how they relate to clinical outcome for two of the rarer ovarian cancer histotypes of EC and CC, along with comparison with the common histotype of HGSC. Cancer Epidemiol Biomarkers Prev; 27(9); 1101-9. ©2018 AACR.


Assuntos
Adenocarcinoma de Células Claras/genética , Biomarcadores Tumorais/genética , Carcinoma Endometrioide/genética , Cistadenocarcinoma Seroso/genética , Neoplasias Ovarianas/genética , Transcriptoma , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/patologia , Cistadenocarcinoma Seroso/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Prognóstico , Taxa de Sobrevida , Adulto Jovem
19.
Mol Med Rep ; 16(5): 7468-7478, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28944855

RESUMO

The World Health Organization classification distinguishes four grades for gliomas. Grade III gliomas, which are brain malignant brain tumors with variable biological behavior and propensity, have been not widely investigated. The objective of the present study was to identify specific gene modules and valuable hubs associated with gliomagenesis and molecular signatures to assist in determining grade III glioma prognosis. mRNAseq and micro (mi)RNAseq data were used to construct a co­expression network of gliomas using weight gene co­expression network analysis, and revealed the prognostic molecular signature of grade III gliomas. The differently expressed miRNAs and mRNAs were identified. A total of 37 mRNAs and 10 miRNAs were identified, which were closely associated with the survival rates of patients with grade III glioma. To further understand the tumorigenesis, Cytoscape software was used to construct a network containing these differently expressed molecules. The result suggested that both the downregulated genes and upregulated genes are vital in the process of glioma deterioration, and certain genes are closely associated with clinical prognosis.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , RNA Mensageiro/isolamento & purificação , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Análise por Conglomerados , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Glioma/genética , Humanos , Masculino , MicroRNAs/química , MicroRNAs/isolamento & purificação , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , RNA Mensageiro/química , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Software
20.
Onco Targets Ther ; 10: 4037-4050, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28860812

RESUMO

Papillary renal cell carcinoma (PRCC) is the second most common subtype of renal cell carcinoma, and it lacks effective therapeutic targets and prognostic molecular biomarkers. Attention has been increasingly focused on long noncoding RNAs (lncRNAs), which can act as competing endogenous RNA (ceRNA) to compete for shared microRNAs (miRNAs) in the tumorigenesis of human tumors. Therefore, to clarify the functional roles of lncRNAs with respect to the mediated ceRNA network in PRCC, we comprehensively integrated expression profiles, including data on mRNAs, lncRNAs and miRNAs obtained from 289 PRCC tissues and 32 normal tissues in The Cancer Genome Atlas. As a result, we identified 2,197 differentially expressed mRNAs (DEmRNAs) and 84 differentially expressed miRNAs (DEmiRNAs) using a threshold of |log2 (fold change)| >2.0 and an adjusted P-value <0.05. To determine the hub DEmRNAs that could be key target genes, a weighted gene co-expression network analysis was performed. A total of 28 hub DEmRNAs were identified as potential target genes. Seven dysregulated DEmiRNAs were identified that were significantly associated with the 28 hub potential target genes. In addition, we found that 16 differentially expressed lncRNAs were able to interact with the DEmiRNAs. Finally, we used Cytoscape software to visualize the ceRNA network with these differently expressed molecules. From these results, we believe that the identified ceRNA network plays a crucial role in the process of PRCC deterioration, and some of the identified genes are strongly related to clinical prognosis.

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