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1.
World J Clin Oncol ; 15(6): 745-754, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38946833

ABSTRACT

BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive peripheral T-cell lymphoma with historically dismal outcomes, representing less than one percent of non-Hodgkin lymphomas. Given its rarity, the true incidence of HSTCL is unknown and most data have been extrapolated through case reports. To the best of our knowledge, the largest and most up to date study addressing the epidemiology and outcomes of patients with HSTCL in the United States covered a period from 1996 to 2014, with a sample size of 122 patients. AIM: To paint the most updated epidemiological picture of HSTCL. METHODS: A total of 186 patients diagnosed with HSTCL, between 2000 and 2017, were ultimately enrolled in our study by retrieving data from the Surveillance, Epidemiology, and End Results database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of HSTCL. Variables with a P value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio of greater than 1 representing adverse prognostic factors. RESULTS: Male gender was the most represented. HSTCL was most common in middle-aged patients (40-59) and less common in the elderly (80+). Non-Hispanic whites (60.75%) and non-Hispanic blacks (20.97%) were the most represented racial groups. Univariate Cox proportional hazard regression analysis of factors influencing all-cause mortality showed a higher OM among non-Hispanic black patients. CSM was also higher among non-Hispanic blacks and patients with distant metastasis. Multivariate Cox proportional hazard regression analysis of factors affecting CSM revealed higher mortality in patients aged 80 or older and non-Hispanic blacks. CONCLUSION: Overall, the outlook for this rare malignancy is very grim. In this retrospective cohort study of the United States population, non-Hispanic blacks and the elderly had a higher CSM. This data highlights the need for larger prospective studies to investigate factors associated with worse prognosis in one ethnic group, such as treatment delays, which have been shown to increase mortality in this racial/ethnic group for other cancers.

2.
Cureus ; 16(4): e57724, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38711723

ABSTRACT

Introduction  The purpose of this study was to determine the prevalence of ventricular tachycardia (VT) among patients admitted with takotsubo cardiomyopathy (TCM) as well as to analyze the predictors of VT and the predictors of mortality among patients admitted with TCM. Methods Data were obtained from the National Inpatient Sample (NIS) database from January 2016 to December 2019. Patients with a primary diagnosis of TCM were selected using ICD-10 code I51.81. Subsequently, the study population was divided into patients who developed VT vs. patients who did not develop this complication. We then used multivariate logistic regression to assess the predictors of VT in our patient cohort as well as the predictors of mortality among patients admitted with TCM. Results  Of 40114 patients with TCM, 1923 developed VT (4.8%) during their hospital stay. Predictors of VT include atrial fibrillation (AF) (adjusted odds ratio (aOR): 1.592; 95% confidence interval (CI): 0.00-1.424; p=0.001), congestive heart failure (aOR: 1.451; 95% CI: 1.307-1.610; p=0.001), coagulopathy (aOR: 1.436; 95% CI: 1.150-1.793; p=0.001), and patients who self-identify in the race category as Other (aOR: 1.427; 95% CI: 1.086-1.875; p=0.011). Female sex was found to be protective against VT (aOR: 0.587; 95% CI: 0.526-0.656; p=0.001). Predictors of mortality among patients admitted with TCM include, among other factors, age (aOR: 1.014; 95% CI: 1.011-1.018; p=0.001), Asian or Pacific Islander race (aOR: 1.533; 95% CI: 1.197-1.964; p=0.001), Black race (aOR: 1.242; 95% CI: 1.062-1.452; p=0.007), VT (aOR: 1.754; 95% CI: 1.505-2.045; p=0.001), and AF (aOR: 1.441; 95% CI: 1.301-1.597; p=0.001). Some comorbidities that were protective against mortality in TCM include tobacco use disorder (aOR: 0.558; 95% CI: 0.255-0.925; p=0.028) and obstructive sleep apnea (aOR: 0.803; 95% CI: 0.651-0.990; p=0.028). The female sex was found to be protective against mortality (aOR: 0.532; 95% CI: 0.480-0.590; p=0.001).  Conclusion  In a large cohort of women admitted with TCM, we found the prevalence of VT to be 4.8%. Predictors of VT included conditions such as AF and congestive heart failure. The female sex was found to be protective against VT and protective against mortality among patients admitted with TCM.

3.
Diseases ; 12(5)2024 May 08.
Article in English | MEDLINE | ID: mdl-38785751

ABSTRACT

BACKGROUND: Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. METHODS: Conducted retrospectively, the study involved 3346 patients, utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis centered on investigating demographic characteristics, clinical features, overall mortality (OM), and cancer-specific mortality (CSM) among the cohort. Variables showing a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox regression analysis. A Hazard Ratio (HR) > 1 indicated an unfavorable prognosis. RESULTS: In the multivariate analysis, higher OM and CSM were observed in males, older age groups, tumors with distant metastasis, poorly differentiated tumors, and those who underwent chemotherapy. Non-Hispanic Black individuals showed elevated mortality rates. CONCLUSION: Delayed diagnosis may contribute to the increased mortality in this community. Improved access to healthcare and treatment is crucial for addressing these disparities. Larger prospective studies are needed to pinpoint the underlying causes of elevated mortality in non-Hispanic Black populations, and randomized controlled trials (RCTs) are warranted to evaluate therapies for advanced-stage appendix NETs.

4.
Gerodontology ; 40(4): 518-522, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37971285

ABSTRACT

BACKGROUND: Psoriasis is a common cutaneous disease; however, information about psoriasis-related oral mucosal lesions is scarce in the literature. CASE DESCRIPTION: We report a case of a 73-year-old male patient with cutaneous and oral palatal alterations. An incisional biopsy of these lesions revealed psoriasis. CONCLUSION: The current case highlights the importance of a systematic examination of the oral cavity in psoriasis patients for the appropriate diagnosis and management on the control of these lesions.


Subject(s)
Mouth Mucosa , Psoriasis , Male , Humans , Aged , Mouth Mucosa/pathology , Psoriasis/complications , Psoriasis/diagnosis , Psoriasis/pathology , Diagnosis, Differential , Biopsy
5.
J Cardiothorac Vasc Anesth ; 37(9): 1677-1682, 2023 09.
Article in English | MEDLINE | ID: mdl-37330331

ABSTRACT

OBJECTIVE: The primary aim of the authors' study was to evaluate the capacity of the portal vein pulsatility index (PVP) to detect fluid unresponsiveness in patients admitted to intensive care. DESIGN: This was a retrospective, diagnostic accuracy study SETTING: At a tertiary medical-surgical intensive care unit in Buenos Aires, Argentina. PARTICIPANTS: Patients were included during usual care in the intensive care unit, who were evaluated by ultrasonography for the flow of the portal vein, calculating their PVP prior to fluid expansion. INTERVENTIONS: Patients who exhibited an increase of <15% in left ventricle outflow tract velocity-time integral after receiving 500 mL of Ringer Lactate were considered non-responders to fluids. MEASUREMENTS AND MAIN RESULTS: The authors included a total of 63 patients between January 2022 and October 2022. The area under the receiver operating characteristic curve for PVP to predict fluid unresponsiveness was 0.708 (95% CI 0.580 to 0.816). A value of the PVP >32% predicted fluid unresponsiveness with a sensitivity of 30.8% (95% CI 17% to 47.6%) and specificity of 100% (95% CI 85.8 to 100). The positive predictive value was 100%, and the negative predictive value was 47.1% (95% CI 41.9% to 52.3%). CONCLUSIONS: Although PVP has limited value as the sole indicator for fluid management decisions, it can be used as a stopping rule or combined with other diagnostic tests to improve the accuracy of fluid responsiveness assessment.


Subject(s)
Intensive Care Units , Portal Vein , Humans , Portal Vein/diagnostic imaging , Retrospective Studies , Predictive Value of Tests , ROC Curve , Fluid Therapy
6.
J Fungi (Basel) ; 9(5)2023 May 17.
Article in English | MEDLINE | ID: mdl-37233290

ABSTRACT

The human pathogenic fungus Candida glabrata is the second leading cause of candidemia, a life-threatening invasive mycosis. Clinical outcomes are complicated by reduced susceptibility of C. glabrata to azoles together with its ability to evolve stable resistance to both azoles and echinocandins following drug exposure. Compared to other Candida spp., C. glabrata displays robust oxidative stress resistance. In this study, we investigated the impact of CgERG6 gene deletion on the oxidative stress response in C. glabrata. CgERG6 gene encodes sterol-24-C-methyltransferase, which is involved in the final steps of ergosterol biosynthesis. Our previous results showed that the Cgerg6Δ mutant has a lower ergosterol content in its membranes. Here, we show that the Cgerg6Δ mutant displays increased susceptibility to oxidative stress inducing agents, such as menadione, hydrogen peroxide and diamide, accompanied with increased intracellular ROS production. The Cgerg6Δ mutant is not able to tolerate higher concentrations of iron in the growth media. We observed increased expression of transcription factors, CgYap1p, CgMsn4p and CgYap5p, together with increased expression of catalase encoding the CgCTA1 gene and vacuolar iron transporter CgCCC1 in the Cgerg6Δ mutant cells. However, it seems that the CgERG6 gene deletion does not influence the function of mitochondria.

7.
Folia Microbiol (Praha) ; 68(6): 835-842, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37145224

ABSTRACT

The rising number of invasive fungal infections caused by drug-resistant Candida strains is one of the greatest challenges for the development of novel antifungal strategies. The scarcity of available antifungals has drawn attention to the potential of natural products as antifungals and in combinational therapies. One of these is catechins-polyphenolic compounds-flavanols, found in a variety of plants. In this work, we evaluated the changes in the susceptibility of Candida glabrata strain characterized at the laboratory level and clinical isolates using the combination of catechin and antifungal azoles. Catechin alone had no antifungal activity within the concentration range tested. Its use in combination with miconazole resulted in complete inhibition of growth in the sensitive C. glabrata isolate and a significant growth reduction in the azole resistant C. glabrata clinical isolate. Simultaneous use of catechin and miconazole leads to increased intracellular ROS generation. The enhanced susceptibility of C. glabrata clinical isolates to miconazole by catechin was accompanied with the intracellular accumulation of ROS and changes in the plasma membrane permeability, as measured using fluorescence anisotropy, affecting the function of plasma membrane proteins.


Subject(s)
Antifungal Agents , Catechin , Antifungal Agents/pharmacology , Miconazole/pharmacology , Candida glabrata , Catechin/pharmacology , Reactive Oxygen Species , Microbial Sensitivity Tests , Drug Resistance, Fungal , Azoles/pharmacology
8.
Article in English | MEDLINE | ID: mdl-36814069

ABSTRACT

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

9.
J Clin Gastroenterol ; 57(4): 325-334, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36753461

ABSTRACT

BACKGROUND AIMS: Preventative care plays an important role in maintaining health in patients with inflammatory bowel disease (IBD). We aimed to assess the overall quality, strength, and transparency of conflicts among guidelines on preventative care in IBD. METHODS: A systematic literature search was performed in multiple databases to identify all guidelines pertaining to preventative care in IBD in April 2021. All guidelines were reviewed for the transparency of conflicts of interest and funding, recommendation quality and strength, external guideline review, patient voice inclusion, and plan for update-as per Institute of Medicine standards. In addition, recommendations and their quality were compared between societies. RESULTS: Fifteen distinct societies and a total of 89 recommendations were included. Not all guidelines provided recommendations on the key aspects of preventative care in IBD-such as vaccinations, cancer prevention, stress reduction, and diet/exercise. Sixty-seven percent of guidelines reported on conflicts of interest, 20% underwent external review, and 27% included patient representation. In all, 6.7%, 21.3%, and 71.9% of recommendations were based on high, moderate, and low-quality evidence, respectively. Twenty-seven percent, 23.6%, and 49.4% of recommendations were strong, weak/conditional, and did not provide a strength, respectively. The proportion of high-quality evidence ( P =0.28) and strong recommendations ( P =0.41) did not significantly differ across societies. CONCLUSIONS: Many guidelines do not provide recommendations on key aspects of preventative care in IBD. As over 70% of recommendations are based on low-quality evidence, further studies on preventative care in IBD are warranted to improve the overall quality of evidence.


Subject(s)
Inflammatory Bowel Diseases , Humans , Inflammatory Bowel Diseases/therapy , Exercise
10.
J. Health Biol. Sci. (Online) ; 11(1): 1-5, Jan. 2023. tab
Article in Portuguese | LILACS | ID: biblio-1524593

ABSTRACT

Objetivo: identificar o perfil clínico dos pacientes internados por COVID-19 na Unidade de Terapia Intensiva (UTI) de um hospital privado. Métodos: trata-se deum estudo de caráter descritivo, documental, retrospectivo, de corte transversal e análise quantitativa, conduzido em um hospital, no município de Montes Claros, MG, por meio da análise de prontuários de 142 pacientes da UTI com diagnóstico de COVID-19 no período de janeiro de 2020 a abril de 2021. Resultados: dos 142 indivíduos, a média de idadefoi de 64,1 anos, com 58,5% do sexo masculino. Das comorbidades prévias, as que tiveram maior prevalência foram a hipertensão arterial sistêmica com 26,8% e diabetes mellitus com 9,2%. Destes, 133 indivíduos utilizaram ventilação mecânica, com a prevalência de 47,9% no modo ventilação com volume controlado. O tempo médio de internação foi de 6 dias, sendo que 93,7% dos indivíduos foram a óbito, 4,9% receberam alta e 1,4% transferidos para outro hospital. Conclusão: evidenciou-se predominância do sexo masculino, com média de idade de 64,1 anos, o modo ventilatório mais utilizado foi o controlado o volume, com tempo de uso médio de uso 7,9 dias, ou seja, pouco tempo, fato que pode ser justificado pelo alto índice de óbitos na amostra estudada.


Objective: to identify the clinical profile of patients hospitalized for COVID-19 in the Intensive Care Unit (ICU) of a private hospital. Methods: this is a descriptive, documentary, retrospective, cross-sectional study with quantitative analysis conducted in a hospital in the city of Montes Claros, MG, through the analysis of medical records of 142 ICU patients diagnosed with COVID-19 from January 2020 to April 2021. Results: of the 142 individuals, the mean age was 64.1 years, with 58.5% male. Of the previous comorbidities, those with the highest prevalence were systemic arterial hypertension at 26.8% and diabetes mellitus at 9.2%. Of these, 133 individuals used mechanical ventilation, with a prevalence of 47.9% using volume-controlled ventilation. The average length of stay was 6 days, with 93.7% of the individuals dying, 4.9% being discharged, and 1.4% being transferred to another hospital. Conclusion: there was a predominance of males, with an average age of 64.1 years, the most used ventilatory mode was volume-controlled, with an average use time of 7.9 days, that is, a short time, a fact that can be justified by the high rate of deaths in the studied sample.


Subject(s)
Cross-Sectional Studies , COVID-19 , Intensive Care Units
11.
FEMS Yeast Res ; 21(1)2022 09 24.
Article in English | MEDLINE | ID: mdl-36047961

ABSTRACT

ERG6 gene encodes C-24 methyltransferase, one of the specific enzymes that differ in mammalian and yeast sterol biosynthesis. To explore the function of CgErg6p in the yeast pathogen Candida glabrata, we have constructed the Cgerg6Δ deletion mutant. We found that C. glabrata cells lacking CgErg6p exhibit reduced susceptibility to both antifungal azoles and polyenes. The reduced content of ergosterol in the Cgerg6 deletion mutant was accompanied by increased expression of genes encoding the last steps of the ergosterol biosynthetic pathway. The absence of CgErg6p leads to plasma membrane hyperpolarization and decrease in its fluidity compared to the parental C. glabrata strain. The absence of sterols containing C-24 alkyls influenced the susceptibility of Cgerg6Δ mutant cells to alkali metal cations and several other metabolic inhibitors. Our results thus show that sterols lacking C-24 alkyls are not sufficient substitutes for maintaining yeast plasma membrane function. The absence of CgErg6p influences also the cell wall integrity and calcineurin signaling in C. glabrata.


Subject(s)
Antifungal Agents , Candida glabrata , Antifungal Agents/metabolism , Antifungal Agents/pharmacology , Azoles/pharmacology , Calcineurin/metabolism , Candida glabrata/genetics , Candida glabrata/metabolism , Cell Membrane/metabolism , Cell Wall/metabolism , Drug Resistance, Fungal/genetics , Ergosterol , Methyltransferases/genetics , Methyltransferases/metabolism , Microbial Sensitivity Tests , Polyenes/metabolism , Polyenes/pharmacology , Sterols/metabolism
12.
NPJ Precis Oncol ; 6(1): 68, 2022 Sep 24.
Article in English | MEDLINE | ID: mdl-36153348

ABSTRACT

Resistance to aromatase inhibitor (AI) treatment and combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) are crucial clinical challenges in treating estrogen receptor-positive (ER+) breast cancer. Understanding the resistance mechanisms and identifying reliable predictive biomarkers and novel treatment combinations to overcome resistance are urgently needed. Herein, we show that upregulation of CDK6, p-CDK2, and/or cyclin E1 is associated with adaptation and resistance to AI-monotherapy and combined CDK4/6i and ET in ER+ advanced breast cancer. Importantly, co-targeting CDK2 and CDK4/6 with ET synergistically impairs cellular growth, induces cell cycle arrest and apoptosis, and delays progression in AI-resistant and combined CDK4/6i and fulvestrant-resistant cell models and in an AI-resistant autocrine breast tumor in a postmenopausal xenograft model. Analysis of CDK6, p-CDK2, and/or cyclin E1 expression as a combined biomarker in metastatic lesions of ER+ advanced breast cancer patients treated with AI-monotherapy or combined CDK4/6i and ET revealed a correlation between high biomarker expression and shorter progression-free survival (PFS), and the biomarker combination was an independent prognostic factor in both patients cohorts. Our study supports the clinical development of therapeutic strategies co-targeting ER, CDK4/6 and CDK2 following progression on AI-monotherapy or combined CDK4/6i and ET to improve survival of patients exhibiting high tumor levels of CDK6, p-CDK2, and/or cyclin E1.

13.
Front Pharmacol ; 13: 881617, 2022.
Article in English | MEDLINE | ID: mdl-35662726

ABSTRACT

Cannabidiol (CBD) is a non-psychotomimetic constituent of the Cannabis plant, with potential therapeutic properties for many physical and neuropsychiatric conditions. Isolated CBD has been suggested to have favorable safety and tolerability. Although CBD-related rash is described, few case reports are well documented in the literature, and usually, CBD was used concomitantly with other medications. Thus, we report four women who presented a skin rash after ongoing CBD use. Other causes of these skin rashes were ruled out after conducting an extensive viral and serological detection panel, and three patients had their lesions biopsied. Two patients were re-exposed to the vehicle (MCT) without developing a new skin rash. Therefore, clinicians must be aware of this potential adverse effect of CBD use.

14.
Folia Microbiol (Praha) ; 67(4): 641-647, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35352326

ABSTRACT

KlUpc2p, a transcription factor belonging to the fungal binuclear cluster family, is an important regulator of ergosterol biosynthesis and azole drug resistance in Kluyveromyces lactis. In this work, we show that the absence of KlUpc2p generates Rag- phenotype and modulates the K. lactis susceptibility to oxidants and calcofuor white. The KlUPC2 deletion leads to increased expression of KlMGA2 gene, encoding an important regulator of hypoxic and lipid biosynthetic genes in K. lactis and also KlHOG1 gene. The absence of KlUpc2p does not lead to statistically significant changes in glycerol, corroborating the expression of KlGPD1 gene, encoding NAD+-dependent glycerol-3-phosphate dehydrogenase, that is similar in both the deletion mutant and the parental wild-type strain. Increased sensitivity of Klupc2 mutant cells to brefeldin A accompanied with significant increase in KlARF2 gene expression point to the involvement of KlUpc2p in intracellular signaling. Our observations highlight the connections between ergosterol and fatty acid metabolism to modulate membrane properties and point to the possible involvement of KlUpc2p in K. lactis oxidative stress response.


Subject(s)
Fungal Proteins , Kluyveromyces , Ergosterol/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Deletion , Gene Expression Regulation, Fungal , Kluyveromyces/genetics , Kluyveromyces/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
17.
Pediatr Dermatol ; 38(5): 1247-1250, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34409648

ABSTRACT

Generalized verrucosis is a clinical manifestation of human papillomavirus infection. Patients with generalized verrucosis present with over 20 verrucae distributed over various anatomical sites. The disorder occurs in association with several genetic syndromes with immunodeficiency, including GATA2 deficiency. We report a 12-year-old boy with GATA2 deficiency and generalized verrucosis that worsened after cyclosporine use following bone marrow transplant. Systemic treatment with acitretin and topical application of trichloroacetic acid, likely along with immune reconstitution, led to complete remission.


Subject(s)
GATA2 Deficiency , Warts , Acitretin/therapeutic use , Child , GATA2 Transcription Factor , Humans , Male , Papillomaviridae , Trichloroacetic Acid , Warts/drug therapy
18.
NPJ Breast Cancer ; 7(1): 2, 2021 Jan 04.
Article in English | MEDLINE | ID: mdl-33398005

ABSTRACT

Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser315,33), CHK1(Ser317), and cdc25b(Ser323), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.

19.
Cell Physiol Biochem ; 54(5): 994-1012, 2020 Oct 03.
Article in English | MEDLINE | ID: mdl-33006449

ABSTRACT

BACKGROUND/AIMS: Down syndrome associated disorders are caused by a complex genetic context where trisomy 21 is a central component in relation to other changes involving epigenetic regulators and signaling molecules. This unique genetic context is responsible for the predisposition of people with Down syndrome to acute leukemia. Although, the research in this field has discovered some important pathogenic keys, the exact mechanism of this predisposition is not known. METHODS: In this study we applied functional enrichment analysis to evaluate the interactions between genes localized on chromosome 21, genes already identify as having a key role in acute leukemia of Down syndrome, miRNAs and signaling pathways implicated in cancer and cell development and found that miR-155 has a high impact in genes present on chromosome 21. Forward, we performed next generation sequencing on DNA samples from a cohort of patients diagnosed with acute leukemia of Down syndrome and in vitro functional assay using a CMK-86 cell line, transfected with either mimic or inhibitor of the microRNA-155-5p. RESULTS: Our results show that the epigenetic alteration of the TNF superfamily receptors in Down syndrome, which can be correlated to microRNA-155-5p aberrant activity, may play an important role in cell signaling and thus be linked to acute myeloid leukemia. CONCLUSION: Some genes, already shown to be mutated in AML-DS, are potential targets for miR-155. Our results show that the epigenetic alteration of the TNF superfamily receptors in Down syndrome may play an important role in cell signaling and thus be linked to acute myeloid leukemia.


Subject(s)
Down Syndrome/complications , Epigenesis, Genetic , Gene Expression Regulation, Leukemic , Leukemia, Myeloid, Acute/pathology , Leukemoid Reaction/pathology , MicroRNAs/genetics , Receptors, Tumor Necrosis Factor/genetics , Cell Differentiation , Cohort Studies , Down Syndrome/etiology , Down Syndrome/genetics , Down Syndrome/metabolism , Down Syndrome/pathology , Female , High-Throughput Nucleotide Sequencing , Humans , Leukemia, Myeloid, Acute/etiology , Leukemia, Myeloid, Acute/metabolism , Leukemoid Reaction/etiology , Leukemoid Reaction/metabolism , Male , Receptors, Tumor Necrosis Factor/metabolism
20.
J Biomater Appl ; 35(3): 405-421, 2020 09.
Article in English | MEDLINE | ID: mdl-32571173

ABSTRACT

Although, the excellent level of success of titanium surfaces is based on the literature, there are some biological challenges such as unfavorable metabolic conditions or regions of poor bone quality where greater surface bioactivity is desired. Seeking better performance, we hypothesized that silica-based coating via sol-gel route with immersion in potassium hydroxide basic solution induces acceleration of bone mineralization. This in vitro experimental study coated titanium surfaces with bioactive glass synthesized by route sol-gel via hydrolysis and condensation of chemical alkoxide precursor, tetraethylorthosilicate (TEOS) and/or deposition of chemical compound potassium hydroxide (KOH) to accelerate bone apposition. The generated surfaces titanium(T), titanium with potassium hydroxide deposition (T + KOH), titanium with bioactive glass deposition synthesized by sol-gel route via tetraethylorthosilicate hydrolysis (TEOS), titanium with bioactive glass deposition synthesized by sol-gel route via tetraethylorthosilicate hydrolysis with potassium hydroxide deposition (TEOS + KOH) were characterized by 3D optical profilometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), contact angle by the sessile drop method, x-ray excited photoelectron spectroscopy (XPS) and energy dispersive x-ray spectrometer (EDX). The addition of the KOH group on the pure titanium (T) or bioactive glass (TEOS) surfaces generated a tendency for better results for mineralization. Groups covered with bioactive glass (TEOS, TEOS + KOH) tended to outperform even groups with titanium substrate (T, T + KOH). The addition of both, bioactive glass and KOH, in a single pure titanium substrate yielded the best results for the mineralization process.


Subject(s)
Coated Materials, Biocompatible/chemistry , Gels/chemistry , Hydroxides/chemistry , Potassium Compounds/chemistry , Silicon Dioxide/chemistry , Titanium/chemistry , Animals , Calcification, Physiologic , Cell Adhesion , Cell Proliferation , Coated Materials, Biocompatible/metabolism , Dental Implantation , Humans , Mice , Osteogenesis , Silanes/chemistry , Surface Properties , Titanium/metabolism
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