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1.
Cureus ; 16(6): e62812, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39036159

RESUMO

Complex regional pain syndrome (CRPS) is an uncommon neuropathic pain illness characterized by extreme discomfort, muscular weakness, limb edema, and hyperhidrosis. Fracture, surgery, stroke, and spinal cord damage are all potential risk factors. This case report study provides a detailed description of no-traumatic CRPS, a complex pain illness characterized by sensory, vasomotor, sudomotor, motor, trophic, and edematous changes and persistent discomfort. We reported a case of a 39-year-old male with a seven-year history of severe right shoulder-hand pain. He presented with recurrent hand and shoulder pain characterized by burning sensations and weakness, despite not having experienced this before, and he denied any history of trauma or fracture. Surgical procedure and pharmaceutical therapy were provided, but there was no outcome, as evidenced by the patient's clinical condition and the medical records. Despite extensive investigation, no imaging or laboratory tests have been developed for diagnosis, necessitating further research for a comprehensive understanding and diagnosis.

2.
Dig Dis Sci ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811504

RESUMO

INTRODUCTION: Esophageal Stents are used to maintain esophageal lumen patency in esophageal strictures caused by intrinsic and/or extrinsic malignancies and the occlusion of concomitant esophageal fistulas. While data on the efficacy and safety of esophageal stents exist, comprehensive evaluation of adverse events is limited. The aim of this study is to investigate the reported adverse events and device failures associated with esophageal self-expandable metal stents (SEMS) using the FDA's Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: Post-marketing surveillance data for the esophageal SEMSs were analyzed using the FDA's MAUDE database from January 2014 to December 10, 2023. The outcomes of interest were patient-related adverse events and device failures. Statistical analysis was performed using Microsoft Excel 2010 and SPSS. Pooled numbers and percentages were calculated for each adverse event. Continuous variables underwent analysis using a two-tailed student t test, and significance was set to p ≤ 0.05. RESULTS: During the study period, 548 MAUDE reports revealed 873 device failures and 186 patient-related adverse events. The most common device issues were stent activation, positioning, or separation problems (4 n = 403; 46.2%), followed by device detachment or migration (n = 109, 12.5%), and material problems (n = 93, 10.7%). Patient complications included dysphagia/odynophagia (10%), perforation, pain, and bleeding (each 7.6%). The most common device failures in over-the-wire (OTW) stents and through-the-scope (TTS) stents were activation, positioning, or separation problems (TTS: n = 183, 52.6% vs OTW: n = 220, 41.9%). Compared to OTW stents, TTS stents had higher migration and breakage (13.5% vs. 11.8%, p = 0.24), and (9.2% vs. 6.7%, p = 0.08) respectively, while OTW stents had more challenges with stent advancement or removal (5.1% vs. 0.3%, p < 0.001 and 4.6% vs 3.4%, p = 0.19, respectively) and material problems (14.7% vs. 4.6%, p < 0.001). Activation, positioning, and separation problems were the most frequent device failures in fully covered (FC) and partially covered (PC) stents (FC: n = 62, 32.8%, PC: n = 168, 43.5%). FC stents had higher migration rates (20.6% vs 9.8%, p < 0.001), while PC stents exhibited more material problems (17.4% vs. 5.8%, p < 0.001) and difficulties with advancing the stents (6.7% vs. 0%, p < 0.001). CONCLUSION: Our examination showed a prevalence of reported device complications associated with stent activation, positioning, and separation problems. Dysphagia or odynophagia emerged as the most frequently reported patient complication. Furthermore, our analysis, provides insights into TTS vs. OTW and FC vs. PC esophageal SEMSs, enabling endoscopists and manufacturers to better understand adverse events and potentially optimize device design for future iterations.

3.
Radiol Case Rep ; 19(4): 1280-1283, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38292782

RESUMO

This case report presents a unique instance of a 25-year-old male patient successfully treated with Titanium elastic nail (TEN) for a distal clavicle fracture, a method typically reserved for midshaft clavicle fractures. Distal clavicular fractures, constituting 12%-15% of all clavicle fractures, often necessitate surgical intervention to avoid complications such as malunion and persistent pain. While standard surgical therapies include Kirschner wire and hook plate fixation, this case explores the benefits of TEN, known for minimal tissue disruption and faster recovery. The patient, who suffered a severe left shoulder injury after falling, underwent a minimally invasive TEN procedure. Post-surgery, he showed a significant reduction in pain and improvement in shoulder mobility, with radiographic evaluations confirming successful fracture reduction and stable fixation. The case underscores the potential of TEN as a viable alternative for distal clavicular fractures, though further research is needed to establish comprehensive guidelines for its application.

4.
Biol Trace Elem Res ; 202(1): 1-8, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37268844

RESUMO

This study assessed aluminum concentrations in breast milk samples obtained from breastfeeding women in resource-limited countries, estimated daily intake of aluminum by breastfed infants, and identified predictors of higher breast milk aluminum concentrations. A descriptive analytical approach was used in this multicenter study. Breastfeeding women were recruited from different maternity health clinics in Palestine. Aluminum concentrations in 246 breast milk samples were determined using an inductively coupled plasma-mass spectrometric method. The mean breast milk aluminum concentration was 2.1 ± 1.5 mg/L. The mean estimated daily intake of aluminum by infants was 0.37 ± 0.26 mg/kg body weight/day. Multiple linear regression showed that breast milk aluminum concentrations were predicted by living in urban areas, closer to industrial areas, waste disposals, frequent use of deodorants, and less frequent use of vitamins. Breast milk aluminum levels among Palestinian breastfeeding women were comparable to those previously determined in occupationally unexposed women.


Assuntos
Aleitamento Materno , Leite Humano , Lactente , Feminino , Humanos , Gravidez , Leite Humano/química , Alumínio/análise
5.
Perioper Med (Lond) ; 12(1): 47, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620871

RESUMO

BACKGROUND: Preoperative anxiety is a health concern among patients scheduled for surgical interventions. Little is known about the prevalence of preoperative anxiety among patients in different healthcare systems of developing countries. This study was conducted to determine the prevalence of preoperative anxiety among patients undergoing surgery in Palestine. Another objective was to identify the factors associated with preoperative anxiety. METHODS: This study was conducted in a cross-sectional descriptive design. Patients scheduled for surgical interventions were interviewed using an interviewer-administered questionnaire. The questionnaire collected the demographic, clinical, and surgical variables of the patients. The questionnaire also contained the Amsterdam preoperative anxiety and information scale (APAIS), and a short version of the Spielberger state-trait anxiety inventory (STAIS-5/STAIT-5). RESULT: A total of 280 patients were included. The mean APAIS total score was 13.6 ± 5.9, the mean APAIS anxiety domain score was 8.3 ± 4.3, and the mean APAIS need for information domain was 1.6 ± 0.50. Of the patients, 76 (27.1%) had high anxiety and 160 (57.1%) expressed a high need for information. The higher APAIS anxiety scores were predicted by being female, having chronic diseases, being scheduled to be operated on within 24 h, and having experienced surgical complications. The mean STAIS-5 score was 10.0 ± 4.2 and the mean STAIT-5 was 10.3 ± 3.8. Of the patients, 140 (50.0%) had high state anxiety and 56 (20.0%) had high trait anxiety. Higher STAIS-5 scores were predicted by being female, younger than 42 years, and scheduled to be operated on within 24 h. Higher STAIT-5 scores were predicted by being female. A positive correlation was identified between APAIS total, APAIS anxiety, APAIS need for information, STAIS-5, and STAIT-5 scores. CONCLUSION: Preoperative anxiety was prevalent among patients scheduled for surgical operations in Palestinian hospitals. Anesthesiologists and other providers of perioperative care should screen preoperative patients who are female, have chronic diseases, are scheduled to be operated on within 24 h, and having had experienced surgical complications for preoperative anxiety. More studies are still needed to investigate the effects of the implemented measures on the prevalence of preoperative anxiety.

7.
Int Breastfeed J ; 18(1): 36, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37501132

RESUMO

BACKGROUND: Despite the undisputed benefits of breastfeeding, infants might become exposed to xenobiotics that could be excreted into breast milk following maternal exposure. This study was conducted to assess breastmilk cadmium levels among lactating women in Palestine, a resource-limited country. Estimated daily intake (EDI) of cadmium via breastmilk was also calculated and predictors of high breastmilk cadmium levels and high infant exposure via breastmilk were identified. METHODS: This multicenter study was conducted using a descriptive-analytical design. The lactating women were recruited from different maternity and public health clinics in all regions of Palestine. Demographic variables and exposure to sources of cadmium were collected in an interviewer-administered questionnaire. Foremilk samples (about 5 mL) were collected in polyethylene tubes using the hand-expression technique. The breast milk samples were collected in the period between December 2020 and March 2021. A pre-validated method using inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify breastmilk cadmium levels. EDI values were calculated from the quantified breastmilk cadmium levels. RESULTS: Breastmilk samples were obtained from 256 lactating women. The mean breastmilk cadmium level was 0.34 (SD: 0.33) µg / L and the mean EDI of cadmium via breastmilk was 0.059 (SD: 0.058) µg / kg per body weight / day. Breastmilk cadmium levels were quantified in 92.6% of the breastmilk samples. Of the breastmilk samples, 13 (5.1%) had cadmium levels above those reported as "normal" by the World Health Organization (WHO). Multiple linear regression showed that higher breastmilk cadmium levels and higher EDI were predicted by being a smoker, living in a refugee camp, living close to an industrial area, living close to disposal of wastes, living close to paint shops, living in a house with peeling / chipping paint, frequent use of cosmetics, frequent use of hair dyes, and not using vitamins. CONCLUSION: The breastmilk cadmium levels and infant exposure were predicted by maternal exposure to sources of cadmium. The findings reported in this study are valuable to antenatal and postnatal healthcare service providers. More studies are needed to plan and implement measures to reduce breastmilk cadmium levels and infants' exposure to cadmium via breastmilk.


Assuntos
Aleitamento Materno , Leite Humano , Feminino , Lactente , Humanos , Gravidez , Leite Humano/química , Lactação , Cádmio/análise , Colostro
8.
J Investig Med High Impact Case Rep ; 11: 23247096231173397, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37154166

RESUMO

We present the case of a 51-year-old woman with severe tricuspid valve regurgitation due to aseptic tricuspid valve vegetation. She presented with bilateral lower extremity edema and a tricuspid valve vegetation was found on echocardiography. Initially, infectious and autoimmune causes of valve vegetation were considered; however, on biopsy, the mass was ultimately found to be a benign metastasizing leiomyoma (BML). Additional history revealed clinical features consistent with uterine leiomyomas, which metastasized to all leaflets the tricuspid valve, causing symptoms of heart failure. Benign metastasizing leiomyoma is rare itself, but when found, typically presents as asymptomatic pulmonary nodules. Mechanism of spread is unknown. Diagnosis is typically made long after a hysterectomy or fibroidectomy, but in our case, the BML was found prior to an actual fibroid diagnosis. By comparison, metastasis to the heart is extremely rare and has a higher potential for morbidity. Our patient required open heart surgery and tricuspid valve replacement for management of her symptoms, but her risk of further or recurrent metastasis going forward is unknown. Management strategy to prevent metastases in such cases of aggressive disease is not an established protocol and needs to be further studied.


Assuntos
Insuficiência Cardíaca , Leiomioma , Neoplasias Pulmonares , Insuficiência da Valva Tricúspide , Neoplasias Uterinas , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Uterinas/complicações , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia , Insuficiência da Valva Tricúspide/etiologia , Neoplasias Pulmonares/diagnóstico , Leiomioma/complicações , Leiomioma/diagnóstico , Leiomioma/patologia , Insuficiência Cardíaca/etiologia
9.
World Neurosurg ; 166: e632-e644, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35872130

RESUMO

BACKGROUND: This study explored medication errors in the perioperative care of patients with epilepsy and developed consensus-based recommendations to prevent/minimize these errors. METHODS: A mixed method was used in this study. Medication error situations were explored in semi-structured in-depth interviews with nurses (n = 12), anesthesiologists (n = 5), anesthesia technicians (n = 5), surgeons (n = 4), neurologists (n = 4), and patients with epilepsy (n = 10). The qualitative data were analyzed using the qualitative interpretive description approach. A two-round Delphi technique was used among nurses (n = 22), anesthesiologists (n = 9), anesthesia technicians (n = 7), surgeons (n = 7), and neurologists (n = 5). RESULTS: A total of 1400 minutes of interview time was analyzed in this study. Of the panelists, 39 (78.0%) agreed that patients with epilepsy present unique challenges to providers of perioperative care that make them prone to medication errors. The interviewees in this study described 32 different medication error situations that occurred while providing perioperative care services to patients with epilepsy. In this study, 35 consensus-based recommendations to prevent/minimize medication errors in the perioperative care of patients with epilepsy were developed. CONCLUSIONS: The findings of this study are informative to decision-makers in health care facilities and other stakeholders in health regulatory authorities who need to design measures to prevent/minimize medication errors and improve perioperative outcomes of patients with epilepsy. Studies are needed to investigate if these recommendations can be effective in preventing/reducing medication errors in the perioperative care of patients with epilepsy.


Assuntos
Epilepsia , Erros de Medicação , Anestesiologistas , Consenso , Epilepsia/tratamento farmacológico , Epilepsia/cirurgia , Humanos , Erros de Medicação/prevenção & controle , Assistência Perioperatória
10.
Sci Adv ; 6(3): eaax2861, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31998832

RESUMO

The malignancy potential is correlated with the mechanical deformability of the cancer cells. However, mechanical tests for clinical applications are limited. We present here a Triangular Correlation (TrC) between cell deformability, phagocytic capacity, and cancer aggressiveness, suggesting that phagocytic measurements can be a mechanical surrogate marker of malignancy. The TrC was proved in human prostate cancer cells with different malignancy potential, and in human bladder cancer and melanoma cells that were sorted into subpopulations based solely on their phagocytic capacity. The more phagocytic subpopulations showed elevated aggressiveness ex vivo and in vivo. The uptake potential was preserved, and differences in gene expression and in epigenetic signature were detected. In all cases, enhanced phagocytic and aggressiveness phenotypes were correlated with greater cell deformability and predicted by a computational model. Our multidisciplinary study provides the proof of concept that phagocytic measurements can be applied for cancer diagnostics and precision medicine.


Assuntos
Neoplasias/etiologia , Neoplasias/metabolismo , Algoritmos , Animais , Linhagem Celular Tumoral , Movimento Celular , Modelos Animais de Doenças , Progressão da Doença , Suscetibilidade a Doenças , Endocitose , Xenoenxertos , Humanos , Camundongos , Modelos Teóricos , Metástase Neoplásica , Neoplasias/patologia , Fagocitose
11.
Rom J Anaesth Intensive Care ; 27(1): 11-14, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34056118

RESUMO

OBJECTIVE: Maternal heart disease is one of the major causes for mortality among parturients. In our study, we surveyed 220 patients with different valvular disorders who gave birth in our medical center in the years 2012-2018. The aim of this study was to characterize various valvular pathologies and compare the results of different anesthetic approaches. METHODS: In this retrospective study, the computerized system and file archive were searched for maternal valvular pathologies according to the International Classification of Diseases, Ninth Revision (ICD-9). The women included in the study were defined as American Society of Anesthesiology (ASA)-II or more, who suffer from valvular heart disease. RESULTS: The most common pathology was mitral valve regurgitation (57.73% of all cardiac patients). Most women were defined as having mild insufficiency, and 82.68% had normal vaginal delivery. In 17.3% of patients who had cesarean section, the main type of anesthesia was neuraxial anesthesia (95.45%). The second most common pathology was tricuspid valve regurgitation (22.73%). Most patients (78%) had normal vaginal delivery, and epidural analgesia was used in 64.1%. A minority of cardiac patients in our study were patients with stenotic heart diseases, such as aortic stenosis, mitral stenosis and pulmonic stenosis (8.18%, 4.55%, and 1.36%, respectively). No complications were observed in the peripartum period. CONCLUSION: The use of regional anesthesia is recommended for all valvular pathologies without exception, as we observed no cases in which the severity of cardiac condition had not allowed the use of various types of regional anesthesia, for surgery or vaginal delivery.

12.
Cell Stem Cell ; 24(6): 983-994.e7, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31031139

RESUMO

Following fertilization, totipotent cells undergo asymmetric cell divisions, resulting in three distinct cell types in the late pre-implantation blastocyst: epiblast (Epi), primitive endoderm (PrE), and trophectoderm (TE). Here, we aim to understand whether these three cell types can be induced from fibroblasts by one combination of transcription factors. By utilizing a sophisticated fluorescent knockin reporter system, we identified a combination of five transcription factors, Gata3, Eomes, Tfap2c, Myc, and Esrrb, that can reprogram fibroblasts into induced pluripotent stem cells (iPSCs), induced trophoblast stem cells (iTSCs), and induced extraembryonic endoderm stem cells (iXENs), concomitantly. In-depth transcriptomic, chromatin, and epigenetic analyses provide insights into the molecular mechanisms that underlie the reprogramming process toward the three cell types. Mechanistically, we show that the interplay between Esrrb and Eomes during the reprogramming process determines cell fate, where high levels of Esrrb induce a XEN-like state that drives pluripotency and high levels of Eomes drive trophectodermal fate.


Assuntos
Blastocisto/fisiologia , Endoderma/fisiologia , Fibroblastos/fisiologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Trofoblastos/fisiologia , Animais , Diferenciação Celular , Linhagem da Célula , Células Cultivadas , Reprogramação Celular , Implantação do Embrião , Camundongos , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Fatores de Transcrição/metabolismo
13.
Plast Reconstr Surg Glob Open ; 6(11): e1913, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30881776

RESUMO

Constructing arteriovenous (AV) loops saves a crushed limb when healthy recipient vessels are unavailable at the site of injury by supporting a transferred free flap. Literature about using AV loops in the upper limb defect is scarce. We present a case with a devastating upper limb crush injury that was successfully managed with fibula flap transfer preceded by AV loop construction. A 38-year-old woman was admitted to our hospital with severe crushing trauma to her right forearm and hand. There was significant skin loss with injuries to blood vessels and tendons. She underwent multiple staged operations beginning with repair of the ulnar artery, debridement of necrotic tissue, and placement of 2 K-wires to stabilize the bones. Thereafter, a long saphenous AV loop was constructed between the brachial artery and the basilic vein. Finally, transfer of the fibula flap to the forearm. We used the staged procedure to provide adequate time for the AV loop maturation and adaptation. At around the patient's 7-month follow-up visit, her forearm and hand were stable, no complications related to the AV loop or the transferred fibula flap were noted. Utilizing AV loops to support transferred free flaps upper limb defects showed a promising successful outcome.

15.
J Cancer Res Ther ; 12(2): 616-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27461620

RESUMO

BACKGROUND: Somatic mutations of the epidermal growth factor receptor (EGFR) gene have been associated with tumor response to tyrosine kinase inhibitors (TKIs) and favorable outcome in patients with non-small-cell lung cancer (NSCLC). The activating mutations that confer sensitivity to EGFR TKIs are present in the TK domain of the EGFR gene. This study aims to report on the prevalence of EGFR mutations in NSCLC and non-squamous lung cancer patients at diagnosis, using genomic deoxyribonucleic acid (DNA) obtained from paraffin-embedded tissue samples. MATERIALS AND METHODS: We collected formalin.fixed, paraffin.embedded. (FFPE) tissue samples from 166. cases of lungadenocarcinomas referring to Jordan University Hospital and King Hussein Cancer Center between 2007 and first half of 2013. None of the patients met the definition of never smoker defined as those who smoked less than 100 cigarettes in their lifetime. We evaluated EGFR mutations by nested polymerase chain reaction. (PCR) followed by direct sequencing of the EGFR kinase domain from exon 18 to 21. RESULTS: Six different point mutations were detected in 24 patients (14.46%) of the study population. The resultant mutations were as follows: Ten patients have deletion in exon 19, sevenpatients have L858R, two patients have L861P, and one of each of the following: A735T, D770_N771 insY, L858P, L861Q, and G917C. CONCLUSION: The present study revealed that the EGFR mutations rate in Jordanian patients with adenocarcinoma of the lung was higher than in African-American, and some white Caucasian patients, and was lower than in patients in East Asia, and other countries of South Asia.


Assuntos
Adenocarcinoma/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Cell Mol Life Sci ; 71(13): 2517-33, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24177339

RESUMO

Mammalian protease-activated-receptor-1 and -2 (PAR1 and PAR2) are activated by proteases found in the flexible microenvironment of a tumor and play a central role in breast cancer. We propose in the present study that PAR1 and PAR2 act together as a functional unit during malignant and physiological invasion processes. This notion is supported by assessing pro-tumor functions in the presence of short hairpin; shRNA knocked-down hPar2 or by the use of a truncated PAR2 devoid of the entire cytoplasmic tail. Silencing of hPar2 by shRNA-attenuated thrombin induced PAR1 signaling as recapitulated by inhibiting the assembly of Etk/Bmx or Akt onto PAR1-C-tail, by thrombin-instigated colony formation and invasion. Strikingly, shRNA-hPar2 also inhibited the TFLLRN selective PAR1 pro-tumor functions. In addition, while evaluating the physiological invasion process of placenta extravillous trophoblast (EVT) organ culture, we observed inhibition of both thrombin or the selective PAR1 ligand; TFLLRNPNDK induced EVT invasion by shRNA-hPar2 but not by scrambled shRNA-hPar2. In parallel, when a truncated PAR2 was utilized in a xenograft mouse model, it inhibited PAR1-PAR2-driven tumor growth in vivo. Similarly, it also attenuated the interaction of Etk/Bmx with the PAR1-C-tail in vitro and decreased markedly selective PAR1-induced Matrigel invasion. Confocal images demonstrated co-localization of PAR1 and PAR2 in HEK293T cells over-expressing YFP-hPar2 and HA-hPar1. Co-immuno-precipitation analyses revealed PAR1-PAR2 complex formation but no PAR1-CXCR4 complex was formed. Taken together, our observations show that PAR1 and PAR2 act as a functional unit in tumor development and placenta-uterus interactions. This conclusion may have significant consequences on future breast cancer therapeutic modalities and improved late pregnancy outcome.


Assuntos
Neoplasias da Mama/genética , Receptor PAR-1/genética , Receptor PAR-2/genética , Microambiente Tumoral/genética , Animais , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Camundongos , Oligopeptídeos/metabolismo , Gravidez , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptor PAR-1/metabolismo , Receptor PAR-2/metabolismo , Receptores CXCR4/genética , Ensaios Antitumorais Modelo de Xenoenxerto
17.
FASEB J ; 26(5): 2031-42, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22291441

RESUMO

A pivotal role is attributed to the estrogen-receptor (ER) pathway in mediating the effect of estrogen in breast cancer progression. Yet the precise mechanisms of cancer development by estrogen remain poorly understood. Advancing tumor categorization a step forward, and identifying cellular gene fingerprints to accompany histopathological assessment may provide targets for therapy as well as vehicles for evaluating the response to treatment. We report here that in breast carcinoma, estrogen may induce tumor development by eliciting protease-activated receptor-1 (PAR(1)) gene expression. Induction of PAR(1) was shown by electrophoretic mobility shift assay, luciferase reporter gene driven by the hPar(1) promoter, and chromatin-immunoprecipitation analyses. Functional estrogen regulation of hPar1 in breast cancer was demonstrated by an endothelial tube-forming network. Notably, tissue-microarray analyses from an established cohort of women diagnosed with invasive breast carcinoma exhibited a significantly shorter disease-free (P=0.006) and overall (P=0.02) survival of patients that were positive for ER and PAR(1), compared to ER-positive but PAR(1)-negative patients. We propose that estrogen transcriptionally regulates hPar(1), culminating in an aggressive gene imprint in breast cancer. While ER(+) patients are traditionally treated with hormone therapy, the presence of PAR(1) identifies a group of patients that requires additional treatment, such as anti-PAR(1) biological vehicles or chemotherapy.


Assuntos
Neoplasias da Mama/metabolismo , Estrogênios/fisiologia , Regulação da Expressão Gênica/fisiologia , Receptor PAR-1/genética , Sequência de Bases , Neoplasias da Mama/patologia , Imunoprecipitação da Cromatina , Estudos de Coortes , DNA , Primers do DNA , Ensaio de Desvio de Mobilidade Eletroforética , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas
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