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1.
Cancer Immunol Immunother ; 71(11): 2731-2742, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35428910

RESUMO

Melanoma is responsible for 90% of skin cancer-related deaths. Major therapeutic advances have led to a considerable improvement in the prognosis of patients, with the development of targeted therapies (BRAF or MEK inhibitors) and immunotherapy (anti-CTLA-4 or -PD-1 antibodies). However, the tumor constitutes an immunosuppressive microenvironment that prevents the therapeutic efficacy and/or promotes the development of secondary resistances. CD160 is an activating NK-cell receptor initially described as delineating the NK and CD8+ T-cell cytotoxic populations. Three forms of CD160 have been described: (1) the GPI isoform, constitutively expressed and involved in the initiation of NK-cells' cytotoxic activity, (2) the transmembrane isoform, neo-synthesized upon cell activation, allowing the amplification of NK cells' cytotoxic functions and (3) the soluble form, generated after cleavage of the GPI isoform, which presents an immuno-suppressive activity. By performing immunohistochemistry analyses, we observed a strong expression of CD160 at the primary cutaneous tumor site of melanoma patients. We further demonstrated that melanoma cells express CD160-GPI isoform and constitutively release the soluble form (sCD160) into the tumor environment. sCD160 was shown to inhibit the cytotoxic activity of NK-cells towards their target cells. In addition, it was found in the serum of melanoma patients and associated with increased tumor dissemination. Altogether these results support a role for sCD160 in the mechanisms leading to the inhibition of anti-tumor response and immune surveillance in melanoma.


Assuntos
Melanoma , Receptores Imunológicos , Antígenos CD , Proteínas Ligadas por GPI , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno , Receptor de Morte Celular Programada 1 , Isoformas de Proteínas/metabolismo , Proteínas Proto-Oncogênicas B-raf , Receptores Imunológicos/metabolismo , Microambiente Tumoral
2.
Breast J ; 27(7): 595-602, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34251074

RESUMO

INTRODUCTION: The Grisotti technique consists to excise central breast tumor with nipple areolar and mobilize a dermo-glandular flap which is de-epithelized in order to reshape the breast and recreate an areola. The objective was to assess oncological results, postoperative side-effects, and patient and surgeon satisfaction rates resulting from this technique. MATERIALS AND METHODS: From September 2016 to December 2019, 38 patients have been treated with a central breast tumor using the Grisotti technique. RESULTS: The mean age was 61.6 ± 11. The median body mass index was 27 kg/m² [20-42]. Thirty one patients benefited from a sentinel lymph node dissection. Preoperative histology found a majority of invasive ductal carcinomas (IDC) (71%). There were no intraoperative complications, and the average operating time was 90 min [60-200]. Postoperative histology found IDC associated with ductal carcinoma in situ in 28 patients. The surgical margins were invaded in two patients (reoperated by mastectomy after adjuvant treatment) and invasion of a margin of less than 1 mm in another six patients (supplemented by re-excision). The main postoperative complications were an abscess of the operating site and a partial necrosis of the neo-areola. The appearance of the breasts after radiotherapy gives a high satisfaction rate, both for patients and for surgeons. CONCLUSION: The Grisotti technique is an easily reproducible procedure without major complications. It makes it possible to perform a carcinological satisfactory central lumpectomy, correction of the central glandular defect, and reconstruction of a new areola.


Assuntos
Neoplasias da Mama , Mamoplastia , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mamoplastia/efeitos adversos , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Mamilos/cirurgia , Estudos Retrospectivos
3.
Cancer Immunol Immunother ; 69(7): 1337-1352, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32219500

RESUMO

Cleavage of the MUC1 glycoprotein yields two subunits, an extracellular alpha-subunit bound to a smaller transmembrane beta-subunit. Monoclonal antibodies (mAbs) directed against the MUC1 alpha-beta junction comprising the SEA domain, a stable cell-surface moiety, were generated. Sequencing of all seven anti-SEA domain mAbs showed that they clustered into four groups and sequences of all groups are presented here. mAb DMB5F3 with picomolar affinity for the MUC1 SEA target was selected for further evaluation. Immunohistochemical staining of a series of malignancies with DMB5F3 including lung, prostate, breast, colon, and pancreatic carcinomas revealed qualitative and qualitative differences between MUC1 expression on normal versus malignant cells: DMB5F3 strongly stained malignant cells in a near-circumferential pattern, whereas MUC1 in normal pancreatic and breast tissue showed only weak apical positivity of ductal/acinar cells. Humanized chimeric DMB5F3 linked to ZZ-PE38 (ZZ IgG-binding protein fused to Pseudomonas exotoxin) induced vigorous cytotoxicity of MUC1+ malignant cells in vitro. The intensity of cell killing correlated with the level of MUC1 expression by the target cell, suggesting a MUC1 expression threshold for cell killing. MUC1+ Colo357 pancreatic cancer cells xenotransplanted into nude and SCID mice models were treated with the chDMB5F3:ZZ-PE38 immunocomplex. In both transplant models, chDMB5F3:ZZ-PE38 exhibited significant in vivo anti-tumor activity, suppressing up to 90% of tumor volume in the SCID model compared with concomitant controls. The efficacy of chDMB5F3:ZZ-PE38 immunotoxin in mediating tumor killing both in vitro and in vivo strongly suggests a clinical role for anti-MUC1 SEA antibody in the treatment of MUC1-expressing malignancies.


Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos/farmacologia , Imunotoxinas/imunologia , Mucina-1/química , Mucina-1/imunologia , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Apoptose , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Nus , Camundongos SCID , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Domínios Proteicos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Ann Pathol ; 39(6): 383-398, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31257035

RESUMO

Neoadjuvant therapy is an increasing treatment option in the management of breast cancer. The tumor response to neoadjuvant therapy, especially the pathological complete response, is a validated endpoint frequently used in clinical trials. However, there is still a lack of standardization for the surgical specimen management in the neoadjuvant setting. This leads to heterogeneity in the specimen handling and might lead to significant bias for the prognostic assessment of patients or in clinical trials. The GEFPICS group, composed of expert breast cancer pathologists, herein presents guidelines for the management of breast and axillary specimen before treatment (management of biopsy, items of the pathological report) and after neoadjuvant therapy (specimen handling, histological assessment of response, items of the pathological report and response grading systems).


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Linfonodos/patologia , Terapia Neoadjuvante , Manejo de Espécimes/normas , Biomarcadores Tumorais , Biópsia/métodos , Biópsia/normas , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Quimioterapia Adjuvante/normas , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , França , Humanos , Linfonodos/efeitos dos fármacos , Linfonodos/cirurgia , Prontuários Médicos/normas , Microscopia , Neoplasia Residual/patologia , Prognóstico , Biópsia de Linfonodo Sentinela/métodos , Manejo de Espécimes/métodos , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
5.
Int J Mol Sci ; 19(12)2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30518157

RESUMO

Breast cancer (BC) is the most common cancer in women worldwide and remains a major cause of mortality with an expected 137,000 death this year in Europe. Standard management of metastatic BC comprises hormonotherapy, chemotherapy, and targeted therapies. Cyclin dependent kinase (CDK) and mammalian target of rapamycin (mTOR) inhibitors have recently proved their efficiency in hormonal receptor expressing BC. Checkpoint proteins inhibition is being evaluated in phase 3 studies. Since inflammation is constantly present in cancers, research teams have focused their attention on the interleukin-17 (IL-17) family of proinflammatory cytokines. Preclinical experiments have reported both pro and antitumor effects depending on the conditions. In the present article, we review the accumulating evidences about the roles of IL-17 in BC and discuss whether this family of cytokines could be a new target in anticancer treatments.


Assuntos
Neoplasias da Mama/metabolismo , Interleucina-17/metabolismo , Animais , Feminino , Humanos , Modelos Biológicos , Transdução de Sinais
6.
Int J Mol Sci ; 17(9)2016 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-27589729

RESUMO

The inflammatory process contributes to immune tolerance as well as to tumor progression and metastasis. By releasing extracellular signals, cancerous cells constantly shape their surrounding microenvironment through their interactions with infiltrating immune cells, stromal cells and components of extracellular matrix. Recently, the pro-inflammatory interleukin 17 (IL-17)-producing T helper lymphocytes, the Th17 cells, and the IL-17/IL-17 receptor (IL-17R) axis gained special attention. The IL-17 family comprises at least six members, IL-17A, IL-17B, IL-17C, IL-17D, IL-17E (also called IL-25), and IL-17F. Secreted as disulfide-linked homo- or heterodimers, the IL-17 bind to the IL-17R, a type I cell surface receptor, of which there are five variants, IL-17RA to IL-17RE. This review focuses on the current advances identifying the promoting role of IL-17 in carcinogenesis, tumor metastasis and resistance to chemotherapy of diverse solid cancers. While underscoring the IL-17/IL-17R axis as promising immunotherapeutic target in the context of cancer managing, this knowledge calls upon further in vitro and in vivo studies that would allow the development and implementation of novel strategies to combat tumors.


Assuntos
Imunoterapia/métodos , Interleucina-17/metabolismo , Neoplasias/imunologia , Microambiente Tumoral/imunologia , Animais , Humanos , Interleucina-17/genética , Neoplasias/classificação , Neoplasias/terapia , Linfócitos T Auxiliares-Indutores/imunologia
7.
Oncologist ; 20(3): 243-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25637380

RESUMO

BACKGROUND: Neoadjuvant treatment provides a unique opportunity to evaluate individual tumor sensitivity. This study evaluated whether a response-guided strategy could improve clinical outcome compared with a standard treatment. METHODS: Overall, 264 previously untreated stage II-III operable breast cancer patients were randomized to receive either standard treatment (arm A, n = 131), consisting of fluorouracil, epirubicin, and cyclophosphamide (FEC100: 500, 100, and 500 mg/m(2), respectively, for 3 cycles) followed by docetaxel (100 mg/m(2) for 3 cycles), or adapted treatment (arm B, n = 133), beginning with 2 cycles of FEC100 and switching to docetaxel if tumor size decreased by <30% after 2 cycles or <50% after 4 cycles of FEC100 (ultrasound assessments according to World Health Organization criteria). Otherwise, FEC100 was given for six cycles before surgery. Intent-to-treat analysis was performed. RESULTS: Similar results were observed for clinical response (objective response was 54% vs 56%, p = .18), breast conservation surgery (BCS; 67% vs 68%, p = .97), and pathological complete response rate (Chevallier classification: 14% vs 11%, p = .68; Statloff classification: 16% vs 13%, p = .82) between arms A and B. Similar toxicities were observed, even with unbalanced numbers of FEC100 and docetaxel courses. CONCLUSION: Adapted and standard treatments had similar results in terms of tumor response, BCS rate, and tolerability. Further survival outcome data are expected.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Ciclofosfamida/administração & dosagem , Docetaxel , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Receptor ErbB-2 , Taxoides/administração & dosagem , Resultado do Tratamento
8.
Oncology ; 88(5): 261-72, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25573741

RESUMO

OBJECTIVE: Neoadjuvant chemotherapy (NACT) allows for a more frequent use of breast-conservative surgery; it is also an in vivo model of individual tumor sensitivity which permits to determine new prognostic factors to personalize the therapeutic approach. METHODS: Between 2000 and 2012, 318 patients with primary invasive breast cancer were treated with a median of 6 cycles of NACT; they received either an anthracycline-based FEC 100 protocol (31.1%), or anthracyclines + taxanes (53.5%), with trastuzumab if indicated (15.4%). RESULTS: After a median follow-up of 44.2 months, the pathological complete response rate according to the classification of Chevallier et al. [Am J Clin Oncol 1993;16:223-228] was 19.3%, and overall (OS) and disease-free survival (DFS) at 10 years were 60.2 and 69.6%, respectively. Univariate analyses demonstrated that the Residual Disease in Breast and Nodes (RDBN) index was the most significant prognostic factor for OS (p = 0.0082) and DFS (p = 0.0022), and multivariate analyses mainly revealed that the residual tumor size, residual involved node number and post-chemotherapy Scarff-Bloom-Richardson (SBR) grading were the most significant prognostic factors. CONCLUSIONS: In a cohort of patients who were all homogeneously treated with some of the most common drugs for breast cancer, we demonstrate that NACT may provide additional prognostic factors and confirm the RDBN index. As this index allows for the prediction of survival with different breast cancer subtypes, we suggest that it should be calculated routinely to help clinicians to select patients who need adjuvant treatments.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/epidemiologia , Terapia Neoadjuvante/métodos , Neoplasia Residual/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Quimioterapia Adjuvante , Fatores de Confusão Epidemiológicos , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , França/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Mastectomia Segmentar , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxoides/administração & dosagem , Resultado do Tratamento
9.
Ann Pathol ; 34(5): 366-72, 2014 Oct.
Artigo em Francês | MEDLINE | ID: mdl-25439989

RESUMO

Biomarker assessment of breast cancer tumor samples is part of the routine workflow of pathology laboratories. International guidelines have recently been updated, with special regards to the pre-analytical steps that are critical for the quality of immunohistochemical and in situ hybridization procedures, whatever the biomarker analyzed. Fixation and specimen handling protocols must be standardized, validated and carefully tracked. Cooperation and training of the personnel involved in the specimen workflow (e.g. radiologists, surgeons, nurses, technicians and pathologists) are of paramount importance. The GEFPICS' update of the recommendations herein details and comments the different steps of the pre-analytical process. Application of these guidelines and participation to quality insurance programs are mandatory to ensure the correct evaluation of oncotheranostic biomarkers.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Receptor ErbB-2/análise , Receptores de Esteroides/análise , Neoplasias da Mama/patologia , Feminino , Fixadores , França , Técnicas Histológicas , Humanos , Prognóstico , Controle de Qualidade , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Manejo de Espécimes/métodos
10.
Ann Pathol ; 34(5): 352-65, 2014 Oct.
Artigo em Francês | MEDLINE | ID: mdl-25439988

RESUMO

International guidelines on HER2 determination in breast cancer have just been updated by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP), on the basis of more than ten-year practice, results of clinical trials and concordance studies. The GEFPICS group, composed of expert pathologists in breast cancer, herein presents these recommendations, adapted to the French routine practice. These guidelines highlight the possible diagnosis difficulties with regards to HER2 status determination, such as intra-tumor heterogeneity, special histological subtypes and biomarker re-evaluation during metastatic relapse. Pre-analytical issues and updated scoring criteria (especially for equivocal cases) are detailed, in order to decrease the occurrence of false negative cases. In the era of personalized medicine, pathologists are more than ever involved in the quality of oncotheranostic biomarker evaluation.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Receptor ErbB-2/análise , Neoplasias da Mama/tratamento farmacológico , Reações Falso-Negativas , Feminino , França , Humanos , Imuno-Histoquímica/métodos , Hibridização In Situ , Hibridização in Situ Fluorescente , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia , Prognóstico
11.
J Immunoassay Immunochem ; 34(3): 232-45, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23656244

RESUMO

Over-expression of MUC1/CD227 is observed in 90% of breast tumors. Classical morphologic description and semi-quantitative digital measurement of MUC1 were performed from immunohistochemical stained slides of 123 routine histological samples. Measures of MUC1 expression showed statistical differences between non tumoral (NT) breast tissue and Ductal Carcinoma In Situ (DCIS) or infiltrating carcinoma (IC), p < 0.0001. Loss of MUC1 was correlated with high Ki67 index (p = 0.001) and loss of hormonal receptors (p = 0.03), whereas no correlations were found with HER2 expression. High-grade DCIS or IC showed increasing loss of apical polarised and cytoplasmic expression of MUC1.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Regulação Neoplásica da Expressão Gênica , Mucina-1/biossíntese , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/biossíntese , Pessoa de Meia-Idade , Receptor ErbB-2/biossíntese
12.
Front Oncol ; 12: 804868, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847954

RESUMO

Luminal breast cancers represent 70% of newly diagnosed breast cancers per annum and have a relatively good prognosis compared with triple-negative breast cancers. Luminal tumors that are responsive to hormonal therapy are particularly associated with a favorable prognosis. Nonetheless, the absolute number of metastatic relapses in luminal cancers is larger than in triple-negative breast cancers. A better understanding of the biology of luminal cancers, control of metastases formation, and identification of predictive markers of their evolution are therefore still necessary. In this context, we previously disclosed the key role of NFAT3 in regulating luminal breast cancer invasion. We have now identified a specific inhibitory region, in the C-terminal part of NFAT3, required for the inhibition of invasion of the human luminal breast cancer cell line T-47D. Indeed, we showed that this 85 amino acid C-terminal region acts as a dominant negative form of NFAT3 and that its overexpression in the T-47D cell line led to increased cell invasion. Mechanistically, we have revealed that this region of NFAT3 interacts with the small Ras GTPase RERG (RAS like estrogen regulated growth inhibitor) and shown that RERG expression is required for NFAT3 to impede T-47D cell invasion. We have validated the association of NFAT3 with RERG in human luminal breast cancer tissues. We have shown an increase of the quantity of the NFAT3/RERG complexes in patients without axillary lymph node colonization and therefore proposed that the detection of this complex may be a non-invasive marker of axillary lymph node colonization.

14.
Cancer Med ; 11(24): 4865-4879, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35593199

RESUMO

BACKGROUND: The COVID-19 pandemic led to a widely documented disruption in cancer care pathway. Since a resurgence of the pandemic was expected after the first lockdown in France, the global impact on the cancer care pathway over the year 2020 was investigated. AIMS: This study aimed to describe the changes in the oncology care pathway for cancer screening, diagnosis, assessment, diagnosis annoucement procedure and treatment over a one-year period. MATERIALS & METHODS: The ONCOCARE-COV study was a comprehensive, retrospective, descriptive, and cross-sectional study comparing the years 2019 and 2020. All key indicators along the cancer care pathway assessing the oncological activity over four periods were described. This study was set in a high-volume, public, single tertiary care center divided in two complementary sites (Reims University Hospital and Godinot Cancer Institute, Reims, France) which was located in a high COVID-19 incidence area during both peaks of the outbreak. RESULTS: A total of 26,566 patient's files were active during the year 2020. Breast screening (-19.5%), announcement dedicated consultations (-9.2%), Intravenous and Hyperthermic Intraoperative Intraperitoneal Chemotherapy (HIPECs) (-25%), and oncogeriatric evaluations (-14.8%) were heavily disrupted in regard to 2020 activity. We identified a clear second outbreak wave impact on medical announcement procedures (October, -14.4%), radiotherapy sessions (October, -16%), number of new health record discussed in multidisciplinary tumor board meeting (November, -14.6%) and HIPECs (November, -100%). Moreover, 2020 cancer care activity stagnated compared to 2019. DISCUSSION: The oncological care pathway was heavily disrupted during the first and second peaks of the COVID-19 outbreak. Between lockdowns, we observed a remarkable but non-compensatory recovery as well as a lesser impact from the pandemic resurgence. However, in absence of an increase in activity, a backlog persisted. CONCLUSION: Public health efforts are needed to deal with the consequences of the COVID-19 pandemic on the oncology care pathway.


Assuntos
COVID-19 , Neoplasias , Humanos , Pandemias , COVID-19/epidemiologia , Estudos Transversais , SARS-CoV-2 , Procedimentos Clínicos , Estudos Retrospectivos , Controle de Doenças Transmissíveis , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapia
15.
Int J Surg Case Rep ; 78: 270-273, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33373921

RESUMO

INTRODUCTION: Synovial sarcoma (SS) is a mesenchymal neoplasm that is characterized by its unique histological pattern and is most commonly found near the joints of the extremity. Stomach involvement is very rare. This work aimed to present the case of a patient with gastric SS. We also conducted a review of 39 gastric SS cases reported in the literature. PRESENTATION OF CASE: Here we report a case of primary gastric synovial sarcoma in a 32-year-old male patient revealed by gastric reflux. Partial gastrectomy was performed showing a 35 mm lesion with a high spindle cell component. Immunohistochemistry revealed 18q11.2 translocation expression in most of the cells asserting a diagnosis of SS. No local or distant recurrence occurred at 8 months post-operative follow-up. DISCUSSION: The majority of SS occurs in the extremities and is most often associated with tendons in the large articulations of young adults. Gastric SS are very scarce and a molecular biology approach to detect the SYT-SSX fusion gene is required for conclusive diagnosis. We carried out a clinical review of the 40 cases of primary gastric SS, including our case. They all underwent an excisional surgery, most of them by partial gastectomy or wedge resection. Recurrences were rare and early when they occurred. CONCLUSION: Gastric SS is a very uncommon neoplasia although it is henceforth a described entity. Immunohistochemical detection of a pathognomonic translocation is needed to make the diagnosis of SS. Best therapeutic approach for these tumors remains surgical resection with no specific excisional technique recommended.

16.
Sci Rep ; 11(1): 22278, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782679

RESUMO

Numerous recent studies have shown that in the continuum of cardiovascular diseases, the measurement of arterial stiffness has powerful predictive value in cardiovascular risk and mortality and that this value is independent of other conventional risk factors, such as age, cholesterol levels, diabetes, smoking, or average blood pressure. Vascular stiffening is often the main cause of arterial hypertension (AHT), which is common in the presence of obesity. However, the mechanisms leading to vascular stiffening, as well as preventive factors, remain unclear. The aim of the present study was to investigate the consequences of apelin deficiency on the vascular stiffening and wall remodeling of aorta in mice. This factor freed by visceral adipose tissue, is known for its homeostasic role in lipid and vascular metabolisms, or again in inflammation. We compared the level of metabolic markers, inflammation of white adipose tissue (WAT), and aortic wall remodeling from functional and structural approaches in apelin-deficient and wild-type (WT) mice. Apelin-deficient mice were generated by knockout of the apelin gene (APL-KO). From 8 mice by groups, aortic stiffness was analyzed by pulse wave velocity measurements and by characterizations of collagen and elastic fibers. Mann-Whitney statistical test determined the significant data (p < 5%) between groups. The APL-KO mice developed inflammation, which was associated with significant remodeling of visceral WAT, such as neutrophil elastase and cathepsin S expressions. In vitro, cathepsin S activity was detected in conditioned medium prepared from adipose tissue of the APL-KO mice, and cathepsin S activity induced high fragmentations of elastic fiber of wild-type aorta, suggesting that the WAT secretome could play a major role in vascular stiffening. In vivo, remodeling of the extracellular matrix (ECM), such as collagen accumulation and elastolysis, was observed in the aortic walls of the APL-KO mice, with the latter associated with high cathepsin S activity. In addition, pulse wave velocity (PWV) and AHT were increased in the APL-KO mice. The latter could explain aortic wall remodeling in the APL-KO mice. The absence of apelin expression, particularly in WAT, modified the adipocyte secretome and facilitated remodeling of the ECM of the aortic wall. Thus, elastolysis of elastic fibers and collagen accumulation contributed to vascular stiffening and AHT. Therefore, apelin expression could be a major element to preserve vascular homeostasis.


Assuntos
Aorta/metabolismo , Aorta/fisiopatologia , Apelina/deficiência , Matriz Extracelular/metabolismo , Rigidez Vascular/genética , Animais , Apelina/genética , Apelina/metabolismo , Biomarcadores , Pressão Sanguínea , Expressão Gênica , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Elastase Pancreática/genética , Elastase Pancreática/metabolismo
17.
Eur J Echocardiogr ; 11(7): 622-9, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20400764

RESUMO

AIMS: The aim of the present study was to evaluate left ventricular (LV) function and contractile reserve (CR) with Doppler myocardial imaging (DMI) in a small animal model for type 1 diabetes. METHODS AND RESULTS: Cardiac function was assessed in anaesthetized Wistar rats 6 and 8 weeks after injection of 60 mg/kg of streptozotocin. At 6 weeks of diabetes, colour DMI echocardiography was performed at rest and during incremental dosages of dobutamine (5, 10, 20 microg/kg/min). Left ventricular fractional shortening was decreased after 8 weeks of follow-up [36 +/- 5 (D) vs. 41 +/- 4% (C); P = 0.049]. After 6 weeks of diabetes, DMI measurements were reduced in the diabetic rats in the inferolateral wall at rest [systolic velocity: 2.5 +/- 0.4 (D) vs. 4.4 +/- 0.3 (C) cm/s; P < 0.001; systolic strain rate: 12.2 +/- 3.4 (D) vs. 17.4 +/- 3.2 (C) 1/s; P = 0.012] and during inotropic stimulation [delta velocity (cm/s): 0.2 +/- 0.1 (D) vs. 0.5 +/- 0.3 (C)/5 microg dobutamine; P = 0.002; delta strain rate (1/s): 1.4 +/- 0.9 (D) vs. 3.3 +/- 2.2 (C)/5 microg dobutamine; P = 0.049]. Furthermore, the intraventricular delay in time-to-peak systolic strain was larger in diabetes [20 +/- 18 (D) vs. 10 +/- 7 (C) ms; P= 0.01]. Systolic mitral annular velocity was also lower in the diabetic rats at rest [2.7 +/- 0.4 (D) vs. 3.5 +/- 0.4 (C) cm/s; P < 0.001] and in response to dobutamine [delta velocity (cm/s): 0.1 +/- 0.1 (D) vs. 0.3 +/- 0.2 (C)/5 microg dobutamine; P = 0.013]. CONCLUSION: In experimental diabetes, a reduction in radial and longitudinal LV function and CR can be detected with DMI before the onset of a reduced global LV function.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Ecocardiografia sob Estresse , Sístole , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Algoritmos , Animais , Diabetes Mellitus Experimental/complicações , Modelos Animais de Doenças , Ecocardiografia sob Estresse/métodos , Masculino , Contração Miocárdica , Ratos , Ratos Wistar , Disfunção Ventricular Esquerda/etiologia
18.
Cardiovasc Diabetol ; 7: 26, 2008 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-18764943

RESUMO

UNLABELLED: The role of structural and functional abnormalities of small vessels in diabetes cardiomyopathy remains unclear. Myocardial contrast echocardiography allows the quantification of myocardial blood flow at rest and during dipyridamole infusion. The aim of the study was to determine the myocardial blood flow reserve in normal rats compared with streptozotocin-induced diabetic rats using contrast echocardiography. METHODS: We prospectively studied 40 Wistar rats. Diabetes was induced by intravenous streptozotocin in 20 rats. All rats underwent baseline and stress (dipyridamole: 20 mg/kg) high power intermittent imaging in short axis view under anaesthesia baseline and after six months. Myocardial blood flow was determined and compared at rest and after dipyridamole in both populations. The myocardial blood flow reserve was calculated and compared in the 2 groups. Parameters of left ventricular function were determined from the M-mode tracings and histological examination was performed in all rats at the end of the study. RESULTS: At six months, myocardial blood flow reserve was significantly lower in diabetic rats compared to controls (3.09 +/- 0.98 vs. 1.28 +/- 0.67 ml min-1 g-1; p < 0.05). There were also a significant decrease in left ventricular function and a decreased capillary surface area and diameter at histology in the diabetic group. CONCLUSION: In this animal study, diabetes induced a functional alteration of the coronary microcirculation, as demonstrated by contrast echocardiography, a decrease in capillary density and of the cardiac systolic function. These findings may offer new insights into the underlying mechanisms of diabetes cardiomyopathy.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Circulação Coronária , Diabetes Mellitus Experimental/diagnóstico por imagem , Miocárdio/patologia , Fosfolipídeos/administração & dosagem , Hexafluoreto de Enxofre/administração & dosagem , Animais , Capilares/diagnóstico por imagem , Capilares/fisiopatologia , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Circulação Coronária/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Dipiridamol/administração & dosagem , Masculino , Variações Dependentes do Observador , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Ultrassonografia , Função Ventricular Esquerda
19.
BJU Int ; 101(3): 293-8, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17922870

RESUMO

OBJECTIVE: To assess the extent to which prostate HistoScanning (PHS), a new ultrasound-based technology that uses computer-aided analysis to quantify tissue disorganization induced by malignant processes, can identify and characterize foci of prostate cancer compared with step-sectioned radical prostatectomy (RP) specimens. PATIENTS AND METHODS: Between September 2004 and February 2006, 29 men had PHS before their scheduled RP. A three-dimensional ultrasound raw-data file was acquired, and PHS analysed regions of interest (ROI) corresponding to tissue volumes of approximately 0.04 mL. In 13 men the histology was examined on sections of the whole-mount prostate onto which a grid of 5 x 5 mm squares was applied. On a test set of 14 of the 29 patients, PHS analysis was used before knowing the histology results (blinded data), to predict the maximum tumour diameter, focality, laterality and extraprostatic extension (EPE). RESULTS: Identification and characterization by PHS of the index tumour in the 14 patients in the test set correlated closely (r = 0.95, P < 0.001) with the reference test. The concordance in the attribution of multifocality (present/absent), unilateral/bilateral disease between PHS and histology was 100%. EPE as determined by PHS was attributed to all three pT3a pathological specimens in the blinded paired data. In the same set of data, EPE was attributed to one prostate cancer that on pathological inspection was deemed to be organ-confined (pT2b). CONCLUSIONS: PHS has the potential to identify and characterize prostate cancer foci noninvasively. The precision appears to be sufficient to suggest that PHS might be useful as a triage test for men deemed to be at risk of prostate cancer and who wish to avoid prostate biopsy.


Assuntos
Interpretação de Imagem Assistida por Computador/normas , Antígeno Prostático Específico/sangue , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Biópsia por Agulha , Estudos de Coortes , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco , Ultrassonografia
20.
Acta Cytol ; 52(4): 418-23, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18702358

RESUMO

OBJECTIVE: To compare 2 different series of fine needle aspirations (FNA) performed by conventional smears (CS) and liquid-based cytology (TriPath PREP). STUDY DESIGN: From January 1, 2001, to December 31, 2005, we selected 139 FNA samples of lymph node, if the diagnosis was histologically proven after the initial cytologic diagnosis. Samples came from 2 university hospitals from Brussels: UZ-Brussel (n=96) using liquid-based cytology (LBC) and Hospital Erasme ULB (n=43) using CS. RESULTS: The number of inadequate samples was greater for LBC than CS, but there was no statistical difference (17.7% vs. 4.7%, p = 0.059). No differences were found between LBC and CS in sensitivity (respectively, 85.0% vs. 85.2%), specificity (84.2% vs. 85.7%) and efficiency (84.8% vs. 85.4%). CONCLUSION: Despite the cost, the efficiency of lymph node FNA cytology is identical between the CS and LBC performed by the TriPath PREP system. The quality of the smears, both LBC and CS, depends mainly on practitioner dexterity. Nevertheless, one advantage of LBC is that it provides an ancillary technique to improve FNAC diagnosis. In the future, a combination of these technologies with FNAC alone could in some cases take the place of surgical lymph node excision.


Assuntos
Biópsia por Agulha Fina/métodos , Hospitais Universitários , Linfonodos/patologia , Transtornos Linfoproliferativos/patologia , Adulto , Idoso , Bélgica , Feminino , Humanos , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade
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