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Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the most frequently used rheumatoid arthritis (RA) diagnostic markers, but they are unable to anticipate the patient's evolution or response to treatment. The aim of this study was to identify possible severity biomarkers to predict an upcoming flare-up or remission period. To address this objective, sera and anticoagulated blood samples were collected from healthy controls (HCs; n = 39) and from early RA (n = 10), flare-up (n = 5), and remission (n = 16) patients. We analyzed leukocyte phenotype markers, regulatory T cells, cell proliferation, and cytokine profiles. Flare-up patients showed increased percentages of cluster of differentiation (CD)3+CD4- lymphocytes (p < 0.01) and granulocytes (p < 0.05) but a decreased natural killer (NK)/T lymphocyte ratio (p < 0.05). Analysis of leukocyte markers by principal component analysis (PCA) and receiver operating characteristic (ROC) curves showed that CD45RO+ (p < 0.0001) and CD45RA+ (p < 0.0001) B lymphocyte expression can discriminate between HCs and early RA patients, while CD3+CD4- lymphocyte percentage (p < 0.0424) and CD45RA+ (p < 0.0424), CD62L+ (p < 0.0284), and CD11a+ (p < 0.0185) B lymphocyte expression can differentiate between flare-up and RA remission subjects. Thus, the combined study of these leukocyte surface markers could have potential as disease severity biomarkers for RA, whose fluctuations could be related to the development of the characteristic pro-inflammatory environment.
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Oxidative stress has been linked to the onset and progression of different neoplasia. Antioxidants might help prevent it by modulating biochemical processes involved in cell proliferation. Here, the aim was to evaluate the in vitro cytotoxic effect of Haloferax mediterranei bacterioruberin-rich carotenoid extracts (BRCE) (0-100 µg/ml) in six BC cell lines, representative of the intrinsic phenotypes and a healthy mammary epithelium cell line. Cell index values were obtained using xCELLigence RTCA System. Furthermore, cell diameter, viability, and concentration were measured at 12 h, 24 h, and 30 h. We found that BC cells were selectively affected by BRCE (SI > 1, p < 0.005). After 30 h, the population of BC cells exposed to 100 µg/ml was 11.7-64.6% of the control (p = 0.0001-0.0009). Triple-negative cells were significantly affected [MDA-MB-231 (IC50 51.8 µg/ml, p < 0.0001) and MDA-MB-468 (IC50 63.9 µg/ml, p < 0.0001)]. Cell size was also reduced after 30 h treatment in 3.8 (± 0.1) µm and 3.3 (± 0.02) µm for SK-BR-3 (p < 0.0001) and MDA-MB-468 (p < 0.0001), respectively. In conclusion, Hfx. mediterranei BRCE exerts a cytotoxic effect on BC cell lines representative of all studied intrinsic subtypes. Furthermore, results obtained for MDA-MB-231 and MDA-MB-468 are very promising, considering the aggressive behaviour of the triple-negative BC subtype.
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Antineoplásicos , Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Proliferação de Células , Neoplasias de Mama Triplo Negativas/genética , Carotenoides/farmacologia , Carotenoides/uso terapêutico , ApoptoseRESUMO
Advances in immunotherapy have increased interest in knowing the role of the immune system in breast cancer (BC) pathogenesis. Therefore, immune checkpoints (IC) and other pathways related to immune regulation, such as JAK2 and FoXO1, have emerged as potential targets for BC treatment. However, their intrinsic gene expression in vitro has not been extensively studied in this neoplasia. Thus, we evaluated the mRNA expression of tumor-cell-intrinsic CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3), JAK2, and FoXO1 in different BC cell lines, derived mammospheres, and co-cultures with peripheral blood mononuclear cells (PBMCs) by real-time quantitative polymerase chain reaction (qRT-PCR). Our results showed that intrinsic CTLA-4, CD274 (PD-L1), and PDCD1LG2 (PD-L2) were highly expressed in triple-negative cell lines, while CD276 was predominantly overexpressed in luminal cell lines. In contrast, JAK2 and FoXO1 were under-expressed. Moreover, high levels of CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), and JAK2 were found after mammosphere formation. Finally, the interaction between BC cell lines and peripheral blood mononuclear cells (PBMCs) stimulates the intrinsic expression of CTLA-4, PCDC1 (PD1), CD274 (PD-L1), and PDCD1LG2 (PD-L2). In conclusion, the intrinsic expression of immunoregulatory genes seems very dynamic, depending on BC phenotype, culture conditions, and tumor-immune cell interactions.
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Antígeno B7-H1 , Biomarcadores Tumorais , Neoplasias da Mama , Humanos , Antígenos B7 , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/imunologia , Técnicas de Cocultura , Antígeno CTLA-4 , Leucócitos Mononucleares/metabolismo , Células MCF-7 , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismoRESUMO
Objetivo: conocer la tasa de concordancia del ganglio marcado con semilla Magseed® con el ganglio centinela marcado mediante tecnecio, en las pacientes con enfermedad ganglionar en el momento del diagnóstico que han recibido tratamiento neoadyuvante. Pacientes y métodos: estudio descriptivo retrospectivo de 44 mujeres diagnosticadas de carcinoma de mama estadios cT1-4/cN1/cM0, que recibieron quimioterapia neoadyuvante entre enero 2016 y diciembre 2020, y que tras una reevaluación radiológica se realizaron una cirugía mamaria con ganglio centinela en el Hospital General Universitario de Alicante. En las pacientes cN1 con respuesta radiológica axilar completa, la detección del ganglio centinela se llevó a cabo mediante doble técnica, extrayéndose por lo menos 3 ganglios. Además, se realizó una disección axilar dirigida mediante semilla magnética Magseed®, para su correcta localización y escisión. Resultados: la tasa de concordancia al realizar la disección axilar dirigida fue del 93,2%. La tasa de respuesta completa tras la quimioterapia neoadyuvante fue del 45,45%. Conclusiones: la disección axilar dirigida mejora la estadificación axilar tras la quimioterapia neoadyuvante, ya que reduce la tasa de falsos negativos respecto a la biopsia selectiva del ganglio centinela de manera aislada. (AU)
Objectives:To know the concordance rate of the ganglion marked with Magseed® with the sentinel node marked by technetium, in patients with limph node disease at diagnosis, that had received neoadjuvant treatment. Patients and methods: Retrospective descriptive study of 44 women, diagnosed with stage cT1-4 / cN1 / cM0 breast carcinoma, who received neoadjuvant chemotherapy between January 2016 and December 2020, and who after radiological re-evaluation, have undergone breast surgery with sentinel node at the General University Hospital of Alicante. In cN1 patients with a complete axillary radiological response, detection of the sentinel node is performed using a double technique, removing at least 3 nodes. In addition, axillary dissection directed by Magseed® magnetic seed is performed, for its correct location and excision. Results: The concordance rate when performing targeted axillary dissection was 93.2%. The complete response rate after neoadjuvant chemotherapy was 45.45%. Conclusions: Targeted axillary dissection improves the axillary staging after neoadjuvant chemotherapy, since it improves the false negative rate with respect to sentinel lymph node biopsy in isolation. (AU)
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Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/diagnóstico , Biópsia de Linfonodo Sentinela , Axila , Estudos Retrospectivos , Epidemiologia Descritiva , Terapia NeoadjuvanteRESUMO
Absent in melanoma 2 (AIM2) is a cytosolic dsDNA sensor that has been broadly studied for its role in inflammasome assembly. However, little is known about the function of AIM2 in adaptive immune cells. The purpose of this study was to investigate whether AIM2 has a cell-intrinsic role in CD4+ T cell differentiation or function. We found that AIM2 is expressed in both human and mouse CD4+ T cells and that its expression is affected by T cell receptor (TCR) activation. Naïve CD4+ T cells from AIM2-deficient (Aim2-/-) mice showed higher ability to maintain forkhead box P3 (FOXP3) expression in vitro, while their capacity to differentiate into T helper (Th)1, Th2 or Th17 cells remained unaltered. Transcriptional profiling by RNA sequencing showed that AIM2 might affect regulatory T cell (Treg) stability not by controlling the expression of Treg signature genes, but through the regulation of the cell's metabolism. In addition, in a T cell transfer model of colitis, Aim2-/--naïve T cells induced less severe body weight loss and displayed a higher ability to differentiate into FOXP3+ cells in vivo. In conclusion, we show that AIM2 function is not confined to innate immune cells but is also important in CD4+ T cells. Our data identify AIM2 as a regulator of FOXP3+ Treg cell differentiation and as a potential intervention target for restoring T cell homeostasis.
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Proteínas de Ligação a DNA/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Animais , Diferenciação Celular/fisiologia , Colite/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Inflamassomos/metabolismo , Ativação Linfocitária/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Th17/metabolismoRESUMO
Breast cancer is the leading cause of death among women worldwide. Over the years, oxidative stress has been linked to the onset and progression of cancer. In addition to the classical histological classification, breast carcinomas are classified into phenotypes according to hormone receptors (estrogen receptor-RE-/progesterone receptor-PR) and growth factor receptor (human epidermal growth factor receptor-HER2) expression. Luminal tumors (ER/PR-positive/HER2-negative) are present in older patients with a better outcome. However, patients with HER2-positive or triple-negative breast cancer (TNBC) (ER/PR/HER2-negative) subtypes still represent highly aggressive behavior, metastasis, poor prognosis, and drug resistance. Therefore, new alternative therapies have become an urgent clinical need. In recent years, anticancer agents based on natural products have been receiving huge interest. In particular, carotenoids are natural compounds present in fruits and vegetables, but algae, bacteria, and archaea also produce them. The antioxidant properties of carotenoids have been studied during the last years due to their potential in preventing and treating multiple diseases, including cancer. Although the effect of carotenoids on breast cancer during in vitro and in vivo studies is promising, clinical trials are still inconclusive. The haloarchaeal carotenoid bacterioruberin holds great promise to the future of biomedicine due to its particular structure, and antioxidant activity. However, much work remains to be performed to draw firm conclusions. This review summarizes the current knowledge on pre-clinical and clinical analysis on the use of carotenoids as chemopreventive and chemotherapeutic agents in breast cancer, highlighting the most recent results regarding the use of bacterioruberin from haloarchaea.
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Antineoplásicos/farmacologia , Organismos Aquáticos , Produtos Biológicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Carotenoides/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Produtos Biológicos/química , Produtos Biológicos/uso terapêutico , Carotenoides/química , Carotenoides/uso terapêutico , Feminino , Humanos , Áreas AlagadasRESUMO
The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 µm intervals and examined by hematoxylin-eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/µL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.
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PURPOSE: Hedgehog (Hh) signaling is a crucial developmental regulatory pathway recognized as a primary oncogenesis driver in various human cancers. However, its role in breast carcinoma (BC) has been underexplored. METHODS: We analyzed the expression of several Hh associated genes in a clinical series and breast cancer cell lines. We included 193 BC stratified according to intrinsic immunophenotypes. Gene expression profiling ofBOC, PTCH, SMO, GLI1, GLI2, and GLI3 was performed by qRT-PCR. Results were correlated with clinical-pathological variables and outcome. RESULTS: We observed expression ofGLI2 in triple-negative/basal-like (TN/BL) and GLI3 in luminal cells. In samples, BOC, GLI1, GLI2, and GLI3 expression correlated significantly with luminal tumors and good prognostic factors. In contrast, PTCH and SMO correlated with TN/BL phenotype and nodal involvement. Patients whose tumors expressed SMO had a poorer outcome, especially those with HER2 phenotype. Positive lymph-node status and high SMO remained independent poor prognostic factors. CONCLUSION: Our results support a differential Hh pathway activation in BC phenotypes.SMO levels stratified patients at risk of recurrence and death in HER2 phenotype, and it showed an independent prognostic value. Therefore, SMO could be a potential therapeutic target for a subset of BC patients.
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Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Proteínas Hedgehog/genética , Receptor Smoothened/genética , Transcriptoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas Hedgehog/metabolismo , Humanos , Células MCF-7 , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Receptor Patched-1/genética , Receptor Patched-1/metabolismo , Intervalo Livre de Progressão , Estudos Retrospectivos , Transdução de Sinais , Receptor Smoothened/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína Gli2 com Dedos de Zinco/genética , Proteína Gli2 com Dedos de Zinco/metabolismo , Proteína Gli3 com Dedos de Zinco/genética , Proteína Gli3 com Dedos de Zinco/metabolismoRESUMO
Inhibitor of differentiation (ID) proteins are a family of transcription factors that contribute to maintaining proliferation during embryogenesis as they avoid cell differentiation. Afterward, their expression is mainly silenced, but their reactivation and contribution to tumor development have been suggested. In breast cancer (BC), the overexpression of ID1 has been previously described. However, whether the remaining ID genes have a specific role in this neoplasia is still unclear. We studied the mRNA expression of all ID genes by q RT-PCR in BC cell lines and 307 breast carcinomas, including all BC subtypes. Our results showed that ID genes are highly expressed in all cell lines tested. However, ID4 presented higher expression in BC cell lines compared to a healthy breast epithelium cell line. In accordance, ID1 and ID4 were predominantly overexpressed in Triple-Negative and HER2-enriched samples. Moreover, high levels of both genes were associated with larger tumor size, histological grade 3, necrosis and vascular invasion, and poorer patients' outcomes. In conclusion, ID1 and ID4 may act as biomarkers of tumor aggressiveness and worse prognosis in breast cancer, and they could be used as potential targets for new treatments discover.
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Triple-negative breast cancer (TNBC) is more aggressive than other breast cancer subtypes. TNBC is characterized by increased expression of Programmed Death-ligand 1 (PD-L1), a signal used by many tumors to escape the immune response. Expression of PD-L1 is a positive predictor of response to immunotherapy; therefore, it should be investigated in TNBC in order to select patients who may benefit from anti-PD-L1 therapies. While many PD-L1 assays are available, only the VENTANA platform with the anti-PD-L1 (SP142) antibody is licensed as a companion diagnostic device for selecting patients with metastatic/advanced TNBC who are candidates for treatment with atezolizumab. In this article, we provide a summary of an expert round-table discussion about PD-L1 testing, using the SP142 antibody in metastatic TNBC.
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Anticorpos Monoclonais , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais , Imuno-Histoquímica , Neoplasias de Mama Triplo Negativas/diagnóstico , Tomada de Decisão Clínica , Gerenciamento Clínico , Feminino , Humanos , Imuno-Histoquímica/métodos , Terapia de Alvo Molecular , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias de Mama Triplo Negativas/etiologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
Primary peritoneal malignant tumors are exceptional. Among them, clear cell carcinoma is extremely rare, being only thirteen cases previously reported in the literature since 1990. We report a case of a 48-year-old Caucasian woman who was treated at the University General Hospital of Alicante. She consulted because of progressive abdominal pain over the last seven months, with the initial diagnosis of renal-ureteral colic. Ultrasound and computed tomography of the abdomen and pelvis revealed a 25 × 15 cm, well-defined cystic lesion with papillary projections, centrally located in the abdomen. The radiology report suggested a primary ovarian tumor versus peritoneal implant as the first option. The patient underwent an exploratory laparotomy showing a large cystic mass located in the urinary bladder peritoneum, firmly attached to the mesentery. The entire abdominal tumor was completely excised, and total hysterectomy with bilateral salpingo-oophorectomy and infra-colical omentectomy were performed. The final histological study revealed a new case of primary peritoneal clear cell carcinoma located in the urinary bladder peritoneum, firmly attached to the mesentery. Grossly, it was well-circumscribed and multicystic with papillary growth involving part of the inner wall. Microscopically, it showed tubulocystic and papillary patterns with highly atypical tumor cells. After an extensive immunohistochemical analysis, the most relevant finding was an ARID1A loss that was corroborated by molecular analysis showing an ARID1A deletion. The patient received systemic chemotherapy with carboplatin and paclitaxel protocol (Å ~ 4 cycles). Patient follow-up after the eighth month showed peritoneal implants predominantly in the right diaphragmatic cupule that were histologically confirmed as recurrence. She has just received another six cycles of chemotherapy with carboplatin and paclitaxel. Recognition of primary peritoneal clear cell carcinoma in this uncommon location, and exclude metastasis from the ovary, represents a diagnostic challenge.
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Bacterioruberin and its derivatives have been described as the major carotenoids produced by haloarchaea (halophilic microbes belonging to the Archaea domain). Recently, different works have revealed that some haloarchaea synthetize other carotenoids at very low concentrations, like lycopene, lycopersene, cis- and trans-phytoene, cis- and trans-phytofluene, neo-ß-carotene, and neo-α-carotene. However, there is still controversy about the nature of the pathways for carotenogenesis in haloarchaea. During the last decade, the number of haloarchaeal genomes fully sequenced and assembled has increased significantly. Although some of these genomes are not fully annotated, and many others are drafts, this information provides a new approach to exploring the capability of haloarchaea to produce carotenoids. This work conducts a deeply bioinformatic analysis to establish a hypothetical metabolic map connecting all the potential pathways involved in carotenogenesis in haloarchaea. Special interest has been focused on the synthesis of bacterioruberin in members of the Haloferax genus. The main finding is that in almost all the genus analyzed, a functioning alternative mevalonic acid (MVA) pathway provides isopentenyl pyrophosphate (IPP) in haloarchaea. Then, the main branch to synthesized carotenoids proceeds up to lycopene from which ß-carotene or bacterioruberin (and its precursors: monoanhydrobacterioriberin, bisanhydrobacterioruberin, dihydrobisanhydrobacteriuberin, isopentenyldehydrorhodopsin, and dihydroisopenthenyldehydrorhodopsin) can be made.
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Carotenoides/metabolismo , Euryarchaeota/metabolismo , Redes e Vias Metabólicas , Antioxidantes/metabolismo , Euryarchaeota/classificação , Euryarchaeota/genética , Regulação Bacteriana da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Genoma Bacteriano , Genômica/métodos , Redes e Vias Metabólicas/genética , Filogenia , Pigmentos Biológicos/biossínteseRESUMO
Chronic liver inflammation is crucial in the pathogenesis of hepatocellular carcinoma (HCC). Activation of the inflammasome complex is a key inflammatory process that has been associated with different liver diseases, but its role in HCC development remains largely unexplored. Here we analyzed the impact of different inflammasome components, including absent in melanoma 2 (AIM2) and NOD-like receptor family pyrin domain containing 3 (NLRP3), in the development of diethylnitrosamine (DEN)-induced HCC in mice. Genetic inactivation of AIM2, but not NLRP3, reduces liver damage and HCC development in this model. AIM2 deficiency ameliorates inflammasome activation, liver inflammation and proliferative responses during HCC initiation. We also identified that AIM2 is highly expressed in Kupffer cells, and that AIM2-mediated production of IL-1ß by these cells is enhanced after DEN-induced liver damage. Our data indicate that AIM2 promotes inflammation during carcinogenic liver injury and that it contributes to genotoxic HCC development in mice, thereby recognizing AIM2 as a potential therapeutic target in this disease.
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Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proteínas de Ligação a DNA/deficiência , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Animais , Proliferação de Células/fisiologia , Inflamassomos/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/metabolismo , Células de Kupffer/metabolismo , Células de Kupffer/patologia , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
Aims: To assess the expression of cathepsins in pancreatic samples obtained by endoscopic ultrasonography and fine needle aspiration (EUS-FNA) and to investigate their relationship with the staging of the pancreatic ductal adenocarcinoma (PDAC). Methods: We prospectively included patients with solid pancreatic masses, in which EUS-FNA were performed. Cathepsins B, L, S and H expression was determined in FNA samples. Results: Seventeen FNA were performed. All cytological material was from PDAC. Expression of cathepsins was predominantly low (B 65%, L 23%, S 76%, and H 41%). We found no correlation between the expression levels and the extension of the neoplasm. Conclusion: Expression of cathepsins in the cytological material of PDAC is diverse but still poor to be useful in the pre-operative diagnosis. There is no correlation between the expression levels of cathepsins and the extension of the PDAC
No disponible
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Humanos , Neoplasias Pancreáticas/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Catepsinas/isolamento & purificação , Biomarcadores Tumorais/análise , Estudos Prospectivos , Carcinoma Ductal Pancreático/patologia , Reprodutibilidade dos Testes , Reprodutibilidade dos TestesRESUMO
AIMS: To assess the expression of cathepsins in pancreatic samples obtained by endoscopic ultrasonography and fine needle aspiration (EUS-FNA) and to investigate their relationship with the staging of the pancreatic ductal adenocarcinoma (PDAC). METHODS: We prospectively included patients with solid pancreatic masses, in which EUS-FNA were performed. Cathepsins B, L, S and H expression was determined in FNA samples. RESULTS: Seventeen FNA were performed. All cytological material was from PDAC. Expression of cathepsins was predominantly low (B 65%, L 23%, S 76%, and H 41%). We found no correlation between the expression levels and the extension of the neoplasm. CONCLUSION: Expression of cathepsins in the cytological material of PDAC is diverse but still poor to be useful in the pre-operative diagnosis. There is no correlation between the expression levels of cathepsins and the extension of the PDAC.
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Catepsinas/biossíntese , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Pancreatopatias/diagnóstico por imagem , Pancreatopatias/diagnóstico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatopatias/metabolismo , Neoplasias Pancreáticas/metabolismo , Valor Preditivo dos Testes , Estudos ProspectivosRESUMO
BACKGROUND: Breast cancer is one of the most important neoplasia among women. It was recently suggested that biological agents could be the etiological cause, particularly Human Papilloma Virus (HPV). The aim of this study was to explore the presence of HPV DNA in a case-control study. METHODS: We performed our study including 251 cases (breast cancer) and 186 controls (benign breast tumors), using three different molecular techniques with PCR (GP5/GP6, CLART® and DIRECT FLOW CHIP®). RESULTS: HPV DNA was evidenced in 51.8% of the cases and in 26.3% of the controls (p < 0.001). HPV-16 was the most prevalent serotype. The odds ratio (OR) of HPV within a multivariate model, taking into account age and breastfeeding, was 4.034. CONCLUSIONS: Our study, with methodological rigour and a sample size not previously found in the literature, demonstrate a significant presence of HPV DNA in breast cancer samples. A possible causal relationship, or mediation or not as a cofactor, remains to be established by future studies.
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Neoplasias da Mama/virologia , Papillomavirus Humano 16 , Infecções por Papillomavirus/complicações , Adulto , Neoplasias da Mama/complicações , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Prevalência , Espanha/epidemiologiaRESUMO
We studied the relationship between CD44 and Forkhead box P3 (FOXP3) gene expression in cell lines and breast carcinomas and their association with clinicopathological variables and patient outcome. We assessed messenger RNA (mRNA) expression of CD44 and FOXP3 by quantitative real-time PCR and determined the number of FOXP3+ Tregs by immunohistochemistry in 264 breast cancer specimens. CD44 was stimulated with hyaluronan treatment, and the accompanying changes in FOXP3 mRNA expression in breast cancer cell lines representing breast cancer subtype were assessed. We found that lower CD44 expression correlated with the presence of necrosis, lymph-vascular invasion, grade 3 tumors, and aggressive phenotype (HER2 and basal-like). FOXP3 mRNA correlated positively with CD44 mRNA expression and Treg content. Moreover, stimulation of CD44 expression by hyaluronan in cell lines increased FOXP3 expression, which supports that their regulation is associated. Survival analysis revealed that low CD44 expression is associated with higher frequency of recurrence. Our findings indicate that CD44 has a regulatory role in FOXP3 expression and is associated with good prognostic factors in breast cancer.
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Biomarcadores Tumorais/análise , Neoplasias da Mama/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Receptores de Hialuronatos/metabolismo , Recidiva Local de Neoplasia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Prognóstico , Linfócitos T Reguladores/metabolismo , Adulto JovemRESUMO
Background and aims: To assess the expression levels of cathepsins in malignant and premalignant lesions. Methods: We retrospectively included patients who underwent pancreatic surgery on pancreatic solid or cystic masses. The expression of cathepsin H, L, B and S was determined in both types of samples. Lesions were divided into three categories: malignant (pancreatic adenocarcinoma and malignant mucinous neoplasms), premalignant (mucinous neoplasms) and benign (other lesions). Results: Thirty-one surgical resection samples were studied. The expression of cathepsins was significantly higher in malignant lesions than in premalignant and benign lesions (H 75%, 27%, 37% p = 0.05; L 92%, 36%, 37% p = 0.011; B 83%, 36%, 62% p = 0.069; S 92%, 36%, 25% p = 0.004, respectively). Conclusions: Cathepsins are overexpressed in histological samples of malignant lesions compared to premalignant and benign lesions. However, the expression of cathepsins is similar in both premalignant and benign lesions (AU)
No disponible
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Humanos , Masculino , Feminino , Catepsinas/administração & dosagem , Catepsinas/análise , Neoplasias Pancreáticas/diagnóstico , Cistadenocarcinoma Mucinoso/complicações , Cistadenocarcinoma Mucinoso/diagnóstico , Estudos Retrospectivos , Imuno-Histoquímica/métodos , Imuno-Histoquímica , 28599RESUMO
BACKGROUND AND AIMS: To assess the expression levels of cathepsins in malignant and premalignant lesions. METHODS: We retrospectively included patients who underwent pancreatic surgery on pancreatic solid or cystic masses. The expression of cathepsin H, L, B and S was determined in both types of samples. Lesions were divided into three categories: malignant (pancreatic adenocarcinoma and malignant mucinous neoplasms), premalignant (mucinous neoplasms) and benign (other lesions). RESULTS: Thirty-one surgical resection samples were studied. The expression of cathepsins was significantly higher in malignant lesions than in premalignant and benign lesions (H 75%, 27%, 37% p = 0.05; L 92%, 36%, 37% p = 0.011; B 83%, 36%, 62% p = 0.069; S 92%, 36%, 25% p = 0.004, respectively). CONCLUSIONS: Cathepsins are overexpressed in histological samples of malignant lesions compared to premalignant and benign lesions. However, the expression of cathepsins is similar in both premalignant and benign lesions.