Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Inibidores da Aromatase , Neoplasias da Mama , Receptor ErbB-2 , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Inibidores da Aromatase/uso terapêutico , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Acrilamidas/uso terapêutico , Receptores de Progesterona/metabolismo , Aminopiridinas , BenzimidazóisRESUMO
BACKGROUND: Targeting new molecular pathways leading to Osteoporosis (OP) and Osteoarthritis (OA) is a hot topic for drug discovery. Clusterin (CLU) is a glycoprotein involved in inflammation, proliferation, cell death, neoplastic disease, Alzheimer disease and aging. The present study focuses on the expression and the role of CLU in influencing the decrease of muscle mass and fiber senescence in OP-OA condition. METHODS: Vastus lateralis muscle biopsies were collected from 20 women with OP undergoing surgery for fragility hip fracture and 20 women undergoing arthroplasty for hip osteoarthritis. RESULTS: We found an overexpression of CLU in degenerated fibers in OP closely correlated with interleukin 6 (IL6) and histone H4 acetylation level. Conversely, in OA muscle tissues we observed a weak expression of CLU but no nuclear histone H4 acetylation. Ex vivo studies on isolated human myoblasts confirmed CLU overexpression in OP as compared to OA (p < 0.001). CLU treatment of isolated OP and OA myoblasts showed: modulation of proliferation, morphological changes, increase of histone H4 acetylation and induction of myogenin (MYOG) activation in OP myoblast only. In OP condition, functional knockdown of CLU by siRNA restores proliferative myoblasts capability and tissue damage repair, carried out by an evident upregulation of Transglutaminase 2 (TGM2). We also observed downmodulation of CX3CR1 expression with consequent impairing of the inflammatory infiltrate recruitment. CONCLUSIONS: Results obtained suggest a potential role of CLU in OP by influencing myoblasts terminal differentiation, epigenetic regulation of muscle cell differentiation and senescence. Moreover, CLU silencing points out its role in the modulation of tissue damage repair and inflammation, proposing it as a new diagnostic marker for muscle degeneration and a potential target for specific therapeutic intervention in OP related sarcopenia.
Assuntos
Clusterina/genética , Inativação Gênica , Inflamação/patologia , Mioblastos/metabolismo , Mioblastos/patologia , Osteoporose/metabolismo , Osteoporose/patologia , Acetilação/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptor 1 de Quimiocina CX3C/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Clusterina/metabolismo , DNA/metabolismo , Feminino , Inativação Gênica/efeitos dos fármacos , Histonas/metabolismo , Humanos , Inflamação/complicações , Interleucina-6/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Mioblastos/efeitos dos fármacos , Miogenina/metabolismo , Osteoartrite do Quadril/metabolismo , Osteoartrite do Quadril/patologia , Osteoporose/complicações , Proteínas Recombinantes/farmacologiaRESUMO
BACKGROUND: Presently, few options are available for refractory colorectal cancer (CRC). O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation is a frequent and early event in CRC tumourigenesis. This epigenetic silencing is a predictor of response to the alkylating drug temozolomide in glioblastoma. Preclinical evidences and some case reports showed temozolomide activity in CRC with MGMT silencing, but the available data from clinical trials are inconsistent. METHODS: This was a multicentre, phase 2 trial, planned according to a two-stage Simon's optimal design to investigate activity and safety of temozolomide in refractory CRC harbouring MGMT promoter methylation. The primary end point was overall response rate (ORR). Patients who failed two or more prior treatments received temozolomide at a dose of 150-200 mg m-2 per day on days 1-5 every 28 days. RESULTS: From July 2012 to June 2016, 225 patients were screened, 80 showed MGMT promoter methylation and 41 were enrolled. Overall response rate was 10% and disease control rate was 32%. Median progression-free survival and overall survival were 1.9 and 5.1 months, respectively. CONCLUSIONS: Temozolomide showed a modest activity in this heavily pretreated population and the study did not meet its primary end point. The role of temozolomide in CRC remains still controversial and further research is warranted.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Dacarbazina/análogos & derivados , Proteínas Supressoras de Tumor/genética , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Colorretais/patologia , Metilação de DNA , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Feminino , GTP Fosfo-Hidrolases/genética , Humanos , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Náusea/induzido quimicamente , Metástase Neoplásica , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Retratamento , Taxa de Sobrevida , Temozolomida , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Vômito/induzido quimicamenteRESUMO
BACKGROUND: We report the first successful treatment of limbal lesions and corneal erosion experienced by a breast cancer patient undergoing trastuzumab treatment. CASE PRESENTATION: A 49-year-old Caucasian woman with early stage breast cancer was treated with adjuvant trastuzumab and subsequently showed persistent bilateral corneal marginal infiltrates resistant to topical steroid and antibiotic treatment. Autologous serum was applied in the conjunctival sac as an experimental treatment to antagonize the inhibitory effect of the HER2 receptor antibody on the corneal epithelial cells. Topical application of autologous serum led to rapid improvement of the ulcerative keratitis, with complete healing of the corneal defect after 7 days. Continued administration of the serum allowed the resumption of trastuzumab therapy without any further side effects. CONCLUSIONS: Persistent bilateral corneal marginal infiltrates may occasionally arise as a side effect of trastuzumab treatment. Topical medication with autologous serum may be an effective therapeutic option for the ocular side effects of trastuzumab therapy.
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Úlcera da Córnea/induzido quimicamente , Trastuzumab/efeitos adversos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The therapeutic management of psoriasis includes conventional treatments as well as the new generation of highly effective TNF-α inhibitors. However, psoriasis has proven to be a complex therapeutic challenge and treatment failures are not uncommon. Thus, laboratory biomarkers of disease progression/therapeutic efficacy may greatly help in the clinical management of psoriasis. AIMS: To identify laboratory biomarkers for clinical management and therapeutic monitoring of psoriasis. METHODS: An observational study performed on 59 patients, presenting moderate to severe psoriasis, undergoing treatment with anti-TNF-α agents (etanercept, adalimumab, and infliximab). Soluble and cellular immune/inflammatory parameters were assessed at baseline and after 12 and 24 weeks of treatment. RESULTS: Clinical efficacy was achieved in 88% of the subjects at 12 weeks, reaching 90% after 24 weeks. IL-6 and IL-22, which were elevated at baseline, were significantly reduced, in association with a significant decrease of CLA+ T cells and an increase of Treg lymphocytes. T, B, and NK cell subsets and T cell response to recall antigens did not show any evidence of immune suppression. CONCLUSIONS: Immune/inflammatory parameters including IL-6 and IL-22, CLA+ T cells, and Treg lymphocytes may prove to be valuable laboratory tools for the clinical and therapeutic monitoring of psoriasis.
Assuntos
Biomarcadores/sangue , Psoríase/sangue , Psoríase/imunologia , Adalimumab , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Etanercepte , Feminino , Humanos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/uso terapêutico , Infliximab , Interleucina-6/sangue , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psoríase/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/administração & dosagem , Receptores do Fator de Necrose Tumoral/uso terapêutico , Linfócitos T Reguladores/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/sangue , Interleucina 22RESUMO
BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) beyond second line is still questioned. Besides the standard of care agents (regorafenib, REG, or trifluridine/tipiracil, FTD/TPI), chemotherapy rechallenge or reintroduction (CTr/r) are commonly considered in clinical practice, despite weak supporting evidence. The prognostic performance of CTr/r, REG and FTD/TPI in this setting are herein evaluated. PATIENTS AND METHODS: PROSERpYNa is a multicenter, observational, retrospective study, in which patients with refractory mCRC, progressing after at least 2 lines of CT, treated with CTr/r, REG or FTD/TPI, are considered eligible and were enrolled in 2 independent data sets (exploratory and validation). Primary endpoint was overall survival (OS); secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (RR) and safety. A propensity score adjustment was accomplished for survival analyses. RESULTS: Data referring to patients treated between Jan-10 and Jan-19 from 3 Italian institutions were gathered (341 and 181 treatments for exploratory and validation data sets respectively). In the exploratory cohort, median OS (18.5 vs. 6.5 months), PFS (6.1 vs. 3.5 months) and RR (28.6% vs. 1.4%) were significantly longer for CTr/r compared to REG/FTD/TPI. Survival benefits were retained at the propensity score analysis, adjusted for independent prognostic factors identified at multivariate analysis. Moreover, these results were confirmed within the validation cohort analyses. CONCLUSIONS: Although the retrospective fashion, CTr/r proved to be a valuable option in this setting in a real-world context, providing superior outcomes compared to standard of care agents at the price of a moderate toxicity.
RESUMO
BACKGROUND: In this study, we evaluated the possibility that KRAS mutational status might be predictive of oxaliplatin (OXA) efficacy. We also explored the role of excision repair cross complementing group-1 (ERCC-1). METHODS: Ninety anti-epidermal growth factor receptor-naive advanced colorectal cancer patients were retrospectively analysed. In all patients KRAS mutational status was assessed. In 60 patients mRNA ERCC-1 expression was also investigated. Response rate (RR) and progression-free survival (PFS) after FOLFOX-6±bevacizumab were evaluated according to KRAS status and mRNA ERCC-1 expression. RESULTS: Among 90 patients 47% wild-type (wt) and 53% mutated (mt) KRAS tumours were found. Response rate was 26% in the wt KRAS group, whereas it was 56% in the mt KRAS group; the difference is statistically significant in the total sample (P=0.008) and when only patients receiving FOLFOX-6±bevacizumab as first-line are considered (P=0.01). Progression-free survival was longer in mt than in wt KRAS patients over all patients (10 vs 8 months, respectively, P=0.001) and in those treated as first-line (10 vs 8 months, respectively, P=0.0069). Mt KRAS patients experienced a longer survival (24 vs 18 months; P=0.01). ERCC-1 mRNA expression was not found to correlate with FOLFOX activity in our analysis. CONCLUSION: Our results suggest that activating mutation of KRAS oncogene may predict response to OXA. Basal expression of ERCC-1 mRNA does not explain the high efficacy of FOLFOX-6 in mt KRAS patients.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Genes ras , Mutação , Compostos Organoplatínicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaliplatina , RNA Mensageiro/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: Cerebral cavernous malformations (CCM) comprise enlarged capillary cavities in the central nervous system, with possible retinal or cutaneous vascular malformations. This condition is associated with CCM1, CCM2, and CCM3 gene mutations. OBJECTIVE: Cutaneous clinical, histological and cerebral MRI findings, including CCM1, CCM2, and CCM3 gene sequencing, of two unrelated, neurological symptom-free patients who consulted for late-onset of deep multiple cutaneous angiomatoid lesions, are described. RESULTS: The diagnosis of multiple cutaneous angiomatosis was confirmed and related to CCM as detected by MRI in both cases. Analysis of our patients showed normal nucleotide sequences of the genes proposed. CONCLUSIONS: A progressive late-onset of multiple, deep cutaneous venous malformations may indicate the need to investigate a potential coexistence of CCM by MRI. Early diagnosis and prompt treatment is required in these patients. The absence of CCM1, CCM2, and CCM3 mutations might indicate that different genes could be involved in the pathogenesis of these late-onset patients. Careful questioning about family history of CCM is important; our first patient's daughter had a history of cerebral cavernoma.
Assuntos
Angiomatose/etiologia , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Dermatopatias Vasculares/etiologia , Adulto , Angiomatose/patologia , Feminino , Predisposição Genética para Doença , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mutação/genética , Reação em Cadeia da Polimerase em Tempo Real , Dermatopatias Vasculares/patologiaRESUMO
Breast cancer is the most common cancer among women worldwide. Molecular and clinical evidence indicated that Fragile X Messenger Ribonucleoprotein 1 (FMRP) plays a role in different types of cancer, including breast cancer. FMRP is an RNA binding protein that regulates the metabolism of a large group of mRNAs coding for proteins involved in both neural processes and in epithelial-mesenchymal transition, a pivotal mechanism that in cancer is associated to tumor progression, aggressiveness and chemoresistance. Here, we carried out a retrospective case-control study of 127 patients, to study the expression of FMRP and its correlation with metastasis formation in breast cancer. Consistent with previous findings, we found that FMRP levels are high in tumor tissue. Two categories have been analyzed, tumor with no metastases (referred as control tumors, 84 patients) and tumor with distant metastatic repetition, (referred as cases, 43 patients), with a follow-up of 7 years (mean). We found that FMRP levels were lower in both the nuclei and the cytoplasm in the cases compared to control tumors. Next, within the category cases (tumor with metastases) we evaluated FMRP expression in the specific sites of metastasis revealing a nuclear staining of FMRP. In addition, FMRP expression in both the nuclear and cytoplasmic compartment was significantly lower in patients who developed brain and bone metastases and higher in hepatic and pulmonary sites. While further studies are required to explore the underlying molecular mechanisms of FMRP expression and direct or inverse correlation with the secondary metastatic site, our findings suggest that FMRP levels might be considered a prognostic factor for site-specific metastasis.
Assuntos
Neoplasias da Mama , Síndrome do Cromossomo X Frágil , Neoplasias Mamárias Animais , Animais , Humanos , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Estudos de Casos e Controles , Estudos Retrospectivos , Proteínas/metabolismo , Neoplasias da Mama/genética , Síndrome do Cromossomo X Frágil/genéticaRESUMO
Alveolar type II pneumocytes (ATII cells) are considered putative alveolar stem cells. Since no treatment is available to repair damaged epithelium and prevent lung fibrosis, novel approaches to induce regeneration of injured alveolar epithelium are desired. The objective of this study was to assess both the capacity of human embryonic stem cells (HUES-3) to differentiate in vitro into ATII cells and the ability of committed HUES-3 cells (HUES-3-ATII cells) to recover in vivo a pulmonary fibrosis model obtained by silica-induced damage. In vitro differentiated HUES-3-ATII cells displayed an alveolar phenotype characterised by multi-lamellar body and tight junction formation, by the expression of specific markers such as surfactant protein (SP)-B, SP-C and zonula occludens (ZO)-1 and the activity of cystic fibrosis transmembrane conductance regulator-mediated chloride ion transport. After transplantation of HUES-3-ATII cells into silica-damaged mice, histological and biomolecular analyses revealed a significant reduction of inflammation and fibrosis markers along with lung function improvement, weight recovery and increased survival. The persistence of human SP-C, human nuclear antigen and human DNA in the engrafted lungs indicates that differentiated cells remained engrafted up to 10 weeks. In conclusion, cell therapy using HUES-3 cells may be considered a promising approach to lung injury repair.
Assuntos
Células-Tronco Embrionárias/transplante , Fibrose Pulmonar/terapia , Dióxido de Silício/toxicidade , Silicose/terapia , Transplante de Células-Tronco/métodos , Animais , Diferenciação Celular/fisiologia , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Modelos Animais de Doenças , Células Alimentadoras/citologia , Feminino , Fibroblastos/citologia , Humanos , Camundongos , Camundongos Nus , Alvéolos Pulmonares/patologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Proteína C Associada a Surfactante Pulmonar/metabolismo , Silicose/patologia , Resultado do TratamentoRESUMO
Pituitary adenomas are a diverse group of tumors arising from the pituitary gland. Typically, they are small, slow-growing, hormonally inactive lesions that come to light as incidental findings on radiologic or postmortem examinations, although some small, slow-growing lesions with excessive hormonal activity may manifest with a clinical syndrome. The family of neurotrophins plays a key role in the development and maintenance of the pituitary endocrine cell function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. The objective of our experimental study is to investigate the localization of the neurotrophins, their relative receptors and to detect the expression level of Ki-67 to determine whether all these factors participate in the transformation and development of human pituitary adenomas. A very strong expression of Neurotrophin-3 (NT-3) and its receptor TrKC was observed in the extracellular matrix (ECM) and vessel endothelium, together with a clear/marked presence of Brain-derived neurotrophic factor (BDNF), and its receptor TrKB, thus confirming their direct involvement in the progression of pituitary adenomas. On the contrary, NGF (Nerve growth factor) and its receptor TrKA and p75NTR were weakly expressed in the epithelial gland cells and the ECM.
Assuntos
Adenoma/química , Adenoma Hipofisário Secretor de Hormônio do Crescimento/química , Antígeno Ki-67/análise , Fatores de Crescimento Neural/análise , Matriz Extracelular/química , Humanos , Imuno-Histoquímica , Proteínas do Tecido Nervoso/análise , Receptor trkA/análise , Receptor trkB/análise , Receptor trkC/análise , Receptores de Fator de Crescimento Neural/análiseRESUMO
Numerical models indicate that collective animal behavior may emerge from simple local rules of interaction among the individuals. However, very little is known about the nature of such interaction, so that models and theories mostly rely on aprioristic assumptions. By reconstructing the three-dimensional positions of individual birds in airborne flocks of a few thousand members, we show that the interaction does not depend on the metric distance, as most current models and theories assume, but rather on the topological distance. In fact, we discovered that each bird interacts on average with a fixed number of neighbors (six to seven), rather than with all neighbors within a fixed metric distance. We argue that a topological interaction is indispensable to maintain a flock's cohesion against the large density changes caused by external perturbations, typically predation. We support this hypothesis by numerical simulations, showing that a topological interaction grants significantly higher cohesion of the aggregation compared with a standard metric one.
Assuntos
Comportamento Animal/fisiologia , Aves/fisiologia , Voo Animal/fisiologia , Agressão/fisiologia , Algoritmos , Animais , Comportamento Predatório/fisiologia , Meio Social , Fatores de Tempo , Visão Ocular/fisiologiaRESUMO
This paper presents guidelines for the safe outpatient practice of aesthetic surgery. These guidelines have been prepared by the Lombard Association of Plastic Surgery for Outpatients (ALChiPlA), an association confined to board certified plastic surgeons and holders of official authorizations issued by the Lombard ASL to perform outpatient surgery. The cornerstone of these guidelines is the health and safety of patients, who are turning to this type of surgery in ever increasing numbers. This is the first and thus far the only attempt of its kind and its value is increased by the fact that it has been prepared by specialists who have been carrying out this type of surgery in outpatient situations for years.
Assuntos
Procedimentos Cirúrgicos Ambulatórios/normas , Procedimentos de Cirurgia Plástica , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , HumanosRESUMO
PURPOSE: To analyze the relationships between background parenchymal enhancement (BPE) of the contralateral healthy breast and tumor response after neoadjuvant chemotherapy (NAC) in women with breast cancer. MATERIALS AND METHODS: A total of 228 women (mean age, 47.6 years±10 [SD]; range: 24-74 years) with invasive breast cancer who underwent NAC were included. All patients underwent breast magnetic resonance imaging (MRI) before and after NAC and 127 patients underwent MRI before, during (after the 4th cycle of NAC) and after NAC. Quantitative semi-automated analysis of BPE of the contralateral healthy breast was performed. Enhancement level on baseline MRI (baseline BPE) and MRI after chemotherapy (final BPE), change in enhancement rate between baseline MRI and final MRI (total BPE change) and between baseline MRI and midline MRI (early BPE change) were recorded. Associations between BPE and tumor response, menopausal status, tumor phenotype, NAC type and tumor stage at diagnosis were searched for. Pathologic complete response (pCR) was defined as the absence of residual invasive cancer cells in the breast and ipsilateral lymph nodes. RESULTS: No differences were found in baseline BPE, final BPE, early and total BPE changes between pCR and non-pCR groups. Early BPE change was higher in non-pCR group in patients with stages 3 and 4 breast cancers (P=0.019) and in human epidermal growth factor receptor 2 (HER2)-negative patients (P=0.020). CONCLUSION: Early reduction of BPE in the contralateral breast during NAC may be an early predictor of loss of tumor response, showing potential as an imaging biomarker of treatment response, especially in women with stages 3 or 4 breast cancers and in HER2 - negative breast cancers.
Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) was originally reported to reveal melanoma-associated mRNAs (MAMs) in melanoma cells but not in the peripheral blood of healthy individuals. OBJECTIVES: To evaluate the expression of MAMs in the peripheral blood of melanoma patients at different American Joint Committee on Cancer (AJCC) stages, and to correlate their presence with early and/or advanced stages of the disease. MATERIALS AND METHODS: One hundred blood samples of melanoma patients (AJCC I-IV) were analysed using multimarker RT-PCR to assess the co-expression of Tyr-OH, MART-1, MAGE-3, MUC-18/MCAM and p97. Patients were stratified into two disease categories: early and advanced stages. The former includes in situ and melanoma stages AJCC I-II, the latter AJCC III-IV. chi(2) and Fisher's exact tests were used to statistically evaluate the association between each MAM and disease categories. The recognized significant associations were subsequently resubmitted to univariate logistic regression. Furthermore, sensitivity and specificity were established. RESULTS: At least one MAM could be detected in 24% of our series. Tyr-OH was the most common marker (14%), followed by MUC-18 (12%), MART-1 (5%), MAGE-3 (4%) and p97 (3%). No significant association among Tyr-OH, MART-1, MAGE-3, p97 and disease stages were evidenced. Only MUC-18 was statistically associated (P < 0.009) with advanced stages alone or co-expressed with other MAMs. According to logistic regression univariate analysis, MUC-18 increases the probability (odds ratio: 33) being in advanced stages and the incidence of recurrences (95% CI 2.9-374). CONCLUSIONS: MUC-18 RT-PCR assay could be proposed as an adjunctive molecular method in the management of melanoma patients and is useful in the monitoring of study protocols.
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Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Melanoma/metabolismo , Proteínas de Neoplasias/análise , Neoplasias Cutâneas/metabolismo , Adulto , Idoso , Antígenos de Neoplasias/genética , Antígeno CD146/análise , Antígeno CD146/genética , Linhagem Celular Tumoral , Feminino , Humanos , Antígeno MART-1 , Masculino , Melanoma/patologia , Antígenos Específicos de Melanoma , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologiaRESUMO
Osteoarthritis is a progressive joint disease characterized by cartilage degradation and bone remodeling. Transglutaminases catalyze a calcium-dependent transamidation reaction that produces covalent cross-linking of available substrate glutamine residues and modifies the extracellular matrix. Increased transglutaminases-mediated activity is reported in osteoarthritis, but the relative contribution of transglutaminases-2 (TG2) is uncertain. We describe TG2 expression in human femoral osteoarthritis and in wild-type and homozygous TG2 knockout mice after surgically-induced knee joint instability. Increased TG2 levels were observed in human and wild-type murine osteoarthritic cartilage compared to the respective controls. Histomorphometrical but not X-ray investigation documented in osteoarthritic TG2 knockout mice reduced cartilage destruction and an increased osteophyte formation compared to wild-type mice. These differences were associated with increased TGFbeta-1 expression. In addition to confirming its important role in osteoarthritis development, our results demonstrated that TG2 expression differently influences cartilage destruction and bone remodeling, suggesting new targeted TG2-related therapeutic strategies.