ABSTRACT
Despite advances in understanding of carcinogenesis and of treatment of acute myeloid leukemia, this neoplasm still has a lethality of at least 30%. The search for biomarkers that can predict the response to treatment in the early stages of the disease is still necessary. In recent years, a new form of cellular communication between tumor and non-neoplastic cells has been discovered: the exchange of information through extracellular vesicles. These are small vesicles released by membrane-coated cells that carry proteins, lipids, messenger RNAs, microRNA and DNA, which can be internalized and promote biological changes in target cells. Exosomes are qualified as a type of extracellular vesicle and, in tumors, carry immunoinhibitory signals that promote the escape of immune control. Recent studies have showed their involvement in communication with the cells of the tumor microenvironment and with chemoresistance in several tumors. To date, there is no information about immunoregulatory microRNAs transported by exosomes and their correlation with clinical evolution during chemotherapy for acute myeloid leukemia. Knowledge about immunomodulatory microRNAs obtained by leukemic cells and transported by exosomes can direct us towards the design of new diagnostic and treatment tools in this type of leukemia.
Subject(s)
Exosomes , Leukemia, Myeloid, Acute , MicroRNAs , Biomarkers , Cell Communication , Exosomes/genetics , Exosomes/metabolism , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , MicroRNAs/metabolism , Tumor Microenvironment/geneticsABSTRACT
ABSTRACT Despite advances in understanding of carcinogenesis and of treatment of acute myeloid leukemia, this neoplasm still has a lethality of at least 30%. The search for biomarkers that can predict the response to treatment in the early stages of the disease is still necessary. In recent years, a new form of cellular communication between tumor and non-neoplastic cells has been discovered: the exchange of information through extracellular vesicles. These are small vesicles released by membrane-coated cells that carry proteins, lipids, messenger RNAs, microRNA and DNA, which can be internalized and promote biological changes in target cells. Exosomes are qualified as a type of extracellular vesicle and, in tumors, carry immunoinhibitory signals that promote the escape of immune control. Recent studies have showed their involvement in communication with the cells of the tumor microenvironment and with chemoresistance in several tumors. To date, there is no information about immunoregulatory microRNAs transported by exosomes and their correlation with clinical evolution during chemotherapy for acute myeloid leukemia. Knowledge about immunomodulatory microRNAs obtained by leukemic cells and transported by exosomes can direct us towards the design of new diagnostic and treatment tools in this type of leukemia.
Subject(s)
Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , MicroRNAs/metabolism , Exosomes/genetics , Exosomes/metabolism , Biomarkers , Cell Communication , Tumor Microenvironment/geneticsABSTRACT
BACKGROUND/AIM: Nodular and superficial are the most common subtypes of basal cell carcinoma (BCC). Signaling pathways such as Hedgehog (HH) and Wingless (WNT) signaling are associated with BCC phenotypic variation. The aim of the study was to evaluate of the expression profiles of 84 genes related to the WNT and HH signaling pathways in patients with nodular and superficial BCC. MATERIALS AND METHODS: A total of 58 BCCs and 13 samples of normal skin were evaluated by quantitative real-time polymerase chain reaction (qPCR) to detect the gene-expression profile. RESULTS: qPCR array showed segregation in BCC subtypes compared to healthy skin. PRKX, WNT3 and WNT16 were significantly (p<0.05) altered: PRKX was up-regulated, and WNT3 and WNT16 were down-regulated in nodular BCC. CONCLUSION: PRKX, WNT3 and WNT16 genes, belonging to the WNT signaling pathway, are involved in the tumorigenic process of nodular BCC.
Subject(s)
Carcinoma, Basal Cell/metabolism , Gene Expression Regulation, Neoplastic , Protein Serine-Threonine Kinases/metabolism , Skin Neoplasms/metabolism , Wnt Proteins/metabolism , Wnt3 Protein/metabolism , Aged , Aged, 80 and over , Cell Proliferation , Cluster Analysis , Female , Gene Expression Profiling , Humans , Male , Middle Aged , Phenotype , Real-Time Polymerase Chain Reaction , Signal Transduction , Skin/metabolism , Up-RegulationABSTRACT
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Although several clinical characteristics can be associated with worse prognosis, more robust biological markers still remains uncovered. SMYD2, a member of SMYD protein family, regulates the activity of several proteins through methylation. In this study, we performed quantitative real time PCR to compare the expression of SMYD2 in 83 pediatric ALL patients and non-neoplastic bone marrow samples (BMS). The study revealed that SMYD2 expression is altered in ALL BMS and its high expression was correlated with a bad prognosis. Moreover, we also revealed that SMYD2 expression level significantly decreases in patients that respond to chemotherapy treatment.
Subject(s)
Biomarkers, Tumor/genetics , Histone-Lysine N-Methyltransferase/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Adolescent , Antineoplastic Agents/therapeutic use , Biomarkers, Pharmacological , Case-Control Studies , Child , Child, Preschool , Female , Gene Expression Regulation, Leukemic , Humans , Infant , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , Survival Analysis , Up-RegulationABSTRACT
BACKGROUND: The current study was devised with the objective of using a split-mouth, controlled clinical trial to compare conventional mechanical debridement (scaling and root planing) treatment (T1) with conventional mechanical treatment followed by photodynamic therapy (PDT) (T2) in patients with severe periodontitis. METHODS: Four PDT sessions were completed, and clinical parameters such as bleeding upon probing (BOP positive), plaque index (PI), probing pocket depth (PPD) and clinical attachment loss (CAL) were evaluated before and after the treatment series. In addition, gingival biopsies were collected at the start and finish of treatment, and were used for qPCR gene expression analysis of TNFA, IL1B, IL8, IL10, IL17, MMP13, FGF2, RANK, RANKL and OPG. RESULTS: The clinical results showed a significant improvement in BOP with treatment T2 (p=0.03). The molecular data showed an up-regulation of FGF2, RANK and OPG gene expression after T2. The expression levels of the other genes were not significantly different between T1 and T2. PDT increased the expression of RANK and OPG, which could indicate a reduction in osteoclastogenesis. Furthermore, the use of PDT in conjunction with conventional treatment significantly increased the expression of FGF2, which has an important role in the periodontal repair process. CONCLUSIONS: PDT technology could be a means to improve conventional periodontitis treatment. Our results suggest that PDT acts in part by controlling bone resorption and increasing the expression of genes important for tissue repair.
Subject(s)
Gene Expression/drug effects , Gingiva/drug effects , Inflammation Mediators/metabolism , Photochemotherapy/methods , Adult , Dental Plaque Index , Dental Scaling , Female , Humans , Male , Periodontal Index , Root Planing/methods , Up-RegulationABSTRACT
BACKGROUND: Trilateral retinoblastoma (TRB) is a syndrome consisting of unilateral or bilateral hereditary retinoblastoma (Rb) associated with an intracranial neuroblastic tumor. Although its incidence is low, the prognosis is very poor. This article reports four cases of TRB and discusses the role of neuroimaging screening for early detection. PROCEDURE: From January 1986 to December 2003, 470 children with Rb were admitted to the Pediatrics and Ophthalmology Departments, A C Camargo Hospital, São Paulo, Brazil. RESULTS: There were four patients with pineoblastoma, two of whom had a positive familial history. The age at diagnosis of Rb was 4, 6, 10, and 24 months while the age of diagnosis of TRB was 10, 25, 57, and 72 months. One patient presented TRB at initial diagnosis of Rb. Three patients had bilateral disease and all of them had one eye enucleated, followed by chemotherapy and/or external beam radiation therapy (EBRT). One child with unilateral disease was only submitted to enucleation. In spite of intensive treatment, all patients died with progressive disease within 7, 8, 12, and 12 months after diagnosis of TRB. CONCLUSIONS: Early diagnosis as well as new therapeutic approaches are needed to achieve better results.
Subject(s)
Eye Neoplasms/pathology , Neoplasms, Multiple Primary/pathology , Neoplasms, Second Primary/pathology , Pinealoma/pathology , Retinoblastoma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child, Preschool , Cisplatin/administration & dosage , Combined Modality Therapy , Cranial Irradiation , Cyclophosphamide/administration & dosage , Disease Progression , Etoposide/administration & dosage , Eye Enucleation , Eye Neoplasms/drug therapy , Eye Neoplasms/genetics , Eye Neoplasms/radiotherapy , Eye Neoplasms/surgery , Fatal Outcome , Female , Humans , Idarubicin/administration & dosage , Ifosfamide/administration & dosage , Male , Methotrexate/administration & dosage , Neoplasms, Multiple Primary/drug therapy , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/radiotherapy , Neoplasms, Multiple Primary/surgery , Neoplasms, Second Primary/drug therapy , Neoplasms, Second Primary/genetics , Neoplasms, Second Primary/radiotherapy , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/pathology , Pinealoma/drug therapy , Pinealoma/genetics , Pinealoma/radiotherapy , Pinealoma/surgery , Prognosis , Retinoblastoma/drug therapy , Retinoblastoma/genetics , Retinoblastoma/radiotherapy , Retinoblastoma/surgery , Vincristine/administration & dosageABSTRACT
Improvements in multimodal therapy for osteosarcoma (OS) have increased event-free and overall survival. But have also led to a greater number of recurrences in uncommon sites. We report a young adult with OS who developed late bilateral renal relapse. Late recurrences to the kidneys have a more aggressive clinical behavior and poor prognosis documented by 15 cases of OS metastastic to the kidney in the literature. Two of those patients had a long survival after chemotherapy and surgery. This suggests that the disease can be controlled with early detection and treatment.
