Regulation of Immune Cells by microRNAs and microRNA-Based Cancer Immunotherapy.

MicroRNAs (miRNAs) are small (~21 nucleotides) endogenous noncoding RNA molecules involved in the posttranscriptional regulation of gene expression. Modulation of gene expression by miRNAs occurs via base-pairing of the specific miRNA primary sequence to its corresponding target messenger RNA, which can be located either in the 3' untranslated region or within the coding sequence. This pairing can lead to either translational repression or cleavage of the mRNA, resulting in reduced levels of the target protein. MiRNAs are involved in mediating and controlling several interactions between immune and cancer cells and are also important regulators of immune responses. Increasing interest has focused on elucidating the role of miRNAs in the regulation of anticancer immune responses and how this could affect the efficacy of different cancer therapeutics. Indeed, immune responses have both pro- and anti-oncogenic effects, and functional interactions between immune and cancer cells in the tumor microenvironment are crucial in determining the course of cancer progression. Thus, understanding the role of miRNAs in controlling cancer immunity is important for revealing mechanisms that could be modulated to enhance the success of immunotherapy for patients with cancer. In this chapter, we discuss the involvement of miRNAs in the regulation of immune cells and potential therapeutic approaches in which miRNAs are used for cancer immunotherapy.

Orbital Burkitt's Lymphoma: An Aggressive Presentation.

Objective. To present the case of an aggressive orbital Burkitt's lymphoma. Methods. Chart review. Case Presentation. A 24-year-old Haitian man came to our clinic complaining of rapidly progressive right eye proptosis. On examination, a large friable exophytic mass with necrotic areas and exudative/hemorrhagic secretions was noted protruding from his right orbit. A biopsy revealed the characteristic "starry-sky" appearance of a Burkitt lymphoma. The patient died shortly after due to complications from systemic involvement. Discussion. This case is meant to raise physicians' awareness on the healthcare situation in some underdeveloped countries, emphasizing the importance of education in preventive medicine.

Presumed sturge weber syndrome in a haitian boy: a case of delayed diagnosis.

Purpose. To report an untypical presentation of a presumed Sturge-Weber Syndrome (SWS), and to highlight the indispensable value of thorough clinical examination as primary means for proper diagnosis and management. Methods. Chart review. Results. A 7 year-old boy, with a long history of ocular symptoms and an unspecified ocular surgery, presents with a painful blind left eye. Based on clinical examination, the suspicion of SWS was raised. The presentation was not typical in the sense that no evident port-wine stain was observed on the face. However, facial asymmetry and gum discoloration were guiding clinical clues to pursue further investigations. Unfortunately, due to poor treatment response, the patient underwent enucleation. Tissue pathology revealed diffuse choroidal hemangiomas, consistent with the diagnosis of SWS. Conclusion. SWS presents with hamartomatous malformations and venous dilation affecting the skin, central nervous system and eye. The ocular involvement may vary, with the most common complications being glaucoma, buphthalmos and diffuse choroidal hemangiomas. This case report helps remind physicians of the importance of a thorough clinical examination, and highlights the ophthalmologists' responsibility of examining beyond the eye.

Differential expression of HDAC3, HDAC7 and HDAC9 is associated with prognosis and survival in childhood acute lymphoblastic leukaemia.

Altered expression of histone deacetylases (HDACs) is a common feature in several human malignancies and may represent an interesting target for cancer treatment, including haematological malignancies. We evaluated the mRNA gene expression profile of 12 HDAC genes by quantitative real-time polymerase chain reaction in 94 consecutive childhood acute lymphoblastic leukaemia (ALL) samples and its association with clinical/biological features and survival. ALL samples showed higher expression levels of HDAC2, HDAC3, HDAC8, HDAC6 and HDAC7 when compared to normal bone marrow samples. HDAC1 and HDAC4 showed high expression in T-ALL and HDAC5 was highly expressed in B-lineage ALL. Higher than median expression levels of HDAC3 were associated with a significantly lower 5-year event-free survival (EFS) in the overall group of patients (P = 0·03) and in T-ALL patients (P = 0.01). HDAC7 and HADC9 expression levels higher than median were associated with a lower 5-year EFS in the overall group (P = 0.04 and P = 0.003, respectively) and in B-lineage CD10-positive patients (P = 0.009 and P = 0·005, respectively). Our data suggest that higher expression of HDAC7 and HDAC9 is associated with poor prognosis in childhood ALL and could be promising therapeutic targets for the treatment of refractory childhood ALL.

Cryptic SYT/SXX1 fusion gene in high-grade biphasic synovial sarcoma with unique complex rearrangement and extensive BCL2 overexpression.

Synovial sarcomas are high-grade malignant mesenchymal tumors that account for 10% of all soft-tissue sarcomas. Almost 95% of these tumors are characterized by a nonrandom chromosomal abnormality, t(X;18)(p11.2;q11.2), that is observed in both biphasic and monophasic variants. In this article, we present the case of a 57-year-old woman diagnosed with high-grade biphasic synovial sarcoma in which conventional cytogenetic analysis revealed the constant presence of a unique t(18;22)(q12;q13), in addition to trisomy 8. The rearrangement was confirmed by fluorescence in situ hybridization. The use of the whole chromosome painting probes WCPX did not detect any rearrangements involving chromosome X, although reverse-transcriptase polymerase chain reaction (PCR) analysis demonstrated the conspicuous presence of a SYT/SXX1 fusion gene. Spectral karyotyping (SKY) was also performed and revealed an insertion of material from chromosome 18 into one of the X chromosomes at position Xp11.2. Thus, the karyotype was subsequently interpreted as 47,X,der(X)ins(X;18)(p11.2;q11.2q11.2),der(18)del(18)(q11.2q11.2)t(18;22)(q12;q13),der(22)t(18;22). Real-time PCR analysis of BCL2 expression in the tumor sample showed a 433-fold increase. This rare finding exemplifies that thorough molecular-cytogenetic analyses are required to elucidate complex and/or cryptic tumor-specific translocations.

mRNA expression of matrix metalloproteinases (MMPs) 2 and 9 and tissue inhibitor of matrix metalloproteinases (TIMPs) 1 and 2 in childhood acute lymphoblastic leukemia: potential role of TIMP1 as an adverse prognostic factor.

This study evaluates the mRNA expression profile of genes TIMP1, TIMP2, MMP2 and MMP9 in diagnostic bone marrow samples from 134 consecutive ALL children by real-time quantitative PCR. A significant association was observed between higher expression levels of MMP9 and low risk group and absence of extramedullary infiltration and higher expression levels of TIMP2 and MMP2 with T-ALL. TIMP1 gene expression values higher than the median were associated with a significantly lower 5-year event free-survival in univariable (P=0.04) and multivariable analysis (P=0.01). Our data address new information in the complex interaction of the migration/adhesion genes and childhood ALL.

Pitfalls in the differential diagnosis of renal tumor in an adolescent.

The differential diagnosis of renal tumors, particularly in adolescents, may be challenging. We describe an 11-year-old female with a primary intra-renal mass. Initial differential diagnoses included primitive neuroectodermal tumor (PNET), desmoplastic small round cell tumor (DSRCT), and Wilms Tumor (WT). Extensive pathologic and molecular analysis on initial and relapsed tumor samples confirmed WT. The EWS-WT1 and EWS-FLI1 rearrangements, distinctive of DSRCT and PNET were negative. The differential diagnosis on monophasic blastemal WT may be complex. Primary renal DSRCT and PNET have been rarely described. Nevertheless, molecular confirmation for these rare conditions may be necessary in selected cases.

MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression at the posttranscriptional level by degrading or blocking translation of messenger RNA (mRNA) targets. MiRNAs play important regulatory roles in a variety of cellular functions as well as in several diseases, including cancer. MiRNA-specific expression profiles have been reported for several pathological conditions. Recently, the discovery of miRNAs in serum opens up the possibility of using miRNAs as biomarkers of disease. In this review, we discuss the potential use of miRNAs as clinically diagnostic biomarkers of various cancers and other diseases as well as the approaches used to detect these molecules in serum and plasma.

Pediatric glioblastoma cell line shows different patterns of expression of transmembrane ABC transporters after in vitro exposure to vinblastine.

BACKGROUND: Resistance to drug is a major cause of treatment failure in pediatric brain cancer. The multidrug resistance (MDR) phenotype can be mediated by the superfamily of adenosine triphosphate-binding cassette (ABC) transporters. The dynamics of expression of the MDR genes after exposure to chemotherapy, especially the comparison between pediatric brain tumors of different histology, is poorly described. OBJECTIVE: To compare the expression profiles of the multidrug resistance genes ABCB1, ABCC1, and ABCG2 in different neuroepithelial pediatric brain tumor cell lines prior and following short-term culture with vinblastine. METHODS: Immortalized lineages from pilocytic astrocytoma (R286), anaplasic astrocytoma (UW467), glioblastoma (SF188), and medulloblastoma (UW3) were exposed to vinblastine sulphate at different schedules (10 and 60 nM for 24 and 72 h). Relative amounts of mRNA expression were analyzed by real-time quantitative polymerase chain reaction. Protein expression was assessed by immunohistochemistry for ABCB1, ABCC1, and ABCG2. RESULTS: mRNA expression of ABCB1 increased together with augmenting concentration and time of exposure to vinblastine for R286, UW467, and UW3 cell lines. Interestingly, ABCB1 levels of expression diminished in SF188. Following chemotherapy, mRNA expression of ABCC1 decreased in all cell lines other than glioblastoma. ABCG2 expression was influenced by vinblastine only for UW3. The mRNA levels showed consistent association to protein expression in the selected sets of cell lines analyzed. CONCLUSIONS: The pediatric glioblastoma cell line SF188 shows different pattern of expression of multidrug resistance genes when exposed to vinblastine. These preliminary findings may be useful in determining novel strategies of treatment for neuroepithelial pediatric brain tumors.

Perfluorocarbon liquid left in vitreous cavity after recovery of dropped nuclei by anterior segment surgeons after cataract surgery.

BACKGROUND: Perfluorocarbon liquid (PFC) has been used for almost 2 decades in many intraocular procedures. In this report we comment on 3 patients with retained PFC in vitreous cavity (VC) following complicated phacoemulsification surgery. METHODS: Retrospective chart review. RESULTS: All patients had pars plana vitrectomy performed after the initial complicated cataract surgery in which PFC was inappropriately used to recover a dropped nuclei. The time between the first and the second surgery was 1 week for the first patient, 2 weeks for the second patient, and 3 months for the third patient. A better outcome was seen in the patient with the shorter interval between the surgeries. Reduced visual acuity, retinal and optic nerve pallor were found in the patient that had the PFC in the VC for a longer period. INTERPRETATION: Complete consideration of the potential risks should be performed before attempting to recover fallen nuclei by injecting PFC. If complications cannot be resolved in the same surgical procedure, it is advisable to reschedule the patient for a posterior segment surgery.

Evaluación de centros nacionales de capacitación en salud sexual y reproductiva (CNCSSR) / Evaluation of national centers of training in sexual and reproductive health (CNCSSR)

Esta investigación, pretende evaluar la situación actual de los Centros Nacionales de Capacitación, sus perspectivas y potencialidades para adecuarse a las actuales políticas de salud. El documento presenta conclusiones organizadas en función a los objetivos señalados para la investigación y también recomendaciones que permitan decidir el futuro de los CNCSSR en la nueva política de desarrollo de recursos humanos del sector salud. Además de las recomendaciones, se propone un plan de acciones inmediatas para la gestión 1999 que permitiría al MSPS contar con planes de capacitación regionales para el año 2000

Evaluación de centros nacionales de capacitación en salud sexual y reproductiva (CNCSSR) / Evaluation of national centers of training in sexual and reproductive health (CNCSSR)

Esta investigación, pretende evaluar la situación actual de los Centros Nacionales de Capacitación, sus perspectivas y potencialidades para adecuarse a las actuales políticas de salud. El documento presenta conclusiones organizadas en función a los objetivos señalados para la investigación y también recomendaciones que permitan decidir el futuro de los CNCSSR en la nueva política de desarrollo de recursos humanos del sector salud. Además de las recomendaciones, se propone un plan de acciones inmediatas para la gestión 1999 que permitiría al MSPS contar con planes de capacitación regionales para el año 2000

Resultados y recomendaciones del estudio de cinco centros nacionales de capacitación: informe de consultoria para el Fondo de Población de las Naciones Unidas

Esta investigación no pretende evaluar el logro de los objetivos que cada proyecto formuló en su momento, si no la situación actual de los mismos, sus perspectivas y potencialidades para adecuarse a las actuales políticas de salud. El trabajo se ha realizado en el Departamento de Cochabamba, La Paz, Santa Cruz y Sucre, y se ha basado en la recopilación de información secundaria, entrevistas, elaboración y aplicación de encuestas a personal de salud en los ámbitos nacional, regional local, institucional y la población. El documento presenta conclusiones organizadas en función a los objetivos señalados para la investigación y también recomendaciones que permitan decidir el futuro de la CNCSSR