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Comments on a research which analyzed the implications of frequent loss of Rb2/p130 in human ovarian carcinoma. Role of the protein levels of the retinoblastoma gene in the development of ovarian cancer; Lack of medical detection systems which would contribute to the early detection of the disease; Importance of the research to the development of treatments for the disease.

Cancer diagnosis not only shakes the lives of those who are affected, but also has impacts on the entire family system, which is involved as if it were itself an organism affected by cancer. The oncological illness may cause a breakdown of the existing balance in the family system and demands a progressive degree of mutual adaptation to family members. The 'VoiNoi' Listening Centre of the Campus Bio-Medico University Hospital in Rome has been close to caregivers for several years, to support them in the difficult task of providing assistance through individual or group psychological support therapy and health education. The 'Charter of Rights for Family Caregivers' stems from the experience gained over the years, with the aim of protecting, supporting and strengthening the role and the assistance activity that families carry out in support of their loved ones under conditions of fragility., Competing Interests: Competing interests: None declared.

Objective:: to identify the level of attributed, perceived and real job satisfaction of oncology nursing professionals and analyze the relationships between the levels of satisfaction among these workers., Method:: a descriptive, quantitative cross-sectional study was conducted using the Index of Work Satisfaction (IWS) to evaluate the nursing team, nurses and technicians/auxiliaries. A total of 348 workers answered the questionnaire, of which 216 were fully completed and considered for the IWS calculation., Results:: Autonomy was considered the most important item in attributed satisfaction for the nursing team and nurses. Salary was valorized most by the technicians/auxiliaries. For perceived satisfaction, Professional Status was the most important for all workers. Regarding real satisfaction, Interaction was the most important for the nursing team and technicians/auxiliaries; while the nurses valorized Autonomy. The nurses presented the greatest job satisfaction., Conclusion:: a discrepancy was observed in job satisfaction among the oncology nurses, indicating the importance of further quantitative research., Objetivo:: identificar o nível de satisfação profissional atribuído, percebido e o real no trabalho de profissionais de enfermagem oncológica e analisar as relações entre os níveis de satisfação desses trabalhadores., Método:: estudo quantitativo, descritivo, transversal que utilizou o Índice de Satisfação Profissional (ISP) para avaliar a equipe de enfermagem, enfermeiros e técnicos/auxiliares. Dentre os profissionais, 348 destes responderam o questionário, dos quais 216 foram totalmente preenchidos e considerados para o cálculo do ISP., Resultados:: Autonomia foi mais importante na satisfação atribuída para a equipe de enfermagem e enfermeiros, Remuneração foi mais valorizada pelos técnicos/auxiliares. Para a satisfação percebida, Status profissional foi mais importante para todos os profissionais. Sobre a real satisfação, Interação foi o mais importante para a equipe de enfermagem e técnicos/auxiliares; os enfermeiros valorizaram Autonomia. Os enfermeiros obtiveram maior satisfação profissional., Conclusão:: Observou-se discrepância quanto à satisfação profissional dos trabalhadores de enfermagem oncológica, sendo importante maior aprofundamento qualitativo.

To assess the quality of the primary health care network, the Ministry of Health created the Program for Improving Access and Quality in Primary Care (PMAQ), a national evaluation of family health teams. Thus, this study aims to present the geolocation of PMAQ 2012 quality indicators in the city of Rio de Janeiro. The PMAQ data show that, in the city of Rio de Janeiro, 65% of the teams achieved the performances "good" or "excellent," 34.7% "regular," and 0.3% "unsatisfactory." The results show a clear PMAQ polarization between teams units classified as optimal and regular in program areas 5 and 3, respectively.

This study sought to evaluate the occurrence of adverse events and their impacts on length of stay and mortality in an intensive care unit (ICU). This is a prospective study carried out in a teaching hospital in Rio de Janeiro, Brazil. The cohort included 355 patients over 18 years of age admitted to the ICU between August 1, 2011 and July 31, 2012. The process we used to identify adverse events was adapted from the method proposed by the Institute for Healthcare Improvement. We used a logistical regression to analyze the association between adverse event occurrence and death, adjusted by case severity. We confirmed 324 adverse events in 115 patients admitted over the year we followed. The incidence rate was 9.3 adverse events per 100 patients-day and adverse event occurrence impacted on an increase in length of stay (19 days) and in mortality (OR = 2.047; 95%CI: 1.172-3.570). This study highlights the serious problem of adverse events in intensive care and the risk factors associated with adverse event incidence. Resumo: Este estudo teve como objetivo avaliar a ocorrência de eventos adversos e o impacto deles sobre o tempo de permanência e a mortalidade na unidade de terapia intensiva (UTI). Trata-se de um estudo prospectivo desenvolvido em um hospital de ensino do Rio de Janeiro, Brasil. A coorte foi formada por 355 pacientes maiores de 18 anos, admitidos na UTI, no período de 1º de agosto de 2011 a 31 de julho de 2012. O processo de identificação de eventos adversos baseou-se em uma adaptação do método proposto pelo Institute for Healthcare Improvement. A regressão logística foi utilizada para analisar a associação entre a ocorrência de evento adverso e o óbito, ajustado pela gravidade do paciente. Confirmados 324 eventos adversos em 115 pacientes internados ao longo de um ano de seguimento. A taxa de incidência foi de 9,3 eventos adversos por 100 pacientes-dia, e a ocorrência de evento adverso impactou no aumento do tempo de internação (19 dias) e na mortalidade (OR = 2,047; IC95%: 1,172-3,570). Este estudo destaca o sério problema dos eventos adversos na assistência à saúde prestada na terapia intensiva e os fatores de risco associados à incidência de eventos.

Introduction: Osteoporosis is a chronic disease that leads to bone fragility and is associated with fracture risks and serious consequences for mobility., Objective: To verify the effects of two linear programs of resistance training (RT) on bone mineral density (BMD), functional autonomy (FA), muscular strength and quality of life (QoL) of postmenopausal women in pharmacological treatment., Study Design: Randomized controlled trial, code: RBR-6bqsw8., Methods: 52 volunteers were distributed into three groups, according to randomly parallel form: RT3times-per-week (RT3, n=20); RT2times-per-week (RT2, n=16) and control group (CG, n=16). The following assessment tools were used: bone mineral density (BMD) by dual X-ray absorptiometry, 'Latin America Group for maturity' (GDLAM) protocol for FA, 10RM test for leg exercises and the 'Osteoporosis Assessment Questionnaire' (OPAQ) for QoL. The physical activities were planned for 13 months in cycles with different intensities. A two-way ANOVA with Bonferroni post-hoc test were used., Results: The results showed that the RT3/week was significantly more efficient (p<0.05) compared with RT2/week, including: All BMD variables, FA (Δ%=29.3%), leg press at 45° (Δ%=24.97%) and OPAQ (Δ%=20.23%). In addition, both RT3 and RT2 groups were more efficient (p<0.05) compared with CG, including: total BMD (Δ%=0.09%) and (Δ%=0.06%); FA (Δ%=7.1%) and RT2 (Δ%=3.78%); Leg press at 45° (Δ%=84.1%) and (Δ%=59.1%); keen extension (Δ%=15.28%) and (Δ%=20.37%); OPAQ (Δ%=57.61%) and (Δ%=37.37%), respectively., Conclusion: The study showed that both experimental groups presented favorable results for BMD, strength, FA and QoL. However, the RT3 showed the best results compared to other groups after 13 months of intervention., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival.

An understanding of the mechanisms that uncover the dynamic changes in the distribution of the chromatin modifying enzymes and regulatory proteins on their target loci could provide further insight into the phenomenon of malignant transformation. Based on the current available data, it seems more and more clear that an abnormal expression of Ezh2, a member of the Polycomb group (PcG) protein, may be involved in the tumorigenesis process, in addition, different studies identify Ezh2 as a potential marker that distinguish aggressive prostate and breast cancer from indolent one. Recent investigation show that ectopic expression of Ezh2 provides proliferative advantage to primary cells through interaction with the pathways of key elements that control cell growth arrest and differentiation, like members of the retinoblastoma (Rb) family. Here, we outline how these pathways converge and we review the recent advances on the molecular mechanisms that promote cell cycle progression through deregulation of Ezh2 protein level, providing novel links between cancer progression and chromatin remodeling machineries., ((c) 2007 Wiley-Liss, Inc.)

This ecological study presented analyze of the birth pathways in the Rio de Janeiro City and identification of the relationship between the health services offer and pregnant flow between their households and the maternity. It was used the data available in the Mortality Information System (MIS) and Live Birth Information System (LBIS) in 2004. The TabWin program processed the data and drew the maps. The LBIS processed 99,042 declarations of live birth and MIS processed 1,318 declarations of deaths in less than one year old in the Rio Janeiro City. The conclusion was that the possibility of intervention in the infantile and maternal mortality profile has happened at the health services, and the access to the quality assistance has fundamental hole in the mortality determination. The existence of access inequalities to the services must be investigated.

During the past 20 years, the pendulum of opinion in the HIV-1 vaccine field has swung between two extremes, initially favoring the induction of antibodies only, and subsequently favoring the induction of cell-mediated immune responses only. At present, the consensus seems to be that induction of both humoral and cellular immunity by an HIV-1 vaccine will be required to achieve maximum protection. One obstacle to the development of an effective HIV-1 vaccine has been the difficulty in inducing broadly reactive, potent antibodies with protective functions. Defining epitopes and designing immunogens that will induce these antibodies is one of the main challenges that currently confronts the HIV-1 vaccine field.

Purpose: In addition to their original function as cell cycle regulators, retinoblastoma (Rb) family members were recently reported to modulate the sensitivity of cancer cells to chemotherapeutic agents. The purpose of this study is to investigate the possible role of pRb2/p130 in the sensitivity of ovarian cancer to camptothecin, doxorubicin, and taxol., Experimental Design: pRb2/p130 was overexpressed in the CAOV-3 ovarian cancer cell line, and the effect of pRb2/p130 overexpression on sensitivity to apoptosis trigged by IC(50) doses of different drugs was evaluated by various methods, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and Western blot analyses., Results: The results reported in this study support the conclusion that overexpression of pRb2/p130 in the CAOV-3 ovarian cancer cell line lacking wild-type p53 is able to inhibit apoptosis triggered by camptothecin and doxorubicin through the c-Jun NH(2)-terminal kinase signaling transduction pathway. Conversely, taxol-induced cell death is not influenced by the pRb2/p130 protein level., Conclusions: A careful analysis of pRb2/p130 expression in tumor specimens could help to identify the best clinical protocol to be used for each patient, improving efficacy and tolerance and therefore offering additional progress in the treatment of advanced ovarian cancer.

The polycomb group (PcG) proteins are known to be involved in maintaining the silenced state of several developmentally regulated genes. Enhancer of zeste homolog 2 (Ezh2), a member of this large protein family, has also been shown to be deregulated in different tumor types and its role, both as a potential primary effector and as a mediator of tumorigenesis, has become a subject of increased interest. We observed that Ezh2 binds to pRb2/p130, a member of the retinoblastoma family; as such, we were led to consider the possible ability of Ezh2 to modulate cell cycle progression. Both Ezh2 and pRb2/p130 repress gene expression by recruiting histone deacetylase (HDAC1), which decreases DNA accessibility for activating transcription factors. Additionally, we observed that Ezh2 interacts with the C-terminal region of pRb2/p130, essential for interaction with HDAC1. We show that Ezh2 is able to reverse pRb2/p130-HDAC1-mediated repression of the cyclin A promoter. This indicates a functional role of this complex in regulating cyclin A expression, known to be crucial in mediating cell cycle advancement. We also detected a significant decrease in the retention of HDAC1 activity associated with pRb2/p130 when Ezh2 was overexpressed. Finally, electromobility shift assays (EMSA) demonstrated that overexpression of Ezh2 caused the abrogation of the pRb2/p130-HDAC1 complex on the cyclin A promoter. These data, taken together, suggest that Ezh2 competes with HDAC1 in binding to pRb2/p130, disrupting their occupancy on the cyclin A promoter. In this study, we propose a new mechanism for the functional inactivation of pRb2/p130 that ultimately contributes to cell cycle progression and malignant transformation., (Copyright 2004 Nature Publishing Group)

Purpose: RB2/p130, a member of the retinoblastoma gene family, maps to human chromosome 16q12.2, a region in which deletions have been found in several human neoplasms including breast, prostatic, and ovarian carcinoma. We sought to evaluate pRb2/p130 protein expression and function in ovarian carcinoma., Experimental Design: pRb2/p130 expression was detected by immunohistochemical and Western blot analyses in 45 primary ovarian carcinoma samples., Results: Immunohistochemical analysis revealed loss or decrease of pRb2/p130 expression in 18 cases (40%). pRb2/p130 expression was mostly nuclear and inversely correlated to the tumor grade (P < 0.05). Western blot analysis correlated with immunohistochemical expression. Reverse transcription-PCR followed by Southern blot analysis was performed on a representative set of 20 ovarian carcinomas. RB2/p130 mRNA levels were consistent with protein expression. We found a significant increase in the percentage of G(1)-phase-arrested cells in CAOV3 and A2780 ovarian carcinoma cell lines after transduction with an adenovirus carrying the RB2/p130 gene (Ad-CMV-RB2/p130)., Conclusions: These data indicate that loss or decrease of pRb2/p130 expression is a frequent event in ovarian carcinoma and is regulated mostly at the transcriptional level. Moreover, pRb2/p130 overexpression is able to arrest cell growth in ovarian carcinoma cells, suggesting the putative role of pRb2/p130 as a tumor suppressor in this malignancy.

Angiogenesis is a term that describes the formation of new capillaries from a pre-existing vasculature. This process is very important in physiologic conditions because it helps healing injured tissues, and in female populations it helps forming the placenta after fertilization and reconstructs the inside layer of the uterus after menstruation. Angiogenesis is the result of an intricate balance between proangiogenic and antiangiogenic factors and is now very well recognized as a powerful control point in tumor development. In this particular environment, the fine modulation among proangiogenic and antiangiogenic factors is disrupted, leading to inappropriate vessels growth. In this review, we discuss the molecular basis of angiogenesis during tumor growth and we also illustrate some of the molecules that are involved in this angiogenic switch.

The latest generation of lentiviral vectors based on HIV-1 is one of the most efficient tools for gene transduction of mammalian cells. However, the possible employment of HIV-based vectors in clinical trials is a very controversial issue, mainly due to safety and ethical concerns. HIV-1 is a lethal pathogenic agent, which induces AIDS. Genetic vectors must derive either from viruses that are not pathogenic in humans, or that eventually just cause mild illnesses. Patients exposed to HIV-based vectors will test seropositive to certain components of HIV-1. In addition, there might be other possible adverse effects in patients that cannot be predicted, as many aspects of the pathogenesis of AIDS have not been completely understood yet. On these grounds, it seems necessary to improve the design of other lentiviral vectors, which derive from viruses that are not pathogenic in humans and are distantly related to primate retroviridae.

The destiny of a cell--whether it undergoes division, differentiation or death--results from an intricate balance of many regulators, including oncoproteins, tumor-suppressor proteins and cell-cycle-associated proteins. One of the better-studied tumor suppressors is the retinoblastoma protein, known as pRb or p105. Two recently identified proteins, pRb2/p130 and p107, show structural and functional similarities to pRb, and these proteins and their orthologs make up the retinoblastoma (Rb) family. Members of the family have been found in animals and plants, and a related protein is known in the alga Chlamydomonas. Members of the Rb family are bound and inactivated by viral proteins and, in turn, bind cellular transcription factors and repress their function, and can also form complexes with cyclins and cyclin-dependent kinases and with histone deacetylases. They are found in the nucleus and their subnuclear localization depends on binding to the nuclear matrix. Members of the family form part of a signal-transduction pathway called the Rb pathway, which is important in cell-cycle regulation and have roles in growth suppression, differentiation and apoptosis in different organisms and cell types.

The ultimate destiny of a cell to undergo division, differentiation, survival, and death results from an intricate balance between multiple regulators including oncogenes, tumor suppressor genes, and cell cycle associated proteins. Deregulation of the cell cycle machinery switches the phenotype from a normal cell to a cancerous cell. Fundamental alterations of tumor suppressor genes may result in an unregulated cell cycle with the accumulation of mutations and eventual neoplastic transformation. As such, one may define cancer as a genetic disease of the cell cycle. In this review, we will emphasize our current understanding of how the cell cycle machinery maintains cellular homeostasis by studying the consequences of its deregulation., (Copyright 2002 Wiley-Liss, Inc.)

Immunoglobulin heavy chain gene (IgH) rearrangement was studied in a patient showing the occurrence of classical Hodgkin disease and large B-cell lymphoma (LBCL) in the same lymph node. The VHDHJH region was amplified by polymerase chain reaction, the template being the DNA extracted from single Hodgkin and Reed-Sternberg and LBCL cells, microdissected on hematoxylin-eosin-stained sections by laser capture. A repeated VH4DH3JH4 segment was found in Reed-Sternberg cells, whereas a repeated VH3DH3JH4 segment was observed in LBCL cells. Rearranged VH genes carried somatic mutations in both populations, indicating a common germinal center cell origin. The IgH rearrangement found in clonally related Reed-Sternberg cells differed from the one of LBCL cells in the VH region but showed the same JH and DH segments with no variation from the respective germline sequence. The DH-JH junction is the first immunoglobulin gene segment rearranged in precursor B cells. Because the possibility of secondary Ig gene rearrangement in peripheral lymphoid organs has recently been reported, in the patient described here Reed-Sternberg and LBCL cells might originate from a common precursor in which secondary VH replacement took place during the germinal center reaction, giving rise to two different clonally related lymphomas.

ninaE(D1), a dominant allele of the major Drosophila rhodopsin gene, expresses a rhodopsin that is predominantly recovered in a 80-kD complex that likely represents rhodopsin dimers. By driving either ninaE(D1) or ninaE+ expression from a heat-shock promoter, we show that the 80-kD rhodopsin complex forms immediately after gene activation. In wild type, but not ninaE(D1), rhodopsin monomeric forms are detected at later times. The generation of monomeric forms of wild-type rhodopsin is suppressed in vitamin A-deprived flies or in flies heterozygous for the dominant rhodopsin mutation. We also show that ninaE(D1) expression does not affect the maturation of another Drosophila visual pigment, Rh3. These results are consistent with the view that the ninaE(D1) rhodopsin antagonizes an early posttranslation process that is specific for maturation of the ninaE-encoded rhodopsin.