RESUMO
OBJECTIVES: Adherence to healthy lifestyle recommendations has been reported to improve health-related quality of life (HRQL) in breast cancer (BC) patients, but the influence of long-term behavioral changes remains unknown. We evaluated the association between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and HRQL both, at BC diagnosis and the change 7-12 years later. DESIGN: Prospective cohort study. SETTINGS AND PARTICIPANTS: A total of 406 breast cancer survivors, from the EpiGEICAM study, were recruited in 16 Spanish hospitals. MEASUREMENTS: Epidemiological, clinical, dietary, physical activity and HRQL information was collected both at recruitment and 7-12 years later. A 7-item score to measure compliance with recommendations was assessed according to the 2018 WCRF/AICR scoring criteria. HRQL was evaluated using SF-36 questionnaire. Linear mixed models for longitudinal data were used to assess the cross-sectional and longitudinal association between adherence score and the physical and mental component summary scores. RESULTS: At diagnosis, for each unit increase in WCRF/AICR score adherence, the HRQL physical domain increased 0.78 points (95%CI: -0.04 to 1.60; P trend:0.06). The mean change in physical HRQL from diagnosis to follow-up per unit increase in within-subject adherence score was 0.73 points (95%CI: -0.18 to 1.65; P trend: 0.12). For the mental domain, no association was observed with compliance with the recommendations at diagnosis, nor with changes in adherence over time. CONCLUSIONS: Our results suggest that Increased adherence to WCRF/AICR cancer prevention recommendations over time could contribute to slightly improved long-term physical HRQoL in BC survivors.
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In Italy, the National Register on Occupational Exposure to Carcinogens (SIREP) is established pursuant to article 243 of Legislative Decree 81/2008 and is aimed to collect information on the exposure of workers to carcinogens transmitted by employers. The aim of this study is to assess its level of implementation comparing prevailing carcinogens reported in SIREP with the monitoring of risks in the workplace evidenced by the International Agency for Research on Cancer (IARC). The data reported in the SIREP have been integrated with IARC and the database on carcinogenic risk in the workplace named MATline in order to build a matrix containing the carcinogens classified according to the IARC (Group 1 and 2A agents) and to a semi-quantitative indicator of risk level (High or Low) calculated upon the number of exposures reported in SIREP. The matrix contains the following data: carcinogens, economic sector (NACE Rev2 coding) and cancer sites. The comparison between SIREP and IARC evidence allowed us to highlight situations with a high risk of carcinogenicity and to address appropriate actions of prevention to contain the risks of exposure to carcinogenic substances.
Assuntos
Neoplasias , Exposição Ocupacional , Humanos , Carcinógenos/toxicidade , Exposição Ocupacional/prevenção & controle , Itália/epidemiologia , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Agências InternacionaisRESUMO
Mortality from occupational diseases significantly afflicts society, in terms of both economic costs and human suffering. The International Labour Organization (ILO) estimated that 2.4 million workers die from work-related diseases every year. In Europe, around 80,000 workers die from cancer attributed to occupational exposure to carcinogens. This study developed the Occupational Mortality Matrix (OMM) aimed to identify significant associations between causes of death and occupational sectors through an individual record linkage between mortality data and the administrative archive of occupational histories. The study population consisted of 6,433,492 deceased subjects in Italy (in the period 2005-2015), of which 2,723,152 records of work histories were retrieved (42%). The proportional mortality ratio (PMR) was estimated to investigate the excess of mortality for specific causes associated with occupational sectors. Higher PMRs were reported for traditionally risky occupations such as shipbuilding for mesothelioma cases (PMR: 8.15; 95% CI: 7.28-9.13) and leather production for sino-nasal cancer (PMR: 5.04; 95% CI: 3.54-7.19), as well as for unexpected risks such as male breast cancer in the pharmaceutical industry (PMR: 2.56; 95% CI: 1.33-4.93) and brain cancer in railways (PMR: 1.43; 95% CI: 1.24-1.66). The OMM proved to be a valid tool for research studies to generate hypotheses about the occupational etiology of diseases, and to monitor and support priority actions for risk reduction in workplaces.
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Mesotelioma Maligno , Mesotelioma , Doenças Profissionais , Exposição Ocupacional , Humanos , Armazenamento e Recuperação da Informação , Masculino , Mesotelioma/epidemiologia , Doenças Profissionais/etiologiaRESUMO
Aims: To obtain real-world data on ramucirumab use and effectiveness for the treatment of advanced gastric cancer (AGC) or gastroesophageal junction adenocarcinoma (GEJ). Methods: Observational, retrospective study carried out in 20 Spanish hospitals, in patients who started ramucirumab treatment between December 2015 and December 2018. Descriptive analysis was conducted for patient characteristics, treatment patterns and effectiveness outcomes. Results: Three hundred seventeen patients were included (93.7% treated with ramucirumab-paclitaxel and 6.3% with ramucirumab); age 62.5 (11.3) years; 66.9% male. Median progression-free survival and overall survival were 3.9 months (95% CI: 3.4-4.3) and 7.4 (95% CI: 6.4-8.9) in combination regimen and 2.0 (1.1-2.8) and 4.3 (95% CI: 1.9-7.3) in monotherapy, respectively. Conclusion: The study findings were consistent with available real-world studies and randomized clinical trials.
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Adenocarcinoma/terapia , Anticorpos Monoclonais Humanizados/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Gástricas/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Paclitaxel/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Espanha/epidemiologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , RamucirumabRESUMO
The hypothesis of transgenerational induction of increased cancer susceptibility after paternal radiation exposure has long been controversial because of inconsistent results and the lack of a mechanistic interpretation. Here, exploiting Ptch1 heterozygous knockout mice, susceptible to spontaneous and radiation-induced medulloblastoma, we show that exposure of paternal germ cells to 1 Gy X-rays, at the spermatogonial stage, increased by a considerable 1.4-fold the offspring susceptibility to medulloblastoma induced by neonatal irradiation. This effect gained further biological significance thanks to a number of supporting data on the immunohistochemical characterization of the target tissue and preneoplastic lesions (PNLs). These results altogether pointed to increased proliferation of cerebellar granule cell precursors and PNLs cells, which favoured the development of frank tumours. The LOH analysis of tumor DNA showed Ptch1 biallelic loss in all tumor samples, suggesting that mechanisms other than interstitial deletions, typical of radiation-induced medulloblastoma, did not account for the observed increased cancer risk. This data was supported by comet analysis showing no differences in DNA damage induction and repair in cerebellar cells as a function of paternal irradiation. Finally, we provide biological plausibility to our results offering evidence of a possible epigenetic mechanism of inheritance based on radiation-induced changes of the microRNA profile of paternal sperm.
Assuntos
Neoplasias Cerebelares/etiologia , Neoplasias Cerebelares/genética , Meduloblastoma/etiologia , Meduloblastoma/genética , Neoplasias Induzidas por Radiação/genética , Receptores de Superfície Celular/genética , Animais , Neoplasias Cerebelares/patologia , Ensaio Cometa , Feminino , Masculino , Meduloblastoma/patologia , Camundongos , Camundongos Transgênicos , Análise em Microsséries , Receptores Patched , Receptor Patched-1RESUMO
OBJECTIVE: To explore the possibility of choriocarcinoma syndrome developing as a potentially fatal complication in patients with this pathology. METHOD: Choriocarcinoma syndrome consists of hemorrhagic manifestations of metastases in advanced germ cell cancer containing large elements of choriocarcinoma. It should be suspected in patients with high tumor mass, multiple metastases and elevated tumor markers characteristic of germ cell tumors. It usually occurs before and during the onset of systemic treatment with chemotherapy. Failure to diagnose it can lead to fatal consequences and may require aggressive diagnostic and therapeutic measures such as surgery. It can also be prevented by developing a good therapeutic strategy that includes an interdisciplinary team, raising the possibility of deferring testicular surgery and beginning chemotherapy beforehand. RESULTS: We report two cases of men with the diagnosis of choriocarcinoma syndrome on liver metastases. We provide ultrasound and CT images of the two cases of hemorrhage on liver metastases and radiological characteristics peculiar to each case that have never been published before. CONCLUSIONS: There should be a high index of suspicion of life-threatening complications in patients with germ cell tumors with a choriocarcinoma component, including the development of life-threatening choriocarcinoma syndrome.
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Coriocarcinoma , Hemorragia , Neoplasias Embrionárias de Células Germinativas , Coriocarcinoma/complicações , Feminino , Hemorragia/etiologia , Humanos , Masculino , Gravidez , SíndromeRESUMO
Poly(ADP-ribose)polymerase-1 (PARP1) is a nuclear protein implicated in DNA repair, recombination, replication, and chromatin remodeling. The aim of this study was to evaluate possible differences between PARP1(-/-) and wild-type mice regarding induction and repair of DNA lesions in irradiated male germ cells. Comet assay was applied to detect DNA damage in testicular cells immediately, and two hours after 4 Gy X-ray irradiation. A similar level of spontaneous and radiation-induced DNA damage was observed in PARP1(-/-) and wild-type mice. Conversely, two hours after irradiation, a significant level of residual damage was observed in PARP1(-/-) cells only. This finding was particularly evident in round spermatids. To evaluate if PARP1 had also a role in the dynamics of H2AX phosphorylation in round spermatids, in which γ-H2AX foci had been shown to persist after completion of DNA repair, we carried out a parallel analysis of γ-H2AX foci at 0.5, 2, and 48 h after irradiation in wild-type and PARP1(-/-) mice. No evidence was obtained of an effect of PARP1 depletion on H2AX phosphorylation induction and removal. Our results suggest that, in round spermatids, under the tested experimental conditions, PARP1 has a role in radiation-induced DNA damage repair rather than in long-term chromatin modifications signaled by phosphorylated H2AX.
Assuntos
Dano ao DNA/efeitos da radiação , Reparo do DNA/efeitos da radiação , Células Germinativas/metabolismo , Células Germinativas/efeitos da radiação , Poli(ADP-Ribose) Polimerases/metabolismo , Raios X/efeitos adversos , Animais , Ensaio Cometa , Citometria de Fluxo , Histonas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/genéticaRESUMO
The phosphorylation of histone H2AX at serine 139 (γ-H2AX) is one of the first steps of DNA damage response and its detection is widely used as a sensitive marker for DNA double-strand breaks induced by ionizing radiation or other genotoxic agents. Immuno-stained phosphorylated histone can be measured in single cells by flow cytometry or single γ-H2AX foci can be visualized and counted microscopically in histological or cytological preparations. Animal studies are well recognized as important tools to study mechanisms of in vivo response to genotoxic stress. Tissues are composed by many cell types differing for function, differentiation, and proliferative capacity. In particular, due to the complexity of spermatogenesis and the heterogeneity of testicular cell subpopulations, an accurate characterization of damage in this tissue is difficult and requires an approach which allows the identification of damage in the different cellular compartments. This chapter presents techniques for γ-H2AX detection in mouse bone marrow and testicular cells. Furthermore, advantages and weaknesses of flow cytometric and microscopic methods are described.
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Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Histonas/metabolismo , Testículo/citologia , Animais , Dano ao DNA , Citometria de Fluxo , Imuno-Histoquímica , Masculino , Camundongos , Microscopia de Fluorescência , Fosforilação , Fixação de TecidosRESUMO
Male germ cells have been shown to differ in their DNA damage response (DDR) with respect to somatic cells. In addition, DDR pathways are modulated along spermatogenesis, accompanying profound chromatin modifications. Histone H2AX phosphorylation is a fundamental step of DDR. Few data are available on the long-term kinetics of phosphorylated H2AX (γ-H2AX) after in vivo irradiation. We have investigated, by microscopic and flow cytometric immunochemistry, γ-H2AX induction and removal in testicular cells of irradiated mice, in comparison with bone marrow cells. In unirradiated testicular cells, much higher levels of γ-H2AX were measured by flow cytometry with respect to bone marrow cells. Irradiation induced a redistribution of γ-H2AX into discrete foci detectable by microscopy. In irradiated bone marrow, the percentage of labelled cells peaked at 1 h and rapidly declined, in agreement with data on in vitro cell lines. In contrast, spermatocytes and round spermatids showed persistent labelling until 48 h. During this time, in spermatids, topological changes were observed in γ-H2AX foci from a pattern of many uncountable dots to a pattern of few large spots. Observations of testicular sections confirmed this trend in the reduction of foci number in spite of substantially invariable percentages of labelled cells in the analysed timeframe. To assess whether γ-H2AX persistence in testicular cells was due to unrepaired DNA breaks, we performed comet assay and immunofluorescence analysis of Mdc1, a marker of DDR different from γ-H2AX. Comet assay showed that most breaks were repaired within 2 h. Forty-eight hours after irradiation, contrary to γ-H2AX foci that remained detectable in 80% of initially labelled cells, Mdc1 foci were observed in only 20-30% of cells. These data suggest that, at long times after irradiation, mechanisms additional to impairment of DNA break repair may account for the long persistence of γ-H2AX foci in male germ cells.