RESUMO
BACKGROUND: Patterns of recurrence after surgery with postoperative chemoradiotherapy (S-CCRT) or surgery alone in patients with oesophageal squamous cell carcinoma (SCC) may differ. This might influence the nature and timing of subsequent management strategies. METHODS: Patients with SCC who had undergone R0 resection were included. Propensity score matching was used to select matched groups. Survival and recurrence were compared by Kaplan-Meier analysis. Univariable and multivariable Cox regression analyses were used to identify prognostic factors for overall and disease-free survival. RESULTS: A total of 1390 patients were included, of whom 1000 had surgery alone and 390 underwent S-CCRT. Propensity score matching yielded 213 well balanced pairs. The 3-year overall survival rate and median survival time in the S-CCRT group were 0·50 and 36·5 (95 per cent c.i. 25·1 to 52·6) months respectively, compared with 0·38 and 22·8 (18·2 to 29·0) months in the surgery-alone group (P = 0·006). The 3-year disease-free survival rate and median disease-free survival time in the S-CCRT group were 0·46 and 30·6 (22·2 to 39·3) months respectively, compared with 0·36 and 17·6 (11·3 to 23·9) months in the surgery-alone group (P = 0·006). The 2-year freedom from locoregional recurrence rate was 0·87 and 0·77 in the S-CCRT and surgery-alone groups respectively (P = 0·003). In multivariable analysis, independent prognostic factors for disease-free survival included age over 56 years, pT3-4 category, pN category, poor differentiation, tumour length exceeding 4·0 cm, and receiving postoperative chemoradiotherapy (hazard ratio 0·62, 95 per cent c.i. 0·47 to 0·81; P < 0·001). CONCLUSION: Oesophagectomy with postoperative chemoradiotherapy was associated with longer survival and lower recurrence rates, especially at a locoregional level, compared with surgery alone.
Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia Adjuvante , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Esofagectomia , Recidiva Local de Neoplasia/epidemiologia , Fatores Etários , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Pontuação de Propensão , Taiwan/epidemiologiaRESUMO
Cancer has become one the most common causes of death in developed countries and has been defined as the medical challenge of our times. Accumulating evidence support the notion that prevention can be a major component of cancer control. Chemoprevention, a relatively new and promising strategy to prevent cancer, is defined as the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. Plant-based foods, containing significant amounts of bioactive phytochemicals, may provide desiderable health benefits beyond basic nutrition to reduce the process of cancer. In the last few years, proteins and peptides have become one group of nutraceuticals that show potential results in preventing the different stages of cancer including initiation, promotion, and progression. Lunasin is a 43- amino acid peptide identified in soybean and other plants whose anti-carcinogenic activity has been demonstrated both in in vitro and in vivo assays. Moreover, this peptide has been found to exert anti-inflammatory and antioxidant properties that could contribute to its chemopreventive effects. Lunasin's bioactivity and its molecular mechanism(s) of actions are summarized in this review.
Assuntos
Anticarcinógenos/farmacologia , Proteínas de Soja/farmacologia , Sequência de Aminoácidos , Animais , Anticarcinógenos/química , Anticarcinógenos/uso terapêutico , Disponibilidade Biológica , Humanos , Dados de Sequência Molecular , Proteínas de Plantas/química , Proteínas de Plantas/farmacologia , Sementes/química , Proteínas de Soja/química , Proteínas de Soja/farmacocinética , Proteínas de Soja/uso terapêuticoRESUMO
Self-aggregation of transforming growth factor ß (TGF-ß)1-induced antiapoptotic factor (TIAF1) is known in the nondemented human hippocampus, and the aggregating process may lead to generation of amyloid ß (Aß) for causing neurodegeneration. Here, we determined that overexpressed TIAF1 exhibits as aggregates together with Smad4 and Aß in the cancer stroma and peritumor capsules of solid tumors. Also, TIAF1/Aß aggregates are shown on the interface between brain neural cells and the metastatic cancer cell mass. TIAF1 is upregulated in developing tumors, but may disappear in established metastatic cancer cells. Growing neuroblastoma cells on the extracellular matrices from other cancer cell types induced production of aggregated TIAF1 and Aß. In vitro induction of TIAF1 self-association upregulated the expression of tumor suppressors Smad4 and WW domain-containing oxidoreductase (WOX1 or WWOX), and WOX1 in turn increased the TIAF1 expression. TIAF1/Smad4 interaction further enhanced Aß formation. TIAF1 is known to suppress SMAD-regulated promoter activation. Intriguingly, without p53, self-aggregating TIAF1 spontaneously activated the SMAD-regulated promoter. TIAF1 was essential for p53-, WOX1- and dominant-negative JNK1-induced cell death. TIAF1, p53 and WOX1 acted synergistically in suppressing anchorage-independent growth, blocking cell migration and causing apoptosis. Together, TIAF1 shows an aggregation-dependent control of tumor progression and metastasis, and regulation of cell death.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose , Proteínas Nucleares/metabolismo , Proteína Smad4/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Células COS , Linhagem Celular , Movimento Celular , Chlorocebus aethiops , Matriz Extracelular/metabolismo , Humanos , Camundongos , Camundongos Nus , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Oxirredutases/metabolismo , Regiões Promotoras Genéticas , Proteína Smad4/genética , Proteínas Supressoras de Tumor/metabolismo , Oxidorredutase com Domínios WWRESUMO
BACKGROUND: The size of the breast stem-cell pool could underlie the intrauterine roots of breast cancer. We studied whether breast stem cells exist in umbilical cord blood and if they correlate with hematopoietic stem-cell measurements that have been positively associated with perinatal risk factors for breast cancer. SUBJECTS AND METHODS: We isolated mononuclear cells from umbilical cord blood of 170 singleton full-term pregnancies and determined, by reverse transcription polymerase chain reaction, the presence of genes of putative breast epithelial stem-cell/progenitor markers [including epithelial cell adhesion molecule (EpCAM), CD49f (α6-integrin), CD117 (c-kit receptor), CD24, and CD29 (ß1-integrin)]. By immunocytochemistry, we colocalized protein expressions of EpCAM+CD49f+, CD49f+CD24+, and CD24+CD29+. We correlated concentrations of putative breast stem-cell/progenitor subpopulations, quantified by flow cytometry, with concentrations of hematopoietic stem cells. RESULTS: Mammary stem-cell phenotypes were identified in umbilical cord blood. The measured EpCAM+ subpopulation was positively correlated with concentrations of CD34+ and CD34+CD38- hematopoietic stem cells (both P=0.006). Additionally, EpCAM+CD49f+ and CD49f+CD24+ subpopulations were positively correlated to the CD34+ cells (P=0.03 and 0.008, respectively). CONCLUSION: The positive association between measurable breast and hematopoietic stem cells in human umbilical cord blood suggests plausible mechanisms for a prenatal influence on breast cancer risk.
Assuntos
Biomarcadores Tumorais/análise , Mama/citologia , Sangue Fetal/citologia , Células-Tronco/citologia , Antígenos de Neoplasias/análise , Antígenos de Neoplasias/biossíntese , Mama/metabolismo , Neoplasias da Mama/metabolismo , Antígeno CD24/análise , Antígeno CD24/biossíntese , Moléculas de Adesão Celular/análise , Moléculas de Adesão Celular/biossíntese , Separação Celular , Suscetibilidade a Doenças , Molécula de Adesão da Célula Epitelial , Feminino , Citometria de Fluxo , Células-Tronco Hematopoéticas/citologia , Humanos , Imuno-Histoquímica , Integrina alfa6/análise , Integrina alfa6/biossíntese , Integrina beta1/análise , Integrina beta1/biossíntese , Leucócitos Mononucleares/citologia , Microscopia Confocal , Proteínas Proto-Oncogênicas c-kit/análise , Proteínas Proto-Oncogênicas c-kit/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células-Tronco/metabolismoRESUMO
Asthma is a chronic airway inflammatory disease. Chronic aspiration by gastric fluid in gastroesophageal reflux disease (GERD) is considered a primary inflammatory factor exacerbating or predisposing patients to asthma. Airway smooth muscle cells (SMCs) are considered an important component in airway remodeling. To investigate the role of gastric fluid in airway SMC inflammation and airway remodeling, we examined gastric fluid-induced cytokine and chemokine profiles, airway SMC migration and matrix metalloproteinase expression in rat primary rat airway SMCs. The T helper cell type 2 (Th2) cytokines interleukin 4, interleukin 6 and tumor necrosis factor 2 (TNF-α) and the chemokines, lipopolysaccharide-induced CXC chemokine (LIX/CXCL5), cytokine-induced neutrophil chemoattractant 2 (CINC-2), CINC-3, fractalkine, ciliary neurotrophic factor (CNTF), and vascular endothelial growth factor were induced by gastric fluid in primary cultured rat airway SMCs. Migration of rat airway SMCs was enhanced by gastric fluid and conditioned medium. The migration of rat airway SMCs enhanced by gastric fluid was associated with actin polymerization and activation of focal adhesion kinase. Matrix metalloproteinase 2 expressions in airway SMCs was enhanced by gastric fluid and conditioned medium. The results suggest potential mechanisms by which gastric fluid aspiration might influence SMC-mediated airway remodeling.
Assuntos
Remodelação das Vias Aéreas , Líquidos Corporais/metabolismo , Quimiocinas/metabolismo , Miócitos de Músculo Liso/metabolismo , Estômago/fisiologia , Traqueia/citologia , Actinas/metabolismo , Animais , Linhagem Celular , Movimento Celular , Técnicas de Cocultura , Ativação Enzimática , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Macrófagos/citologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/enzimologia , Polimerização , Ratos , Ratos WistarRESUMO
BACKGROUND: The molecular chaperone heat shock protein-90 (Hsp90) is a promising cancer drug target, but current Hsp90-based therapy has so far shown limited activity in the clinic. METHODS: We tested the efficacy of a novel mitochondrial-targeted, small-molecule Hsp90 inhibitor, Gamitrinib (GA mitochondrial matrix inhibitor), in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. The TRAMP mice receiving 3-week or 5-week systemic treatment with Gamitrinib were evaluated for localised or metastatic prostate cancer, prostatic intraepithelial neoplasia (PIN) or localised inflammation using magnetic resonance imaging, histology and immunohistochemistry. Treatment safety was assessed histologically in organs collected at the end of treatment. The effect of Gamitrinib on mitochondrial dysfunction was studied in RM1 cells isolated from TRAMP tumours. RESULTS: Systemic administration of Gamitrinib to TRAMP mice inhibited the formation of localised prostate tumours of neuroendocrine or adenocarcinoma origin, as well as metastatic prostate cancer to abdominal lymph nodes and liver. The Gamitrinib treatment had no effect on PIN or prostatic inflammation, and caused no significant animal weight loss or organ toxicity. Mechanistically, Gamitrinib triggered acute mitochondrial dysfunction in RM1 cells, with loss of organelle inner membrane potential and release of cytochrome-c in the cytosol. CONCLUSIONS: The Gamitrinib has pre-clinical activity and favourable tolerability in a genetic model of localised and metastatic prostate cancer in immunocompetent mice. Selective targeting of mitochondrial Hsp90 could provide novel molecular therapy for patients with advanced prostate cancer.
Assuntos
Adenocarcinoma/prevenção & controle , Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Guanidinas/uso terapêutico , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Lactamas Macrocíclicas/uso terapêutico , Neoplasias da Próstata/prevenção & controle , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Antineoplásicos/farmacologia , Células Cultivadas , Modelos Animais de Doenças , Progressão da Doença , Avaliação Pré-Clínica de Medicamentos , Feminino , Predisposição Genética para Doença , Guanidinas/farmacologia , Proteínas de Choque Térmico HSP90/metabolismo , Lactamas Macrocíclicas/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Terapia de Alvo Molecular/métodos , Metástase Neoplásica , Neoplasia Prostática Intraepitelial/genética , Neoplasia Prostática Intraepitelial/patologia , Neoplasia Prostática Intraepitelial/prevenção & controle , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND: Breast cancer is less common in China than in the United States and perinatal characteristics predict breast cancer risk in the offspring. We determined levels of pregnancy hormones in Boston and Shanghai to identify those possibly involved in the intrauterine origin of breast cancer. PARTICIPANTS AND METHODS: We compared maternal and cord blood levels of estradiol, estriol, testosterone, progesterone, prolactin, insulin-like growth factors (IGF) 1 and 2, insulin-like growth factor-binding protein 3, adiponectin and sex hormone-binding globulin (SHBG) in 241 Caucasian and 295 Chinese women. RESULTS: In both centers, hormone levels at the 16th were predictive of those at the 27th gestational week, but there was little correlation between maternal and cord blood levels. In cord blood, we found significantly (P < 0.01) higher levels of estradiol (44.2%), testosterone (54.5%), IGF-2 (22.7%) and strikingly SHBG (104.6%) in Shanghai women, whereas the opposite was true for IGF-1 (-36.8%). CONCLUSIONS: Taking into account the current understanding of the plausible biological role of the examined endocrine factors, those likely to be involved in the intrauterine origin of breast cancer are SHBG and IGF-2, with higher cord blood levels among Chinese, and IGF-1, with higher cord blood levels among Caucasian women.
Assuntos
Neoplasias da Mama/etiologia , Sangue Fetal/metabolismo , Hormônios/sangue , Adiponectina/sangue , Adulto , Neoplasias da Mama/sangue , Neoplasias da Mama/epidemiologia , China , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Gravidez , Prolactina/sangue , Globulina de Ligação a Hormônio Sexual/análise , Estatísticas não Paramétricas , Estados Unidos , Adulto JovemRESUMO
Significant heterogenity of stage IB (sixth edition of the TNM staging system) nonsmall cell lung cancer (NSCLC) has been identified, and further subclassification according to tumour size has been proposed. The aim of this study is to evaluate the prognostic factors in patients with resected stage IB NSCLC > 3 cm. From January 1980 to December 2000, 525 patients underwent surgical resection for stage IB NSCLC > 3 cm at Taipei Veterans General Hospital, Taipei, Taiwan. The clinicopathological characteristics of these patients were retrospectively reviewed. The 5- and 10-yr overall survival rates were 44.9% and 27.3%, respectively. Age (p < 0.001), tumour size (p = 0.002), extent of pulmonary resection (p = 0.002), histological type (p = 0.005) and number of mediastinal lymph nodes dissected/sampled (p = 0.004) were significant predictors for overall survival in multivariate analysis. Patients with tumour size >7 cm, or > 5 to ≤ 7 cm, had a worse survival than those with tumour size > 3 to ≤ 5 cm. However, visceral pleural invasion did not influence overall survival. Stage IB NSCLC with a diameter > 3 cm may be subclassified according to tumour size regardless of visceral pleural invasion.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Pleura/patologia , Pleura/cirurgia , Prognóstico , Estudos Retrospectivos , Fumar/efeitos adversos , Taxa de SobrevidaRESUMO
Anoectochilus formosanus HAYATA, a Chinese herb, is a valued folk medicine for fever, pain, and diseases of the lung and liver. Allergic asthma is characterized by increased serum IgE level and inflammation of the airways with high levels of interleukin (IL)-4 and IL-5 in bronchoalveolar lavage fluids (BALF). Constriction of airway smooth muscle and development of airway hyperresponsiveness (AHR) are the most important symptoms of allergic asthma. In our previous study, a standardized aqueous extract of A. formosanus (SAEAF) was used to modulate innate immunity of normal mice. In this study, airway inflammatory infiltrations, including T cell differentiation, cytokine modulation, allergic antibodies estimation, pulmonary pathology, and enhanced pause (Penh) of AHR were used to evaluate SAEAF treatment of an ovalbumin (OVA)-inhaled airway allergic murine model. The resulting cytokine profiles demonstrated that SAEAF can significantly reduce Th2 polarization after administration of SAEAF in OVA inhalation. These results also suggest that SAEAF modulates cytokine secretion in allergic asthma. Modulated natural T regulatory cells (CD25+/CD4+, Treg) were also shown to increase immuno-suppression in the allergic lung inflammation and further down-regulate airway inflammatory infiltration in eosinophils and macrophages. Finally, decreased airway anti-OVA IgE secretion and reduced AHR were observed. Our results indicate that the administration of SAEAF can modulate cytokines and T cell subpopulation by regulating inflammatory cell infiltration and modulating the allergic response.
Assuntos
Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Hiper-Reatividade Brônquica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Orchidaceae , Animais , Anti-Inflamatórios/farmacologia , Antígenos/metabolismo , Asma/imunologia , Asma/metabolismo , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Eosinófilos/efeitos dos fármacos , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Imunoglobulina E/sangue , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Fitoterapia , Valores de Referência , Linfócitos T Reguladores/efeitos dos fármacos , Células Th2/efeitos dos fármacosRESUMO
Breast cancer is generally managed surgically with adjuvant agents which include hormone therapy, chemotherapy, radiotherapy and bisphosphonate therapy. However, some of these adjuvant therapies may cause adverse events, including wound infection, neutropenia, bone marrow suppression and fever. The simultaneous presentation of osteonecrosis and osteomyelitis has not previously been described in patients with breast cancer undergoing hormone therapy and chemotherapy. We report a patient with breast cancer who developed bone infarcts in both legs as well as osteomyelitis in the right distal tibia after treatment which included a modified radical mastectomy, hormone therapy and chemotherapy. Simultaneous osteonecrosis and osteomyelitis should be considered in patients with breast cancer who are receiving chemotherapy and hormone therapy who present with severe bone pain, especially if there have been infective episodes during treatment.
Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Osteomielite/induzido quimicamente , Osteonecrose/induzido quimicamente , Adulto , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/diagnóstico por imagem , Feminino , Humanos , Osteomielite/diagnóstico por imagem , Osteonecrose/diagnóstico por imagem , RadiografiaRESUMO
Breast cancer incidence and birth weight are higher among Caucasian than Asian women, and birth size has been positively associated with breast cancer risk. Pregnancy hormone levels, however, have been generally lower in Caucasian than Asian women. We studied components of the insulin-like growth factor (IGF) system in cord blood from 92 singleton babies born in Boston, USA, and 110 born in Shanghai, China, in 1994-1995. Cord blood IGF-1 was significantly higher among Caucasian compared with Chinese babies (P<10(-6)). The opposite was noted for IGF-2 (P approximately 10(-4)). IGF-1 was significantly positively associated with birth weight and birth length in Boston, but not Shanghai. In contrast, stronger positive, though statistically non-significant, associations of IGF-2 with birth size were only evident in Shanghai. The associations of birth weight and birth length were positive and significant in taller women (for IGF-1 in Boston P approximately 0.003 and 0.03, respectively; for IGF-2 in Shanghai P approximately 0.05 and approximately 0.04, respectively), among whom maternal anthropometry does not exercise strong constraints in foetal growth. The documentation of higher cord blood levels of IGF-1, a principal growth hormone that does not cross the placenta, among Caucasian than in Asian newborns is concordant with breast cancer incidence in these populations.
Assuntos
Peso ao Nascer , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Sangue Fetal/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Adulto , Boston/epidemiologia , China/epidemiologia , Feminino , Humanos , Recém-Nascido , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Masculino , Fatores de RiscoRESUMO
OBJECTIVE: Resection is the best treatment for patients with stage I non-small cell lung cancer (NSCLC). Patterns of disease recurrence after complete resection in stage I NSCLC have not been well demonstrated. The aim of this study was to evaluate the prognostic predictors of post-recurrence survival in patients with resected stage I NSCLC with local recurrence. METHODS: The clinicopathological characteristics of 123 patients with local recurrence after complete resection of stage I NSCLC in Taipei Veterans General Hospital between 1980 and 2000 were retrospectively reviewed. Post-recurrence survival and their predictors were analysed. RESULTS: The patterns of local recurrence included local only in 74 (60.2%) and both local and distant in 49 (39.8%) patients. The 1 and 2 year post-recurrence survival rates for the 74 patients with local only recurrence were 48.7% and 17.6%, respectively. Tumour size (p = 0.033) and treatment for initial recurrence (p<0.001) were significant predictors for post-recurrence survival in 74 patients with local only recurrence in univariate analyses. The hazard of death was greater in patients with larger tumour size. Treatment for initial recurrence (p = 0.001) was still a significant prognostic indicator in multivariate analyses. Patients who underwent reoperation after local recurrence survived longer than those who received chemotherapy and/or radiotherapy and those that received no treatment. CONCLUSIONS: Treatment for initial recurrence is a prognostic predictor for post-recurrence survival in resected stage I NSCLC with local recurrence. Complete surgical resection should be considered in selected candidates with resectable local recurrent disease.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Recidiva Local de Neoplasia/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Carga TumoralRESUMO
Birth size of a woman has been positively associated with her breast cancer risk, particularly before menopause, but no study has investigated neonatal growth in relation to this risk. We conducted a case-control study nested within a population-based cohort of women, born in Sweden between 1901 and 1961, covering all 405 breast cancer patients and 1081 age- and hospital-matched controls, who were born after newborn charts became available. Compared to neonates who lost <200 g after birth and grew at a rate <25 g day(-1) after reaching postnatal weight nadir (ie, the minimum, before starting to regain weight), those who either lost >/=200 g after birth or grew >/=25 g day(-1) after nadir, or both, were at an approximately 50% increased breast cancer risk. The excess risk was striking and statistically significant among women below 50 years of age, but was not evident among older women. Immediate postnatal weight loss (an indicator of water loss, likely to reflect water retention associated with pregnancy hormones) as well as neonatal weight gain rate after the nadir (known to reflect growth hormone levels) was significantly positively associated with premenopausal breast cancer risk.
Assuntos
Neoplasias da Mama/etiologia , Recém-Nascido/crescimento & desenvolvimento , Adulto , Idoso , Peso ao Nascer , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Aumento de PesoRESUMO
In uncomplicated pregnancies, first trimester androgen, oestrogen and prolactin concentrations were higher in nulliparous (n=160) than parous (n=260) mothers. Androgens and estrogens were higher in younger than older mothers. These data are consistent with elevated hormone concentrations mediating the breast cancer protection from a first pregnancy and pregnancies occurring at younger ages.
Assuntos
Hormônios Esteroides Gonadais/sangue , Primeiro Trimestre da Gravidez , Feminino , Humanos , GravidezRESUMO
Brian MacMahon was born in Sheffield, UK in 1923. He served as chair of the Department of Epidemiology at Harvard School of Public Health for more than 30 years. He was admired as a noble and generous man and respected for his shining intellect, scientific integrity, and broad culture. He set the pace for modern epidemiology and led the way for a whole school of epidemiologists who are now spread around the nation and the world. He made major scientific contributions, received several distinguished prizes and awards, and continued to publish insightful papers until the very end. Brian MacMahon was the first editor-in-chief of Cancer Causes and Control.
Assuntos
Epidemiologia/história , História do Século XX , Saúde Pública/história , Ciência/história , Reino UnidoRESUMO
OBJECTIVES: Rhabdomyoma, the most common primary fetal cardiac tumor, is often associated with tuberous sclerosis (TS). We aimed to evaluate outcome in cases diagnosed with fetal cardiac rhabdomyoma. METHODS: This study presents 11 cases with fetal cardiac rhabdomyoma. In addition, all relevant published cases of antenatally diagnosed cardiac rhabdomyoma since 1982 were identified from MEDLINE. We evaluated the following risk factors associated with clinical impact and perinatal outcome: family history of TS, gestational age at diagnosis, tumor size, site and number of tumors, tumor progression, and associated intracardiac and extracardiac anomalies. RESULTS: In this meta-analysis, 138 cases, including nine newly added by us, were categorized into Group A (107 live babies) and Group B (16 neonatal deaths and 15 intrauterine fetal deaths). Univariate analysis showed that large cardiac tumors (P < 0.0001), fetal dysrhythmia (P < 0.0001) and hydrops (P < 0.0001) were strong predictors of neonatal outcome. Tumor size >or= 20 mm (relative risk (RR), 20.6; 95% CI, 2.2-195.9; P = 0.009) and fetal dysrhythmia (RR, 13.6; 95% CI, 2.9-62.3; P = 0.001) were significantly associated with neonatal morbidity. TS, present in 85/133 (63.9%) cases, was significantly associated with multiple cardiac tumors (P < 0.0001) and family history of TS (P = 0.02). CONCLUSIONS: Large tumor size and hydrops are significantly associated with poor neonatal outcome, whereas family history of TS and multiple fetal cardiac tumors are associated with TS. Any sonographic detection of a fetal cardiac tumor should warrant further investigation for the possible presence of associated disorders.
Assuntos
Doenças Fetais/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico por imagem , Rabdomioma/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Ecocardiografia , Feminino , Doenças Fetais/patologia , Coração Fetal/patologia , Idade Gestacional , Neoplasias Cardíacas/patologia , Humanos , Lactente , Análise Multivariada , Gravidez , Resultado da Gravidez , Prognóstico , Rabdomioma/patologia , Esclerose Tuberosa/complicações , Esclerose Tuberosa/diagnóstico por imagem , Esclerose Tuberosa/genéticaRESUMO
We examined the relation with birth weight and umbilical cord blood concentrations of haematopoietic stem and progenitor populations in 288 singleton infants. Across the whole range of birth weight, there was a positive relation between birth weight and CD34+CD38(-) cells, with each 500 g increase in birth weight being associated with a 15.5% higher (95% confidence interval: 1.6-31.3%) cell concentration. CD34+ and CD34+c-kit+ cells had J-shaped relations and CFU-GM cells had a U-shaped relation with birth weight. Among newborns with >or=3000 g birth weights, concentrations of these cells increased with birth weight, while those below 3000 g had higher stem cell concentrations than the reference category of 3000-3499 g. Adjustment for cord blood plasma insulin-like growth factor-1 levels weakened the stem and progenitor cell-birth weight associations. The positive associations between birth weight and stem cell measurements for term newborns with a normal-to-high birth weight support the stem cell burden hypothesis of cancer risk.
Assuntos
ADP-Ribosil Ciclase 1/sangue , Peso ao Nascer , Contagem de Células Sanguíneas , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/fisiologia , Feminino , Humanos , Recém-Nascido , Masculino , Neoplasias/epidemiologia , RiscoRESUMO
OBJECTIVE: Epicardial and abdominal adipose tissues have recently been demonstrated to play inflammatory roles in coronary atherosclerosis. We sought to compare tissue adipocytokine levels of these two anatomically distinct adipose stores in patients with and without coronary artery diseases (CAD). DESIGN: Samples of abdominal and epicardial fat tissues were harvested to detect the levels of adipocytokines and proinflammatory mediators. SUBJECTS: Forty-six patients with CAD who underwent coronary artery bypass surgery and 12 non-CAD control subjects who underwent other types of open-heart surgery. MEASUREMENTS: Tissue levels of adipocytokines (adiponectin, leptin and visfatin) and proinflammatory mediators (tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)) were determined by enzyme-linked immunosorbent assay. RESULTS: Tissue levels of TNF-alpha, IL-6, leptin and visfatin were significantly higher in CAD patients relative to control subjects. In addition, significantly higher tissue levels of these four cytokines from abdominal fat depots were found compared to those from epicardial fat in CAD patients. Conversely, in comparison with control subjects, tissue levels of adiponectin were significantly reduced in CAD patients with a significantly lower tissue levels of abdominal than epicardial fat depots demonstrated. CONCLUSION: Abdominal adiposity may play more significant role than epicardial fat in the pathogenesis of coronary atherosclerosis.
Assuntos
Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Doença da Artéria Coronariana/metabolismo , Mediadores da Inflamação/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Doença da Artéria Coronariana/etiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismoRESUMO
BACKGROUND: Cancer survivors experience muscular weakness and reduced mobility, thereby compromising quality of life. This investigation utilized moderate prescriptive exercise to improve upper- and lower-body muscular fitness, flexibility, depression and quality of life in cancer patients. PATIENTS AND METHODS: One hundred and thirty-five breast and prostate cancer survivors received cancer and medical history screening and a medical examination, as well as assessments of muscular strength (handgrip dynamometer) and endurance (bench press, lateral pull-down, leg press, shoulder press and curl-up crunch test), flexibility (Modified Sit and Reach), depression (Beck Depression Inventory) and quality of life (Quality of Life Index). Following the exercise assessments, cancer survivors trained in resistance exercise for 6 months during treatment or following treatment based on their results from the assessments and health status. RESULTS: Cancer survivors following treatment showed significant (P = 0.006) improvements in upper-body muscular endurance (+46.8%), lower-body muscular endurance (+67.1%), core muscular endurance (+32.5%) and flexibility (+6.2%), with concomitant improvements (P = 0.013) in depression (-25.6%) and total quality of life (+7.2%). Cancer survivors during treatment showed significant (P = 0.012) improvements in upper-body muscular endurance (+79.1%) and lower-body muscular endurance (+49.7%) while maintaining core endurance and flexibility in conjunction with improvements (P = 0.022) in depression (-43.0%) and quality of life (+11.5%). CONCLUSIONS: Moderate-intensity individualized prescriptive exercise is a safe and efficacious means to augment muscular function and improve the quality of life of cancer survivors.
Assuntos
Neoplasias da Mama/fisiopatologia , Músculo Esquelético/fisiopatologia , Neoplasias da Próstata/fisiopatologia , Qualidade de Vida , Levantamento de Peso , Idoso , Neoplasias da Mama/psicologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/psicologiaRESUMO
UNLABELLED: The effectiveness of extended thymectomy for the treatment of myasthenia gravis is well documented. Most of the postoperative complications have been related to respiratory distress or wound complication, but chylothorax following thymectomy has been reported as a rare complication. From January 1995 to December 2004, 217 patients underwent extended thymectomy for myasthenia gravis at Taipei Veterans General Hospital. Three cases (1.38%) developed chylothorax after operation. Injury to the unseen division of the mediastinal lymphatics and branches from the thoracic duct during extensive dissection of perithymic fat tissue, which is seldom performed in classical thymothymectomy procedures, may have been the main cause of this complication. Two of the cases received conservative treatment and recovered uneventfully. The other patient (0.46%) underwent ligation of the thoracic duct 3 months later, which also resulted in the complication being cured. CONCLUSIONS: Post-thymectomy chylothorax is rare and seems to be related to extended thymectomy. Even a small invasive procedure such as VATS for extended thymectomy formyasthenia gravis could be complicated by chylothorax. We recommend that if chylothorax develops after thymectomy, conservative treatment is the treatment of choice; however, thoracic duct ligation is a useful method for treating long-term unhealed chylothorax.