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1.
Indian J Pathol Microbiol ; 64(4): 633-637, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34673578

RESUMEN

BACKGROUND: Tanycytic ependymoma (TE) (WHO grade II) is a rare and morphologically distinct variant of ependymoma with only 77 cases reported worldwide so far. Variable clinical and radio-pathological features lead to misdiagnosis as WHO grade 1 tumors. On imaging, differentials of either schwannoma, meningioma, low-grade glial (like angiocentric glioma), or myxopapillary ependymoma are considered. In this study, we aim to discuss clinical, radiological, and pathological features of TE from our archives. METHOD: We report clinicopathological aspects of six cases of TE from archives of tertiary care center between 2016 and 2018. Detailed histological assessment in terms of adequate tissue sampling and immunohistochemistry was done for each case. RESULT: The patient's age ranged between 10 and 53 years with a slight male predilection. Intraspinal location was seen in two cases (intramedullary and extramedullary), three cases were cervicomedullary (intramedullary), and one was intracranial. One case was associated with neurofibromatosis type 2. Four cases mimicked as either schwannoma or low-grade glial tumor on squash smears. On imaging, ependymoma as differential was kept in only two cases and misclassified remaining either as low-grade glial or schwannoma. DISCUSSION: In initial published reports, the spine is the most common site (50.4%) followed by intracranial (36.4%) and cervicomedullary (3.9%). They have also highlighted the challenges in diagnosing them intraoperatively and radiologically. Treatment is similar to conventional ependymoma if diagnosed accurately. A multidisciplinary approach with the integration of neurosurgeon, neuroradiologist, and neuropathologist is required for accurate diagnosis and better treatment of patients.


Asunto(s)
Encefalopatías/fisiopatología , Ependimoma/diagnóstico , Ependimoma/fisiopatología , Ependimoma/terapia , Inmunohistoquímica/métodos , Neoplasias Glandulares y Epiteliales/fisiopatología , Enfermedades de la Médula Espinal/fisiopatología , Adolescente , Adulto , Encefalopatías/diagnóstico por imagen , Niño , Ependimoma/diagnóstico por imagen , Femenino , Técnicas Histológicas , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/diagnóstico por imagen , Enfermedades de la Médula Espinal/diagnóstico por imagen , Adulto Joven
2.
Curr Biol ; 28(20): 3220-3228.e6, 2018 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-30293715

RESUMEN

Cancers develop in a complex mutational landscape. Genetic models of tumor formation have been used to explore how combinations of mutations cooperate to promote tumor formation in vivo. Here, we identify lactate dehydrogenase (LDH), a key enzyme in Warburg effect metabolism, as a cooperating factor that is both necessary and sufficient for epidermal growth factor receptor (EGFR)-driven epithelial neoplasia and metastasis in a Drosophila model. LDH is upregulated during the transition from hyperplasia to neoplasia, and neoplasia is prevented by LDH depletion. Elevated LDH is sufficient to drive this transition. Notably, genetic alterations that increase glucose flux, or a high-sugar diet, are also sufficient to promote EGFR-driven neoplasia, and this depends on LDH activity. We provide evidence that increased LDHA expression promotes a transformed phenotype in a human primary breast cell culture model. Furthermore, analysis of publically available cancer data showed evidence of synergy between elevated EGFR and LDHA activity linked to poor clinical outcome in a number of human cancers. Altered metabolism has generally been assumed to be an enabling feature that accelerates cancer cell proliferation. Our findings provide evidence that sugar metabolism may have a more profound role in driving neoplasia than previously appreciated.


Asunto(s)
Proteínas de Drosophila/metabolismo , Receptores ErbB/metabolismo , Regulación Neoplásica de la Expresión Génica , Hidroliasas/metabolismo , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias/metabolismo , Neoplasias/fisiopatología , Receptores de Péptidos de Invertebrados/metabolismo , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Drosophila melanogaster , Humanos
3.
Wien Klin Wochenschr ; 130(19-20): 575-580, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30178070

RESUMEN

BACKGROUND: Preoperative hyponatremia and thrombocytosis are associated with perioperative morbidity in patients with epithelial ovarian cancer (EOC). The aim of the present study was to evaluate preoperative hyponatremia and thrombocytosis as prognostic parameters in patients with EOC. METHODS: In a retrospective cohort study, serum levels of sodium and thrombocyte counts were evaluated in 498 patients with EOC. Data were extracted from the prospectively maintained database. Results were correlated with clinicopathological parameters and patient survival. RESULTS: Mean (standard deviation) overall pretherapeutic serum sodium levels and thrombocyte counts in patients with EOC were 138.8 (2.9) mmol/l and 340.1 (122.6)â€¯× 103/µl, respectively. Hyponatremia (serum sodium levels ≤ 134 mmol/l) was found in 33 (6.7%) patients and thrombocytosis (thrombocytes ≥ 450/µl) in 88 (17.7%) patients. Serum sodium levels were associated with the presence or absence of residual tumor tissue after primary surgery. Thrombocyte counts were associated with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) tumor stage, presence/absence of residual tumor, histological grade and histological type. Patients with thrombocytosis presented with advanced tumor stage, a higher rate of postoperative residual tumor mass, higher tumor grade, and a higher rate of serous ovarian cancer. In a multivariate logistic regression analysis, only the established clinicopathological parameters but not serum sodium and thrombocyte count were independent predictors of patient overall survival. CONCLUSION: Preoperative hyponatremia and thrombocytosis are not useful as additional independent prognostic parameters in patients with EOC.


Asunto(s)
Carcinoma Epitelial de Ovario , Hiponatremia , Neoplasias Ováricas , Trombocitosis , Carcinoma Epitelial de Ovario/fisiopatología , Femenino , Humanos , Hiponatremia/etiología , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Ováricas/fisiopatología , Pronóstico , Estudios Retrospectivos , Trombocitosis/etiología
4.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 45(3): 98-108, jul.-sept. 2018. tab, graf
Artículo en Español | IBECS | ID: ibc-180039

RESUMEN

Introducción: Las lesiones inflamatorias mamarias precisan con frecuencia de estudio histopatológico por su capacidad de imitar a los tumores mamarios malignos. El objetivo es proponer una secuencia diagnóstica de las inflamaciones mamarias benignas crónicas. Material y método: Se han revisado en la literatura los métodos y algoritmos diagnósticos de las mastitis crónicas. Resultados: Se propone un algoritmo diagnóstico para los procesos inflamatorios crónicos mamarios. Requiere determinar el patrón histopatológico inflamatorio y su localización, así como un estudio microbiológico apropiado. Posteriormente puede precisar de nuevas pruebas bioquímicas y serológicas orientadas por una correlación clinicopatológica para establecer un diagnóstico específico. Discusión: No se han identificado en la literatura otros algoritmos diagnósticos avalados por estudios de alto nivel de evidencia. Los patrones histopatológicos no son uniformes. Conclusiones: El diagnóstico etiológico precisa identificar patrones histopatológicos inflamatorios benignos y su localización, un estudio microbiológico y pruebas orientadas por correlación clinicopatológica. Se precisan estudios de investigación con niveles de evidencia altos


Introduction: Inflammatory breast lesions require histopathological study due to their ability to clinically and radiologically mimic malignant mammary tumours. The objective is to propose a diagnostic technique for benign chronic inflammatory processes of the breast. Material and methods: We reviewed the literature on the diagnostic methods used in chronic mastitis. Results: We propose a diagnostic algorithm for chronic inflammatory processes of the breast. The aetiological diagnosis requires identifying benign inflammatory histopathologic patterns and locations, and microbiological study. New biochemical and serological tests oriented by clinicopathological correlation may then be required to establish a specific diagnosis. Discussion: No diagnostic algorithms based on studies with a high level of evidence have been identified. No uniformity in histopathologic patterns has been described. Conclusions: The etiologic diagnosis requires identifying benign inflammatory histopathologic patterns and locations, microbiological study and tests oriented by clinicopathological correlation. There is a lack of studies with a high level of evidence


Asunto(s)
Humanos , Femenino , Mastitis/etiología , Algoritmos , Granuloma/diagnóstico , Eritema Nudoso/etiología , Neoplasias Glandulares y Epiteliales/fisiopatología , Mastitis/patología , Mastitis/diagnóstico , Necrosis/clasificación , Necrosis/diagnóstico , Infecciones/complicaciones
5.
Chem Biol Interact ; 292: 24-29, 2018 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-29932878

RESUMEN

Elevated cyclooxygenase-2 (COX-2) closely associates with tumor progression and distant metastasis in various human cancers. However, the role of COX-2 in epithelial ovarian cancer (EOC), and its mechanistic details, remain poorly understood. In the present study, we tested hypothesis that COX-2 induces loss of expression of E-cadherin, with resulting promotion of cancer cells' invasiveness in ovarian cancer. First, we observed an inverse relationship between COX-2 and E-cadherin expression as COX-2 was enhanced but E-cadherin was decreased in surgically-resected specimens of EOC. Depletion of COX-2, by celecoxib treatment, resulted in attenuated nuclear translocation of Snail, and, in turn, significantly increased E-cadherin in EOC cell line SKOV3, which was established to be due to the reduced binding of Snail onto E-cadherin promoter. Such COX-2 inhibition resulted in reduced invasion of EOC cells, similar to what was achieved through Snail silencing in SKOV as well as ES-2 EOC cells. These results suggest that COX-2-Snail signaling plays a critical role in regulation of E-cadherin and might provide insights into mechanisms for paracrine inflammation-mediated aggressiveness in EOC.


Asunto(s)
Cadherinas/genética , Cadherinas/metabolismo , Celecoxib/farmacología , Ciclooxigenasa 2/metabolismo , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Ováricas/fisiopatología , Factores de Transcripción de la Familia Snail/metabolismo , Western Blotting , Cadherinas/antagonistas & inhibidores , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Regulación hacia Abajo , Femenino , Humanos , Inflamación/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas , Transducción de Señal/efectos de los fármacos
6.
Radiat Res ; 190(2): 142-150, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29781764

RESUMEN

Astronauts traveling in deep space are exposed to high-charge and energy (HZE) particles from galactic cosmic rays. We have previously determined that irradiation of adult female mice with iron HZE particles induces DNA double-strand breaks, oxidative damage and apoptosis in ovarian follicles, causing premature ovarian failure. These effects occur at lower doses than with conventional photon irradiation. Ovarian failure with resultant loss of negative feedback and elevated levels of gonadotropin hormones is thought to play a role in the pathophysiology of ovarian cancer. Therefore, we hypothesized that charged-iron-particle irradiation induces ovarian tumorigenesis in mice. In this study, three-month-old female mice were exposed to 0 cGy (sham) or 50 cGy iron ions and aged to 18 months. The 50 cGy irradiated mice had increased weight gain with age and lack of estrous cycling, consistent with ovarian failure. A total of 47% and 7% of mice irradiated with 50 cGy had unilateral and bilateral ovarian tumors, respectively, whereas 14% of mice in the 0 cGy group had unilateral tumors. The tumors contained multiple tubular structures, which were lined with cells positive for the epithelial marker cytokeratin, and had few proliferating cells. In some tumors, packets of cells between the tubular structures were immunopositive for the granulosa cell marker FOXL2. Based on these findings, tumors were diagnosed as tubular adenomas or mixed tubular adenoma/granulosa cell tumors. In conclusion, charged-iron-particle-radiation induces ovarian tumors in mice, raising concerns about ovarian tumors as late sequelae of deep space travel in female astronauts.


Asunto(s)
Radiación Cósmica/efectos adversos , Medio Ambiente Extraterrestre , Hierro/efectos adversos , Neoplasias Glandulares y Epiteliales/etiología , Neoplasias Inducidas por Radiación/etiología , Neoplasias Ováricas/etiología , Animales , Astronautas , Peso Corporal/efectos de la radiación , Carcinoma Epitelial de Ovario , Daño del ADN , Relación Dosis-Respuesta en la Radiación , Células Epiteliales/patología , Células Epiteliales/efectos de la radiación , Ciclo Estral/efectos de la radiación , Femenino , Ratones , Ratones Endogámicos C57BL , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Inducidas por Radiación/genética , Neoplasias Inducidas por Radiación/patología , Neoplasias Inducidas por Radiación/fisiopatología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/fisiopatología , Ovario/patología , Ovario/efectos de la radiación
7.
Gynecol Oncol ; 149(2): 263-269, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29550182

RESUMEN

OBJECTIVE: To investigate whether patients' altered body composition (measured with bioimpedentiometry), due to a poor nutritional status, predicts the incidence of no residual disease at primary debulking and the risk of complications in patients with newly-diagnosed advanced epithelial ovarian cancer (EOC). METHODS: Data regarding patients with newly-diagnosed stage IIIC-IV EOC undergoing elective nutritional assessment between December 2016 and March 2017, were prospectively collected. Bioelectrical impedance analysis (BIA) with measurement of BIA-derived phase angle [PhA] at 50KHz, was accomplished. Only patients with disease which was considered resectable at staging laparoscopy were submitted to open primary cytoreduction. The rate of residual tumor (RT)=0 and the incidence of complications were assessed. RESULTS: Seventy patients were included. Fifty-two of them were submitted to primary cytoreduction (74.3%) and 48 (68.6% of the entire cohort, 92.3% of those who underwent primary debulking) had RT=0 at the end of surgery. Median values of PhA were significantly lower in patients with RT>vs. =0 (4.7, range: 3.6-5.8 vs. 5.3, range: 4.2-6.8; p=0.001). Twenty-four (out of the 52 operated) patients (46.2%) developed at least one complication. PhA was significantly lower in patients with vs. without complications (5, range: 3.6-6.4, vs. 5.4, range 4.5-6.8; p=0.03). After multivariable analysis, Fagotti score and PhA were the only independent predictors of residual disease (OR:13.56; 95%CI:1.33-137.6; p=0.027 and 9.24; 1.16-73.43; p=0.036, respectively) and of any complication (OR:4.9;95%CI:1.17-20.6; p=0.03 and 7.27; 1.45-36.4; p=0.01, respectively). CONCLUSIONS: Derangement of body composition (likely due to disease-related malnutrition) expressed as a low phase angle, is an independent predictor of residual disease and peri-operative complications at the time of upfront cytoreduction for advanced EOC.


Asunto(s)
Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Glandulares y Epiteliales/cirugía , Estado Nutricional/fisiología , Neoplasias Ováricas/fisiopatología , Neoplasias Ováricas/cirugía , Adulto , Anciano , Composición Corporal , Carcinoma Epitelial de Ovario , Estudios de Cohortes , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Procedimientos Quirúrgicos de Citorreducción/métodos , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasia Residual , Evaluación Nutricional , Periodo Preoperatorio , Resultado del Tratamiento
8.
Vitam Horm ; 107: 453-472, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29544640

RESUMEN

Follicular development and ovulation are complex development processes that are regulated by multiple, interacting pathways and cell types. The oocyte, cumulus cells, granulosa cells, and theca cells communicate to impact follicular development and ovulation. Many hormones and cytokines control intracellular regulatory networks and transcription factors, some of which are cell type specific. Molecular biology approaches and mutant mouse models have contributed immensely to our knowledge of what genes and signaling cascades impact each stage of follicular development and ovulation, and how the alteration of gene expression profiles and the activation of specific signaling pathways can impact ovarian cancer development in ovarian surface epithelial cells as well as granulosa cells. This chapter explores how pathways controlling normal follicle development and ovulation can be diverted to abnormal development.


Asunto(s)
Fase Folicular , Modelos Biológicos , Oogénesis , Neoplasias Ováricas/fisiopatología , Ovario/fisiopatología , Ovulación , Animales , Carcinoma Epitelial de Ovario , Femenino , Predisposición Genética a la Enfermedad , Tumor de Células de la Granulosa/genética , Tumor de Células de la Granulosa/patología , Tumor de Células de la Granulosa/fisiopatología , Humanos , Infertilidad Femenina/etiología , Mutación , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Ovario/patología , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo
9.
PLoS One ; 12(10): e0186725, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29059209

RESUMEN

OBJECTIVE: To assess whether neoadjuvant chemotherapy (NACT) is superior to primary debulking surgery (PDS) with regard to optimal cytoreduction, peri-operative morbidity, mortality, and quality of life (QOL) in advanced epithelial ovarian cancer (EOC). METHODS: We searched the PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Registers of Clinical Trials for randomized controlled trials (RCTs) comparing NACT to PDS in women with Federation of International Gynaecologists and Obstetricians stage Ⅲ-Ⅳ EOC. RevMan 5.3 software was utilized for statistical analysis. RESULTS: Four RCTs involving 1,607 women with advanced EOC were included. Compared with PDS, NACT provided a higher rate of complete cytoreduction (risk ratio [RR], 1.95; 95% confidence interval [CI], 1.33 to 2.87), optimal cytoreduction (RR: 1.61 [95%CI: 1.05 to 2.47]), but there was no significant difference in residual disease 0-1 cm (p = 0.49). NACT was associated with lower peri-operative morbidity with respect to infection (RR: 0.30 [95% CI: 0.16 to 0.56]), gastrointestinal fistula (RR: 0.24 [95% CI: 0.06 to 0.95]), any grade 3 or 4 adverse event (RR: 0.29 [95% CI: 0.11 to 0.78]), and less post-surgical death within 28 days (RR: 0.14 [95% CI: 0.04 to 0.49]). NACT provided better QOL in terms of fatigue (weight mean difference [WMD], -3.28; [95% CI: -3.99 to -2.57]), role functioning (WMD: 5.29 [95% CI: 4.44 to 6.14]), emotional functioning (WMD: 6.19 [95% CI: 5.57 to 6.82]), and cognitive functioning (WMD: 1.02 [95% CI: 0.43 to 1.61]) at 6-month follow-up compared with PDS. CONCLUSIONS: NACT is associated with superior optimal cytoreduction, lower peri-operative morbidity as well as post-surgical mortality, and better QOL compared to initial surgery in patients with advanced EOC. Future research should focus on improving the efficacy of NACT.


Asunto(s)
Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Carcinoma Epitelial de Ovario , Quimioterapia Adyuvante , Femenino , Humanos , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Ováricas/fisiopatología , Calidad de Vida , Resultado del Tratamiento
10.
Interact Cardiovasc Thorac Surg ; 25(2): 167-172, 2017 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-29050375

RESUMEN

Tumours show an increased interstitial fluid pressure, which correlates with various pathophysiological features. Moreover, interstitial fluid pressure is a prognostic factor for cervical and lung cancer. However, there have been no reports on the usefulness of measuring interstitial fluid pressure in thymic epithelial tumours. Therefore, this study aimed to examine the relationship between interstitial fluid pressure and the clinicopathological characteristics of thymic epithelial tumours. Interstitial fluid pressure was prospectively measured at the centre of the tumour using a 1-Fr Mikro-Tip sensor catheter in 44 patients with thymic epithelial tumours, 40 with thymomas and 4 with thymic carcinomas. Data from these 44 patients were analysed for correlations between interstitial fluid pressure and clinicopathological and demographic factors including sex, age, tumour size, World Health Organization histological subtypes, myasthenia gravis, capsular invasion, mediastinal pleura invasion, lung invasion, pericardium invasion, dissemination, Masaoka-Koga stage, maximal standardized uptake value and recurrence-free survival (RFS). The mean interstitial fluid pressure was 11.3 mmHg; interstitial fluid pressure was significantly correlated with maximal standardized uptake value, lung invasion, dissemination and Masaoka-Koga stage. Low interstitial fluid pressure (≤14 mmHg) showed a tendency for better RFS compared with high interstitial pressure (P = 0.053). Lung invasion, dissemination and Masaoka-Koga stage were correlated with RFS in univariable analysis; lung invasion was selected as an independent prognostic factor in multivariable analysis. On the basis of these results, interstitial fluid pressure of thymic epithelial tumours has been shown to correlate with their clinicopathological features.


Asunto(s)
Líquido Extracelular , Estadificación de Neoplasias/métodos , Neoplasias Glandulares y Epiteliales/diagnóstico , Neoplasias del Timo/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/fisiopatología , Tomografía de Emisión de Positrones , Presión , Estudios Prospectivos , Neoplasias del Timo/fisiopatología
11.
Endocr Regul ; 51(2): 117-128, 2017 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-28609287

RESUMEN

Thyrostimulin is a glycoprotein heterodimer of GPA2 and GPB5, first described in 2002. It is involved in the physiological function of several tissues. Moreover, evidence points towards the ability of thyrostimulin's individual monomers to induce a biological effect, which could denote the circulatory/systemic effects of the molecule when found in higher concentrations. From the evolutionary point of view, thyrostimulin shares a binding epitope with the thyroid-stimulating hormone for the thyroid stimulating hormone receptor, whilst possessing affinity for another unique binding site on the same receptor. Although thyrostimulin can be involved in the hypothalamicpituitary- thyroid axis, its presence in various tissues in an eclectic array of different species renders it multifunctional. From weight loss via increasing metabolic rate to progression of cancer in human ovaries, it is certainly not a signaling molecule to overlook. Furthermore, thyrostimulin has been implicated in bone metabolism, acute illness, and reproductive function. In summary, to our knowledge, this is the first review dealing with the physiological role of thyrostimulin and its potential applications in the clinical practice.


Asunto(s)
Glicoproteínas/metabolismo , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Ováricas/metabolismo , Receptores de Tirotropina/metabolismo , Enfermedad Aguda , Animales , Carcinoma Epitelial de Ovario , Femenino , Glicoproteínas/química , Glicoproteínas/fisiología , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Ratones , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Ováricas/fisiopatología , Receptores de Tirotropina/fisiología , Reproducción/fisiología , Glándula Tiroides/metabolismo , Glándula Tiroides/fisiología , Pérdida de Peso/fisiología
12.
Semin Cancer Biol ; 44: 67-71, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28450177

RESUMEN

Epithelial ovarian cancer is a highly lethal disease, which is usually diagnosed at a late stage with extensive metastases in the abdominal cavity. Ovarian cancer either develops from the ovarian surface epithelium (OSE) or from serous intra-epithelial carcinoma (STIC). Primary therapy consists of debulking surgery and platinum based chemotherapy. The success of debulking surgery depends on surgical skills but also on the gene signature of the tumour. Debulking surgery combined with first line platinum based chemotherapy, frequently leads to complete remission. However, most ovarian cancers relapse. Once the disease has relapsed, the interval between subsequent therapies decreases steadily due to rapid progression and therapy resistance. Research on therapy resistance of ovarian cancer is frequently devoted to genetic alterations in cancer cells, leading to drug inactivation, enhanced DNA repair mechanisms and intracellular pathway derangements. However the knowledge of ovarian cancer stem cells (OCSC) and the role they play in the development of cancer and therapy resistance is sparse. In this review current knowledge on the characteristics of OCSCs and the micro environmental mechanisms leading to the development or activation of OCSCs resulting in ovarian cancer is reviewed. Moreover the role of OCSC in both surgical and systemic therapy resistance and the relation with epithelial mesenchymal transformation (EMT) is discussed, as are micro-environmental signals leading to OCSC or EMT activation.


Asunto(s)
Resistencia a Antineoplásicos/genética , Transición Epitelial-Mesenquimal/genética , Neoplasias Glandulares y Epiteliales/terapia , Células Madre Neoplásicas/patología , Neoplasias Ováricas/terapia , Carcinoma Epitelial de Ovario , Femenino , Humanos , Neoplasias Glandulares y Epiteliales/epidemiología , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Neoplasias Ováricas/fisiopatología
13.
Cancer Epidemiol Biomarkers Prev ; 26(1): 104-109, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27672055

RESUMEN

BACKGROUND: Pelvic inflammatory disease (PID) has been proposed as a risk factor for ovarian cancer. However, the existing literature on the association between PID and ovarian cancer risk is inconclusive, and only few cohort studies have been conducted. METHODS: Using nationwide Danish registries, we conducted a population-based cohort study including all women from the birth cohorts 1940 to 1970 in Denmark during 1978-2012 (n = 1,318,929) to investigate the association between PID and subsequent risk of epithelial ovarian cancer. Among women in the cohort, 81,281 women were diagnosed with PID and 5,356 women developed ovarian cancer during follow-up through 2012. Cox regression models were used to estimate HRs and 95% confidence intervals (CI) for the association between PID and ovarian cancer, both overall and according to histotype. RESULTS: For ovarian cancer overall, we observed no association with PID (HR, 1.05; 95% CI, 0.92-1.20). However, in histotype-specific analyses, we found a statistically significantly increased risk of serous ovarian cancer among women with PID (HR, 1.19; 1.00-1.41; P = 0.047). Conversely, PID was not convincingly associated with risk of any of the other histotypes of ovarian cancer. CONCLUSIONS: PID was associated with a modestly increased risk of serous ovarian cancer, but not other histotypes. IMPACT: Our results indicate that PID is not a strong risk factor for ovarian cancer. Whether PID is slightly associated with risk of serous ovarian cancer has to be confirmed in other studies. Cancer Epidemiol Biomarkers Prev; 26(1); 104-9. ©2016 AACR.


Asunto(s)
Transformación Celular Neoplásica/patología , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/patología , Enfermedad Inflamatoria Pélvica/epidemiología , Enfermedad Inflamatoria Pélvica/patología , Adulto , Factores de Edad , Carcinoma Epitelial de Ovario , Estudios de Cohortes , Intervalos de Confianza , Dinamarca , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/epidemiología , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Ováricas/fisiopatología , Enfermedad Inflamatoria Pélvica/fisiopatología , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo
14.
Support Care Cancer ; 25(3): 795-800, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27771784

RESUMEN

PURPOSE: The aim of this study was to evaluate whether body weight changes in patients undergoing chemotherapy for epithelial ovarian cancer (EOC) influence progression-free survival (PFS) and overall survival (OS). METHODS: An analysis of 190 patients diagnosed with ovarian cancer after first-line chemotherapy was conducted. Changes in body weight were assessed by comparing measurements at baseline to those of the third and sixth cycles of chemotherapy. PFS and OS were calculated with the Kaplan-Meier method and multivariate Cox model. RESULTS: Significant reduction in body weight in advanced EOC was observed with no changes in early EOC. Significant differences in PFS were observed in advanced EOC patients that lost more than 5 % of their body weight (6 months), maintained weight (13 months), or gained more than 5 % of their body weight (15 months). Similarly, significant differences in OS were noted in advanced EOC at the following time points: 24.3, 42.4, and 66.2 months. No effect was reported for early EOC patients. The multivariate Cox analysis showed significant body weight changes from the first to the sixth chemotherapy cycle for PFS (HR = 0.97; 95 % CI 0.95-0.99) and OS (HR = 0.94; 95 % CI 0.91-0.97) as well as from the first to the third chemotherapy cycle for OS (HR = 0.93; 95 % CI 0.88-0.98). CONCLUSIONS: Body weight changes can be recognized as a prognostic factor for PFS and OS in advanced EOC patients undergoing chemotherapy. Weight loss is associated with poorer survival while weight gain improved outcomes.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Peso Corporal/fisiología , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/fisiopatología , Adulto , Anciano , Carcinoma Epitelial de Ovario , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/fisiopatología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Aumento de Peso/fisiología , Pérdida de Peso/fisiología
15.
Artículo en Inglés | MEDLINE | ID: mdl-27925846

RESUMEN

The primary objective of this study is to understand the profiles, sources and cytotoxic effects of atmospheric polycyclic aromatic hydrocarbons (PAHs), which are closely related to urban air contamination and public health, in urban roadside environments. On-road sampling campaigns were conducted from 2014 to 2015 at three urban road sites in Hangzhou, China. Sixteen gaseous and particulate matter (PM) 2.5-bound PAHs were identified and quantified using gas chromatography-mass spectrometry (GC-MS). The total PAH concentrations at the three sites ranged from 750 to1142 ng/m3 and 1050 to 1483 ng/m3 in summer and winter, respectively. Low molecular weight PAHs were the most abundant compounds (77-86%) and primarily existed in gas phase. The concentrations and phase distributions of high molecular weight PAHs were varied at three sites due to the differences in traffic volume, vehicle composition, engine loading, and nearby artificial activity. Diagnostic ratios of the principal mass (m/z,178, 202, 228 and 276) parent PAHs were statistically described to determine the PAH sources to urban roadsides; principal component analysis (PCA) was applied to apportion the sources. The results indicated that high- and low-temperature fuel processes, as well as residential and industrial emissions, were major contributors to roadside PAHs. The cytotoxic potential of the roadside PAHs was evaluated using a human epithelial lung cell line (A549). Cell viability was measured after a direct exposure to PAH extract. The results reflected the profiles of roadside PAHs at the three sites. The cytotoxicity of reference PAHs was evaluated to provide further insights into the cytotoxic potential of PAHs. We found that low molecular weight PAHs, which are less cytotoxic compounds, synergistically promoted the lethal effect of cytotoxic compounds, posing a potential threat to public health.


Asunto(s)
Contaminantes Atmosféricos/toxicidad , Monitoreo del Ambiente/métodos , Neoplasias Glandulares y Epiteliales/inducido químicamente , Material Particulado/toxicidad , Hidrocarburos Policíclicos Aromáticos/toxicidad , Emisiones de Vehículos/toxicidad , Contaminantes Atmosféricos/análisis , Línea Celular Tumoral/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , China , Ciudades , Cromatografía de Gases y Espectrometría de Masas , Humanos , Neoplasias Glandulares y Epiteliales/fisiopatología , Material Particulado/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Estaciones del Año , Emisiones de Vehículos/análisis
16.
Ann Oncol ; 27(11): 1994-2004, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27502723

RESUMEN

Since the last two decades, the feasibility of fertility-sparing surgery (FSS) in early-stage epithelial ovarian cancer (EOC) has been explored by several teams and is reconsidered in this systematic review undertaken using the PRISMA guidelines. Borderline ovarian tumours and non-EOCs were excluded. This review comprises 1150 patients and 139 relapsing patients reported by 21 teams. This conservative treatment can be safely carried out for stage IA and IC grade 1 and 2 disease and stage IC1 according to the new FIGO staging system. Nevertheless, the number of patients reported with grade 2 disease is too small to definitively confirm whether FSS is safe in this subgroup. For patients with 'less favourable' prognostic factors (grade 3 or stage IC3 disease), the safety of FSS could not be confirmed, but patients should be informed that radical treatment probably may not necessarily improve their oncological outcome, because the poorest survival observed could be related to the natural history of the disease itself and not specifically to the use of conservative therapy. FSS could probably be considered in stage I clear-cell tumours but should remain contraindicated for stage II/III disease (whatever the histologic subtype). As the disease stage and the histologic data (tumour type and grade) are crucial to patient selection for this treatment, this implies careful and mandatory complete surgical staging surgery in this context and a pathological analysis (or review) of the tumour by an expert pathologist.


Asunto(s)
Preservación de la Fertilidad , Fertilidad/fisiología , Recurrencia Local de Neoplasia/cirugía , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Ováricas/cirugía , Carcinoma Epitelial de Ovario , Femenino , Humanos , Oncología Médica , Recurrencia Local de Neoplasia/fisiopatología , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Ováricas/fisiopatología
17.
Eur Rev Med Pharmacol Sci ; 20(10): 1986-92, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27249596

RESUMEN

OBJECTIVE: Epithelial ovarian cancer is a highly fatal gynecologic malignancy with a poor prognosis. Therefore, identification of new modifiable prognostic factors is important. Due to the fact that the effect of body weight changes during chemotherapy for EOC is still not very well known we aimed to describe, considering evidence, role of body weight changes in relation to survival. MATERIALS AND METHODS: Between October 2014 and August 2015 we systematically searched the following databases: Medline, Scopus, Web of Science and EMBASE to identify the studies describing the influence of body weight changes on survival in patients undergoing chemotherapy for EOC. RESULTS: We identified 601 potentially relevant publications, however finally only one article was included for data extraction and analysis. The overall survival in the selected paper was significantly associated with body weight changes during the first-line chemotherapy. Nevertheless, no influence on progression free survival was found. CONCLUSIONS: The analyzed data provides initial evidence, showing poorer overall survival  associated with body weight loss and improved overall survival associated with body weight gain during primary chemotherapy for epithelial ovarian cancer. Prospective and retrospective trials are an urgent calling to confirm this conclusion.


Asunto(s)
Peso Corporal , Neoplasias Glandulares y Epiteliales , Neoplasias Ováricas , Carcinoma Epitelial de Ovario , Femenino , Humanos , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/fisiopatología , Estudios Retrospectivos , Análisis de Supervivencia
18.
Curr Biol ; 26(4): 419-27, 2016 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-26853367

RESUMEN

Cell competition is a homeostatic process in which proliferating cells compete for survival. Elimination of otherwise normal healthy cells through competition is important during development and has recently been shown to contribute to maintaining tissue health during organismal aging. The mechanisms that allow for ongoing cell competition during adult life could, in principle, contribute to tumorigenesis. However, direct evidence supporting this hypothesis has been lacking. Here, we provide evidence that cell competition drives tumor formation in a Drosophila model of epithelial cancer. Cells expressing EGFR together with the conserved microRNA miR-8 acquire the properties of supercompetitors. Neoplastic transformation and metastasis depend on the ability of these cells to induce apoptosis and engulf nearby cells. miR-8 expression causes genome instability by downregulating expression of the Septin family protein Peanut. Cytokinesis failure due to downregulation of Peanut is required for tumorigenesis. This study provides evidence that the cellular mechanisms that drive cell competition during normal tissue growth can be co-opted to drive tumor formation and metastasis. Analogous mechanisms for cytokinesis failure may lead to polyploid intermediates in tumorigenesis in mammalian cancer models.


Asunto(s)
Carcinogénesis , Transformación Celular Neoplásica , Drosophila melanogaster/crecimiento & desarrollo , Neoplasias Glandulares y Epiteliales/etiología , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Glandulares y Epiteliales/fisiopatología , Receptores de Péptidos de Invertebrados/genética , Receptores de Péptidos de Invertebrados/metabolismo
19.
Support Care Cancer ; 24(6): 2619-25, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26732766

RESUMEN

PURPOSE: This study was conducted to evaluate the dietary intake at different time points of the chemotherapeutic cycle. METHODS: Fifty-five ovarian cancer patients receiving at least 2 cycles of chemotherapy were deemed eligible for this study, of which 41 participants completed the study. Anthropometrical measurements and Subjective Global Assessment were used to estimate nutritional status. The dietary intake was evaluated by 3-day food records: 3 days prior to, the day of, and the following day after chemotherapy. RESULTS: Mean energy intake was the lowest on the day of chemotherapy and the highest 3 days before treatment (mean difference, 413.8 kcal; p < 0.001). Similarly, some vitamins and macro- and micronutrients (K, Ca, vit D, folate, vit C) failed to reach 50 % of the recommended dietary allowances. When dividing patients into BMI categories, the energy intake per kilogram of body weight, in the normal-weight patients, was statistically higher than that in overweight and obese subjects (23.6 vs. 20.9 vs. 12.3 kcal, respectively; p = 0.0015). Similarly, the statistically significant differences were observed by the intake of fats (0.80 vs. 0.69 vs. 0.39 g, p = 0.0283) and carbohydrates (3.52 vs. 3.05 vs. 1.71 g, p = 0.0004). CONCLUSIONS: Dietary intake varies in the cycle of chemotherapy, with the lowest intake at the day of cytotoxic treatment and the highest before the next chemotherapy. Further studies evaluating dietary intake in patients undergoing chemotherapy should include in the protocol the exact time point of dietary assessment. The intake of energy, fats, and carbohydrates differs significantly across BMI categories.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Dieta , Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Peso Corporal , Carcinoma Epitelial de Ovario , Esquema de Medicación , Ingestión de Energía , Femenino , Humanos , Micronutrientes/administración & dosificación , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Glandulares y Epiteliales/fisiopatología , Estado Nutricional , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/fisiopatología , Vitaminas/administración & dosificación
20.
Clin Nucl Med ; 41(1): 8-14, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26284773

RESUMEN

PURPOSE: The aim of this study was to investigate the value of morphologic, functional, and metabolic biomarkers acquired concurrently at PET/MRI in patients with thymic epithelial tumors. PATIENTS AND METHODS: During 1 year, 9 patients with suspected thymic epithelial tumors at contrast-enhanced chest CT were prospectively enrolled and underwent preoperative 18F-FDG PET/MRI. Two chest radiologists prospectively reviewed the CT and MRI scans of PET/MRI in consensus, and 2 nuclear physicians reviewed the PET images. Visual assessment of the tumor morphology, functional biomarkers such as apparent diffusion coefficient from diffusion-weighted images, and metabolic biomarkers (including SUVmax, metabolic tumor volume, total lesion glycolysis, and heterogeneity index) were recorded. All patients underwent operation, and their pathologic reports served as the reference standard. RESULTS: Thymic epithelial tumors were demonstrated in all 9 patients at pathologic examination. Tumor contour (P = 0.012) and shape (P = 0.033) had an association with the World Health Organization subtype, and the presence of septum (P = 0.048) on MRI scans had an association with the Masaoka stage. In terms of functional and metabolic biomarkers, SUVmax (ρ = 0.683, P = 0.042) and SUV/apparent diffusion coefficient (ρ = 0.703, P = 0.035) correlated with the Masaoka stage. Metabolic tumor volume (P = 0.024), heterogeneity index (P = 0.024), and total lesion glycolysis (P = 0.048) were useful for classification between low- and high-risk thymic epithelial tumors. CONCLUSIONS: Although limited by the small number of patients enrolled, morphologic, functional, and metabolic biomarkers derived from PET/MRI scans were useful for the stratification of thymic epithelial tumors.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Fluorodesoxiglucosa F18 , Imagen por Resonancia Magnética , Imagen Multimodal , Neoplasias Glandulares y Epiteliales/diagnóstico por imagen , Neoplasias Glandulares y Epiteliales/metabolismo , Tomografía de Emisión de Positrones , Neoplasias del Timo/diagnóstico por imagen , Neoplasias del Timo/metabolismo , Adulto , Anciano , Biomarcadores , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/fisiopatología , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Neoplasias del Timo/patología , Neoplasias del Timo/fisiopatología , Tomografía Computarizada por Rayos X , Carga Tumoral
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