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2.
Mod Pathol ; 35(1): 69-76, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34480081

RESUMO

We report nine examples of a previously undescribed type of peritoneal circumscribed nodular mesothelial tumor characterized by nests or sheets of mesothelial cells with sharp cell borders and extremely bland, sometimes grooved, nuclei. In some cases, nests were separated by fibrous bands. All patients were women, age range 30-72 years (median 52 years). All tumors were incidental findings during surgery and grossly were either solitary nodules or a few small nodules on the peritoneal surface. Referring pathologic diagnoses included diffuse malignant mesothelioma, localized malignant mesothelioma, well-differentiated papillary mesothelioma, and adenomatoid tumor. No tumor showed BAP1 loss by immunohistochemistry nor deletion of CDKN2A by FISH. RNA-seq revealed that these tumors clustered together and were distinct from peritoneal diffuse malignant mesotheliomas. Very few mutations or translocations were found, none of them recurrent from tumor to tumor, and no tumor showed an abnormality in any of the genes typically mutated/deleted in diffuse malignant mesothelioma. Array CGH on three cases revealed two with a completely flat profile and one with a small deletion at 3q26-3q28. On follow-up (range 5-60, median 34 months), there were no deaths, no recurrences, and no evidence of metastatic disease nor local spread; one case that initially had scattered nodules on the pelvic peritoneum had the same pattern of nodules at a second look operation 2 years later. We propose the name solid papillary mesothelial tumor for these lesions. These appear to be either benign or very low-grade tumors that need to be separated from malignant mesotheliomas.


Assuntos
Carcinoma Papilar/patologia , Neoplasias Mesoteliais/patologia , Neoplasias Peritoneais/patologia , Adulto , Idoso , Carcinoma Papilar/genética , Distribuição de Qui-Quadrado , Análise por Conglomerados , Estudos de Coortes , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Achados Incidentais , Pessoa de Meia-Idade , Mutação , Neoplasias Mesoteliais/genética , Neoplasias Peritoneais/genética , Prognóstico , Análise de Sequência de RNA , Transdução de Sinais , Fatores de Tempo , Translocação Genética
6.
PLoS One ; 15(12): e0241500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33270665

RESUMO

The presence of ascites in the peritoneal cavity leads to morphological and functional changes of the peritoneal mesothelial cell layer. Cells loose cell-cell interactions, rearrange their cytoskeleton, activate the production of fibronectin, and change their cell surface morphology in a proinflammatory environment. Moreover, ovarian cancer cell adhesion has been shown to be facilitated by these changes due to increased integrin- and CD44-mediated binding sites. In this study, the biological responsiveness of the human pleural mesothelial cell line MeT-5A to patient-derived and artificial ascites was studied in vitro and adhesion of ovarian cancer cells, i.e. SKOV-3 cells, investigated. Changes were mainly observed in cells exposed to artificial ascites containing higher cytokine concentrations than patient-derived ascites. Interestingly, reduced cell-cell interactions were already observed in untreated MeT-5A cells and effects on tight junction protein expression and permeability upon exposure to ascites were minor. Ascites induced upregulation of CDC42 effector protein 2 expression, which affects stress fiber formation, however significant F-actin reorganization was not observed. Moreover, fibronectin production remained unchanged. Analysis of mesothelial cell surface characteristics showed upregulated expression of intercellular adhesion molecule 1, slightly increased hyaluronic acid secretion and decreased microvillus expression upon exposure to ascites. Nevertheless, the observed changes were not sufficient to facilitate adhesion of SKOV-3 cells on MeT-5A cell layer. This study revealed that MeT-5A cells show a reduced biological responsiveness to the presence of ascites, in contrast to published studies on primary human peritoneal mesothelial cells.


Assuntos
Adesão Celular/efeitos dos fármacos , Citocinas/farmacologia , Neoplasias Mesoteliais/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Ascite/metabolismo , Ascite/patologia , Linhagem Celular Tumoral , Citocinas/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Receptores de Hialuronatos/genética , Integrina beta1/genética , Molécula 1 de Adesão Intercelular/genética , Neoplasias Mesoteliais/genética , Neoplasias Mesoteliais/metabolismo , Neoplasias Mesoteliais/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Pacientes , Peritônio/química , Peritônio/metabolismo , Transdução de Sinais/genética , Proteína cdc42 de Ligação ao GTP/genética
7.
Cell Mol Biol (Noisy-le-grand) ; 66(6): 98-104, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33040793

RESUMO

Capsaicin is one of the most extensively studied phytochemicals and its cytotoxicity on various types of cancer has been demonstrated both in vitro and in vivo. The evaluation of its effect on mesothelioma, however, has remained quite limited. In this study, we investigated the anti-mesothelioma potential of capsaicin by observing its cytotoxicity on healthy, immortalized and cancerous cells of mesothelium in vitro and how this potential be affected by lowered Cyclin E levels, a key regulator of G1/S transition of cell cycle. For this purpose, we determined and compared the IC50 values of capsaicin in both FBS (Fetal Bovine Serum) containing and FBS-deprived medium of each cell population studied. Additionally, we examined the changes in both protein and mRNA levels of caspase-3 upon capsaicin exposure as well as conducted a series of experiments through which the relatively long term effect of capsaicin on the growth rate of the cells was assessed. As a result, the reduced Cyclin E obtained through the absence of FBS in growth medium was found not only to decrease IC50 values for all cell types dramatically (p<0.05) but also to cause a considerable difference between the values determined for cancerous and non-cancerous populations (p<0.05), which had not been observed in regular medium. Moreover, along with the fact that capsaicin exposure did not have an impact on the cell growth in long term in most cases, caspase-3 levels also remained the same when exposed to capsaicin, suggesting a mechanism of cell death independent of caspases.


Assuntos
Capsaicina/farmacologia , Ciclina E/metabolismo , Epitélio/efeitos dos fármacos , Neoplasias Mesoteliais/tratamento farmacológico , Proteínas Oncogênicas/metabolismo , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Epitélio/metabolismo , Humanos , Neoplasias Mesoteliais/metabolismo
8.
Diagn Cytopathol ; 48(12): E22-E26, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32621636

RESUMO

Emperipolesis is a physiologic or pathologic phenomenon characterized by the presence of intact viable cells within the cytoplasm of another cell. It has been described in normal tissues and in a variety of inflammatory and neoplastic lesions such as Rosai-Dorfman disease, tumors, hematopoietic disorders and rarely lymphomas. Emperipolesis by mesothelial cells is rare. Few cases of mesothelial emperipolesis of neoplastic lymphocytes in pleural effusions involved by lymphomas have been reported in the literature. Its etiopathogenesis and significance are controversial and speculative. We report a case of a 36-year-old man who presented with cough, chest pain, breathing difficulty, pericardial, and bilateral pleural effusions secondary to mediastinal T-lymphoblastic lymphoma. Pleural fluid cytology slides and cell block sections showed numerous single dispersed neoplastic lymphoblasts with occasional giant multinucleated mesothelial cells with emperipolesis of lymphocytes. The background showed scattered and clumped apoptotic karyorrhexis debris and reactive mesothelial cells. Cell block immunohistochemistry showed CD3, CD5, CD7, CD10, CD99, and TdT positive lymphocytes, consistent with involvement by T-lymphoblastic lymphoma. The giant cells were positive for cytokeratin, calretinin and WT1 confirming their mesothelial origin. Lymphoid effusions with emperipolesis may raise a potential diagnostic pitfall because they may morphologically be confused with other inflammatory and neoplastic lesions. This cell-in-cell phenomenon can be a helpful clue in the differential diagnosis of lymphocyte-rich effusions since it has been described in association with lymphomas. It might shed some light on the lymphocyte-mesothelial interaction and the potential phagocytic antigen-presenting properties of mesothelial cells under certain circumstances.


Assuntos
Emperipolese/fisiologia , Epitélio/patologia , Linfócitos/patologia , Neoplasias Mesoteliais/patologia , Derrame Pleural/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adulto , Biomarcadores Tumorais/metabolismo , Epitélio/metabolismo , Humanos , Linfócitos/metabolismo , Masculino , Neoplasias Mesoteliais/metabolismo , Derrame Pleural/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo
9.
Ecotoxicol Environ Saf ; 198: 110640, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32330788

RESUMO

Fluoro-edenite (FE) is a silicate mineral identified in the lava products of Monte Calvario from stone quarries located in the southeast of Biancavilla, a small city of the Etnean volcanic complex (Sicily, Italy). Inhalation of FE fibers has been associated with a higher incidence of Malignant Mesothelioma (MM), a highly aggressive neoplasm of the serosal membranes lining the pleural cavity. Only 5% of MM patients are diagnosed at an early stage and the median survival is approximate 6-12 months. Many diagnostic biomarkers have been proposed for MM. Several studies demonstrated that microRNAs (miRNAs) may be used as good non-invasive diagnostics, as well as prognostic biomarkers for various human diseases, including cancer. On these bases, the aim of the present study was to identify a set of miRNAs involved in the development and progression of MM and potentially used as diagnostic biomarkers. For these purposes, in silico analyses were performed on healthy/exposed to asbestos fibers subjects vs. patients with MM. These analyses revealed a set of miRNAs strictly involved in MM by merging the lists of miRNAs found differentially expressed in the three miRNA expression datasets analyzed. The result of these computational evaluations allowed the execution of functional in vitro experiments performed on normal pleural mesothelial cell line (MeT-5A) and MM cell line (JU77) in order to test the carcinogenetic effects and epigenetic modulation induced by FE exposure. The in vitro results showed that the expression levels of hsa-miR-323a-3p vary significantly in both supernatant- and cell-derived miRNAs derived from treated and untreated cells. Secreted and cellular hsa-miR-101-3p in MeT-5A treated with FE fibers and JU77 cells showed different trends of expression. As regard hsa-miR-20b-5p, there was no differential expression between secreted and cellular hsa-miR-20b-5p. This miRNA has been shown a significant up-regulation in JU77 cells vs. control and treated MeT-5A. As a future plan, translational analyses will be performed on a subset of patients chronically exposed to FE fibers to further verify the clinical role of such miRNAs in high-risk individuals and their possible use as biomarkers of FE exposure or MM early onset.


Assuntos
Amiantos Anfibólicos/toxicidade , Amianto/toxicidade , Transformação Celular Neoplásica/induzido quimicamente , Exposição Ambiental , Epitélio/efeitos dos fármacos , MicroRNAs/genética , Neoplasias Mesoteliais/induzido quimicamente , Adulto , Biomarcadores/análise , Linhagem Celular , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Mesoteliais/diagnóstico , Sicília
10.
Cell Transplant ; 28(11): 1384-1389, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31366210

RESUMO

The cytology of peritoneal washing fluids for gastric cancer is the most basic method for judging peritoneal micrometastasis. However, the clinical value of this method is not clear at present. A retrospective analysis was performed on 277 patients with pathologically proven and surgically treated gastric cancer. The peritoneal washing fluids were collected after opening the abdomen and before the operation, and were sent to the cytology laboratory for screening of occult cancer cells in the collected washing fluids. The number of cases diagnosed as cancer cells, reactive mesothelial cells, serosal balls, and traumatic mesothelial cells were 42, 18, 27, and 190, respectively. Typical adenocarcinoma cell nests were found in eight of 10 T4b samples, whereas 34 cases of cancer cells in T3 and T4a showed that these cell nests usually contained mesothelial cells, and the three-dimensional stereoscopic sense of the nests was not obvious. In the specific subcellular morphological changes of both reactive mesothelial cells and serosal balls, the changes of both the contour of nuclear membrane and the polarity of cell alignment were present only in stage T3 and T4a. The presence or absence of mesothelial cells in the nests of cancer cells and the changes of the contour of nuclear membrane and of the polarity of cell alignment in reactive mesothelial cells or serosal balls may help us to predict the depth of invasion of cancer cells.


Assuntos
Adenocarcinoma/secundário , Líquido Ascítico/citologia , Neoplasias Mesoteliais/secundário , Neoplasias Gástricas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Líquido Ascítico/patologia , Epitélio/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Mesoteliais/diagnóstico , Neoplasias Mesoteliais/patologia , Neoplasias Mesoteliais/cirurgia , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia
11.
Cytopathology ; 30(6): 592-600, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31165505

RESUMO

OBJECTIVE: The aim of this study was to investigate the utility of BRCA1-associated protein-1 (BAP1), glucose transporter (GLUT)-1 and desmin expression by immunohistochemistry in the discrimination between reactive and malignant mesothelial proliferations. METHODS: A total of 88 biopsies and 30 effusions from mesothelioma cases were studied. Control groups were composed of 35 tissues and 30 cell blocks. The 88 mesothelioma cases were from 43 males and 45 females (mean age 56 years). Tumours were mostly localised to pleura (66/88, 75%) and of epithelioid histology (75/88, 85%). Cytology samples were from 17 males and 13 females (mean age 58 years), and 16 pleural and 14 peritoneal effusions. Twenty cytology cases had corresponding tissue biopsies. RESULTS: BAP1 loss was detected in 61/88 (69%) tissues and in 20/30 (67%) cytology samples from mesothelioma with a specificity of 100% for both sampling methods. BAP1 loss was observed more frequently in pleural and biphasic tumours. GLUT-1 immunoreactivity was identified in 54/81 (67%) and 23/25 (92%) malignant tissues and effusions, and in 6/33 (18%) and 6/30 (20%) benign tissues and effusions, respectively. Desmin loss was observed in 74/80 (92%) malignant biopsy samples, 16/21 (76%) malignant effusions and 10/34 (29%) of benign tissues, but in none of the reactive effusions. Concordance rate of results between biopsy and cytology was as follows: BAP1 20/20 (100%); GLUT-1 13/18 (72%); and desmin 10/14 (71%). CONCLUSIONS: BAP1, GLUT-1 and desmin are useful markers in the discrimination between reactive and malignant mesothelial proliferations. BAP1 loss seems to be diagnostic for mesotheliomas both in biopsy and cytology samples.


Assuntos
Desmina/genética , Transportador de Glucose Tipo 1/genética , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Neoplasias Mesoteliais/diagnóstico , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Biomarcadores Tumorais/genética , Proliferação de Células/genética , Citodiagnóstico , Diagnóstico Diferencial , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/genética , Mesotelioma/patologia , Mesotelioma Maligno , Pessoa de Meia-Idade , Neoplasias Mesoteliais/genética , Neoplasias Mesoteliais/patologia , Derrame Pleural Maligno
12.
Occup Med (Lond) ; 69(2): 118-125, 2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-30949692

RESUMO

BACKGROUND: The Health and Safety Executive's new Health and Work Strategy is based on an up-to-date assessment of workplace health priorities. Rather than replicating traditional prioritization approaches, a broader assessment of health and work priorities was carried out using a range of stakeholders. AIMS: To develop a set of health priorities for further research and intervention activity. METHODS: Four exercises were carried out, including internal prioritization, two external web-hosted questionnaire studies of younger workers and occupational health professionals, focus groups and tele-depth interviews with workplace health and safety professionals. RESULTS: The highest rated internal priorities (weighted priority scores) were identified as mesothelioma (70), lung cancer (69.25), chronic obstructive pulmonary disease (COPD; 69), musculoskeletal disorders (MSDs; 66.25), hearing loss (65.75), stress (65.5), asthma (64.5) and hand-arm vibration syndrome (61.5). Using the three highest ranked criteria developed by occupational health professionals ((i) the preventability of the condition, (ii) the impact of the condition and (iii) the number of workers affected), mesothelioma, lung cancer, COPD, MSDs, hearing loss, stress and asthma were identified as the top seven priorities. Generic issues identified included ageing and work, obesity, newer technologies, and ethnicity and cultures of workforces. Apprentices identified stress, depression, anxiety, musculoskeletal and respiratory disorders, fatigue and workload as important workplace health considerations. CONCLUSIONS: This process identified a number of expected and new areas of health research interest. We believe the findings reflect the real world requirements of work as assessed by occupational health and safety practitioners and workers.


Assuntos
Doença Crônica/terapia , Prática Clínica Baseada em Evidências/organização & administração , Prioridades em Saúde/organização & administração , Doenças Profissionais/terapia , Saúde do Trabalhador , Grupos Focais , Pessoal de Saúde , Humanos , Neoplasias Pulmonares , Doenças Musculoesqueléticas , Neoplasias Mesoteliais
13.
Clin Lung Cancer ; 20(2): e152-e157, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30594459

RESUMO

Primary pericardial mesothelioma (PPM) is a rare cancer for which there is no consensus on treatment. We evaluated and summarized a large contemporary population of published PPM cases to characterize risk factors, treatment patterns, and clinical outcomes. Using Ovid and PubMed, literature published from 2000 through 2016 was searched using the terms "primary pericardial mesothelioma," "pericardial mesothelioma," and "malignant pericardial mesothelioma." We identified 6 case series and 84 case reports for a total of 103 PPM cases published from 2000 through 2016. The median age at diagnosis was 55 years, and the median overall survival was 6 months. In univariate analyses of clinical characteristics including gender, asbestos exposure, tobacco use, prior radiation exposure, histologic subtype, and metastasis and/or mediastinal spread, only the presence of metastasis and/or mediastinal spread was a significant predictor of decreased survival (P = .015). Surgery did not provide a statistically significant survival benefit (P = .12). A survival benefit was noted in those who received chemotherapy (median survival, 13 months vs. 0.5 months, P = .002), specifically chemotherapy with a platinum agent with or without pemetrexed. In multivariate analysis, only the receipt of chemotherapy was associated with improved survival. PPM remains a rare and poorly understood malignancy with unclear etiology and a poor prognosis. In this retrospective systematic review, a survival benefit was seen in patients who received chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Cardíacas/terapia , Neoplasias Mesoteliais/terapia , Pemetrexede/uso terapêutico , Platina/uso terapêutico , Amianto/efeitos adversos , Exposição Ambiental/efeitos adversos , Neoplasias Cardíacas/mortalidade , Humanos , Neoplasias Mesoteliais/mortalidade , Pericárdio , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
14.
Rev. int. androl. (Internet) ; 16(2): 82-86, abr.-jun. 2018. ilus, tab
Artigo em Português | IBECS | ID: ibc-174629

RESUMO

Os tumores adenomatoides são tumores benignos raros, de origem mesotelial que, no homem, afetam principalmente o epidídimo. Representam mais de um terço dos tumores paratesticulares e o tratamento de eleição é a excisão cirúrgica. Extremamente rara é a origem no parênquima testicular ou na túnica albugínea. Os sinais clínicos e estudos de imagem são frequentemente inconclusivos, não permitindo o diagnóstico diferencial com a neoplasia testicular maligna, resultando em orquidectomias radicais desnecessárias. Os autores descrevem um caso clínico de tumor adenomatoide da túnica albugínea, em que a suspeita clínica e exame anatomopatológico intraoperatório conduziram à realização de uma orquidectomia parcial


The adenomatoid tumors are rare benign mesothelial lesions that in males affect mainly the epididymis. They account for over one third of paratesticular tumors, and the treatment of choice has been surgical excision. The origin in testicular parenchyma or the tunica albuginea is extremely rare. Clinical signs and imaging studies are often inconclusive in differentiate from a more common malignant intratesticular solid tumour, which can result in unnecessary orchiectomies. We present a case of adenomatoid tumor of tunica albuginea where clinical suspicion and intraoperative frozen section analysis led to a partial orchiectomy


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Tumor Adenomatoide/diagnóstico por imagem , Neoplasias Testiculares/diagnóstico por imagem , Tumor Adenomatoide/patologia , Neoplasias Mesoteliais/diagnóstico por imagem , Escroto/diagnóstico por imagem , Escroto/patologia , Imuno-Histoquímica/métodos
16.
BMJ Case Rep ; 20182018 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-29431098

RESUMO

A 46-year-old woman was referred for a second opinion regarding an intra-abdominal mass discovered on imaging performed for abdominal pain and distension. The tumour appeared to involve the small bowel, left colon and mesentery and was initially thought to be consistent with an infiltrative tumour or loculated mucinous ascites. Due to the unusual appearance of the tumour and suspicion for an omental-based mass, a laparoscopic resection was recommended to the patient. Intraoperatively, the tumour was found to be a multiloculated, benign appearing, omental cyst without involvement of the bowel and was completely resected laparoscopically. Pathology demonstrated a multiloculated peritoneal mesothelial cyst.


Assuntos
Cistos/patologia , Laparoscopia/métodos , Omento/patologia , Doenças Peritoneais/patologia , Dor Abdominal/diagnóstico por imagem , Dor Abdominal/etiologia , Cistos/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Mesoteliais/patologia , Omento/cirurgia , Doenças Peritoneais/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Br J Surg ; 105(5): 597-605, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29193022

RESUMO

BACKGROUND: The aim of this study was to monitor the effect of humidified-warm carbon dioxide (HWCO2 ) delivered into the open abdomen of mice, simulating laparotomy. METHODS: Mice were anaesthetized, ventilated and subjected to an abdominal incision followed by wound retraction. In the experimental group, a diffuser device was used to deliver HWCO2 ; the control group was exposed to passive air flow. In each group of mice, surgical damage was produced on one side of the peritoneal wall. Vital signs and core temperature were monitored throughout the 1-h procedure. The peritoneum was closed and mice were allowed to recover for 24 h or 10 days. Tumour cells were delivered into half of the mice in each cohort. Tissue was then examined using scanning electron microscopy and immunohistochemistry. RESULTS: Passive air flow generated ultrastructural damage including mesothelial cell bulging/retraction and loss of microvilli, as assessed at 24 h. Evidence of surgical damage was still measurable on day 10. HWCO2 maintained normothermia, whereas open surgery alone led to hypothermia. The degree of tissue damage was significantly reduced by HWCO2 compared with that in controls. Peritoneal expression of hypoxia inducible factor 1α and vascular endothelial growth factor A was lowered by HWCO2 . These effects were also evident at the surgical damage sites, where protection from tissue trauma extended to 10 days. HWCO2 did not reduce tumorigenesis in surgically damaged sites compared with passive air flow. CONCLUSION: HWCO2 diffusion into the abdomen in the context of open surgery afforded tissue protection and accelerated tissue repair in mice, while preserving normothermia. Surgical relevance Damage to the peritoneum always occurs during open abdominal surgery, by exposure to desiccating air and by mechanical trauma/damage owing to the surgical intervention. Previous experimental studies showed that humidified-warm carbon dioxide (HWCO2 ) reduced peritoneal damage during laparoscopic insufflation. Additionally, this intervention decreased experimental peritoneal carcinomatosis compared with the use of conventional dry-cold carbon dioxide. In the present experimental study, the simple delivery of HWCO2 into the open abdomen reduced the amount of cellular damage and inflammation, and accelerated tissue repair. Sites of surgical intervention serve as ideal locations for cancer cell adhesion and subsequent tumour formation, but this was not changed measurably by the delivery of HWCO2 .


Assuntos
Neoplasias Abdominais/cirurgia , Dióxido de Carbono/administração & dosagem , Hipotermia/prevenção & controle , Insuflação/métodos , Laparotomia , Neoplasias Experimentais , Neoplasias Mesoteliais/cirurgia , Neoplasias Abdominais/diagnóstico , Animais , Epitélio/ultraestrutura , Feminino , Temperatura Alta , Umidade , Período Intraoperatório , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Neoplasias Mesoteliais/diagnóstico , Peritônio
18.
Clin Pharmacol Ther ; 102(5): 748-751, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29023728

RESUMO

Mass spectrometry imaging (MSI) allows visualization of endogenous and exogenous compound in tissue sections based on its molecular mass. The 3D reconstruction by MSI provides a more informative description of the tumor drug distribution compared to the high-performance liquid chromatography method, highlighting the heterogeneity of intratumor drug concentration. This additional information can be important in understanding chemoresistance to target agents. Here, we present the 3D visualization of the tyrosine kinase inhibitor (TKI), imatinib, in a xenograft model of resistant malignant pleural mesothelioma.


Assuntos
Imageamento Tridimensional/métodos , Mesilato de Imatinib/administração & dosagem , Espectrometria de Massas/métodos , Neoplasias Mesoteliais/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Ouro/administração & dosagem , Ouro/metabolismo , Humanos , Mesilato de Imatinib/metabolismo , Nanopartículas Metálicas/administração & dosagem , Camundongos , Neoplasias Mesoteliais/diagnóstico por imagem , Neoplasias Mesoteliais/metabolismo , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/metabolismo , Inibidores de Proteínas Quinases/metabolismo , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia
19.
Int J Surg Pathol ; 25(3): 253-257, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27903930

RESUMO

Lynch syndrome is a hereditary disease with germline mutation in a DNA mismatch repair gene, most often presenting with colorectal and/or endometrial carcinomas; however, the spectrum of Lynch syndrome-associated tumors is expanding. In this article, we report a case of a primary peritoneal epithelioid mesothelioma that developed in a Lynch syndrome patient 10 months after diagnosis of uterine endometrioid adenocarcinoma. To our knowledge, this is the first reported case of a Lynch syndrome patient with metachronous uterine endometrioid adenocarcinoma and primary peritoneal mesothelioma.


Assuntos
Carcinoma Endometrioide/patologia , Síndrome de Lynch II/patologia , Neoplasias Mesoteliais/patologia , Neoplasias Peritoneais/patologia , Neoplasias Uterinas/patologia , Biomarcadores Tumorais/análise , Carcinoma Endometrioide/etiologia , Proteínas de Ligação a DNA/genética , Feminino , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Síndrome de Lynch II/complicações , Síndrome de Lynch II/genética , Pessoa de Meia-Idade , Neoplasias Mesoteliais/etiologia , Neoplasias Peritoneais/etiologia , Neoplasias Uterinas/etiologia
20.
Lima; IETSI; 2017.
Não convencional em Espanhol | BRISA/RedTESA, BRISA/RedTESA | ID: biblio-963828

RESUMO

INTRODUCCIÓN: El presente informe expone la evaluación de la combinación de pemetrexed con quimioterapia como tratamiento de primera línea en los casos de mesotelioma maligno pleural (MMP) estadio clínico IV (metastásico), y III no operable. El mesotelioma maligno pleural (MMP) es un raro tipo de neoplasia que se origina en las células mesoteliales que recubren la cavidad pleural. Más del 80% de los casos están relacionados con la exposición ocupacional a los asbestos; esta condición es significativamente más común en hombres, con una razón de hombre-mujer de 5:1. Con frecuencia la manifestación clínica y el diagnóstico aparecen en estadios avanzados, siendo muy pobre el pronóstico para la mayoría de los afectados. OBJETIVO: Comparar el efecto de la combinación de pemetrexed + cisplatino en la sobrevida global (SG) de los pacientes, respecto al uso de cisplatino solo. TECNOLOGÍA SANITARIA DE INTERÉS: Pemetrexed es un agente anti-folato que ejerce su acción antineoplásica por medio de la alteración de varios procesos metabólicos, dependientes de folato, esenciales de la división celular. Suprime la síntesis de purinas y pirimidinas, las cuales son claves en la formación de bloques de ADN y ARN. METODOLOGÍA: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de la combinación de pemetrexed con platino como tratamiento de primera línea de los casos de mesotelioma maligno pleural (MMP) estadio clínico IV (metastásico), y III no operable. Esta búsqueda se realizó utilizando los meta-buscadores: Translating Research into Practice (TRIPDATABASE), National Library of Medicine (Pubmed-Medline) y Health Systems Evidence. Adicionalmente, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), tales como la Cochrane Group, The National Institute for Health and Care Excellence (NICE), the Agency for Health care Research and Quality (AHRQ), The Canadian Agency for Drugs and Technologies in Health (CADTH) y The Scottish Medicines Consortium (SMC). Esta búsqueda se completó ingresando a la página web www.clinicaltrials.gov, para así poder identificar ensayos clínicos en elaboración o que no hayan sido publicados aún, y así disminuir el riesgo de sesgo de publicación. RESULTADOS: Se realizó la búsqueda bibliográfica y de evidencia científica para el sustento del uso de la combinación de pemetrexed con cisplatino como tratamiento de primera línea de los casos de mesotelioma maligno pleural (MMP) estadio clínico IV (metastásico), y III no operable. La evidencia de mayor calidad disponible es el estudio EMPHACIS. Este estúdio fue un ECA de fase III, ciego simple, cuyo objetivo principal fue comparar el efecto de la combinación de pemetrexed + cisplatino en la sobrevida global (SG) de los pacientes, respecto al uso de cisplatino solo. El estudio EMPHACIS sugiere que pemetrexed + cisplatino puede ofrecer mayor beneficio comparado con cisplatino solo, en pacientes con enfermedad avanzada en términos de ganancia de aproximadamente 2.8 meses en la sobrevida. Se observó una diferencia significativa en la sobrevida a favor de la combinación de pemetrexed + cisplatino, respecto al uso de cisplatino solo. Al considerarse la población por intención a tratar, la mediana de SG fue 12.1 meses (IC 95% 10.0-14.4) en el brazo de pemetrexed + cisplatino, comparado con los 9.3 meses (IC 95% 7.8-10.7) en el brazo de cisplatino (HR=0.77; IC 95%, 0.61 - 0.96; p=0.02). El uso de pemetrexed suplementado con ácido fólico y vitamina B12 puede mejorar la sobrevida cuando es usada en combinación con cisplatino, pero en pacientes con buen funcionamiento general (ECOG 0-1). No obstante, aun seleccionando al paciente según este criterio, la decisión de tratar a un paciente con la combinación de pemetrexed con cisplatino debe también tomar em consideración la toxicidad asociada. En EsSalud, están disponibles vinorelbina y el régimen MVP (mitomicina C, vinblastina y cisplatino), que son los agentes que se han venido usando en el tratamiento del MMP, pero han mostrado ofrecer solo algún alivio de los sintomas con aceptable toxicidad y sin ninguna mejora en la tasa de respuesta ni en la sobrevida global. Actualmente, no hay evidencia de otro agente que haya logrado más allá de respuestas parciales sin ningún efecto en la sobrevida. La única combinación que mostró algún beneficio en la SG es la de pemetrexed con cisplatino. A pesar de las limitantes del estudio, el MMP es una enfermedad con una mediana de sobrevida de alrededor de 12 meses, por lo que, una ganancia en la sobrevida de 2.8 meses en pacientes seleccionados es de utilidad clínica. Por lo tanto, la combinación de pemetrexed con cisplatino puede ser recomendado como una opción para el tratamiento de MMP solamente si los pacientes tienen enfermedad avanzada y con puntuación ECOG 0-1, en quienes la cirugía no está recomendada. CONCLUSIÓN: el Instituto de Evaluación de Tecnologías en Salud e Investigación IETSI, aprueba el uso de pemetrexed + cisplatino con suplementación de ácido fólico y vitamina B12, en pacientes con diagnóstico de MMP estadio avanzado inoperable, estado de funcionamiento de ECOG 0-1, y para quienes la cirugía no está recomendada, según lo establecido en el Anexo N° 1 del presente Dictamen Preliminar, el que tiene una vigencia de dos años a partir de su fecha de publicación.


Assuntos
Humanos , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Mesoteliais/tratamento farmacológico , Pemetrexede/uso terapêutico , Mesotelioma/tratamento farmacológico , Avaliação da Tecnologia Biomédica , Análise Custo-Benefício
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