RESUMO
Two equine patients presented separately with severe abdominal distention, colic, lethargy, and decreased appetite. An ante-mortem diagnosis of lymphoma was reached in each case based on peritoneal fluid cytology. Due to a poor prognosis, the horses were humanely euthanized. Post-mortem examination with histology and immunohistochemistry confirmed both cases as lymphoma: alimentary B-cell lymphoma of the distal jejunum and cecum in one case, and T-cell lymphoma of the cecum in the second case. Both cases exhibited extensive metastasis with peritoneal and pleural serosae covered in small nodules and plaque like masses consistent with lymphomatosis. These cases document a unique presentation of lymphoma in equine patients presenting as peritoneal lymphomatosis with ascites.
Assuntos
Doenças dos Cavalos , Linfoma , Neoplasias Peritoneais , Cavalos , Animais , Neoplasias Peritoneais/complicações , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/veterinária , Linfoma/complicações , Linfoma/patologia , Linfoma/veterinária , Peritônio/patologia , Ascite/etiologia , Ascite/patologia , Ascite/veterinária , Dor Abdominal/veterinária , Dor Abdominal/complicações , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/patologiaRESUMO
INTRODUCTION: Peritoneal tuberculosis (abdominal tuberculosis) can be confused with a malignant neoplasm. OBJECTIVE: To describe clinical and demographic characteristics of patients with abdominal tuberculosis mimicking advanced ovarian cancer, diagnosed in a national reference cancer center. METHODS: Clinical and pathological characteristics of nine patients with abdominal tuberculosis that clinically resembled advanced ovarian cancer are described. RESULTS: Median age was 47 years; the most common socioeconomic status was low (44%). Abdominal pain and weight loss occurred in 77.7%; ascites, in 55.5%; 22.2% had a positive COMBE test, and 100% had no history of pulmonary tuberculosis. CA-125 elevation was reported in 77.7%, with levels > 500 U/mL in 57.1%. Tomography reported carcinomatosis in 50% and pelvic tumor and ascites in 37.5%. All patients underwent surgery, where 62.5% were diagnosed by intraoperative pathology study as neoplastic disease. CONCLUSION: Tuberculosis is considered the great imitator, which is why abdominal tuberculosis diagnosis should be borne in mind when faced with a suspicious case, even when clinical presentation, imaging studies, and even intraoperative examination suggest ovarian cancer.
INTRODUCCIÓN: La tuberculosis peritoneal (tuberculosis abdominal) puede ser confundida con una neoplasia maligna. OBJETIVO: Describir características clínicas y demográficas de pacientes con tuberculosis abdominal que semeja cáncer de ovario avanzado, diagnosticados en un centro oncológico de referencia nacional. MÉTODOS: Se describen las características clínicas y patológicas de nueve pacientes con tuberculosis abdominal que clínicamente semejaba cáncer de ovario avanzado. RESULTADOS: La mediana de edad fue de 47 años, el estrato socioeconómico más común fue bajo (44 %). El dolor abdominal y la pérdida ponderal se presentaron en 77.7 %, ascitis en 55.5 %, prueba COMBE positiva en 22.2 % y ausencia de antecedente de tuberculosis pulmonar en 100 %. La elevación de CA-125 se reportó en 77.7 %, con > 500 U/mL en 57.1 %. La tomografía indicó carcinomatosis en 50 % y tumor pélvico y ascitis en 37.5 %. Todas las pacientes fueron sometidas a cirugía; 62.5 % fueron diagnosticadas mediante estudio patológico transoperatorio como enfermedad neoplásica. CONCLUSIÓN: La tuberculosis es considerada como la gran imitadora, por ello se debe tener en mente el diagnóstico de tuberculosis abdominal ante un caso sospechoso, aun cuando la presentación clínica, estudios de imagen e, incluso, el examen transoperatorio sugieran cáncer de ovario.
Assuntos
Neoplasias Ovarianas , Tuberculose , Ascite/diagnóstico , Ascite/patologia , Antígeno Ca-125 , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Tuberculose/diagnósticoRESUMO
Ovarian cancer is the most lethal gynecological malignancy, with serous histotype as the most prevalent epithelial ovarian cancer (EOC). Peritoneal ascites is a frequent comorbidity in advanced EOC. EOC-associated ascites provide a reliable sampling source for studying lymphocytes directly from tumor environment. Herein, we carried out flow cytometry-based analysis to readdress issues on NK and T lymphocyte subsets in women with advanced EOC, additionally evaluating phenotypic modulation of their intracellular pathways involved in interleukin (IL)-2 and IL-15 signaling. Results depicted ascites as an inflammatory and immunosuppressive environment, presenting significantly (p < 0.0001) higher amounts of IL-6 and IL-10 than in the patients' blood, as well as significantly (p < 0.05) increased expression of checkpoint inhibitory receptors (programmed death protein-1, PD-1) and ectonucleotidase (CD39) on T lymphocytes. However, NK lymphocytes from EOC-associated ascites showed higher (p < 0.05) pS6 phosphorylation compared with NK from blood. Additionally, in vitro treatment of lymphocytes with IL-2 or IL-15 elicited significantly (p < 0.001) phosphorylation of the STAT5 protein in NK, CD3 and CD8 lymphocytes, both from blood and ascites. EOC-associated ascites had a significantly (p < 0.0001) higher proportion of NK CD56bright lymphocytes than blood, which, in addition, were more responsive (p < 0.05) to stimulation by IL-2 than CD56dim NK. EOC-associated ascites allow studies on lymphocyte phenotype modulation in the tumor environment, where inflammatory profile contrasts with the presence of immunosuppressive elements and development of cellular self-regulating mechanisms.
Assuntos
Ascite/imunologia , Antígeno CD56/imunologia , Cistadenocarcinoma Seroso/imunologia , Células Matadoras Naturais/imunologia , Neoplasias Ovarianas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apirase/genética , Apirase/imunologia , Ascite/genética , Ascite/patologia , Antígeno CD56/genética , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imunofenotipagem , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-15/genética , Interleucina-15/imunologia , Interleucina-2/genética , Interleucina-2/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Células K562 , Células Matadoras Naturais/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Fator de Transcrição STAT5/genética , Fator de Transcrição STAT5/imunologia , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/patologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologiaRESUMO
Citrinin (CIT) is a cytotoxic, hepatotoxic, nephrotoxic and cardiotoxic metabolite obtained from Penicillium citrinum, that has been increasingly searched as an anticancer drug candidate. In this study, we assessed the antitumor effects of citrinin, using cytogenetic biomarkers for genotoxicity in Sarcoma 180 (S-180) ascitic fluid cells of mice. Citrinin, extracted from P. citrinum acetonitrile extract, was characterized by LC-MS. Cytotoxic assessment was done through using comet (alkaline version) and micronucleus assays. In S-180 cells, CI50 of CIT was 3.77 µg/mL, while at 12.5 and 100 µg/mL, CIT was as cytotoxic as doxorubicin (2 µg/mL). At 0.5, 1.0 and 2.0 µg/mL, it induced genotoxicity and mutagenicity in S-180 cells, especially at 2 µg/mL, triggering oxidative damage similar to hydrogen peroxide (10 mM). The antitumor effects were evidenced by a marked increase in S-180 cells apoptosis and necrosis due to clastogenic and/or aneugenic cytogenetic effects (micronucleus formation), as well as by induction of nucleoplasm bridges and nuclear buds, culminating in S-180 apoptosis and necrosis. CIT has potential as drug candidate for antitumor purposesbyinvolving cytogenetic mechanisms.
Assuntos
Antineoplásicos/uso terapêutico , Citrinina/uso terapêutico , Análise Citogenética , Sarcoma 180/tratamento farmacológico , Sarcoma 180/genética , Animais , Antineoplásicos/farmacologia , Ascite/patologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citrinina/isolamento & purificação , Citrinina/farmacologia , Modelos Animais de Doenças , Camundongos , Mutagênicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Penicillium/químicaRESUMO
The aim of this study was to evaluate cytokine levels (IL-2, IL-8, TNF-α, IL-5, IL-6 and IL-10) in the peritoneal fluid in non-neoplastic tumours, benign ovarian neoplasms and malignant ovarian neoplasms. Peritoneal fluid or ascites was collected from 117 patients with neoplastic and non-neoplastic ovarian tumours. Cytokine levels were assessed by ELISA. The unpaired groups were compared by the Kruskal-Wallis test with Dunn's post-test. Higher IL-6 levels were found in malignant neoplasms when compared to non-neoplastic tumours (p=.0241). There was no significant difference in the evaluation of other cytokines. Therefore, higher IL-6 levels in peritoneal fluid are related to the diagnosis of ovarian cancer. Further studies should be performed to evaluate the profile of cytokines in the peritoneal fluid of patients with ovarian tumours, and may be a new diagnostic strategy and a future target for treatment.Impact statementWhat is already known on this subject? Cytokines can be dosed in both the serum and peritoneal fluid, and in the ascitic fluid of women with ovarian neoplasia. Elevated levels of IL-6 were found in the ascitic fluid of patients with malignant ovarian tumours.What the results of this study add? To our knowledge, this is the first study in the literature that evaluates a large panel of cytokines in the peritoneal fluid (and not only in ascites), comparing non-neoplastic tumours, benign neoplasms and malignant ovarian neoplasms.What the implications are of these findings for clinical practice and/or further research? The cytokine dosage in the peritoneal fluid should be considered to map a profile of inflammatory cytokines that permeate the peritoneal cavity of patients with ovarian cancer. The dosage of these cytokines can be a potential pre-surgical tumour marker. In addition, a better understanding of the pattern of cytokines around ovarian neoplasia may be targeted for further studies in the development of new therapies for ovarian cancer.
Assuntos
Ascite/metabolismo , Líquido Ascítico/química , Citocinas/análise , Neoplasias Ovarianas/metabolismo , Adolescente , Adulto , Idoso , Ascite/patologia , Biomarcadores Tumorais/análise , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-10/análise , Interleucina-2/análise , Interleucina-5/análise , Interleucina-8/análise , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Fator de Necrose Tumoral alfa/análise , Adulto JovemRESUMO
Ovarian cancer (OC) is the fifth cancer death cause in women worldwide. The malignant nature of this disease stems from its unique dissemination pattern. Epithelial-to-mesenchymal transition (EMT) has been reported in OC and downregulation of Epithelial cadherin (E-cadherin) is a hallmark of this process. However, findings on the relationship between E-cadherin levels and OC progression, dissemination and aggressiveness are controversial. In this study, the evaluation of E-cadherin expression in an OC tissue microarray revealed its prognostic value to discriminate between advanced- and early-stage tumors, as well as serous tumors from other histologies. Moreover, E-cadherin, Neural cadherin (N-cadherin), cytokeratins and vimentin expression was assessed in TOV-112, SKOV-3, OAW-42 and OV-90 OC cell lines grown in monolayers and under anchorage-independent conditions to mimic ovarian tumor cell dissemination, and results were associated with cell aggressiveness. According to these EMT-related markers, cell lines were classified as mesenchymal (M; TOV-112), intermediate mesenchymal (IM; SKOV-3), intermediate epithelial (IE; OAW-42) and epithelial (E; OV-90). M- and IM-cells depicted the highest migration capacity when grown in monolayers, and aggregates derived from M- and IM-cell lines showed lower cell death, higher adhesion to extracellular matrices and higher invasion capacity than E- and IE-aggregates. The analysis of E-cadherin, N-cadherin, cytokeratin 19 and vimentin mRNA levels in 20 advanced-stage high-grade serous human OC ascites showed an IM phenotype in all cases, characterized by higher proportions of N- to E-cadherin and vimentin to cytokeratin 19. In particular, higher E-cadherin mRNA levels were associated with cancer antigen 125 levels more than 500 U/mL and platinum-free intervals less than 6 months. Altogether, E-cadherin expression levels were found relevant for the assessment of OC progression and aggressiveness.
Assuntos
Caderinas/metabolismo , Neoplasias Ovarianas/metabolismo , Antígenos CD , Ascite/metabolismo , Ascite/patologia , Biomarcadores Tumorais/metabolismo , Antígeno Ca-125/sangue , Adesão Celular/fisiologia , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Sobrevivência Celular/fisiologia , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/sangue , Invasividade Neoplásica/patologia , Invasividade Neoplásica/fisiopatologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , RNA Mensageiro/metabolismoRESUMO
Peritoneal ascites are a distinguishable feature of patients with advanced epithelial ovarian cancer (EOC). The presence of different lymphocyte subsets has been reported in EOC-associated ascites, which also can or not contain malignant cells. The goal of this study was to analyze the functional characteristics of natural killer (NK) cells from EOC-associated ascites in terms of their expression of activating receptors and ascites' contents of lymphocyte subtypes, cytokine profile and presence of EOC cells. NK cell function was evaluated by the expression of the degranulation marker CD107a in resting and interleukin (IL)-2 stimulated NK cells from ascites and blood. Degranulation of NK cells from EOC cell-free ascites was significantly (p < 0.05) higher than all the other groups, either in their resting state or after IL-2 stimulation, suggesting a previous local stimulation. In contrast, treatment with IL-2 had no effect on NK cells from ascites with EOC cells. The amount of regulatory T cells was significantly higher in ascites with EOC cells compared to EOC cell-free ascites. Ascites with EOC cells also had higher levels of tumor necrosis factor (TNF)-α, suggesting inflammation related to the malignancy. In conclusion, the functional performance of NK cells was distinct between EOC cell-free ascites and ascites with EOC cells. The impairment of NK cell response to IL-2 in ascites with EOC cells was consistent with an immunosuppressive tumor microenvironment.
Assuntos
Ascite/imunologia , Ascite/patologia , Interleucina-2/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/metabolismo , Idoso , Biomarcadores , Carcinoma Epitelial do Ovário , Estudos de Casos e Controles , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/imunologia , Linhagem Celular Tumoral , Citocinas/genética , Citocinas/metabolismo , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Interleucina-2/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/imunologia , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologiaRESUMO
N-ω-chloroacetyl-L-ornithine (NCAO) is an ornithine decarboxylase (ODC) inhibitor that is known to exert cytotoxic and antiproliferative effects on three neoplastic human cancer cell lines (HeLa, MCF-7, and HepG2). Here, we show that NCAO has antiproliferative activity in 13 cancer cell lines, of diverse tissue origin from human and mice, and in a mouse cancer model in vivo. All cell lines were sensitive to NCAO after 72 h of treatment (the EC50 ranged from 1 to 50.6 µmol/l). The Ca Ski cell line was the most sensitive (EC50=1.18±0.07 µmol/l) and MDA-MB-231 was the least sensitive (EC50=50.6±0.3 µmol/l). This ODC inhibitor showed selectivity for cancer cells, exerting almost no cytotoxic effect on the normal Vero cell line (EC50>1000 µmol/l). NCAO induced apoptosis and inhibited tumor cell migration in vitro. Furthermore, in vivo, this compound (at 50 and 100 mg/kg, daily intraperitoneal injection for 7 days) exerted potent antitumor activity against both solid and ascitic tumors in a mouse model using the myeloma (Ag8) cell line. At these same two doses, the toxicological evaluation showed that NCAO has no obvious systemic toxicity. The current results suggest that the antitumor activity is exerted by apoptosis related not only to a local but also a systemic cytotoxic effect exerted by NCAO on tumor cells. The applications for NCAO as an antitumor agent may be extensive; however, further studies are needed to ascertain the antitumor activity on other types of tumor in vivo and to determine the precise molecular mechanism of its activity.
Assuntos
Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias/tratamento farmacológico , Ornitina/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Ascite/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Neoplasias/patologia , Ornitina/farmacologia , Testes de Toxicidade Subcrônica , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
El mesotelioma peritoneal maligno es una neoplasia de presentación infrecuente, de curso insidioso, sintomática y de presentación poco específica en fase avanzada, de difícil diagnóstico y alta letalidad. Es la neoplasia más común de la serosa peritoneal, ocupando el segundo lugar de localización de los mesoteliomas, después del mesotelioma pleural. Es más frecuente en hombres, en mayores de 60 años y se ha relacionado en un 80% a la exposición crónica al asbesto. Generalmente su primera manifestación es ascitis, que se acompaña de dolor abdominal, astenia, hiporexia y pérdida de peso. Se puede diagnosticar a través del estudio histológico e inmunohistoquímico de líquido ascítico, biopsia peritoneal, y como métodos complementarios, TC de Abdomen y CT-PET. Presentamos el caso de un paciente masculino de 70 años de edad, con antecedente de adenocarcinoma prostático tratado con radioterapia y bloqueo hormonal, en remisión, Cardiopatía Isquémica e Hipertensiva en condición post-Bypass coronario, quien consulta por disnea, ascitis, hiporexia, astenia, con evidencia de líquido ascítico hemorrágico y GASA de bajo gradiente.
Malignant peritoneal mesothelioma is an infrequent neoplasm, of insidious course, symptomatic presentation and usually is diagnosed at an advanced stage diagnosis. It is the most common malignancy of the peritoneum and the the second location of mesothelioma, preceded by pleural mesothelioma. It is more common in men older than 60 year sand has been linked in 80% to chronic exposure to asbestos. Usually ascites, abdominal pain, fatigue, decreased appetite and weight loss are the first signs. It can be diagnosed through histological and immunohistochemical study of ascitic fluid, peritoneal biopsy, abdominal CT and CT-PET. We report the case of a male patient. 70 years with a history of heart disease and prostatic carcinoma treated with radiotherapy and immunosupressive therapy, who consults with dyspnea, ascites, hyporexia, fatigue and evidence of hemorrhagic ascites.