Negative correlation between placental growth factor and endocan-1 in women with preeclampsia / Correlação negativa entre fator de crescimento placentário e endocan-1 emmulheres com pré-eclâmpsia

Abstract Objective To analyze endocan-1, a biomarker of vascular endothelial related pathologies, and the placental growth factor (PlGF), an angiogenic factor and a placental dysfunction marker in patients with preeclampsia (PE). Methods Case-control study conducted at Hospital São Lucas, in the city of Porto Alegre, Brazil. Endocan-1 and PlGF levels were quantified in the maternal plasma using the MagPlexTH-C microsphere system (MAGPIX System, Luminex, Austin, Texas, US) and evaluated through analysis of covariance (ANCOVA) and adjusted by body mass index (BMI), gestational age and maternal age. To estimate the difference between the groups, the mean ratio (MR) and the 95% confidence interval (95%CI) were calculated. The Pearson correlation test was used to establish any association between endocan-1 and PlGF levels. The null hypothesis was rejected when p < 0.05. Results The group of patients was composed by normotensive (n = 67) patients and patients with PE (n = 50). A negative correlation between endocan-1 and the PlGF was noted in the entire normotensive group (linear correlation coefficient [r] = -0.605; p < 0.001), as well as in the PE group (r = -0.545; p < 0.001). Conclusion Endocan-1 levels are increased in patients with PE, and are inversely correlated with PlGF levels. We suggest that it is important to analyze angiogenic and proinflammatory molecules concomitantly in women with PE to better understand the pathophysiology of the disease. Both molecules are strong candidates for PE biomarkers, and future studies will examine any mechanisms connecting these factors in PE.

Resumo Objetivo Analisar o endocan-1, umbiomarcador de patologias vasculares endoteliais, e o fator de crescimento placentário (FCPl), um fator angiogênico, marcador de disfunção placentária em pacientes com pré-eclâmpsia (PE). Métodos Estudo de caso-controle realizado no Hospital São Lucas, em Porto Alegre. Os níveis de endocan-1 e FCPl foram quantificados no plasma materno usando o sistema de microesferas MagPlexTH-C (MAGPIX System, Luminex, Austin, Texas, US) e analisados por análise de covariância (ANCOVA) e ajustados por índice de massa corporal (IMC), idade gestacional e idade materna. Para calcular a diferença entre os grupos, utilizou-se a razão dasmédias (RM) e o intervalo de confiança de 95% (IC95%). O teste de correlação de Pearson foi utilizado para estabelecer a associação entre os níveis de endocan-1 e FCPl. A hipótese nula foi rejeitada quando p < 0,05. Resultados O grupo de pacientes foi composto por pacientes normotensas (n = 67) e pacientes com PE (n = 50). Uma correlação negativa entre o endocan-1 e o FCPl foi observada emtodo o grupo de pacientes normotensas (coeficiente de correlação linear [r] = -0,605; p < 0,001), bem como no grupo com PE (r = -0,545; p < 0,001). Conclusão Os níveis de endocan-1 estão aumentados em pacientes com PE e inversamente correlacionados com os níveis de FCPl. Sugerimos a importância de analisar moléculas angiogênicas e pró-inflamatórias concomitantemente em mulheres com PE para compreender melhor a fisiopatologia da doença. Ambas as moléculas são fortes candidatos a serem considerados biomarcadores de PE, e trabalhos futuros poderão avaliar quaisquer mecanismos que liguem esses fatores na PE.

Tumor del estroma gastrointestinal y trasplante renal / Gastrointestinal stromal tumor and renal transplant

El tumor estromal gastrointestinal (GIST) representa alrededor del 1% de todos los tumores digestivos y su aparición en pacientes trasplantados renales es infrecuente. Aproximadamente el 95% muestra tinción positiva para c-kit/CD117. DOG1 es un anticuerpo recientemente descrito que se sobre-expresa en los GIST, incluso en c-kit/ CD117 negativos. El diagnóstico preciso de GIST resulta imperativo, debido a la disponibilidad y la creciente eficacia de los inhibidores de la tirosina quinasa en estos tumores, incluso en el subgrupo c-kit/ CD117 negativo. Se presenta el caso de una mujer trasplantada renal inicialmente con GIST en intestino delgado y débil positividad para CD117 tratada con cirugía y recidiva tumoral a los tres años, pérdida de la expresión CD117 y tinción positiva para DOG1. Recibió tratamiento exitoso con imatimib sin presentar recaída tumoral durante un seguimiento de cinco años.

Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

Melanoma inhibitory activity in Brazilian patients with cutaneous melanoma

Abstract BACKGROUND: Melanoma inhibitory activity is a protein secreted by melanoma cells and has been used as a tumor marker. Increased Melanoma inhibitory activity serum levels are related to metastatic disease or tumor recurrence. Currently there are no studies on Melanoma inhibitory activity and cutaneous melanoma involving Brazilian patients. OBJECTIVE: To evaluate the performance and feasibility of measuring Melanoma inhibitory activity levels in Brazilian patients with cutaneous melanoma. METHODS: Blood was obtained from ten patients with proved metastatic cutaneous melanoma (Group 1), 15 patients resected for cutaneous melanoma without metastasis (Group 2) and 5 healthy donors (Group 3). Melanoma inhibitory activity was measured using a commercially available ELISA kit. RESULTS: There was a statistically significant difference of Melanoma inhibitory activity levels between patients with and without metastasis (p=0.002), and between patients with metastasis and healthy donors (p=0.002). There was no difference between patients without metastasis and healthy donors (p=0.443). CONCLUSION: Melanoma inhibitory activity is a tumor marker for cutaneous melanoma and the Melanoma inhibitory activity-ELISA test can be easily performed. Patients with metastasis have increased Melanoma inhibitory activity serum levels when compared to patients without metastasis and healthy donors. .

Indicadores del proceso de tamizaje de cáncer de mama en México: un estudio de caso / Breast cancer screening process indicators in Mexico: a study case

Objetivo. Identificar, medir y comparar indicadores de desempeño de productividad, acceso efectivo y calidad en el servicio del programa de detección oportuna de cáncer de mama en México. Material y métodos. Mediante un estudio de caso basado en datos del Sistema de Información de Cáncer de la Mujer (Sicam) 2011, se midieron y compararon los indicadores con la Norma Oficial Mexicana NOM-041-SSA2-2011 y con estándares internacionales. Resultados. El análisis mostró capacidad instalada insuficiente (37%), bajas coberturas en tamizaje (15%), evaluación diagnóstica (16%), biopsia (44%) y tratamiento (57%) y muy baja efectividad en la detección de casos confirmados por número de mastografías realizadas (0.04%). En el Sicam no existe información para estimar el resto de indicadores propuestos. Conclusiones. Se requieren sistemas de información en salud eficientes para monitorear indicadores y generar observatorios del desempeño de los programas de detección.

Objective. To identify, measure and compare the performance indicators of productivity, effective access and quality service for the early detection breast cancer program in Mexico. Material and methods. By means of a study case based on the 2011 Women Cancer Information System (Sicam), the indicators were measured and compared with the Mexican official standard NOM-041-SSA2-2011 and international standards. Results. The analysis showed insufficient installed capacity (37%), low coverage in screening (15%), diagnostic evaluation (16%), biopsy (44%) and treatment (57%), and very low effectiveness in confirmed cases by the total number of screening mammograms performed (0.04%). There was no information available, from Sicam, to estimate the rest of the indicators proposed. Conclusions. Efficient health information systems are required in order to monitor indicators and generate performance observatories of screening programs.

Prostasin, a potential tumor marker in ovarian cancer: a pilot study

INTRODUCTION: Ovarian cancer is generally diagnosed at advanced stages of the disease; therefore, poor prognoses are typical. The development of tumor markers is thus of utmost importance. Prostasin is a protease that in normal tissues is highly expressed only in the prostate gland and seminal fluid. A previous study showed that prostasin is highly overexpressed in ovarian cancer cell lines. This study sought to evaluate the expression of prostasin in ovarian cancer. METHODS: Fresh tumor samples of ovarian epithelial cancer (n: 12) were analyzed for expression of prostasin mRNA (messenger ribonucleic acid) by conventional and real time quantitative PCR (polymerase chain reaction). As a standard control, a normal prostate sample was analyzed. RESULTS: Using conventional PCR, prostasin was detected in all but one sample. Using quantitative PCR, prostasin was over-expressed in all but one of the samples as compared to the control (prostate). CONCLUSIONS: These findings indicate that prostasin is overexpressed in many epithelial ovarian cancers. Further studies of prostasin as a potential biomarker for this disease are warranted.

Pesquisa de células malignas circulantes em pacientes com melanoma maligno de coróide / Detection of circulating malignant cells in patients with uveal melanoma

OBJETIVO: Avaliar a possibilidade de identificação de células malignas circulantes nas amostras de sangue periférico de pacientes brasileiros com melanoma maligno de coróide enviadas para análise no exterior. MÉTODOS: Os marcadores melan-A e tirosinase foram usados para detectar a presença de células malignas circulantes, pela transcrição reversa seguida de reação em cadeia da polimerase e análise seqüencial de DNA (RT-nested-PCR), em seis pacientes com melanoma maligno de coróide, diagnosticados no Brasil. RESULTADOS: Cinco pacientes deste grupo (83,33 por cento) foram considerados positivos. A reação de RT-nested-PCR foi positiva para melan-A em quatro (66,7 por cento) e positiva para tirosinase em quatro (66,7 por cento) dos seis pacientes testados. Três (50 por cento) pacientes foram positivos para os dois marcadores. Um (16,7 por cento) paciente foi negativo para ambos marcadores. CONCLUSÃO: A pesquisa de células malignas circulantes usando RT-nested-PCR, foi positiva na maioria dos pacientes estudados. A qualidade das amostras de sangue periférico dos pacientes brasileiros foi mantida no material preservado mesmo após ter sido enviado ao exterior.

PURPOSE: The purpose of our study was to detect circulating malignant cells (CMCs) in oversea-shipped blood samples of patients with uveal melanoma diagnosed in Brazil. METHODOS: Melan-A and tyrosinase were the two markers used for the detection of CMCs, using reverse transcriptase nested polymerase chain reaction (RT-nested-PCR) in 6 patients with uveal melanoma. The expression of beta-actin and GAPDH were used to assess the quality of the material. RESULTS: Five patients (83.33 percent) tested positive for the presence of CMCs. The RT-nested-PCR was positive for melan-A in 4 patients (66.7 percent) and positive for tyrosinase in 4 (66.7 percent) of the 6 patients. Three (50 percent) patients were positive for both markers. One (16.7 percent) patient was negative for both markers. All negative controls were negative. CONCLUSION: The quality of the blood samples shipped overseas, from patients with uveal melanoma, was preserved. The detection of CMCs using RT-nested-PCR was positive in the majority of the patients.

Carcinoma diferenciado de tireóide: avaliação inicial e acompanhamento / Differentiated thyroid carcinoma: initial evaluation and follow-up

O câncer de tireóide é responsável por cerca de 1 por cento dos novos casos de doença maligna diagnosticados. A maioria destes tumores são carcinomas papilares e foliculares, também denominados de carcinomas diferenciados de tireóide (CDT). Estes carcinomas têm uma taxa de cura de aproximadamente 80 por cento, enquanto 20 por cento apresentarão recorrência local e 5 a 10 por cento desenvolverão metástases à distância. Porém, alguns pacientes apresentam uma doença mais agressiva. A identificação de tais pacientes tem grande impacto no manejo clínico do CDT. Várias classificações de estádio clínico e fatores prognósticos são apresentados, bem como os principais exames para seguimento dos pacientes com CDT.

Treatment of acute promyelocytic leukemia: A single institution experience / Tratamiento de la leucemia promielocítica aguda: Experiencia de una sola institución

The results of the treatment of 14 patients with promyelocytic leukemia (PML) treated with all trans-retinoic acid (ATRA), combined chemotherapy (CT) and prophylactic prednisone are reported; the median age was 30 years (range 7 - 49). A complete remission (CR) was obtained in 13 / 14 patients (93%). All patients were given ATRA fully as outpatients; the CR was achieved after the administration of ATRA in five patients, whereas in the remaining eight, CT was required to achieve it. There were no instances of the ATRA syndrome. One patient relapsed with a PML/RAR-a negative PML 575 days after achieving the CR, failed to respond again to ATRA and died. The median overall (OS) and disease free survival (DFS) has not been reached, being above 4,000 days, whereas the 12-month DFS was 93%, the three and five years DFS being 85%. The treatment employed differs from others in: Oral prednisone is used prophylactically, ATRA is given on an outpatient basis and adriamycin is used instead of other anthracyclines. The results are similar to those obtained in other centers worldwide and it is possible that the prophylactic administration of prednisone precluded the development of the full-blown ATRA syndrome in this group of patients.

Se informan los resultados del tratamiento en una sola institución de 14 pacientes con leucemia aguda promielocítica (LAPM) en quienes se empleó la combinación de ácido holotrans-retinoico (ATRA) quimioterapia combinada y prednisona profiláctica. La mediana de edad fue de 30 años (rango 7-49). Se obtuvo remisión completa (hematológica y molecular) (RC) en 13 pacientes (93%); a todos los pacientes se les administró el ATRA de manera ambulatoria. La RC se obtuvo con el ATRA en cinco pacientes; en los demás la RC se obtuvo después de habérseles administrado la quimioterapia con citarabina/adriamicina. No hubo ningún caso de síndrome de ATRA. Un paciente recayó con una LAPM PML/ RAR-a negativa, 575 días después de haber logrado la RC y falleció. Otro paciente recayó 20 meses después de haber logrado la RC y fue rescatado con el mismo esquema de tratamiento; permanece en segunda remisión molecular por más de seis años. La mediana de supervivencia (SV), tanto global como libre de recaídas de todo el grupo, no se ha alcanzado y es mayor de 4,000 días, en tanto que la SV a 12 meses fue de 93% y a tres y cinco años de 85%. El esquema de tratamiento usado difiere de otros en que se usa prednisona oral, se administra el ATRA de manera ambulatoria y se usa adriamicina y no otras antracidinas; los resultados son similares a los obtenidos con otros esquemas parecidos en otros sitios del mundo; es posible que el uso profiláctico de prednisona haya eliminado la ocurrencia del síndrome de ATRA.

Preliminary clinical evaluation of a protein chip for tumor marker serodiagnosis of various cancers.

This preliminary study aimed to investigate sensitivity and specificity of a protein chip system for multi-tumor marker serodiagnosis of ten types of cancers, and to understand the possible clinical applications of this protein chip for the Thai population. The specific cancers diagnosed by this protein chip are lung, breast, liver, cervix, colo-rectal, stomach, ovary, esophagus, prostate and pancreas cancers. We analyzed 215 serum samples of which 165 were obtained from clinically confirmed cancer patients and 50 from healthy people with no evidence of cancer. The sensitivity and specificity of the protein chip were 82.4% and 94.0%, respectively. The success rate of the protein chip for detecting all 10 types of cancers varied from 57% to 100%. The value of the simultaneous measurement of multiple tumor markers using the protein chip for cancer screening lied in the higher sensitivity compared to using single tumor markers for each type of cancer. In short, protein chips may be useful in mass screening for cancer during health checkups as well as for metastasis follow-up of cancer patients.

Endogenous strychnine, nicotine, and morphine--description of hypo and hyper-strychninergic, nicotinergic and morphinergic state in relation to neuropsychiatric diseases.

Previous work from this laboratory had demonstrated the presence of endogenous morphine, strychnine and nicotine in the mammalian brain and human serum samples. Morphine is synthesised from tyrosine and strychnine and nicotine from tryptophan. This study examines the role of strychnine, nicotine and morphine in neuropsychiatric disorders. The blood levels of tyrosine, tryptophan, strychnine, nicotine and morphine were studied as also RBC membrane Na(+)-K+ ATPase activity. It was found that serum tyrosine levels were reduced and tryptophan levels elevated in all neuropsychiatric disorders studied with a reduction in RBC Na(+)-K+ ATPase activity. Nicotine was present in significant amounts in serum of patients with schizophrenia, CNS glioma and syndrome X with multiple lacunar state. Morphine was present in significant amounts only in the serum of patients with multiple sclerosis and MDP. Strychnine was present in significant amounts in the serum of patients with epilepsy, Parkinson's disease and MDP. The presence of nicotine and strychnine in significant amounts could be related to elevated tryptophan levels suggesting the synthesis of these alkaloids from tryptophan. Morphine was not detected in most of the disorders owing to low tyrosine levels noted in them. Na(+)-K+ ATPase inhibition noticed in most of the disorders could be related to decreased hyperpolarising morphinergic transmission and increased depolarising nicotinergic and strychinergic transmission. The role of morphine, strychnine and nicotine in the pathogenesis of these disorders in the setting of membrane Na(+)-K+ ATPase inhibition is discussed.

Importance of glycoproteins in human cancer.

Usefulness of cell surface glycoprotein components as markers in early detection of cancer and in monitoring progress during treatment has been evaluated. Total sialic acid (TSA), lipid bound sialic acid (LSA) and seromucoid fractions (SF) have been compared in the sera of healthy human volunteers and patients at different stages of diagnosis and treatment of leukemia, cancer of breast, cervix, and oral cavity. The levels of TSA, LSA and SF are found to be increased in cancer and is proportionate with malignancy. Their levels show decline in patients who respond well to treatment and show increase in patients with recurrence of cancer even before any clinical evidence of recurrence is available. Changes have also been noted in the glycoprotein fractions and their ratios.

Significance of serum immunoglobulin levels in conglomeration with trans-sternal phlebography in the phlebography management of breast cancer.

The study was conducted on 63 patients with breast lump and twenty normal healthy females. In benign breast disease, a significant (P < 0.001) rise in serum IgA, significant (P < 0.001) decrease in IgG and no change in IgM levels was seen before operation. A significant decrease (P < 0.001) in serum IgA and significant increase in IgG and IgM was observed post operatively. In carcinoma breast, a significant (P < 0.001) elevation in IgA, IgG and IgM levels was found pre-operatively with a concomitant decrease in serum IgA and IgG and increase in serum IgM levels, post operatively. Trans-sternal phlebography (TSP) carried out with 95.23% success has revealed significant (P < 0.001) change in the staging of carcinoma breast. The increased levels of serum immunoglobulins associated with the patients of carcinoma breast with metastasis has led to conclude that these levels, if punctuated with TSP findings can lead to better assessment of the staging of carcinoma breast and thereby its management.