Correlación entre las cinéticas del PSA y positividad de la tomografía por emisión de positrones 18F-PSMA-1007 en la reestadificación de la recaída del cáncer de próstata / Correlation between PSA kinetics and positivity of f18-PSMA positron emission tomography in the relapsed prostate cancer

Resumen Objetivo: Evaluar la correlación diagnóstica entre las cinéticas del antígeno específico de la próstata (PSA) y la positividad de la PET/TC 18F-PSMA en pacientes con cáncer de próstata con recaída bioquímica (RCP, recurrencia del cáncer de próstata). Material y métodos: Se realizó un trabajo observacional de corte transversal de pacientes con una RCP que fueron evaluados con PET/TC 18F-PSMA-1007 en los que se analizó la concordancia entre el PET/TC PSMA y las cinéticas del PSA. Resultados: Se analizaron un total de 54 pacientes. La edad media fue de 68 ± 8 años. El PSA disparador de la PET/TC mostró una mediana (Q1-Q3) de 3,14 (0,73-8.69) ng/ml. La PET/TC colina mostró una tasa de positividad del 35%, mientras que la PET/TC 18F-PSMA mostró una tasa de positividad del 80%, pero con un PSA disparador ≥ 2 ng/ml la PET/TC 18F-PSMA tuvo un 100% de positividad; mientras que la PET/TC colina un 55% de positivos. En la valoración de las cinéticas de PSA para PET/TC PSMA las curvas ROC mostraron para PSAV un área bajo la curva de 0,93 (IC 95%: 0,83-1; p = 0,0001), presentado el punto de corte 0,85 ng/ml/año una sensibilidad del 88% y una especificidad del 87%. El 97% de las PET/TC 18F-PSMA fueron positivas con un PSAV > 0,85 ng/ml/año (p = 0,0001). Mientras que las curvas ROC mostraron para PSADT un área bajo de la curva de 0,38 (IC 95%: 0,21-0,57; p = 0,321) sin evidenciar valor diagnóstico. Conclusión: Se evidenció que el PSAV fue un muy buen predictor de positividad en la PET/TC 18F-PSMA en pacientes con RCP, no así el PSADT.

Abstract Introduction: Prostate-specific antigen (PSA) kinetics (PSA velocity [PSAV] and PSA doubling time [PSADT]) are predictors of positivity in Choline PET/CT, but this correlation has not been correctly established in PSMA PET/CT. Objective: To evaluate the diagnostic correlation between PSA kinetics and positivity of 18F PSMA PET/CT in patients with relapsed prostate cancer (RPC). Material and methods: We performed an observational cross-sectional study of 54 patients with RPC that were evaluated with 18F-PSMA PET/CT. The concordance between 18F-PSMA PET/CT and PSA kinetics was analyzed. Results: The mean age was 68 ± 8 years. Time to relapse had a median (Q1-Q3) of 29 (8; 48) months. The trigger PSA showed a median of 3.14 (0.73-8.69) ng/dl. 18F-PSMA PET/CT showed a positivity of 80%. The ROC curves showed an AUC of 0.93 for PSAV (95%CI0.83-1; p = 0.0001). A cut-off points of 0.85 ng/ml/year showed a sensitivity of 88% and a specificity of 87%. 97% of the 18F-PSMA PET/CT were positive with a PSAV > 0.85 ng/ml/year (p = 0.0001). While the ROC curves showed an AUC of 0.38 for PSADT (95%CI 0.21- 0.57; p = 0.321) without showing diagnostic value. Conclusion: PSAV was a predictor of positivity in 18F-PSMA PET/CT in patients with RPC, but PSADT was not.

Analysis of the Electrophoretic Profiles of Prion Protein in Carcinous and Pericarcinous Lysates of Six Different Types of Cancers / 生物医学与环境科学（英文）

Objective@#To find the different electrophoretic profiles of prion protein in carcinous and individual pericarcinous tissues in lysates of gastric, colon, liver, lung, thyroid, and laryngeal cancers.@*Methods@#Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot were used to test the amounts and electrophoretic patterns of total PrP and the tolerance of PK (protease K) digestion among six various cancer tissue types.@*Results@#A mass of PrP signals with a large molecular weight were identified in the homogenates of peripheral tissues. The amounts and electrophoretic patterns of total PrP did not differ significantly between carcinous and pericarcinous tissues. PrPs in all types of the tested cancer samples were PK sensitive but showed diversity in the tolerance of PK digestion among various tissue types.@*Conclusions@#The study revealed that the included electrophoretic patterns of carcinous and pericarcinous tissues were almost similar. Unlike PrP-specific immunohistochemical assay, evaluation of PrP electrophoretic patterns in the peripheral organs and tissues by Western blot does not reflect tumor malignancy.

Development of imunohistochemistry services for cancer care in western Kenya: implications for low-and middle-income countries

Background: Cancer is becoming a major cause of mortality in low- and middle-income countries. Unlike infectious disease; malignancy and other chronic conditions require significant supportive infrastructure for diagnostics; staging and treatment. In addition to morphologic diagnosis; diagnostic pathways in oncology frequently require immunohistochemistry (IHC) for confirmation. We present the experience of a tertiary-care hospital serving rural western Kenya; which developed and validated an IHC laboratory in support of a growing cancer care service. Objectives; methods and outcomes: Over the past decade; in an academic North-South collaboration; cancer services were developed for the catchment area of Moi Teaching and Referral Hospital in western Kenya. A major hurdle to treatment of cancer in a resource-limited setting has been the lack of adequate diagnostic services. Building upon the foundations of a histology laboratory; strategic investment and training were used to develop IHC services. Key elements of success in this endeavour included: translation of resource-rich practices to are source-limited setting; such as using manual; small-batch IHC instead of disposable- and maintenance-intensive automated machinery; engagement of outside expertise to develop reagent-efficient protocols and supporting all levels of staff to meet the requirements of an external quality assurance programme. Conclusion: Development of low- and middle-income country models of services; such as the IHC laboratory presented in this paper; is critical for the infrastructure in resource-limited settings to address the growing cancer burden. We provide a low-cost model that effectively develops these necessary services in a challenging laboratory environment

Mecanismos da toxidez de FGF2 em células malignas dependentes de Ras: bloqueio de divisão celular e estresse proteotóxco / Mechanisms of FGF2 toxicity in Ras-driven malignant cells cell division blockage and proteotoxic stress

FGF2 ( Fibroblast Growth Factor 2) é o membro fundador de uma grande família de fatores de crescimento proteícos. Sua atividade se dá através da ligação e ativação de receptores especificos da membrana (FGFRs) com atividade de tirosina quimase. No organismo adulto, a simalização de FGF2 está envolvida na indução de processos de sobrevivência, proliferação e diferenciação celular; além de cicatrização e angiogênese. Por atuar como um clássico fator de crescimento, a atividade de FGF2 está frequentemente implicada em mecanismos pró-tumorais....

FGF2 is the first member of a large family of peptide growth factors. It binds and activates specific membrane receptors ( FGFRs) belonging to a family of tyrosine kinase receptors (RTK). in adult organisms, FGF2 signaling is involved in the induction of cell surveillance, proliferation and differentation; and also wound healing and angiogenesis. FGF2 is a bona fide growth factor and, as such, it is often implicated in pro-tumor mechanisms...

Banco de tumores en Chile, su aporte a la investigación: resultados de un proyecto piloto / A pilot experience with a tumor bank

Background: Despite having the technical facilities and the knowledge, Chile did not have a tumor bank until recently. Aimn: To describe the results of the first three years of a tumor bank. Material and methods: All cases stored in a tumor bank from June 2004 tojune 2007 were included. Samples were frozen in isopentane, afterwards in liquid nitrogen and finally transferred to freezers at -80°C. Quality controls with DNA and RNA extraction and immunohistochemistry, were per formed. Results: In the study period, 1239 cases were collected and 79 percent were malignant tumors. In 78 percent of cases, samples from the tumor and of normal neighaboring tissue, were stored. Twenty six percent of samples were from breast cáncer and 22 percent for digestive tumors. Immunohistochemical expression ofvimentin was measured in 30 cases and the expression of Ki67 an p53 in 20 cases. Thirteen of 15 breast cáncer samples had expression of estrogen receptors. In 30 cases, DNA and RNA extraction was carried out, amplifying B-globin and B-actin. Moreover RNA was extracted from 63 gastríc cáncer, 30 colon cáncer and gallbladder cáncer samples, for specific projects. Conclusions: The creation of a tumor bank is feasible, preserving samples of high biológical quality.

La bioquímica del antígeno específico de próstata (AEP) y sus fracciones / The biochemistry of prostate specific antigen (PSA) and its fractions

El antígeno específico de próstata (AEP) es una kalicreína que está entre los varios tipos de sustancias que secreta la próstata en su función como glándula accesoria de la reproducción. En el semen actúa como una proteasa con preferencia desnaturalizante sobre las semenogelinas, las proteínas procoagulantes del semen producidas en la vesícula seminal, pero que como cualquier proteasa tiene un potencial adicional para metabolizar cualquier proteína. Es por esa acción destructora que la naturaleza toma todas las precauciones para que el AEPproteasa tenga un período de actividad efímero y una serie de fracciones clivadas o desactivadas que explican en su conjunto los porcentajes en plasma del antígeno total y libre en el paciente normal y con patologías. El AEP puede dividirse de una manera simple en dos tipos básicos: activo e inactivo, o bien libre y complejo. Hacia el futuro puede esperarse que el uso del AEP como marcador de cáncer pueda refinarse en sensibilidad y especificidad con el uso de fracciones que se relacionen matemáticamente y además con el uso de otros tipos de antígenos como el antígeno de membrana específico de próstata (PSMA, prostate specific membrane antigen) y el antígeno de células madre de próstata (PSCA, prostate stem cell antigen).

Neutron KERMA factors of human tissues

A program to calculate the neutron KERMA in human tissues has been developed. The program was developed in Mathcad and contains the neutron kerma factors of those elements that are present in different human tissues. Having the elemental composition of any human tissue the neutron kerma can be easily calculated. The program was tested using the elemental composition of tumor tissues such as sarcoma, melanoma, carcinoma and adenoid cystic. Neutron kerma for adipose and muscle tissue for normal adult was calculated. The results are in agreement with those published in literature. The neutron kerma for water was also calculated because in some dosimetric calculations water is used to describe normal and tumor tissues. From this comparison was found that at larger energies kerma factors are approximately the same, but energies less than 100 eV the differences are large.

Papel del gen TP53 en la oncogénesis / Role of the gene TP53 in the oncogénesis

La oncogénesis comprende múltiples etapas que incluyen cambios dinámicos en el genoma ocasionados por diversos factores que afectan principalmente dos grandes grupos de genes: los genes supresores de tumores (GST) y los protooncogenes. ambos intervienen en diferentes e importantes procesos biológicos como la proliferación y diferenciación celular. Dentro de los GST se destaca el gen TP53 que codifica para una fosfoproteína nuclear de 53kD, la cual actúa como factor de transcripción y regula positivamente la expresión de diferentes genes de vital importancia en varios mecanismos celulares: control del ciclo celular, apoptosis, replicación y reparación del ADN, como también en el proceso de envejecimiento. Este gen conocido como "guardián del genoma", ha sido ampliamente estudiado desde su identificacíon y se encuentra alterado en cerca del 60% de todos los tumores; además, tiene notable interés para el diagnóstico y pronóstico de pacientes con cancer.

Oncogénesis is a multistep process including genomic dynamic changes induced by diverse factors mainly affecting two gene great groups: the tumor suppressor genes and proto-oncogenes. Both take part in different and important biological processes as cell proliferation and differentiation. Among the tumor suppresor genes, the gene TP53 ancodes for one 53kD nuclear phosphoprotein wich acts as trnascription factor regulating positively the expression of different and very important genes mediating several cell mechanisms, such as control cell cycle, apoptosis, DNA replication and repair. This gene, aso known as "guardian of genomic integrity", has been extensively studied and has been fond altered in near 60% of all tumors; in addition, it has remarkable interest for the diagnosis ond prognosis of cancer patients.

A dialética da representaçäo do tratamento quimioterápico para o doente oncológico: vida versus morte / Representational dialectics on the oncological patient's chemotherapic treatment: life versus death

Neste estudo buscamos compreender o que é o tratamento quimioterápico para o doente oncológico, especialmente aquele que é tratado no Ambulatório de Quimioterapia de Adultos do Hospital Säo Paulo - Universidade Federal de Säo Paulo. Optamos por buscar as representaçöes do tratamento quimioterápico para o doente oncológico através da análise de discurso e tendo o materialismo histórico e dialético como suporte teórico...

Importancia pronóstica de la medición del ADN en tumores sólidos: I. Introducción (simposio) / The prognostic importance of ADN measurement in solid tumors (symposia)

Se sabe que en los tumores sólidos ocurren frecuentemente cambios en el contenido de ADN, que reflejan cambios genéticos a nivel cromosómico, los que juegan un papel importante en el desarrollo y progresión de los mismos. El estudio citogenético de los tumores sólidos ha mostrado un cariotipo complejo, que ha dificultado la identificación de los cambios cromosómicos específicos. Sin embargo la genética molecular ha identificado a algunos genes asociados con la carcinogenesis y sus alteraciones en los tumores. La citometría de flujo se ha utilizado ampliamente en el análisis del contenido y distribución del ADN en tumores, tanto experimentalmente como en clínica, y relacionarlo en el pronóstico y su progresión. Su aplicación en oncología ha sido muy vasta, principalmente en ginecología, urología y gastroenterología, y se ha concentrado en la identificación de tumores en su estadio inicial y en su pronóstico. En este simposio se presentan la metodología empleada y los resultados obtenidos en el cáncer mamario, prostático y vesical principalmente

Expression of c-erbB-2 oncoprotein in primary human tumors: an immunohistochemistry study.

An immunohistochemical study was performed with 130 primary malignant human tumors of breast (n = 55)..colon/rectum (n = 16), stomach (n = 19), esophagus (n = 14), lung (n = 15) and liver (n = 11) using the 21N c-erbB-2 specific monoclonal antibody to identify the tumors that over-expressed the c-erbB-2 oncoprotein. Positivity appeared as an intense brown granular staining located predominantly at the cell membrane. This occurred in 41.8% of breast carcinomas, 12.5% of colorectal adenocarcinomas. None of the gastric adenocarcinomas, squamous cell carcinomas of the esophagus, small cell lung carcinomas or hepatocellular carcinomas were positive for the oncoprotein. The result of this study suggests that over-expression of the c-erbB-2 oncoprotein is common in breast cancer and relatively rare in other malignancies examined.

Plant lectins--histochemical and cytochemical applications in oncology.

Lectins are sugar binding proteins or glycoproteins of non-immune origin derived from various plants or animals with specific sugar binding capacity. This property of lectins can be used to identify structural differences between normal and malignant cells. Malignant transformation is accompanied by several changes in cell membrane. Studies have shown that the lectin binding pattern of these cells may indicate the invasive potential of tumours. Lectins can also be used as carriers. Lectins conjugated to chemotherapeutic agents has been found to be more useful in the treatment of tumours induced in animals.