ABSTRACT
¿Qué es el cáncer? ¿Cómo podemos prevenirlo? ¿Cómo podemos minimizar su morbilidad y mortalidad?. Nuestro acercamiento a estas preguntas depende de como nosotros conceptualizamos el cáncer. Por más de cien años, nosotros pensamos que las células tumorales están irreversiblemente fuera de control, matando inevitablemente al huésped a menos de que fueran totalmente erradicadas. Desde 1970, los Estados Unidos de Norteamérica declararon la guerra contra el cáncer. Como una real guerra, la posibilidad de batir el cáncer dependerá del poder de nuestro armamentario químico. La premisa central de este modelo asesino es: es necesario luchar nás para matar más, siendo la completa desaparición del tumor la única posibilidad de lograr la cura. Regímenes con intensificación de dosis son usados para matar la última célula. Pero hoy en día, nosotros sabemos que aunque tenemos poderosas armas, nosotros perderemos la guerra en la mayoría de nuestros pacientes. Es tiempo de parar la guerra y cambiar el paradigma del cáncer. Nosotros necesitamos comprender que el cáncer es un proceso dinámico, la consecuencia clínica de los sistemas regulatorios normales parcialmente fuera de control. Este proceso está caracterizado por un desequilibrio regulatorio y este desequilibrio es potencialmente reversible. Esto significa que la cura funcional no requiere una remisión completa. Además, las estrategias asesinas pueden ser contraproducentes. Nuevas tendencias en el diagnóstico y tratamiento y sus resultados dependerán de este nuevo modelo regulatorio. El modelo regulatorio cambia la manera aunque nosotros investigamos, prevenimos y tratamos el cáncer. Le atrae la próxima gran aventura en oncología.
Subject(s)
Humans , Concept Formation , Neoplasms/etiology , Neoplasms/prevention & control , Neoplasms/therapy , Tumor Cells, Cultured/physiology , Growth Substances , Neoplasm Regression, Spontaneous , Neoplasm StagingABSTRACT
This article reviews recent results of studies aiming to elucidate modes of integrating signals initiated in ACTH receptors and FGF2 receptors, within the network system of signal transduction found in Y1 adrenocortical cells. These modes of signal integration should be central to the mechanisms underlying the regulation of the G0->G1->S transition in the adrenal cell cycle. FGF2 elicits a strong mitogenic response in G0/G1-arrested Y1 adrenocortical cells, that includes a) rapid and transient activation of extracellular signal-regulated kinases-mitogen-activated protein kinases (ERK-MAPK) (2 to 10 min), b) transcription activation of c-fos, c-jun and c-myc genes (10 to 30 min), c) induction of c-Fos and c-Myc proteins by 1 h and cyclin D1 protein by 5 h, and d) onset of DNA synthesis stimulation within 8 h. ACTH, itself a weak mitogen, interacts with FGF2 in a complex manner, blocking the FGF2 mitogenic response during the early and middle G1 phase, keeping ERK-MAPK activation and c-Fos and cyclin D1 induction at maximal levels, but post-transcriptionally inhibiting c-Myc expression. c-Fos and c-Jun proteins are mediators in both the strong and the weak mitogenic responses respectively triggered by FGF2 and ACTH. Induction of c-Fos and stimulation of DNA synthesis by ACTH are independent of PKA and are inhibited by the PKC inhibitor GF109203X. In addition, ACTH is a poor activator of ERK-MAPK, but c-Fos induction and DNA synthesis stimulation by ACTH are strongly inhibited by the inhibitor of MEK1 PD98059.
Subject(s)
Humans , Animals , Adrenal Cortex/cytology , Receptors, Corticotropin/physiology , Signal Transduction/physiology , Adrenal Cortex Neoplasms , Cell Cycle/physiology , Mitogen-Activated Protein Kinase Kinases/metabolism , Protein Kinase C/metabolism , Receptors, Fibroblast Growth Factor/physiology , Tumor Cells, Cultured/physiologyABSTRACT
Depletion of chloramphenicol acetyl transferase [CAT] activity was clearly observed in Hu-h7 [high alpha fetoprotein [AFP]] cultured cells, when the cells were transfected with thymidine Kinase [TK] CAT plasmid. On the contrary, Hu-h1/Cl-2 cells [low AFP] had high CAT activity after transfection with the same plasmid. Hu-h7 and Hu- hl/Cl-2 cells exhibited high and very low CAT positive reaction, respectively, when the cells were transfected with AFP 7300 plasmid. Both cell lines showed negative CAT reaction, when the cells were transfected with albumin-CAT as well as AFP 1000 plasmids [AFP deleted enhancers]. The results revealed some differences between human hepatoma cell lines characterized by high and low AFP gene expression in term of gene transfection patterns indicated by CAT assay. This finding could open new avenues for better differential diagnosis of patients suffering from liver cancer
Subject(s)
Humans , Male , Liver Neoplasms/diagnosis , Tumor Cells, Cultured/physiology , Transfection , alpha-Fetoproteins/genetics , Gene Expression , Chloramphenicol O-AcetyltransferaseABSTRACT
CD44 is a glycoprotein expressed in a wide variety of cell types. Recently expression of some alternatively-spliced variants of CD44 transcripts (CD44v) has been suggested to play a potential role in tumor metastasis and the detection of CD44v containing exon 6 to 11 may be helpful for the diagnosis of cancers. Expressions of CD44v containing exon 6 to 11 were investigated in 20 human colorectal cancer samples, peripheral blood leukocytes isolated from colorectal cancer patients, and 4 colorectal cancer cell lines using reverse transcription-polymerase chain reaction and Southern blot analysis. The standard form of CD44 transcripts was expressed in all samples tested. CD44v containing exon 6 to 11 was expressed in 18 cases of colorectal cancers (sensitivity = 90%), 3 out of 4 cell lines, and one normal tissue (specificity = 95%). These results suggest that the expression of CD44v containing exon 6 to 11 can be regarded as tumor specific and that this marker may be helpful for the early diagnosis of colon cancers, if specimens from the early stage are available.
Subject(s)
Adult , Aged , Female , Humans , Male , Adenocarcinoma/genetics , Hyaluronan Receptors/genetics , Base Sequence , Blotting, Southern , Colorectal Neoplasms/diagnosis , DNA Primers , Electrophoresis, Agar Gel , Feces/chemistry , Gene Expression Regulation, Neoplastic/genetics , Middle Aged , Molecular Sequence Data , Polymerase Chain Reaction , RNA Splicing/physiology , RNA, Messenger/analysis , Tumor Cells, Cultured/physiology , Biomarkers, TumorABSTRACT
El presente trabajo es una revision de los pacientes con tumores Oseos y Tumores de partes Blandas atendidas en el Hospital Oncologico de Santa Cruz en el periodo 1986-1993 con 62 casos. No se incluyen los pacientes revisados en la consulta externa, solo aquellos pacientes internados.
Subject(s)
Humans , Male , Female , Adult , Soft Tissue Neoplasms/surgery , Soft Tissue Neoplasms/nursing , Soft Tissue Neoplasms/physiopathology , Bone and Bones/anatomy & histology , Bone and Bones/abnormalities , Bone and Bones/physiology , Bone Neoplasms/diagnosis , Bone Neoplasms/nursing , Bone Neoplasms/etiology , Tumor Cells, Cultured/physiology , Tumor Cells, Cultured/pathologyABSTRACT
Se sabe que ciertas preparaciones tímicas son capaces de estimular la liberación de corticotrofina (ACTH) en células hipofisarias. No resulta claro, sin embargo, si este efecto es mediado por el receptor para la hormona liberadora de ACTH (CRH). En el presente estudio se observó que la timosina fracción cinco (TF5), el péptido tímico MB-35 y posiblemente ciertas histonas de timo de ternera son capaces de estimular la liberación de ACTH en una sublínea insensible al CRH derivada de la línea tumoral coricotropa AtT20 y por lo tanto denominada AtT20(Cl). El rango de concentraciones efectivas en el cual TF5 y MB-35 mostraron un efecto dosis-dependiente sobre la liberación de ACTH fue de 100 a 2000 µg/ml y de 10 a 100 mg/ml para TF5 y MB-35, respectivamente. Aunque ninguna de estas preparaciones indujo cambios significativos en el contenido intracelular de ACTH en las células AtT20(Cl), se observó una tendencia hacia la depleción a las dosis más altas de RF5. Los resultados obtenidos sugieren que ciertos péptidos tímicos son capaces de estimular la liberación de ACTH en células corticotropas por un mecanismo independiente del receptor par CRH
Subject(s)
Animals , Mice , Adrenocorticotropic Hormone/metabolism , Corticotropin-Releasing Hormone/metabolism , Thymus Hormones/pharmacology , Tumor Cells, Cultured/physiology , Analysis of Variance , Immunoradiometric Assay , Oligopeptides/pharmacology , Thymosin/pharmacologyABSTRACT
Um painel de atividade NK nos indivíduos normais de nossa populaçäo foi obtido através da realizaçäo de 221 ensaios em 40 indivíduos, sendo 26 do sexo masculino e 14 do sexo feminino; um padräo próprio de atividade NK para as pessoas testadas com maior freqüência foi encontrado, apesar da grande variabilidade intra-individual. Näo foi encontrada diferença significativa entre a atividade NK de homens e mulheres e entre as diversas faixas etárias, sendo a literatura controversa em relaçäo a esses parâmetros. Apesar do pequeno número de indivíduos testados, nossos dados coincidem com os obtidos de populaçöes norte-americanas. A semelhança dos resultados apresentados pode decorrer do fato de a maioria de nossa amostra ser extraída de um padräo sócio-econômico elevado, näo apresentando problemas de desnutriçäo, embora envolvesse pessoas de diferentes origens étnicas