GENES Y Cancer

Genes y Cancer. : 

Genes y Cancer.

‘Seed’ or ‘Soil’ : 

‘Seed’ or ‘Soil’ Stephen Paget (1855–1926) was an English surgeon — son of the famed surgeon Sir James Paget. Stephen Paget trained at St Bartholomew’s Medical School, and then practiced surgery in London.He developed a strong interest in supporting research into cancer, and in 1908 he founded the Royal Defense Society to provide scientific input into the animal-welfare debate and to support the need for animal research for the benefit of cancer patients.

‘Seed’ or ‘Soil’ : 

‘Seed’ or ‘Soil’ On the basis of his numerous observations of cancer patients, he published an article in 1889 in The Lancet, which commented on the propensity of some types of cancer to give rise to secondary growth (‘metastasis’) in specific organs.

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Exon 17 Lys642Glu Asn822Lys or Asn822His Between Lys550 and Gly592 Type of mutations Frequency of mutations 5-15% 70-85% ~2% ~2% No mutation:5%-10% (juvenile GIST, NF-1 GIST) Asp842Val ets Exon 18 ~2% Various mutation types Exon 12 5-10% Asn659Lys or Asn659Tyr Exon 14 ~1% Asn655Lys ~1% Duplication of Ala502 & Tyr503 Exon 11 Exon 13

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Exon 11 Exon 13 Exon 17 Duplication of Ala502 & Tyr503 Lys642Glu Asn822Lys or Asn822His Between Lys550 and Gly592 Type of mutations Frequency of mutations 5-15% 70-85% ~2% ~2% No mutation:5%-10% (juvenile GIST, NF-1 GIST) Asp842Val ets Exon 18 ~2% Various mutation types Exon 12 5-10% Asn659Lys or Asn659Tyr Exon 14 ~1% Asn655Lys ~1%

Enfermedad metastasica. : 

Enfermedad metastasica. “Las Metastasis resultan, de la diseminacion de celulas del cancer de un sitio primario, y su crecimiento en organos distantes.

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Las metastasis en ocasiones parecen tener un patron especifico de diseminacion ;v.g. ca de mama y prostata metastasize to bone — lo cual puede tomar años,or even decades after apparently successful primary treatment.

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When cancer is detected at an early stage, before it has spread, it can often be treated successfully by surgery or local irradiation, and the patient will be cured. However, when cancer is detected after it is known to have metastasized, treatments are much less successful. Furthermore, for many patients in whom there is no evidence of metastasis at the time of their initial diagnosis, metastases will be detected at a later time.

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La mayoria de las muertes por cancer,son consecuencia de las Metastasis,mas que del primario.

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Blood flow and other mechanical factors influence the delivery of cancer cells to specific organs, whereas molecular interactions between the cancer cells and the new organ influence the probability that the cancer cells grow

Metastasis : 

Metastasis Producto final de un proceso evolutivo Con diversas interacciones entre celulas cancerosas y su microambiente.

Cancer de mama : 

Cancer de mama Gene-expression signatures: Predict clinical outcome , Generally do not overlap , Range from a 70-gene “poor-prognosis” signature (detected with the use of the MammaPrint test) to a hand-picked set of 21 “recurrence” genes (detected with the use of the Oncotype Dx test) that includes estrogenreceptor,HER2, and proliferation markers.

El valor del estadiaje. : 

El valor del estadiaje. Reflejar la capacidad de metastatizar del cancer primario.

Resumen. : 

Resumen. Metastasis resultan de una serie de pasos secuenciales. Desprendimiento de celulas del primario en la circulacion, sobrevivencia , arresto en el nuevo organo,iniciacion y mantenimiento del crecimientod y vascularization del tumor metastasico.

Summary : 

Summary ‘seed’ (the cancer cell) and ‘soil’ (factors in the organ environment) contribute to this organ specificity. Mechanical factors influence the initial fate of cancer cells after they have left a primary tumour.Blood-flow patterns from the primary tumour determine which organ the cells travel to first. There, the relative sizes of cancer cells and capillaries lead to the efficient arrest of most circulating cancer cells in the first capillary bed that they encounter.

Summary : 

Summary Some types of tumour show an organ-specific pattern of metastasis.Both ‘seed’ (the cancer cell) and ‘soil’ (factors in the organ environment) contribute to this organ specificity. Mechanical factors influence the initial fate of cancer cells after they have left a primary tumour.Blood-flow patterns from the primary tumour determine which organ the cells travel to first. There, the relative sizes of cancer cells and capillaries lead to the efficient arrest of most circulating cancer cells in the first capillary bed that they encounter.

Summary : 

Summary •Metastasis is an inefficient process. In vivo videomicroscopy and cell-fate analysis have led to the conclusion that early steps in metastasis are completed very efficiently.By contrast, later steps in the process are inefficient.Metastatic inefficiency is due primarily to the regulation of cancer-cell growth in secondary sites. •

Summary : 

Summary •Metastases can occur many years after primary cancer treatment.Tumour dormancy might be due to pre-angiogenic micrometastases that subsequently acquire the ability to become vascularized, or solitary cells that persist for an extended period of time without division in a secondary site.These cells would be resistant to current cancer therapies that target actively dividing cells. • Because growth of metastases is a primary determinant of metastatic outcome, the growth phase of the metastatic process is a promising therapeutic target.Treatments that target the specific ‘seed–soil’ compatibility that results in

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Correspondence between Molecular Class and Clinicopathological Features of Breast Cancer. Sotiriou C, Pusztai L. N Engl J Med 2009;360:790-800.

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Colorectal Mama 20% Breast Breast . Mama Prostata GI 10% Pulmon 60%

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Model of the Role of Activated β-Catenin in the Progression of CML. Jamieson CH et al. N Engl J Med 2004;351:657-667.

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Assessment of the Risk of Cancer in Patients with Solitary Pulmonary Nodules. Ost D et al. N Engl J Med 2003;348:2535-2542.

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Approach to the Management of Solitary Pulmonary Nodules. Ost D et al. N Engl J Med 2003;348:2535-2542.

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Table 1. Patterns of Genomic Instability in Colorectal Cancer.* Type of Instability and Syndrome Type of Defect Genes Involved Phenotype Chromosomal instability — loss of heterozygosity at multiple loci Somatic Loss of heterozygosity at APC, TP53, SMAD47,8 Characteristic of 80 to 85% of sporadic colorectal cancers, depending on stage DNA mismatch-repair defects Hereditary nonpolyposis colon cancer Germ-line MLH1, MSH2, MSH6 germ-line gene mutations9- 14 Multiple primary colorectal cancers, accelerated tumor progression, and increased risk of endometrial, gastric, and urothelial tumors Sporadic colorectal cancer with mismatch-repair deficiency Somatic MLH1 somatic methylation15- 17 Colorectal cancer with increased risk of poor differentiation, more commonly located in right colon, less aggressive clinical behavior than tumors without mismatch-repair deficiency CpG island methylator phenotype — methylation target loci Somatic Target loci MLH1, MINT1, MINT2, MINT318-23 Characteristic of 15% of colorectal cancers, with most showing mismatchrepair deficiency from loss of tumor MLH1 expression Base excision repair defect — MYH-associated polyposis Germ-line MYH24-26 Development of 15 or more colorectal adenomas with increased risk of

Table 1. Patterns of Genomic Instability in Colorectal Cancer.*Type of Instability and SyndromeType of : 

Table 1. Patterns of Genomic Instability in Colorectal Cancer.*Type of Instability and SyndromeType of Defect Genes Involved Phenotype Chromosomal instability — loss of heterozygosity at multiple loci Somatic Loss of heterozygosity at APC, TP53, SMAD47,8 Characteristic of 80 to 85% of sporadic colorectal cancers, depending on stage DNA mismatch-repair defects Hereditary nonpolyposis colon cancer Germ-line MLH1, MSH2, MSH6 germ-line gene mutations9- 14 Multiple primary colorectal cancers, accelerated tumor progression, and increased risk of endometrial, gastric, and urothelial tumors Sporadic colorectal cancer with mismatch-repair deficiency Somatic MLH1 somatic methylation15- 17 Colorectal cancer with increased risk of poor differentiation, more commonly located in right colon, less aggressive clinical behavior than tumors without mismatch-repair deficiency CpG island methylator phenotype — methylation target loci Somatic Target loci MLH1, MINT1, MINT2, MINT318-23 Characteristic of 15% of colorectal cancers, with most showing mismatchrepair deficiency from loss of tumor MLH1 expression Base excision repair defect — MYH-associated polyposis Germ-line MYH24-26 Development of 15 or more colorectal adenomas with increased risk of

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Copyright restrictions may apply. Starzl, T. E. et al. JAMA 2009;301:2041-2043. Characteristics of the First Successful Transplantations of Kidney Allografts With >=6 mo Survival as of March 1963

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La Proliferacion celular permite el crecimiento del organismo,hasta llegar a una poblacion de cien billones de celulas Dicha Capacidad se preserva en algunos linajes celulares.

Siglo XIX-Mitosis. : 

Siglo XIX-Mitosis. La Meiosis- Microscopio.

La Meiosis- Microscopio. : 

La Meiosis- Microscopio. Siglo XIX-Mitosis.

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Huntington's Chorea Malekpour M, Esfandbod M. N Engl J Med 2010;363:

Triple-Negativo, Cancer de Mama. : 

Triple-Negativo, Cancer de Mama. Aproximadamente 10 a 15% de las pacientes con cancer de mama,son “triple-negativo”. Los tumores Triple- negativo tienen relativamente,pobres resultados;no pueden tratarse con terapia endocrina, o terapias “blanco” al factor epidermico de crecimiento receptor tipo 2 humano (HER2).

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Una variedad del triple-negative es el cancer basal-like (terminos sinonimo incluyen “basal-type,” “basal-epithelial phenotype,” “basal breast cancer,” and “basaloid breast cancer”).

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Este subtipo molecular de cancer de mama esta caracterizado por una expresion genetica, similar al de la capa basal–myoepithelial de la mama normal .2

Breast-Cancer Subtypes.*p1942 : 

Breast-Cancer Subtypes.*p1942 Table 1. Key Features of Triple-Negative, Basal-like, and BRCA1-Related Breast Cancers as Compared with All Other Breast-Cancer Subtypes.*

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Histologic and Immunohistochemical Features of Triple-Negative and Core Basal-like Breast Cancers. Foulkes WD et al. N Engl J Med 2010;363:1938-1948.

Triple-Negative† : 

Triple-Negative† NNN Ductal G 3,2 Er –pr negativos HER2 NEG EGFR + CK5 17 + CYK E + BASAL Ductal G 3 Er –pr negativos

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Key Features of Triple-Negative, Basal-like, and BRCA1-Related Breast Cancers as Compared with All Other Breast-Cancer Subtypes. Foulkes WD et al. N Engl J Med 2010;363:1938-1948.

Pronostico Molecular. : 

Pronostico Molecular. NNN MUTACION TP53 ANEUP ALTA GENOP BASAL LIKE A 5Y INT. RARO RELAPS AFTEEER 10Y BASAL USUAL ALTA SI

El cancer de mama Triple-negativo : 

El cancer de mama Triple-negativo Incluye al so-called claudin-low tumors, que contiene celulas con propiedades similares a stem cells and to have features of epithelial-to-mesenchymal transition; The interferon-rich subgroup, better prognosis than that associated with other triple-negative breast cancers;

Triple-negative breast cancers : 

Triple-negative breast cancers And the normal-breast–like subgroup, which may be an artifact (i.e., it may comprise samples enriched with a disproportionately high content of stromal and normal cells).6,7 Similarly, 18 to 40% of basal-like cancers do not have a triple-negative phenotype on immunohistochemical analysis.9

Triple-negative breast cancers : 

Triple-negative breast cancers Up to 20% of basal-like cancers express ER or overexpress HER2. At the genetic level, triple-negative and basal-like cancers are remarkably heterogeneous. Amplification of numerous genetic regions has been documented, but the prevalence of each of these amplified regions is low.10

OPCIONES TERAPEUTICAS : 

OPCIONES TERAPEUTICAS Triple N. Hormonal: NO Traztuzumab: NO Quimioterapia :SIN Consenso,incluye DOXO,TAX AGENTES ANTIOGENICOS,PLATINO, Inhibidores PARP . BASAL NO NO SI, NO CONSENSO.

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Overview of Cardiac Development. Epstein JA. N Engl J Med 2010;363:1638-1647.