Molecular Biology Of Burkitt Lymphoma

Burkitt lymphoma (BL) is an aggressive malignancy consisting of highly proliferative B-cells which infiltrate lymph nodes and other organs. The tumor cells are distinguished as B-cells by their expression of IgM and k or X light chains and by specific surface markers such as CD19 and CD20. The high proliferative rate is obvious from numerous mitotic figures. Staining for markers such as Ki67 or PCNA, which are characteristic of cycling cells, shows that almost all tumor cells are participating...

Rb1 And The Cell Cycle

The product of the RB1 gene, ppHO 1, is most of all a central regulator of the cell cycle (Figure 5.3). The RB1 protein controls the transition from the G1 to the S phase by binding to E2F1, E2F2, or E2F3 proteins and thereby repressing the promoters of genes needed for the entrance into S phase. This repression is relieved and binding to E2F alleviated when ppHO 1 becomes hyperphosphorylated5 towards the end of G1. At least two successive phosphorylations are needed to inactivate RB1....

Dna Damage And Dna Repair

> DNA in human cells is continuously subject to damage. It is in most cases appropriately repaired, leaving relatively few permanent changes. The various kinds of damage comprise chemical modification or loss of DNA bases, single strand or double strand breaks as well as intra- and interstrand crosslinks. Each type of damage can lead to mutations. An important source of mutations are DNA replication and recombination. DNA replication is a particular critical phase, during which...

Strandbreak Repair

Repair of damaged DNA bases is a permanent process in living cells. It is only one of several processes, including chemical reactions and enzymatic actions, that generate single-strand breaks in DNA. These are therefore common, and it is estimated that 100,000 DNA single-breaks occur per cell each day. In the most simple case, single-strand breaks are repaired by DNA ligase, but components from the short- and long-patch base excision repair or nucleotide excision repair systems may be needed,...

Liver Cancer

> Liver cancer is one of the major lethal malignancies worldwide. The main histological subtype is hepatocellular carcinoma, which is derived from hepatocytes, the predominant epithelial cell type in the liver, and often retains biochemical and morphological markers of hepatocyte differentiation. Hepatocellular carcinoma develops as a rule in the context of chronic inflammation and liver cirrhosis caused by the hepatitis viruses HBV or HCV, by chronic alcohol abuse, or more rarely by...

Cancer

Figure 16.2 The pathophysiological chain of HCC development in hemochromatosis different mutations in the HFE alleles) develop hemochromatosis. In fact, not all do, and only a fraction of these progress towards cirrhosis and hepatocellular cancer (Figure 16.2). This demonstrates that further factors modulate the risk of inflammation and cancer. Nowadays, patients with early signs of hemochromatosis disease can be treated with iron chelators to prevent organ damage, cirrhosis, and cancer. Figure...

Stomach Cancer

Stomach cancer (or gastric cancer) is the second most frequent cause of cancer death worldwide with almost 1 million new cases per year. It poses a serious health problem because of its low cure rate and its severe impact on the quality of life. Fortunately, its incidence has plummeted in many industrialized countries for several decades. The causes of this unique decrease are presumed in improved hygiene, altered diet, and widespread use of antibiotics reducing the prevalence of Helicobacter...

Vonhippellindau Syndrome And Renal Carcinoma

Von-Hippel-Lindau (VHL) syndrome is inherited in an autosomal-dominant fashion, with high penetrance, but variability in its phenotype. The most distinctive lesions in this multi-organ syndrome are angiomas and hemangioblastomas in the retina and cerebellum, respectively. Frequently, the patients also develop adenomas and cysts of the pancreas, epididymis, and the kidneys. All these tumors are benign, but 30 of VHL patients develop RCC, which can be bilateral and multifocal. It is always of the...

Dna Methylation

Dnmt3a Dnmt3b Novo Methylation

DNA methylation is instrumental for both imprinting and X-chromosome inactivation. In mammals, physiological methylation of DNA is restricted to the 5-position of cytosine residues, and again only to those in CpG dinucleotides. Since CG is a palindromic sequence, a CpG site can be non-methylated, hemi-methylated, i.e. in one strand only, or fully methylated, i.e. symmetrically in both strands (Figure 8.4). Except during replication, the usual state of methylated sites in human DNA is...

Info

Epithelial cells, is induced by androgens, and is very likely necessary for the proper differentiation of prostate epithelium. Knockout mice engineered to lack the factor fail to develop a functional prostate and hemizygous mice display hyperproliferation of the prostate epithelium. In these respects, NKX3.1 is as good a tumor suppressor candidate as they come. The problem prohibiting its general acceptance as a tumor suppressor is that in most prostate cancers, including those with LOH or...

Breast Biology

In adult humans, structures like the epidermis ( 12) and the colon mucosa ( 13) undergo a constant turnover, whereas others like the liver parenchyma ( 16) and urothelium ( 14) only proliferate significantly for the purpose of repair after damage. Breast tissue is different from all of these (Figure 18.1). First of all, the organ does not develop fully before puberty, so there is one additional growth phase during the second decade of life. During puberty, the immature ducts elongate into the...

Oncogenes

> The first group of oncogenes to have been discovered form parts of the genomes of acutely transforming retroviruses, which cause hematological or soft tissue cancers in their avian or mammalian hosts. They act in a dominant manner and confer altered growth properties and morphology on specific target cells in mesenchymal tissues or the hematopoetic system. > A second group of oncogenes consists of host proto-oncogenes that become activated when the insertion of slowly transforming...

Limitations Of Current Cancer Therapies

Today, surgery, radiotherapy, and chemotherapy, i.e. 'scalpel, ray, and pill', remain the standard tumor therapies. Novel therapies like gene therapy or immunotherapy are only administered in the setting of experimental studies. In addition, outside 'school' medicine, a variety of 'alternative' treatments are sought by patients and their families who do not have full confidence in standard therapies. This scepticism is, unfortunately, not entirely unfounded. With current therapies, between 30...

Epigenetics Of Cell Differentiation

Genetic changes like the loss of RB1 function or that of a chromatin remodeling protein like hSNF5 INI1 cause cancer by obliteration of epigenetic mechanism in which these proteins are involved. It is perhaps not incidential that the cancers caused in these instances impress primarily as failures of differentiation. One could go one step further and ponder whether some cancers might be caused by purely epigenetic mechanisms and represent a specific, if aberrant form of cell differentiation....

Intravasation

Micrometastasis Formation Stroma Activation Figure 9.1 Steps of invasion and metastasis (3) The tumor continues its growth into the connective tissue. This is one of the more variable steps. Some carcinomas continue to grow as solid, coherent masses compressing the neighboring connective tissue or develop processes that spread into it, breaking up the extracellular matrix (ECM). From other carcinomas, small groups of cells or single cells split off and migrate into the underlying tissue,...

Slowacting Transforming Retroviruses

Slow-acting transforming retroviruses are as a rule replication-competent and do not transduce oncogenes. Instead, they cause transformation by integrating within or in the vicinity of cellular genes and altering their expression. In this fashion they convert cellular genes from proto-oncogenes into oncogenes in a cis-acting manner. Integration of a slow-acting retrovirus disrupts negative regulatory elements of the targeted gene and or activates its transcription by the transcriptional...

Principles Of Targeted Drug Therapy

One strategy to circumvent the problems associated with conventional chemotherapy ( 22.2) is to develop drugs against more specific targets in the cancer. This is not a fundamentally novel idea. Many drugs in current use interact with highly specific targets such as microtubular proteins or topoisomerase enzymes ( 22.2). Their targets are not specific to cancers, though. Those drugs called 'biological agents' in the previous section come closer to the ideal, since they act on specific receptor...

Cell Protection Mechanisms In Cancer

Exogenous carcinogens and potential mutagens arising from endogenous processes are often prevented from encountering DNA by specific cellular protections mechanisms. These highly diverse mechanisms serve as a further tier of cancer prevention in addition to DNA repair and apoptosis. Often, they protect not only DNA, but cells in general from damage. Some of these mechanisms are very specific and some are very general. In the context of cancer, they are particularly important during two very...

Genes And Proteins Involved In Extracellular Matrix Remodeling During Tumor Invasion

The structure of the extracellular matrix is generated by a backbone of fibrillar proteins and proteoglycans. This matrix is in a dynamic state. Structural proteins are synthesized by fibroblasts and other cells embedded in connective tissue. These same cells, together with cells of the immune system and from blood vessels, are responsible for the turnover of the extracellular material. Turnover and remodeling of the ECM are enhanced during inflammation and wound repair, as they are during...

Wolfgang Arthur Schulz

Department of Urology and Center for Biological and Medical Research, Heinrich Heine University, Dusseldorf, Germany eBook ISBN 1-4020-3186-6 Print ISBN 1-4020-3185-8 2005 Springer Science + Business Media, Inc. No part of this eBook may be reproduced or transmitted in any form or by any means, electronic, mechanical, recording, or otherwise, without written consent from the Publisher Created in the United States of America Visit Springer's eBookstore and the Springer Global Website Online at...

Invasion And Metastasis

The spread of solid cancers beyond the confinements of their tissue compartment into other parts of the same tissue and successively into neighboring tissues (invasion) and distant organs (metastasis) is the defining property of malignancy. Invasion and metastasis are decisive for the clinical course of most cancers. > Invasion and metastasis are complex processes, particularly in carcinomas, since normals epithelia are strongly adherent and are confined by a basement membrane. Before or...

Histology And Etiology Of Bladder Cancer

Urothelium Histology

From the renal pelvis through the urinary bladder into the urethra, the urinary tract is lined by a specialized 'transitional' epithelium called 'urothelium' (Figure 14.1), whose structure is in several respects different from that of squamous epithelia in the skin and other organs. The urothelium forms a low permeability barrier that prevents the components of the urine, even water, from seeping back into the body. In a transitional epithelium, cells from several layers retain contact with the...