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A perspective on the biology of malignant cells

Several lines of evidence, some well established and recent, argue emphatically the idea that RNA content is high in cancer cells and genetic events that lead to cancer are often linked directly or indirectly, the ribosome biogenesis . Moreover, the inverse problem is checked in the cases of "idiopathic ineffective anemia (IIE - idiopathic ineffective erythropoiesis), where there are insufficient rates of cell proliferation, and patients have erythroblasts containing only 70% of normal levels of rRNA. Then, in a situation of excessive cell proliferation (aggressive cancers) rRNA levels are amplified, whereas in a situation of insufficient cell proliferation (certain anemias marrow hypoplasia) rRNA levels are depressed. Have been developed oncobilogos investigations have shown that the expression alterations of rDNA (ribosomal deoxyribonucleic acid) and ribosomal protein genes are associated with tumor growth and cytological studies show that the nucleolus of cells cancer are increased because they have an increased transcriptional activity, representing aspects predictive of cell proliferation rate and prognosis of patients. These researchers have shown that cancer cells with high expression of these ribosomal proteins have higher content of ribosomes. The genetic alteration associated with cancer development involves, very often, changes in signaling pathways that lead to the rDNA effect. The scenario described above repeats the known cancer biologists: the ribosome biogenesis and oncogenesis are inextricably linked.

Fighting colon and rectum cancer


New biomolecular method (not invasive) for colon rectal cancer

ABSTRACT
A. FERREIRA ALEMAO, MD PhD.
Associate Professor of Universidad Complutense de Madrid Molecular Pathology and Biology Surgical Oncology Email: ribograma@gmail.com web: www.ribograma.com phone: +351 936715488 LISBON PORTUGAL

RIBOGRAMA: CONCEPT AND APPLICATIONS IN ONCOLOGIC CLINICS OF COLON AND RECTUM The purpose of this research, which is as Doctoral Thesis presented with the above title, is the following: Draft a method of diagnosis, tracking and monitoring the colon and rectum cancer founded on technical and current concepts of Molecular Biology. This Full Version the "pre-carcinoma in situ diagnostic since it is based in the phenotype of mucosal cells composed of very high Quantities of free ribosomes in its cytoplasm, Which can be quantified by means of the of the flow cytometry, after its isolation, and marked with fluorochromes. The repeated records of those Quantities of free ribosomes, established a curve graphic that represents a malignant tendency, above Which A Certain level of concentration, Allows to say that the cells in a tissue (of the colon and rectum, e.g.). Can be considered in the process of developing carcinoma in the colon-rectum mucosa, before any macroscopic viewing (endoscopy). This means, we are facing a new method, on a clear biomolecular level, as shown in this Thesis, Which Full Version for good progress on the macroscopy (endoscopy). This method exceeds the scope of other non-invasive methods of the colon-rectum (test of occult blood in feces and test of DNA mutations in the same feces, the last of which began to be clinically practiced a little more than a year in the USA and is, at the moment, only in an initial phase in Europe. Thanks to this method, it is possible to have a tracking program (through a non-invasive method with great acceptance by the population), in which all citizens who present a great curve of mandatory RIBOGRAMA must be checked with a therapeutic and diagnostic endoscopy, at the same time, remain under observation and therapy (diet food survey and non-steroidal antiinflammatory and acetylsalicylic acid), with proven efficiency in the prevention and reduction of the formation of polyps or premalignant tendency injury, representing savings in the therapeutic inversion of cancer.

Biomolecular base of the cellular machinery The Ribosome as a common element in the biomolecular process of the cells

Accumulation of ribosomes in the process of oncogenesis


In the decades of 60 and 70 were published studies on free ribosomes and ribosomes bound to membranes and their accumulation during induction of growth in many organs and tissues. In the sequence of these investigations were published studies that have attempted to quantify the accumulation of ribosomes in interfollicular areas of the dorsal skin of mice during chemical induction of neoplastic growth in two phases, through initiation by 7, 12dimethylbenz [a] anthracene and promotion caused by 12-O-tetradecanoylphorbol-13-acetate. The epidermis is a surface epithelium and, like other epithelia, which are in direct contact with the external environment, such as the linings of the respiratory and gastrointestinal, show a high incidence of neoplasms. Thus, the epidermis has served as a useful model to form a comprehensive development of the role of ribosome accumulation during neoplastic growth.

DNA

TRANSCRIPTION

m RNA

r RNA

t RNA

Ribosome TRANSLATION

Proteins

RIBOGRAMA: concept and applications


in clinical oncology of colon and rectum
Starting up project concerned with the creation of a very early diagnostic not invasive test of the cancer of colon and rectum (and after other organs and systems).
RIBOGRAMA is a new (and unique) technique in the scientific

A) Isolation of free ribosomes, with standartized techniques; B) Labeling of free ribosomes with fluorochromes; C) Counting free ribosomes, by flow cytometry. The colorectal cancer represents one of the biggest incidences of human cancer in the western type of life and cocked food. This research project has strong potential in public health, medico-hospitalar practice, clinical and laboratorial research, food industry, veterinary, oncologic research, pharmaceutical industry and clinical trials research etc., with great medical and financial impact, firstly, by now, in the lowering significantly the morbidity and mortality of the colorectal cancer disease, in the world, and, after, with other organs and systems. RIBOGRAMA is an objective and quantitative method that provides an unique service to HealthCare Providers worldwide. The method is qualified to deal within all business sectors of the worldwide HealthCare, from the sole practice physician to the largest chain of hospitals. RIBOGRAMA is well suited to be recommended and addressed to many of the challenges facing HealthCare Providers worldwide in todays everchanging business and biomedical environments (public health, medicohospitalar practice, clinical and laboratorial research, food industry, veterinary, oncologic research, pharmaceutical industry and clinical trials research etc), and also offers a certain commonly utility basis in a cross section of bioindustries worldwide. RIBOGRAMA method has no meaningful competition and is recession resistant due in part to a perpetual and potential big and wide demand where its products and services are indicated. This huge and potential big demand supports a low risk rating for its equity, which will increases its value, is liquid and has no volatility. The method forecasts profitability that supports continuous profit distributions that are reliable, predictable and potential increases annually. In summary, the timing for this business to enter the domestic and global markets could not be better! This method seems that will be a big solution for the people and the countries, through the world, to help the control (and part of the solution of) the cancer disease. A. Ferreira Alemo, MD PhD

RIBOGRAMA graphic
Conclusions, the research work:
supporting

CLINICAL LEVEL ALARM LEVEL INCREASED EVEL NORMAL LEVEL LOW LEVEL ZERO LEVEL

community that results from a research on colon and rectum cancer (CRC), in the UNIVERSIDAD COMPLUTENSE DE MADRID (SPAIN), concerning the design and construction of a kit to collect stools and early diagnosis of CRC, through the calculation of the quantity of free ribosomes in colonocytes of stools, before people doing any colonoscopy to check premalignant lesions. The goal derives from the research of a doctoral thesis, in which there are, mainly, the following steps: a) creation of a device (kit to collect stools which have thousands of mucosal cells colonocytes - freed from the colonic and rectal mucosa, which are mixed with and covering the stools voided); b) separation of the cells (colonocytes) from the stools; c) homogenization and calibration of the colonocytes, through rupture of the colonocytes, with certain routine techniques; d) isolation of the free ribosomes, though differential centrifugation; e) labeling of the free ribosomes, utilizing fluorochromes (nanotechnology); and f) - counting labeled free ribosomes, utilizing flow cytometry. The ideas concerning this scientific research are already under the legal intellectual protection, through friendliness links in Madrid, in a specialized company of patents. I send you an Abstract of the subject, which is called RIBOGRAMA (Trade mark). One pretends to discuss the possibility to make a partnership with an enterprise, concerning the creation of a colorectal diagnostic test.
It will be necessary to create a disposable Kit, that will constitute a collector of biological product (stools), once the diagnostic test will be made through the calculation of the free ribosomes contained in the cytoplasm of the colorectal mucosal cells discarded to the intestinal lumen:

(smt: - every six months) Interpretation of RIBOGRAMA curve: Curve that starts at the normal level, and reaching the level increased, which means care for a prophylactic study on the reasons or causes which determine its occurrence. The cells at this level (increased) still have no safety features of malignancy, but increased their number continues to grow free ribosomes, the cell is transformed into a malignant phenotype (alarm level). At this point it is essential there be a food-study survey and identification of potential mutations responsible for non-controlled increase of ribosome biogenesis in the process of carcinogenesis; Segment of the curve derived from the anterior (segment ab), which corresponds to the phenotypic alterations and visible light microscopy, in which cells are already present with phenotypic characteristics of malignancy; Segment of the curve, then the anterior segment, which already represents the level of signs and symptoms of the disease CCR (clinical level); This segment of the curve corresponds to a change in direction of the curve ab to result from a preventive and therapeutic (medications and special diet); Corresponds to a curve in which cells grow (multiply or proliferate) within a self-monitoring increased proliferation mechanisms, as in the case of the seminiferous tubules, or the endometrium. This increased level of ribosome biogenesis, control of these lies within the physiological mechanisms (nonmalignant); Normal curve; This work is intended to study item colorectal cancer (CRC), which ribograma curve is high, so it is not appropriate to talk about the meaning of it on the lower level, which still serve to study conditions of degeneration and involution of tissues and cells, whether the intestinal mucosa, or other extra-intestinal tissue.