Del Dott. Giuseppe
Cotellessa (ENEA)
Il procedimento del brevetto:
può essere utile nella lotta contro il cancro
quando è applicato alle metodologie dell’analisi dell’immagine.
(ESTRATTO IN LINGUA INGLESE LEGGIBILE IN ALTRE LINGUE CON IL
TRADUTTORE DI GOOGLE CROME)
“A
Synthesis of the Beauty and Complexity of How We View Cancer”
Author: Larry H. Bernstein, MD, FCAP
This
document has covered a broad spectrum of the research, translational biology,
diagnostics (both laboratory and imaging methodologies), and treatments for a
variety of cancers, mainly by organs, and selectively by the most common
cancers seen in human populations. A number of observations stand out on review
of all the material presented. 1. The most common cancers affecting humans is
spread worldwide, with some variation by region. 2. Cancers within geographic
regions may be expressed differently in relationship to population migrations,
the incidence of specific environmental pollutants, occurrence of insect
transmitted and sexually transmitted diseases (HIV, HCV, HPV), and possibly
according to age, or relationship to ultraviolet or high dose radiation
exposure. 3. Cancers are expressed within generally recognized age timelines.
For example, acute lymphocytic leukemia and neuroblastoma in children under 10
years age; malignant giant cell tumor and osteosarcoma in the third and fourth
decade; prostate cancer and breast cancer over age 40, and are more aggressive
at an earlier age, both having a strong sex hormone dependence. 4. There is
dispute about the effectiveness of screening for cancer with respect to what
age, excessive risk in treatment modality, and the duration of progression free
survival. Despite the evidence of several years potential life extension, a
long term survival of 10 years is not the expected outcome. However, the
quality of life in the remaining years is a valid point in favor of progress.
5. There has been a significant reduction in toxicity of treatment, but
attention has been focused on a patient-centric decision process. 6. There has
been a dramatic improvement in surgical approaches, post-surgical surveillance,
and in diagnosis by invasive and noninvasive methods, especially in the
combination of needle biopsy and imaging techniques. 7. There is significant
variation within cancer cell types with respect to disease-free survival.
The work
presented has several main components: First, there is the biology and
mechanisms involved in carcinogenesis related to (1) mutations; (2)
carcinogenesis; (3) cell regulatory mechanisms; (4) cell signaling pathways;
(5) apoptosis (6) ubitination (7) mitochondrial dysfunction; (8) cell-cell
interactions; (9) cell migration; (10) metastasis. Then there are large portions
covering (1) imaging; (2) specific targeted therapy; (3) nanotechology-based
therapy; (4) specific organ-type cancers; (5) genomics-based testing; (6)
circulating cancer cells; (7) miRNAs; (8) siRNAs; (9) cancer immunology and
(10) immunotherapy.
Classically,
we refer to cancer development in terms of the germ cell layers – ectoderm,
mesoderm, and endoderm. These are formative in embryonic development. The most
active development occurs during embryonic development, with a high growth rate
of cells and also a high utilization of energy. The cells utilize oxidation for
energy in this period characterized by movement of cells in differentiation and
organogenesis. This was observed to be unlike the cell metabolism in
carcinogenesis, which is characterized by impaired mitochondrial function and
reliance on lactate production for energy – termed anaerobic glycolysis, as
investigated by Meyerhof, Embden, Warburg, Szent-Gyorgy, H. Krebs, Theorell, AV
Hill, B Chance, P Mitchell, P Boyer, F Lippman, and others.
In
addition, the body economy has been divided into two major metabolic
compartments: fat and lean body mass (LBM), which is further denoted as
visceral and structural. This denotes the gut, kidneys, liver, lung, pancreas,
sexual organs, endocrines, brain and fat cells in one compartment, and skeletal
muscle, bone and cardiovascular in another. LBM is calculated as fat free mass.
Further, brown fat is distinguished from white fat. But this was a first layer
of construction of the human body. One peels away this layer to find a second
layer. For example, the gut viscera have an inner (outer) epithelial layer, a
muscularis, and a deep epithelium, which has circulation and fat. There is also
an interstitium between the gut epithelium and muscularis. The lung has an
epithelium exposed to the airspaces, then capillaries, and then epithelium,
designed for exchange of O2 and CO2, the source of heat generation. The
pancreas has an endocrine portion in the islets that are embedded in an
exocrine secretory organ. The sexual organs have a combination of glandular
structures embedded in a mesothelium.
The
structural compartment is entirely accounted for by the force of contraction.
If this is purely anatomical, that is not really the case when one goes into
the functioning substructures of these tissues – cytoplasm, endoplasmic
reticulum (ribosomal), mitochondria, liposomes, chromatin apparatus, cell
membrane and vesicles. Within and between these structures are the working and
interacting mechanisms of the cell in its unique role. What ties these together
was first thought to be found in the dogma following the discovery of the
genetic code in 1953 that begat DNA to RNA to protein.
This led to
many other discoveries that made it clear that it was only a first
approximation. It did not account for noncoding DNA, which became unmasked with
the culmination of the Human Genome Project and concurrent advances in genomics
(mtDNA, mtRNA, siRNA, exosomes, proteomics, synthetic biology, predictive
analytics, and regulatory pathways directed by signaling molecules. Here is a
list of signaling pathways: 1. JAK-STAT 2. GPCR 3. Endocrine 4. Cytochemical 5.
RTK 6. P13K 7. NF-KB 8. MAPK 9. Ubiquitin 10. TGF-beta 11. Stem cell These
signaling pathways have become the basis for the discovery of inhibitors of
signaling pathways (suppressors), as well as activators, as these have been
considered as specific targets for selective therapy. (.See Figure below) Of
course, extensive examination of these pathways has required that all such
findings are validated based on the STRENGTH of their effect on the target and
in the impact of suppression.
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