NADH, the abbreviation for nicotinamide adenine dinucleotide hydride, is also known as reduced Coenzyme I. It is present in every living cell, where it catalyzes more than a thousand metabolic reactions. The most important biological functions of NADH are the following:
1. NADH is the cellular fuel for energy production
2. NADH plays a key-role in DNA and cell damage repair
3. NADH enhances the cellular immune system
4. NADH is the most potent antioxidans
A recent study it has shown NADH can increase ATP levels inside the cell. If the cell has more ATP energy, it can perform its functions better. Hence, by giving the cell NADH, it can produce molecules which are of critical importance for cell regulation. NADH plays also an essential role in DNA and cell damage repair.
The regulation of gene expression, cell cycle progression, stimulation of DNA repair and programmed cell death are important mechanisms for maintaining normal growth and antimutation. Studies in our laboratory have found that NADH can stimulate the biosynthesis of endogenous cell factors which can rescue cells from apoptosic damage. NADH does increase the resistance of PC12 cells to the doxorubicin induced DNA damage and is able to repair the DNA damage. It also promotes survival and differentiation by regulating the c-myc oncogene protein. NADH supports the process of DNA repair by regulating the expression of p53, bcl-12 in PC12 cells damage by doxorubicin. This finding indicates that NADH can act as chemopreventive agent. NADH plays also a crucial role in triggering biological antioxidation and in regulating the expression of membrane and glycoprotein receptors. Furthermore, NADH stimulates the biosynthesis of interleukine-6 (IL-6) which is an important component of the cellular immune system. NADH is one of the best free radicals scavenger. NADH is also a protector against chemotoxicity and radiation. When cells are incubated with cisplatin, one of the most commonly used chemotherapeutic agents, the expression of P53 and bcl-12 was downregulated by more than 90%.
Incubation of the destructed cells which NADH induced a repair process. Based on these findings and the various biological functions, ENADA, the brand name for the patented, stabilized orally absorbable form of NADH has been used in the treatment of certain types of human cancer such as in lung, breast, colon, prostate and brain tumors leading to a reduction of tumor mass or complete remission was observed.
G. D. Birkmayer Department of Medical Chemistry,
University of Graz and Birkmayer Laboratories,
Vienna, Austria
The therapeutic value
of protein monoclonal
antibodies directed
against immunogenic
tumor glycoproteins
M. Arlen
Monoclonal antibodies developed against immunogenic glycoproteins expressed in malignant tumors are unique. These monoclonals suggest that the tumor cell can participate in a system whereby it behaves as a double sided coin. Here, one side serves to allow early recognition of the immunogenic glycoprotein as a diagnostic molecular marker and the other side, a therapeutic target to induce apoptosis of the tumor.
Neogenix Oncology has isolated and characterized several immunogenic molecular markers in a group of common malignancies including those of lung, colon, prostate and ovary. The monoclonals derived from several of the protein moieties of specific tumor glycoproteins have been characterized. These include squamous lung/cervix and colon/pancreas cancers . The monoclonals are seen as IgG2a’s in the hibridomas, changing isotype to IgG1 as they are humanized or chimerized.
What appears unique for these protein monoclonals presently available for study, is the extremely high rate of tumor kill as defined by ADCC and the ability to define the molecular marker diagnostically, months before the phenotypic expression of malignancy can be seen These antibodies are presently being readied for clinical diagnostic studies in patients with early cervix Ca, where those cells characterized on Pap smear as ASCUS I, are associated with a 20% or greater error in interpretation Using an immuno- peroxidase staining technique along with cytospin of the thin prep material , we are finding almost no error in detecting the early cells expressing the tumor marker for the specific disease process.
From a therapeutic view, the ADCC (antibody dependent cell cytotoxicity) used as an in-vitro assay is seen destroying 50-60% of the tumor cells depending on the human tumor cell line being studied. The destruction of the tumor cells are measured by a chromium or indium release assay over 4-6 hrs. In xenograft studies, where 2 million human cancer cells are allowed to grow at the site of injection, reaching 2-3 cm in size by ten days, two intraperitoneal injections of 400 mg of humanized monoclonal antibody given with human effector cells on day 11 and 12 can result in almost complete disappearance of tumor within the subsequent 10 days. Mechanisms of tumor rejection have been studied and appear to be initially associated with a turn on of NK cells that are brought to the tumor, at which time NO is released. It is also postulated that the NO synthase may suppress K-ras function.
When the antibodies are studies in-vitro at 36-48 hrs., we have found suppression in the proliferation index, a high level of annexin V binding as a reflection of apoptosis, and suppression of VEGF, indicating that other mechanisms for tumor inhibition and destruction are occurring simultaneously. Additional mechanisms that may come into play helping to control tumor growth might occur through the appearance of anti-idiotypes inducing the appearance of cytotoxic T cells.
The potential for these antibodies as therapeutic agents given alone or in combination suggest that appears fairly good.
M. Arlen,
A. Bristol Deptartment of Surgery North Shore Univ. Hosp.
Division of Surgical Oncology, Manhasset NY and Neogenix Oncology Inc.
Great Neck NY,
USA
Clinical utility
of cytokeratins
as tumor markers
V. Barak
Cytokeratins, belonging to the intermediate filament protein family, are particularly useful tools in oncology diagnostics. At present, more than 20 different cytokeratins have been identified, of which cytokeratins 8, 18 and 19 are the most abundant in simple epithelial cells. Upon release from proliferating or apoptotic cells, cytokeratins provide useful markers for epithelial malignancies, distinctly reflecting ongoing cell activity. It appears that motifs in certain cytokeratins make them likely substrates for caspase degradation and their subsequent release occurs during the intermediate events in apoptosis.
The clinical value of determining soluble cytokeratin protein fragments in body fluids lies in the early detection of recurrence and the fast assessment of the efficacy of therapy response in epithelial cell carcinomas. The three most applied cytokeratin markers used in the clinic are TPA, TPS and CYFRA 21-1. Broad-spectered, simultaneously measuring a mixture of cytokeratin fragments, as well as more specific cytokeratin assays are available. While TPA measures cytokeratins 8, 18 and 19; TPS and CYFRA 21-1 specifically measure cytokeratin 18 and cytokeratin 19, respectively. By following the patients with repeated testing during management, the oncologist may obtain critical information regarding the growth activity in symptomatic patients. Their main use is during treatment monitoring and evaluation of therapy response, but early prognostic information particularly on tumor progression and metastasis formation is also provided for several types of cancers. Cytokeratin tumor markers can accurately predict disease status prior to conventional methods and offer a simple, non-invasive, cheap and reliable tool for a more efficient treatment.
V. Barak Immunology Laboratory for Tumor Diagnosis,
Oncology Department, Hadassah University Medical Center,
Jerusalem, Israel.
Importance
of cytokines
monitoring
for oncology-pilot
study.
O. Topolcan
Complex changes of the serum levels of the cytokines have been rarely described at cancer diseases. Multiplex analysis at LUMINEX instrument has enabled to perform a pilot study of the changes of a large spectrum of cytokines.
Patients and methods We have examined a total of 54 patients with cancer disease. Measurement of serum level of different cytokines Following parameters were measured 4 -13 of the following parameters: IL-1B, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL- 12p70, IL-13, INF? and TNF? (Linco, USA) using multiplex analysis on LUMINEX instrument. Results were correlated with CEA, CA 19-9 and TPS.
Results A total of 300 cytokine analyses was performed. 40% of these values were at the detection limit, 60% of the values were detectable. Pathologic values were mostly observed at IL-6, IL-8 , IL 10 and TNF?. Other cytokine levels were rarely elevated. IL-10 serum levels were elevated only at 10 patients. All of them represented a very unfavorable prognosis with a short survival. Relationship between the tumor markers and cytokines are demonstrated on the case reports.
Conclusions Methodical conclusion: Multiplex analysis represent a challenging method convenient for research due to the minimal needs of a biological material (10-25µL) and the possibility of the simultaneous measurement of a large number of parameters at the standard condition. This method provides an optimal correlation between the different parameters. Clinical conclusion: Based on our pilot study results we can conclude that the serum levels of cytokines are very often at the detection limit and there are only special conditions when they are increased. It seems that are very often at the detection limit and there are only special conditions when they are increased. It seems that some of them (e.g. IL-10) could potentially be useful markers of a prognosis of the diseaseTumor markers , prognosis, cytokines, multiplex.
Topolcan O., Karlíková M., Treška V., Svobodová Š,
Sutnar A., Holubec L., jr., Fínek J. Medical Faculty of Charles University Pilsen and Faculty Hospitals
Pilsen,
Czech Republic
NADH, the abbreviation for nicotinamide adenine dinucleotide hydride, is also known as reduced Coenzyme I. It is present in every living cell, where it catalyzes more than a thousand metabolic reactions. The most important biological functions of NADH are the following:
It also promotes survival and differentiation by regulating the c-myc oncogene protein. NADH supports the process of DNA repair by regulating the expression of p53, bcl-12 in PC12 cells damage by doxorubicin. This finding indicates that NADH can act as chemopreventive agent. NADH plays also a crucial role in triggering biological antioxidation and in regulating the expression of membrane and glycoprotein receptors. Furthermore, NADH stimulates the biosynthesis of interleukine-6 (IL-6) which is an important component of the cellular immune system. NADH is one of the best free radicals scavenger. NADH is also a protector against chemotoxicity and radiation. When cells are incubated with cisplatin, one of the most commonly used chemotherapeutic agents, the expression of P53 and bcl-12 was downregulated by more than 90%. 
Monoclonal antibodies developed against immunogenic glycoproteins expressed in malignant tumors are unique. These monoclonals suggest that the tumor cell can participate in a system whereby it behaves as a double sided coin. Here, one side serves to allow early recognition of the immunogenic glycoprotein as a diagnostic molecular marker and the other side, a therapeutic target to induce apoptosis of the tumor. 
release assay over 4-6 hrs. In xenograft studies, where 2 million human cancer cells are allowed to grow at the site of injection, reaching 2-3 cm in size by ten days, two intraperitoneal injections of 400 mg of humanized monoclonal antibody given with human effector cells on day 11 and 12 can result in almost complete disappearance of tumor within the subsequent 10 days. Mechanisms of tumor rejection have been studied and appear to be initially associated with a turn on of NK cells that are brought to the tumor, at which time NO is released. It is also postulated that the NO synthase may suppress K-ras function.
Cytokeratins, belonging to the intermediate filament protein family, are particularly useful tools in oncology diagnostics. At present, more than 20 different cytokeratins have been identified, of which cytokeratins 8, 18 and 19 are the most abundant in simple epithelial cells. Upon release from proliferating or apoptotic cells, cytokeratins provide useful markers for epithelial malignancies, distinctly reflecting ongoing cell activity. It appears that motifs in certain cytokeratins make them likely substrates for caspase degradation and their subsequent release occurs during the intermediate events in apoptosis. 
fragments in body fluids lies in the early detection of recurrence and the fast assessment of the efficacy of therapy response in epithelial cell carcinomas. The three most applied cytokeratin markers used in the clinic are TPA, TPS and CYFRA 21-1. Broad-spectered, simultaneously measuring a mixture of cytokeratin fragments, as well as more specific cytokeratin assays are available. While TPA measures cytokeratins 8, 18 and 19; TPS and CYFRA 21-1 specifically measure cytokeratin 18 and cytokeratin 19, respectively. By following the patients with repeated testing during management, the oncologist may obtain critical information regarding the growth activity in symptomatic patients. Their main use is during treatment monitoring and evaluation of therapy response, but early prognostic information particularly on tumor progression and metastasis formation is also provided for several types of cancers. Cytokeratin tumor markers can accurately predict disease status prior to conventional methods and offer a simple, non-invasive, cheap and reliable tool for a more efficient treatment.
Complex changes of the serum levels of the cytokines have been rarely described at cancer diseases. Multiplex analysis at LUMINEX instrument has enabled to perform a pilot study of the changes of a large spectrum of cytokines.