Thursday, August 1, 2013

Genomics And LC-MS/MS mass spectrometry analysis is What’s Next In For A Breast Cancer Cure

Barron’s Medical Journal Reporting From American Association for Clinical Chemistry (AACC) in Houston ,Texas USA At The George R Brown Convention Center

Genomics And LC-MS/MS mass spectrometry analysis is What’s Next In For A Breast Cancer Cure
Houston ( AP ) Genomcis and LC-MS/MS mass spectrometry analysis is What’s Next In For A Breast Cancer Cure. Barron Medical Journal has found that we now have the knowhow and the systems to detect breast cancer genes and now at this year’s show BMJ has found that one of the major advances in science that have been around for over a Hundred years MS mass spectrometry (MS) is an analytical technique that produces spectra (singular spectrum) of the masses of the molecules comprising a sample of material. The great news about MS is that we can now validate our genomic gene finding. The next step is to get this technology out of the University
centers in to commercial use. Here are some success stories on breast cancer and MS mass spectrometry. Early phase of biomarker discovery in three clinically important types of breast cancer using a panel of human cell lines: HER2 positive, hormone receptor positive and HER2 negative, and triple negative (HER2-, ER-, PR-). We identified and characterized the most abundant secreted, sloughed, or leaked proteins released into serum free media from these breast cancer cell lines using a combination of protein fractionation methods before LC-MS/MS mass spectrometry analysis. A total of 249 proteins were detected in the proximal fluid of 7 breast cancer cell lines. The expression of a selected group of high abundance and/or breast cancer-specific potential biomarkers including thromobospondin 1, galectin-3 binding protein, cathepsin D, vimentin, zinc-α2-glycoprotein, CD44, and EGFR from the breast cancer cell lines and in their culture media were further validated by Western blot analysis. Interestingly, mass spectrometry identified a
cathepsin D protein single-nucleotide polymorphism (SNP) by alanine to valine replacement from the MCF-7 breast cancer cell line. Comparison of each cell line media proteome displayed unique and consistent biosignatures regardless of the individual group classifications, demonstrating the potential for stratification of breast cancer. On the basis of the cell line media proteome, predictive Tree software was able to categorize each cell line as HER2 positive, HER2 negative, and hormone receptor positive and triple negative based on only two proteins, muscle fructose 1,6-bisphosphate aldolase and keratin 19. In addition, the predictive Tree software clearly identified MCF-7 cell line overexpresing the HER2 receptor with the SNP cathepsin D biomarker Approximately 30% of malignant breast cancers demonstrate overamplification of the human epidermal receptor type 2 (HER2) gene. HER-2 can be resistant to low-doses of anthracycline-based chemotherapy.
The Good News is that science has advanced. Sections of microarray provide targets for parallel in situ detection of DNA, RNA and protein targets in each specimen on the array. The better News is that Genomics is on the Clock. Genomics provide a faster cheaper more effective way to detect the Her2 gene by using Semiconductor Sequencing. A example of this technique is Gennxeix Biotech Inc Semiconductor Sequencing. "Quantum Theory" In Action for Breast Cancer Patients. One of the major player and touch down makers for breast cancer is Houston Texas Methodist Hospital. In A clinical Trial A Rev. Noel Denison, a retired Methodist minister, was diagnosed with locally advanced HER2-positive breast cancer and is enrolled in the study at Methodist, one of only two locations in the United States. The clinical trial is for locally advanced or metastatic HER2-positive breast cancer and combines standard chemotherapy with trastuzumab emtansine, better known in the breast cancer world as T-DM1, and pertuzumab, a monoclonal antibody that also attaches to HER2 on cancer cells. Using Genomics and semiconductors to detect breast cancer plus T-DM1 to treat breast cancer is a winning combination. What is T-DM1? T-DM1 is in a new class of cancer-fighting agents called antibody
drug conjugates. By combining the antibody trastuzumab directly with docetaxel (standard chemotherapy) and/or pertuzumab, the T-DMI is designed to attack the tumor cells directly and deliver the chemotherapy. Trastuzumab emtansine (T-DM1) consists of our proprietary DM1 cancer-killing agent attached to the HER2-binding antibody, trastuzumab, developed by Genentech (a member of the Roche Group)
using our linker and methods of attachment. Trastuzumab emtansine is in global development by Roche under a collaboration agreement between ImmunoGen and Genentech. Marketing applications for trastuzumab emtansine are under review in the US and Europe. The Defense and the most dangerous aspect of breast cancer is its ability to spread to distant sites, most tumors are initially unable to do that Learning more specifically what triggers metastases may provide additional targets for preventing and treating the malignant process that causes cancer deaths. It’s widely accepted that cancers acquire the ability to spread through the gradual accumulation of genetic changes, and experiments have also shown that these changes occur in parallel with changes in the protein content and 3-dimensional patterning of the protein meshwork that creates their immediate surroundings Gene that stops the growth of KCNK9 Genes is gene is p53. p53 is a fundamental determinant of cancer susceptibility, p53 integrates stress signals and elicits apoplectic responses that maintain genomic stability. When cells sense a decrease in oxygen availability (hypoxia), they develop adaptive responses in order to sustain this condition and survive. If hypoxia lasts too long or is too severe, the cells eventually die. Hypoxia is also known to modulate the p53 pathway, in a manner dependent or not of HIF-1 (hypoxia-inducible factor-1), the main transcription factor activated by hypoxia. The p53 protein is a transcription factor, which is rapidly stabilized by cellular stresses and which has a major role in the cell responses to these stresses. This process is why it is important Conrad says for people that are first degree relatives of breast cancer patients, must take a genomic test to see if they are the carrier of gene KCNK9. By identifying this gene we can direct patients with the correct advise as to deal with the fact that they have a lunp on the breast to they are going to get a lump on their breast. Often what happens is that a breast cancer patients dose not go to the doctor or take important test to see if there is a lump on the breast. what happens is the spread of breast cancer is responsible for more than 90 percent of breast cancer deaths.
A panel of three breast cancer biomarkers (BC1, BC2, and BC3) from serum samples collected at a single hospital based on their Collective contribution to the optimal separation of breast cancer patients and noncancer controls by surface- enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The identities and general applicability of these markers, however, were unknown. In this study, we performed protein expression profiling on samples obtained from a second hospital, included a greater number of ductal carcinoma in situ (DCIS) cases, and performed purification and identification of the 2 confirmed markers.
Methods: Using a case– control study design, we performed protein expression profiling on serum samples from the National Cancer Institute (Milan, Italy). The validation sample cohort consisted of 61 women with
locally invasive breast cancer, 32 with DCIS, 37 with various benign breast diseases (including 13 atypical), and 46 age-matched apparently healthy women (age range, 44–68 years). Validated biomarkers were purified and identified with serial chromatography, 1-dimensional gel electrophoresis, in-gel ASP-N digestion, peptide mass fingerprinting, and tandem mass peptide sequencing. Results: The BC3 and BC2 expression patterns in this sample set were consistent with the first study sample set. BC3 and BC2 were identified to be complement component C3adesArg and a C-terminal–truncated form of C3adesArg, respectively.
Conclusions: Evaluation of biomarkers in independent sample sets can help determine the broader utility of
candidate markers, and protein identification permits understanding of their molecular basis. C3adesArg appears to lack specificity among patients with benign diseases, limiting its utility as a stand-alone tumor marker, but it may still be useful in a multimarker panel for early detection of breast cancer. Barrons Medical Journal Says That we are going to have a breast cancer cure by the end of President Obama 2nd term

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