*Recent trial suggested that Jakafi in combination with Xeloda may be useful in second line therapy against pancreatic cancer particularly those induced or accompanied by strong inflammatory response as suggested by high lebel of CRP (C-reative protein) (Targeted Therapy).
*With over 20% success in patents with NSCL cancers, Nivolumab /Pembrolizumab and other anti PD-1/PD-L1 continue to impress researchers and are bound to change the therapeutic approaches in this disease. Soon everyone will be screened for these antigens as response rates seem to correlate with their presence.
*Does inhibiting Cytokines inducing cachexia in cancer able to change overall survival rates in cancers. What is the relationships between these Cytokines and Mitochondrial changes and telomeres?
Sunday, November 30, 2014
Tuesday, November 25, 2014
After the Cytokine period in a life cycle
First we have a Conception, birth and growth lasting from birth to 10 to 15 years, this period is full of "growth" but seems dominated by the HLA (Histocompatibility build up) but also organ maturation. Trying to establish what is oneself seems to be the priority. Fight against infections seem to be the determinant event. Here women are the most "build"up in preparation for receiving the child, a foreign entity.
Then come 15 to 25 years of "Hormone reign"when most of the purpose is turned to reproductive function. The testicular cancer happen at this stage. And in women, infection driven cancers (cervix) will mark this period. Autoimmune and metabolic diseases will mark this period.
After the reign of the Hormones, after Menopause, commences the "years of the Cytokines". This last another 20 years. One important fact during the years of the Cytokines, Hormone receptor desensitization with marked endothelial effect in women and does have profound epigenic and nuclear effects at cellular level. Most cancers will happen here as Cytokines induce them. In developing countries, most do not reach this period. The cytokine period obviously last all life long as cancer can happen any day but during the years of 50 to 70, cancer risks are clearly higher but so are arthritic conditions that fully fall on the lapse of the Cytokines. Mental disturbances also fall on the Cytokines. Those who are lucky have a good c-fos, c-jun, Fas, FOXO-1, Daf-1 and the Telomeres (families of genes), will enter the new 10-20 years with still the Cytokine but less intense, like the one that make lose weight and muscle tone, the one that induce dementia and further CNS disturbances....
Then come 15 to 25 years of "Hormone reign"when most of the purpose is turned to reproductive function. The testicular cancer happen at this stage. And in women, infection driven cancers (cervix) will mark this period. Autoimmune and metabolic diseases will mark this period.
After the reign of the Hormones, after Menopause, commences the "years of the Cytokines". This last another 20 years. One important fact during the years of the Cytokines, Hormone receptor desensitization with marked endothelial effect in women and does have profound epigenic and nuclear effects at cellular level. Most cancers will happen here as Cytokines induce them. In developing countries, most do not reach this period. The cytokine period obviously last all life long as cancer can happen any day but during the years of 50 to 70, cancer risks are clearly higher but so are arthritic conditions that fully fall on the lapse of the Cytokines. Mental disturbances also fall on the Cytokines. Those who are lucky have a good c-fos, c-jun, Fas, FOXO-1, Daf-1 and the Telomeres (families of genes), will enter the new 10-20 years with still the Cytokine but less intense, like the one that make lose weight and muscle tone, the one that induce dementia and further CNS disturbances....
Saturday, November 22, 2014
DANGER LURKING IN THE DARK? RECURRENT USE OF CIPRO
In this world of infections, Ciprofloxacin has gained prominent place and is widely prescribed and many antibiotics have similar effect of immunomodulation on mainly the monocytes and of course the lymphocytes. Widespread use of these antibiotics call for further discrimination at genetic levels. Ciprofloxacin has been known to amplify several genes including the NFKB, JUN B, C-Myc, AP-1, NFAT, c-fos, c-JUN, fra-1. The NFAT amplification has the most of the attention here...This amplification calls for a check on the GSK3B because a secondary amplification of this gene hits many critical genes in the initiation of cancers! And in a profoundly obese population, the GSK3B has to be assumed to be profoundly disturbed in terms of level. A high amplification of this gene not only affect key genes but is associated with marked phosphorylation of other genes particularly when interacting with SGK3. And phosporylation of genes has been implicated in the expansion neoplastic transformations. i.e the story of Casein Receptors and their relation with breast cancers.
Concurrent amplification of NFAT and GSK3 may be dangerous
1.when interacting with AR- --(Androgen Receptors) because Prostate Cancer may result
2.MUC 1, because Colon cancer may result
3.P53 and the Catenin, the NOTCH, all implicated in various cancers (Breast,tuberous etc..)
Do we check the status of this gene? no, we are still waiting for clinical trials...can't wait to live in the next century when all this will be done! don't take my words for them!
WIKIPEDIA :
GSK3B has been shown to interact with:
Concurrent amplification of NFAT and GSK3 may be dangerous
1.when interacting with AR- --(Androgen Receptors) because Prostate Cancer may result
2.MUC 1, because Colon cancer may result
3.P53 and the Catenin, the NOTCH, all implicated in various cancers (Breast,tuberous etc..)
Do we check the status of this gene? no, we are still waiting for clinical trials...can't wait to live in the next century when all this will be done! don't take my words for them!
WIKIPEDIA :
GSK3B has been shown to interact with:
- AKAP11,[6]
- AXIN1,[7][8]
- AXIN2,[9][10]
- AR,[11]
- CTNNB1,[12][13]
- DNM1L,[14]
- MACF1[15]
- MUC1,[16][17]
- SMAD3[18]
- NOTCH1,[19]
- NOTCH2,[20]
- P53,[21]
- PRKAR2A,[6]
- SGK3,[22] and
- TSC2.[7][23]
- =========================================================================
- " Nuclear import of NFAT proteins is opposed by maintenance kinases in the cytoplasm and export kinases in the nucleus. Export kinases, such as PKA and GSK-3β, must be inactivated for NFAT nuclear retention."
Friday, November 21, 2014
Wednesday, November 19, 2014
cancer detection movement is on the rise
It is generally thought that cells undergoing Neoplastic transformation will exhibit mutation, amplification or some form of new pattern in their genes, and based on this new pattern, observer can diagnose or even anticipate the behavior or prognosis of the cancer. But each time, the question that come to mind is, which genes in which cancer? And with 25,000 genes , the task is not a slim one. And to make matter worse, Neoplastic cells do not remain static! They are in constant flush, trying to survive their environment.
We know for example that prostate cancers grow on Androgen stimulation which has become the focus of most prostate cancer treatment with "abiraterone Acetate which blocks androgen synthesis, and Enzalutamide which block the Androgen Receptor" (Nina Sharifi). We also know now that In their struggle to survive, the prostate cancer cells will acquire the enzyme 3 Beta-Hydroxysteroid dehydrogenase-isoenzyme to self produce DHEA and ultimately DHT.
While it is important to focus on these important driving mechanisms, it is also important to remember that cells use their potentials to fabricate these important enzymes! Other supportive genes continue to play important supportive roles that also need to be disturbed. And that remains a further challenge. At certain times, the supportive role could be the overwhelming activity and detection may be skewed !
Professor Klein proposed 17 Genomic Prostate Core
1.Androgen signaling:
AZGP1
FAM13C
KLK2
SRD5A2
2.Stromal response
BGN
COL1A1
SFRP4
3.Proliferation
TPX2
and there are
4.Cellular organization
and 5. Reference (see article:"Genomics for active surveillance now in Practice")
We, at CRBCM, although reserved on the content as most of these reports may be limited, approve of this model of reporting detection as no single gene could actually reflect cellular activities all the time. The fact is that the Genomic core does not speak about other genes such as the MED1,RAD51, CHEK1, DAPK, MLH1,TIMP3, PPARGs, TMPRSS, ERG, ETV1, SMADs,NBN or miRNAs even though we know they are into play!
Despite our reservations, it is clear and exciting to see the vibrant stand for cancer detection in the general population and of course in targeted markets! We are meeting today at UTEP to discuss what will be tested in collected blood samples...our bank has already 25 vials of blood samples the first week since we launched this study. And more people are coming to donate...
CRBCM, progressing slowly despite adversity!
We know for example that prostate cancers grow on Androgen stimulation which has become the focus of most prostate cancer treatment with "abiraterone Acetate which blocks androgen synthesis, and Enzalutamide which block the Androgen Receptor" (Nina Sharifi). We also know now that In their struggle to survive, the prostate cancer cells will acquire the enzyme 3 Beta-Hydroxysteroid dehydrogenase-isoenzyme to self produce DHEA and ultimately DHT.
While it is important to focus on these important driving mechanisms, it is also important to remember that cells use their potentials to fabricate these important enzymes! Other supportive genes continue to play important supportive roles that also need to be disturbed. And that remains a further challenge. At certain times, the supportive role could be the overwhelming activity and detection may be skewed !
Professor Klein proposed 17 Genomic Prostate Core
1.Androgen signaling:
AZGP1
FAM13C
KLK2
SRD5A2
2.Stromal response
BGN
COL1A1
SFRP4
3.Proliferation
TPX2
and there are
4.Cellular organization
and 5. Reference (see article:"Genomics for active surveillance now in Practice")
We, at CRBCM, although reserved on the content as most of these reports may be limited, approve of this model of reporting detection as no single gene could actually reflect cellular activities all the time. The fact is that the Genomic core does not speak about other genes such as the MED1,RAD51, CHEK1, DAPK, MLH1,TIMP3, PPARGs, TMPRSS, ERG, ETV1, SMADs,NBN or miRNAs even though we know they are into play!
Despite our reservations, it is clear and exciting to see the vibrant stand for cancer detection in the general population and of course in targeted markets! We are meeting today at UTEP to discuss what will be tested in collected blood samples...our bank has already 25 vials of blood samples the first week since we launched this study. And more people are coming to donate...
CRBCM, progressing slowly despite adversity!
Tuesday, November 18, 2014
Progression even in cancer detection
The study of cancer particularly as it comes to genes, gene alterations and their quality and quantity modifications is one of the most exciting field of scientific research. The cell, even the neoplastic cell, continue to be alive meaning undergoing constant changes and molecular transformations. Often times, these transformations seem purposeful and clearly directed. And often times the direction intends to reach "survival". Less often though, the ultimate purpose is clear death ie when the Telomeres are shortened or the Caspases are engaged.
It is obvious that cancer detection should follow these transitions because some genes may not be over-expressed all the time, and some are even depressed during the neoplastic transformation. The shear number of cells may affect secreted membrane proteins (such as the Prostate specific membrane Antigens (PSMA) to influence detection (by antibody) but often the predominant ongoing cellular phenomena can only be detected by studies of gene amplifications.
There seem to be 3-4 phases of cancer progression that require adapted detection:
1. The initial phase
where an amplified gene is inducing changes that will initiate the Neoplastic process,
ie effect of smoking on the MDM-2 gene and resultant effect on the P53.
ie. Viral effect on the Src or CSK genes, this of course before the FUS gets into the frey! YES1! Rho gene...
2.The period of proliferation, that is when the MYC gene is involved to amplify all the genes
but not only the MYC but NPM1, Cyclin B1, and of course the many genes of proliferation
3.Metastatic phase (initial or during disease recurrence) here comes the Ros gene
4. Cellular death where Telomere and Mitochondrial phenomena come into play
we still have to wonder about the NCOA, the EZH2, ATRX, and MED1, TIMP3, where do these fit?
It is obvious that cancer detection should follow these transitions because some genes may not be over-expressed all the time, and some are even depressed during the neoplastic transformation. The shear number of cells may affect secreted membrane proteins (such as the Prostate specific membrane Antigens (PSMA) to influence detection (by antibody) but often the predominant ongoing cellular phenomena can only be detected by studies of gene amplifications.
There seem to be 3-4 phases of cancer progression that require adapted detection:
1. The initial phase
where an amplified gene is inducing changes that will initiate the Neoplastic process,
ie effect of smoking on the MDM-2 gene and resultant effect on the P53.
ie. Viral effect on the Src or CSK genes, this of course before the FUS gets into the frey! YES1! Rho gene...
2.The period of proliferation, that is when the MYC gene is involved to amplify all the genes
but not only the MYC but NPM1, Cyclin B1, and of course the many genes of proliferation
3.Metastatic phase (initial or during disease recurrence) here comes the Ros gene
4. Cellular death where Telomere and Mitochondrial phenomena come into play
we still have to wonder about the NCOA, the EZH2, ATRX, and MED1, TIMP3, where do these fit?
Saturday, November 15, 2014
Amplification of NCK-2 gene is/could be a strong Bio-marker of cancer recurrence
One thing for sure the return of cancer is physiologically one of an extraordinary undertaking in cancer biology. Indeed as cell reconstitute, reoganization has to occur at several cancer cell levels including the Cytoskeleton. One of the little known gene that comes into play is the NCK2 gene, a ligand protein /gene that direct to exacerbation of Actin polymerization and " The protein has no known catalytic function but has been shown to bind and recruit various proteins involved in the regulation of receptor protein tyrosine kinases. It is through these regulatory activities that this protein is believed to be involved in cytoskeletal reorganization" wikipedia. We suggest, It is strong signal that the cancer is back!
BE CAREFUL NOW THIS IS DEFINITELY NOT THE NEK-2 GENE, AN ALL OTHER GENE INVOLVED RATHER WITH THE AURORA!
LET US FOLLOW IT IN OUR CANCER PATIENT PARTICULARLY THOSE ON TAXOTERE!
MAY BE ADD HEF-1, LIMS1 FOR THE FUN OF IT!
BE CAREFUL NOW THIS IS DEFINITELY NOT THE NEK-2 GENE, AN ALL OTHER GENE INVOLVED RATHER WITH THE AURORA!
LET US FOLLOW IT IN OUR CANCER PATIENT PARTICULARLY THOSE ON TAXOTERE!
MAY BE ADD HEF-1, LIMS1 FOR THE FUN OF IT!
Friday, November 14, 2014
ANOTHER INTERESTING CASE...
A 54 Year old hispanic male presented with rectal bleed at an area hospital
and was admitted. A subsequent Colonoscopy reported fragments of Colonic Adenocarcinoma.
The patieent underwent a partial colectomy which revealed an Enteric type Adenocarcinoma Grade 2 (moderatelly differentiated invading the Muscularis propria and into the pericolic fat without involvement of the Serosa
perineurL/VASCULAR/ AND LYMPHATIC INVASION NOT SEEN
13 nodes obtained none with Metastatic disease
the liver contains a calcified granuloma
we elected to observe this patient
since chemotherapy will not benefit him by adding more than 5 % survival rates
Only those with poorly differentiated carcinoma..."T4, perforation or Obstruction, and less than 10 nodes removed, and angiolymphatic invasion" ASCO.
Another rising star! BLINATUMOMAB
Should we use this for Burkitt lymphoma?
It is normally reviewed for Philadelphia negative ALL...involving the T-cell...
"Blinatumomab received the FDA's Breakthrough Therapy designation earlier this year (OT 8/10/14 issue), which was enacted as part of the FDA's 2012 Safety and Innovation Act to expedite the development and review time of a potential new drug for serious or life-threatening disease where early clinical evidence suggests the drug may demonstrate substantial improvement compared with existing therapies." From Oncology Times
It is normally reviewed for Philadelphia negative ALL...involving the T-cell...
"Blinatumomab received the FDA's Breakthrough Therapy designation earlier this year (OT 8/10/14 issue), which was enacted as part of the FDA's 2012 Safety and Innovation Act to expedite the development and review time of a potential new drug for serious or life-threatening disease where early clinical evidence suggests the drug may demonstrate substantial improvement compared with existing therapies." From Oncology Times
Wednesday, November 12, 2014
Blood draw for research
Blood draw for our research is advancing at higher pace than expected
every one is eager to participate, It is incredible that patients and family are lining up for donation
everything voluntary and consents signed! It seems that the idea of participating in an UTEP driven study has energize "the base". El Paso is energized! Thank you to the donors!
every one is eager to participate, It is incredible that patients and family are lining up for donation
everything voluntary and consents signed! It seems that the idea of participating in an UTEP driven study has energize "the base". El Paso is energized! Thank you to the donors!
Tuesday, November 11, 2014
CRBCM, Collecting blood samples from volunteers at large from broader cancer studies
With collaboration from the Biomedical Research At UTEP, (DR Zangh), CRBCM has launched today studies investigating the role of cytokines in the production of cancers. We are collecting blood samples from Volunteers at large, and our cancer patients are going to participate. The theory is that when after age 55, or post Menopause in women, people enter the age of the "Cytokines" which seem to play a major role in the Neoplasm occurrence. Collecting blood samples may give us levels of various Cytokines in patients currently with cancers, or who might develop cancer of the next 5 to 10 years. Also the samples give us opportunity to have genetic testing for cancer screening. This is an exciting time in cancer...further discovery awaits! It is worth mentioning that 80% of our population is of Hispanic origin in El Paso!
Friday, November 7, 2014
On the road again! Back to learning again in Vegas!
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Wednesday, November 5, 2014
Here Come CRBCM to Beijing....NOone own science!
CRBCM has been invited to Beijing!
by professor Baofo Yu
FROM:JN BAOFA CANCER HOSPITAL DATE:2010-05-22 16:46:50
by professor Baofo Yu
FROM:JN BAOFA CANCER HOSPITAL DATE:2010-05-22 16:46:50
Dr. Baofa Yu
BaoFa Yu, M.D
Home Address:
4443 Governor Drive
San Diego, CA 92122
Tel: (858)597-0219, 858-336-4363
Fax: 597-0219, Email: bfyuchina@yahoo.com
CRBCM working on Cancer Research using all means!!!!
Tuesday, November 4, 2014
proposed track in Neurofibromatosis: what we know about the FUS?
GO TO FOLLOW THE MONEY!
NF1----Ras---ERK---MAPK----Myc---Let-7---XPO5---ILF3----FUS---/TLS-RELA SPI-1
let-7 affects Exportin 5
======================
This FUS explain the diversity of sarcoma that may result:
According to Atlas of Genetics and Cytogenetics
NF1----Ras---ERK---MAPK----Myc---Let-7---XPO5---ILF3----FUS---/TLS-RELA SPI-1
let-7 affects Exportin 5
======================
This FUS explain the diversity of sarcoma that may result:
According to Atlas of Genetics and Cytogenetics
| " | t(12;16)(q13;p11) chromosomal translocation. It produces the fusion protein FUS/ATF-1. | |||
| Disease | Angiomatoid fibrous histiocytoma (AFH). | |||
| Hybrid/Mutated Gene | FUS was interrupted at codon 175 (exon 5) and fused to codon 110 (exon 5) of ATF-1, resulting in an in-frame junction with a glycine to valine (GGT to GTT) transition. | |||
| Entity | t(7;16)(q33;p11) chromosomal translocation. It produces the fusion protein FUS/CREB3L2 (also known as BBF2H7). | |||
| Disease | Low grade fibromyxoid sarcoma (LGFMS). | |||
| Hybrid/Mutated Gene | The breakpoints in the fusion transcripts are produced between the exons 6 or 7 of FUS and the exon 5 of CREB3L2. | |||
| Entity | t(12;16)(q13;p11) chromosomal translocation. It produces the fusion protein FUS/DDIT3 (also known as CHOP). | |||
| Disease | Myxoid liposarcoma (MLS). | |||
| Hybrid/Mutated Gene | 9 different types of fusions between the genes FUS and DDIT3 have been reported. The most frequent rearragements join the exons 5, 7 or 8 of FUS with the exon 2 of DDIT3. | |||
| Oncogenesis | The unequivocally relation between FUS/DDIT3 and the MLS was shown by the generation of a transgenic mouse model expressing FUS/DDIT3 from a housekeeping promoter. | |||
| Entity | t(16;21)(p11;q22) chromosomal translocation. It produces the fusion protein FUS/ERG. | |||
| Disease | Acute myeloid leukemia (AML). | |||
| Hybrid/Mutated Gene | The junction of both genes is produced between the exons 6 or 7 of FUS and the exon 9 of ERG,or between the exon 8 of FUS and the exon 7 of ERG." |
Monday, November 3, 2014
Beyond the Myc!
Now as it seems to be suggested the mechanism of Cancer development seems to be multiple but one recognize that stimulation of the Myc or one of its variations seem to still the center piece of many neoplastic transformations. From Burkitt to Small cell cancer, the most aggressive cancer seem to act through this gene. Even Watson the DNA man went after the Myc as a potential drive for neoplasm. Myc can increase proliferation by acting through general proliferation factors (transcription factors) but in specific diseases, it can act specifically on downstream genes to drive the neoplastic transformation by using the Leucine unzipping prong (opening the nuclear machine to proliferation) or by opening the Ribosome to protein production needed in the neoplastic transformation.
Our interest in this area stems from our involvement with one family of 4 members that we suspect have Neurofibromatosis. NF1 has not been established yet but all members have development issues and lipomatous lesions and imaging has suggested diffuse Neurofibromas. One member developed Breast cancer, a BRCA was negative, One member has gait disturbances and speech impairement, and the member with several lipomatous lesions, came to our attention for cough. CT chest suggested a new peripheral nerve sheath tumor that we are following. NF1 is a tumor suppressor of the Ras of which amplification will reach the Myc. The Myc has interactions with BRCA but also several other genes
Our interest in this area stems from our involvement with one family of 4 members that we suspect have Neurofibromatosis. NF1 has not been established yet but all members have development issues and lipomatous lesions and imaging has suggested diffuse Neurofibromas. One member developed Breast cancer, a BRCA was negative, One member has gait disturbances and speech impairement, and the member with several lipomatous lesions, came to our attention for cough. CT chest suggested a new peripheral nerve sheath tumor that we are following. NF1 is a tumor suppressor of the Ras of which amplification will reach the Myc. The Myc has interactions with BRCA but also several other genes
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