NOTIONS ON CERVICAL CANCERS
Cervical cancers provide an opportunity for researchers to explore the pathophysiology of cellular interaction with a virus, and is a good example as to how a virus could lead to Cancer, and how, with a vaccine, one can eradicate or at least influence the prevalence of diseases including a specific cancer. World wide, 1 million people have cervical cancer and almost half that number will die of Cervical cancer. This point to an aggressive disease as compared to prostate cancer for example. The HPV related Cervical cancer is sexually transmitted, and in the United state up to 45% of women 25-29 year of age have tested positive in a particular study. There are over 100 types of HPV with the 16, 18 serotypes being the most cited as particularly prevalent. Their E6, E7 genes has been shown to incorporate themselves in Cervical cell genome. Other factors of causal nature include Smoking (which increases the risk of dysplastic changes at the Cervix), short interval between Coitarhe and Menarche, multiple sexual partners etc...Clearly use of condoms decreases exposure. Immunization is recommended for girls 9-26 years of age. Quadrivalent Vaccine has been advocated for boys to decrease frequency of Genital Warts and Anal cancers!
to be continued! NOW THE QUESTION IS SHOULD A BOOSTER SHOT BE ADVISED TO INCREASE COMPLIANCE?
Wednesday, July 17, 2013
Tuesday, July 16, 2013
ALL THE GOOD REASONS FOR A CANCER SURVIVOR PROGRAM!
Cancer: The Newest Chronic Disease (FROM MEDSCAPE)
Hello. I'm Dr. Sandra Fryhofer. Welcome to Medicine Matters.
The topic: achieving high-quality cancer survivorship care and the American Society of Clinical Oncology's (ASCO®) new blueprint for improving care for cancer survivors, published in the Journal of Clinical Oncology.[1] Here's why it matters.
More and more patients are living with cancer and they're living longer. Right now, more than 13.5 million people are cancer survivors. The 3 most prevalent cancers for men are prostate, colorectal, and melanoma; for women they are breast, uterine, and colorectal cancers.[2]
Review summaries of articles on clinical issues in Type 1 Gaucher disease and gain understanding of patient concerns.
Information from Industry
First, ASCO wants cancer to be considered a chronic disease. This is because the Affordable Care Act calls for Accountable Care Organizations (ACOs) and patient-centered medical homes to promote coordinated care for chronic diseases. Calling cancer survival a chronic disease would promote patient-centered coordinated care based on shared care models and would enhance collaboration.
where is CPRIT!
CRBCM is still looking for signs of life at CPRIT! we will advise our partnes as soon as we learn!
will send a camera to Houston/Austin.
all we could find in the media is this interesting statement:
" What I found particularly interesting, however, is how, in spite of a really nasty, disillusioning scandal like CPIRT having a largely happy ending for Texas taxpayers — the reformers got everything they wanted, from considerably more transparency to radical changes to avoid conflicts of interest — the Texas media largely downplayed Governor Perry’s signing of the bill. In this way, a scandal that started with an indignant outcry from the media and Texas residents ended as a footnote." (Bionews-tex).
A camera has been sent to record if indeed people are still at work! Silence is just too heavy! The involved journalists are just as silent!
will send a camera to Houston/Austin.
all we could find in the media is this interesting statement:
" What I found particularly interesting, however, is how, in spite of a really nasty, disillusioning scandal like CPIRT having a largely happy ending for Texas taxpayers — the reformers got everything they wanted, from considerably more transparency to radical changes to avoid conflicts of interest — the Texas media largely downplayed Governor Perry’s signing of the bill. In this way, a scandal that started with an indignant outcry from the media and Texas residents ended as a footnote." (Bionews-tex).
A camera has been sent to record if indeed people are still at work! Silence is just too heavy! The involved journalists are just as silent!
Lymphoepithelioma
From Wikipedia, the free encyclopedia
| Lymphoepithelioma | |
|---|---|
| Classification and external resources | |
Nasopharyngeal lymphoepithelioma in a lymph node. Note the small, blue lymphocytes between the larger cancer cells.
|
|
| ICD-O: | M8082/3 |
Lymphoepithelioma is a type of poorly differentiated nasopharyngeal carcinoma characterized by prominent infiltration of lymphocytes in the area involved by tumor. Lymphoepithelioma is also known as "class III nasopharyngeal carcinoma" in the WHO classification system. It has a high tendency to metastasize and is responsive to radiotherapy. Most cases are associated with Epstein-Barr virus infection.[1]
Lymphoepithelioma may also be referred to as Schmincke-Regaud tumor, after the German pathologist Alexander Schminke and French radiologist Claude Regaud.
Lymphoepithelioma-like carcinomas are carcinomas that arise outside of the nasopharynx, but resemble a lymphoepithelioma histologically. Lymphoepithelioma-like carcinomas may be found in almost any epithelial organ, including the lung, thymus, breast, colon, endometrium, prostate, and skin,[1] as well as urinary bladder, trachea, esophagus, stomach, salivary glands, vulva.[2]wikipedia
=============================================================================
These tumors are of interest because of their
1. possible viral induction or association: leading to believe that genes associated with the Virus are either imbedded in the normal tissue pathways inducing the transformation and therefore specific targets will be those that can block such incorporation. That indeed a different vaccine can be tried for the EBV virus in endemic regions once drivers of incorporation can be identified. Is it the DNA-ase, RNA-ase or CDK or just the cyclins...Here it appears that epigenetic events involving splicing molecules will be important. There got to be splicing and reconnection of Nuclear materiat, juxta-position to promoters and regulator factors for this disease to progress. Is there a Core binding factor like molecule driving this condition? I believe a genetic study is in order here to tell us!
What is the status of the NF-kB and what are the specific Cytokine (interon1, IL-2,4,6, 11,12,23) TNF and TGF-Beta. Role of some Known integrins (avB) and prominent Metaloproteases.
2. The response to concurrent Radiation and chemotherapy tends to suggest DNA breakdown is critical in this disease
emphasizing that P53 must be amplified (mostly secondarily), that DNA repair potential will have prognosis significance and Microsatellite instability will also have prognosis significance. MDM2, E, Rb genes would be important. Begin a question, can Velcade and the Aurora add something in Maintenance settings in this disease...Certainly an interesting approach!
can Vincristine and others Methotrexate like agents targeting the lymphoid component be given in maintenance setting, have a value in terms of prolonging survival or progression free survival?
A good study should include both the endemic and the non endemic portion to clearly see the importance of viral impact !
CRBCM is still alive!
We can go on
combining Cisplatin, Velcade and Aurora B as a new Induction therapy in Endemic Nasopharyngeal cancer....
Sunday, July 14, 2013
MURKY STATEMENT IN LUNG CANCER PREVENTION
Diets deficient in vitamin A and C and Beta-carotene have been associated with increased risk of lung cancer! However "there is no role for Beta-Carotene, Vitamin A or any other derivatives for the chemoprevention of lung cancer". The truth is Beta-carotene is associated with an increased risk of lung cancer among heavy smokers! A protective role of against lung cancer by Beta-carotene vitamin A or their derivatives, was not found in prospective trials. Briefly if you diet misses it, it is bad, but if you happen to take it, there is no purpose! Go figure! To ask question about such an unresolved issue is clearly dishonest, don't you think...!
Saturday, July 13, 2013
HERE THE WNT COMES AGAIN TO SHOW ITS MIGHT!
WNT, A MAJOR PATHWAY
The Wnt is one of the major pathway involved in many neaoplastic procell. Quite frankly we cannot emphasize enough the value of this patways. And one of the main reason we tend to minimize its importance is that, unlike the the RAS/MAPK, and fascinating PI3K which we can see flowing down the Cytosol, the Wnt occurs deep down the thickness of the Membrane and through the Reticulum Endothelium, reaching the Nucleus in a flash!
Disturbance at the Wnt affect Cellular polarity with severe folllowing consequence
1. Loss of sense of shape for the cell, cellular hyperplasia seems to be linked directly or indirectly to the Wnt.
2. Disturbance at the Wnt involves the E-Cadherin/Beta-Catenin system, leading to loss sanse of Adhesion, A cell that lost the sense and input from its neighbor trigger proliferation as if seeking the fill a perceived GAP! there is a reflex proliferation. With the lack of Adhesion, cellular consensus is impaired and the NOTCH is excited or otherwise profoundly disturbed. The cell find itself with a choice
1.0 Proliferate to fill the GAP
2.0 Activate the Polycystins and make a CYST filled with liquid.(See physio-pathology)
The stimulation of polycystins actually activates the JAK/STAT pathways increasing the proliferation risk. There is a related risk of fibrosis as in Myelofibrosis and Capsular formation for Cystic diseases!
Remember through the Polycystins, there is an influx of Calcium blocking Adenyl Cyclase and activation of cAMP phosphodiesterase. Consumption or Mutations at Polycystins leads to c-AMP build-up favoring Proliferations. All this to stress that Wnt disturbance leads to obligatory loss of cellular adhesion, shape and proliferation.
Remember close by is the RHOC gene
which " cycles between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape and motility. RhoC can activate formins such as mDia1 and FMNL2 to remodel the cytoskelton.[3]
It is prenylated at its C-terminus, and localizes to the cytoplasm and plasma membrane. It is thought to be important in cell locomotion. Overexpression of this gene is associated with tumor cell invasion and metastasis. RhoC-deficient mice can still develop tumors but these fail to metastasize, arguing that RhoC is essential for metastasis.[4]"wikipedia
and also remember the MTA-1, Ap-1, and HDAC-1 to unleash the rest of the neoplastic and metastatic transformation.
The Wnt is one of the major pathway involved in many neaoplastic procell. Quite frankly we cannot emphasize enough the value of this patways. And one of the main reason we tend to minimize its importance is that, unlike the the RAS/MAPK, and fascinating PI3K which we can see flowing down the Cytosol, the Wnt occurs deep down the thickness of the Membrane and through the Reticulum Endothelium, reaching the Nucleus in a flash!
Disturbance at the Wnt affect Cellular polarity with severe folllowing consequence
1. Loss of sense of shape for the cell, cellular hyperplasia seems to be linked directly or indirectly to the Wnt.
2. Disturbance at the Wnt involves the E-Cadherin/Beta-Catenin system, leading to loss sanse of Adhesion, A cell that lost the sense and input from its neighbor trigger proliferation as if seeking the fill a perceived GAP! there is a reflex proliferation. With the lack of Adhesion, cellular consensus is impaired and the NOTCH is excited or otherwise profoundly disturbed. The cell find itself with a choice
1.0 Proliferate to fill the GAP
2.0 Activate the Polycystins and make a CYST filled with liquid.(See physio-pathology)
The stimulation of polycystins actually activates the JAK/STAT pathways increasing the proliferation risk. There is a related risk of fibrosis as in Myelofibrosis and Capsular formation for Cystic diseases!
Remember through the Polycystins, there is an influx of Calcium blocking Adenyl Cyclase and activation of cAMP phosphodiesterase. Consumption or Mutations at Polycystins leads to c-AMP build-up favoring Proliferations. All this to stress that Wnt disturbance leads to obligatory loss of cellular adhesion, shape and proliferation.
Remember close by is the RHOC gene
which " cycles between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape and motility. RhoC can activate formins such as mDia1 and FMNL2 to remodel the cytoskelton.[3]
It is prenylated at its C-terminus, and localizes to the cytoplasm and plasma membrane. It is thought to be important in cell locomotion. Overexpression of this gene is associated with tumor cell invasion and metastasis. RhoC-deficient mice can still develop tumors but these fail to metastasize, arguing that RhoC is essential for metastasis.[4]"wikipedia
and also remember the MTA-1, Ap-1, and HDAC-1 to unleash the rest of the neoplastic and metastatic transformation.
Silencing MTA1 by RNAi reverses adhesion, migration and invasiveness of cervical cancer cells (SiHa) via altered expression of p53, and E-cadherin/β-catenin complex.
" It was speculated that the decreased migration and invasion capability
by inhibiting the MTA1 expression in the SiHa cell line may be mediated
through the altered expression of p53, and E-cadherin/β-catenin complex.
MTA1 could serve as a potential therapeutic target in cervical cancer."
=========================================================
THE WNT, PATHWAY TO CELL PROLIFERATION AND INVASIVENESS/METASTASIS
======================================================
DO NOT FORGET THE WISP3This gene encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the (PATWAY TO BONE METS) / WITH BMPR
FROM Hem/Onc today
*recent study suggests that the survival is not affected by Breast cancer diagnosed during pregnancy.
*IMRT offers lesser local adverse effects than standard RT in patients with early breast cancer
*Maintenance therapy with Gemzar-Taxol improves Progression free and overall survival in patient with metastatic breast cancer (32.3 Vs 25.5 months)
*A study at Baylor suggested circulating tumor DNA to be an "effective Biomarker in Breast cancer".
*Bendamustine and Rituxan appears to be an effective regimen in relapse Diffuse large B-cell lymphoma with ORR 67% and CR 37%, patients received a large dose of Bendamustine (120mg/m2) on day2,3 with great frequency of marrow toxicity.
*21 day R-CHOP (instead of 2weeks) remains the recommended standard in Lymphoma.
*As expected, Tivozanib received a thumb down by the FDA for Renal Cell Cancer, and DARATUMUMAB (Anti-CD 38) RECEIVED "the one to watch status" or Breakthrough status in Myeloma. FDA also approved Tafinlar,Mekinist for Melanoma.
*There is such thing as "an inappropriate Colonoscopy" by age of patients!
*OF SIGNIFICANCE, ZIBOTENTAN/TAXOTERE FAILED TO IMPROVE OVERALL SURVIVAL IN PATIENT WITH HORMONE REFRACTORY PROSTATE CANCER, AND REMEMBER A CANADIAN STUDY SUGGESTED THAT CETUXIMAB FAILED TO DO THE SAME DESPITE AN INCREASING RATE OF EGFR IN ADVANCING HRPC
*Once again Duloxetine works in Chemotherapy induced peripheral Neuropathy...
*don't run out of name,and not making it up!, Nintedamib good for Renal cell cancer, as good as Sunitinib,they say!
=======================================================
CAN PATIENT WITH WITH E.COLI POSITIVE TEST SHOW AN AMPLIFIED NF-kB AND HIGHER LEVEL OF CYCLINS (INTERFERON OR INTERLEUKINES) IN THEIR PERIPHERAL BLOOD CELLS AND SERUM (PICK THE RIGHT MEDIA FOR YOUR TESTING)?
================================================================
*recent study suggests that the survival is not affected by Breast cancer diagnosed during pregnancy.
*IMRT offers lesser local adverse effects than standard RT in patients with early breast cancer
*Maintenance therapy with Gemzar-Taxol improves Progression free and overall survival in patient with metastatic breast cancer (32.3 Vs 25.5 months)
*A study at Baylor suggested circulating tumor DNA to be an "effective Biomarker in Breast cancer".
*Bendamustine and Rituxan appears to be an effective regimen in relapse Diffuse large B-cell lymphoma with ORR 67% and CR 37%, patients received a large dose of Bendamustine (120mg/m2) on day2,3 with great frequency of marrow toxicity.
*21 day R-CHOP (instead of 2weeks) remains the recommended standard in Lymphoma.
*As expected, Tivozanib received a thumb down by the FDA for Renal Cell Cancer, and DARATUMUMAB (Anti-CD 38) RECEIVED "the one to watch status" or Breakthrough status in Myeloma. FDA also approved Tafinlar,Mekinist for Melanoma.
*There is such thing as "an inappropriate Colonoscopy" by age of patients!
*OF SIGNIFICANCE, ZIBOTENTAN/TAXOTERE FAILED TO IMPROVE OVERALL SURVIVAL IN PATIENT WITH HORMONE REFRACTORY PROSTATE CANCER, AND REMEMBER A CANADIAN STUDY SUGGESTED THAT CETUXIMAB FAILED TO DO THE SAME DESPITE AN INCREASING RATE OF EGFR IN ADVANCING HRPC
*Once again Duloxetine works in Chemotherapy induced peripheral Neuropathy...
*don't run out of name,and not making it up!, Nintedamib good for Renal cell cancer, as good as Sunitinib,they say!
=======================================================
CAN PATIENT WITH WITH E.COLI POSITIVE TEST SHOW AN AMPLIFIED NF-kB AND HIGHER LEVEL OF CYCLINS (INTERFERON OR INTERLEUKINES) IN THEIR PERIPHERAL BLOOD CELLS AND SERUM (PICK THE RIGHT MEDIA FOR YOUR TESTING)?
================================================================
Friday, July 12, 2013
THE CRBCM IS ALIVE! and MDHONORS/WORLD-ONE MADE IT POSSIBLE!
IT IS MARTIN LUTHER KING WHO SAID, IF I CAN RECALL EXACTLY OR CLOSE:
"I say to you today my friends that in spite of the difficulties of the moment, the frustrations of today, I still have dream...and with this dream ...we shall stand...until the freedom rings.." "And let freedom ring...our cause is just!".
The CRBCM has gotten the roughest start...looked upon with disdain in Houston..dismissed by notable organizationS...but today we announce that the MDHONORS came through...triggering the start of our first study on early detection of lung cancer.
CRBCM has advanced considerably, securing the the IRS non profit status, IN PROCESS OF shipping medical supply to Africa WITH THE HELP OF DOD, and now opening wide the race for the cure by opening its research wings. The CRBCM is in talks with several funding organizations. And as we strive, we see result because our mission is good and just, and our intentions pure. We strive and struggle not for profit, the time for that has passed, but for the legacy!
the CRBCM, an engine of advancement in medical research.
From the bottom of our hearts, we thank MDHONORS/WORLD-ONE for acting on its promises, and for helping transform what was a dream into reality! The CRBCM thank you!
"I say to you today my friends that in spite of the difficulties of the moment, the frustrations of today, I still have dream...and with this dream ...we shall stand...until the freedom rings.." "And let freedom ring...our cause is just!".
The CRBCM has gotten the roughest start...looked upon with disdain in Houston..dismissed by notable organizationS...but today we announce that the MDHONORS came through...triggering the start of our first study on early detection of lung cancer.
CRBCM has advanced considerably, securing the the IRS non profit status, IN PROCESS OF shipping medical supply to Africa WITH THE HELP OF DOD, and now opening wide the race for the cure by opening its research wings. The CRBCM is in talks with several funding organizations. And as we strive, we see result because our mission is good and just, and our intentions pure. We strive and struggle not for profit, the time for that has passed, but for the legacy!
the CRBCM, an engine of advancement in medical research.
From the bottom of our hearts, we thank MDHONORS/WORLD-ONE for acting on its promises, and for helping transform what was a dream into reality! The CRBCM thank you!
CAN'T ESCAPE THIS ONE
Afatinib Approved by the FDA for EGFRm+ Lung Cancer
About 10% to 15% of NSCLC is EGFRm+ in Western populations, although the incidence of the mutation is higher in Asian populations."
THIS IS SIGNIFICANT AS IT ADDS TO THE ARMAMENTORIUN IN AN OTHERWISE DIFFICULT DISEASE TO TREAT, WE CLEARLY NEED MORE OF THESE NEWS. IT ALSO PROVIDE FURTHER REASON TO TEST FOR THESE MUTATIONS PRIOR TO CHOOSING WHICH FINAL OPTION IS APPROPRIATE AND MORE PALATABLE FOR OUR PATIENTS. IT ALSO PROVIDES FOR A BETTER CHANCE FOR INSURANCE TO COVER THIS PRESCRIPTION...THIS IS A GOOD DAY IN ONCOLOGY!
Thursday, July 11, 2013
SILENCE AT CPRIT
At CRBCM we watch the news trying to see if there is any thing happening with one of the most important organization for Cancer Prevention and Research in Texas (CPRIT). I am afraid to report: SILENCE...
Now I do not know what is worse. The old CPRIT full of politicians that used to lie to us as it turns out! Or the new and improved CPRIT that is completely silent. The old one kept us energized even when it was misleading, filling us with false hope while dealing and diverting funds to friends, but at least we believed to the cost of 7 grant submissions. This new CPRIT, may be overcautious but what is it doing we wonder! Is-it still putting things into place? or is it still planning what to do...Only God and insiders know. Truly I wonder what is worse. Even in my office, when I am a little late, I come out and tell people who were involved, waiting, to tell what is going on behind the curtains! Is it fair to ask that the public be kept abreast!
It's been a month since the legislation was passed refunding CPRIT, even if they are still putting competent people in place, the public should know. There have been complete silence as if the institution is closed, as if nobody works there anymore...what is it about? Did some dark organization take over? Are we going to disappear in the darkness of night for asking. We know where the money will ultimately go so just come out and let us know the new rules of the game! Going under the dark or under water does not help, just come out and lay things straight!
The beneficiaries are MD Anderson, Baylor and you know the rest of the list, the legislators we know them, few new names at CPRIT but the outcome will be the same! I truly doubt the game will have new steps, but it is nice to observe out as it will be unveiled. Whether CPRIT like it or not, CRBCM and others will be watching. The left behind will be there to play their part, disparity will be go on, unless of course true leaders take over CPRIT...and chance of that is minimal to say the least. True Visionaries are often hard to come by for as long as the influencial organizations around CPRIT such as Bioalliances remain close by. My experience with Bioalliances was the worse, but what can I say or do, they keep a hold on CPRIT!
QUI VERRA, VERRA or is it QUI SERA SERA (WHATEVER WILL BE, WILL BE!) ! WE ARE STILL LEAVING AN INTERESTING TIME IN CANCER RESEARCH IN TEXAS!
Now I do not know what is worse. The old CPRIT full of politicians that used to lie to us as it turns out! Or the new and improved CPRIT that is completely silent. The old one kept us energized even when it was misleading, filling us with false hope while dealing and diverting funds to friends, but at least we believed to the cost of 7 grant submissions. This new CPRIT, may be overcautious but what is it doing we wonder! Is-it still putting things into place? or is it still planning what to do...Only God and insiders know. Truly I wonder what is worse. Even in my office, when I am a little late, I come out and tell people who were involved, waiting, to tell what is going on behind the curtains! Is it fair to ask that the public be kept abreast!
It's been a month since the legislation was passed refunding CPRIT, even if they are still putting competent people in place, the public should know. There have been complete silence as if the institution is closed, as if nobody works there anymore...what is it about? Did some dark organization take over? Are we going to disappear in the darkness of night for asking. We know where the money will ultimately go so just come out and let us know the new rules of the game! Going under the dark or under water does not help, just come out and lay things straight!
The beneficiaries are MD Anderson, Baylor and you know the rest of the list, the legislators we know them, few new names at CPRIT but the outcome will be the same! I truly doubt the game will have new steps, but it is nice to observe out as it will be unveiled. Whether CPRIT like it or not, CRBCM and others will be watching. The left behind will be there to play their part, disparity will be go on, unless of course true leaders take over CPRIT...and chance of that is minimal to say the least. True Visionaries are often hard to come by for as long as the influencial organizations around CPRIT such as Bioalliances remain close by. My experience with Bioalliances was the worse, but what can I say or do, they keep a hold on CPRIT!
QUI VERRA, VERRA or is it QUI SERA SERA (WHATEVER WILL BE, WILL BE!) ! WE ARE STILL LEAVING AN INTERESTING TIME IN CANCER RESEARCH IN TEXAS!
MIAMI, HERE WE COME
CRBCM WILL BE REPORTING FROM MIAMI, IT'S ALL CONFIRMED! HEMATOLOGIC MALIGNANCIES, HERE WE COME! NO MORE SECOND HAND INFORMATION, WE ARE GOING TO THE SOURCE, LIKE SAINT THOMAS TOUCHING INTO THE WOUNDS! WE WILL BE LOOKING INTO THE EYES OF PRESENTATRS/LECTURERS FOR A DEEPER FEEL OF THE INFO! EXPECT A SUMMARY REPORT!
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09 AUG 13 - FRIDAY
AMERICAN 862 ECONOMY NONSTOP
LV: EL PASO 910A
AR: DALLAS/FT WOR 1155A CONFIRMED
AIR MILEAGE FOR THIS SEGMENT IS- 551
AA -AOEBRZ
AMERICAN 2024 ECONOMY NONSTOP
LV: DALLAS/FT WOR 1235P
AR: MIAMI 440P CONFIRMED
FOOD TO PURCHASE
AIR MILEAGE FOR THIS SEGMENT IS- 1121
AA -AOEBRZ
11 AUG 13 - SUNDAY
AMERICAN 1665 ECONOMY NONSTOP
LV: MIAMI 850A
AR: DALLAS/FT WOR 1100A CONFIRMED
FOOD TO PURCHASE
AIR MILEAGE FOR THIS SEGMENT IS- 1121
AA -AOEBRZ
AMERICAN 1569 ECONOMY NONSTOP
LV: DALLAS/FT WOR 1235P
AR: EL PASO 115P CONFIRMED
AIR MILEAGE FOR THIS SEGMENT IS- 551
AA -AOEBRZ
Update in some Hematology Malignancies
We will be in Miami for a full report on this Topic in early August, but in the meantime,
about Ibrutinib " Now, updated data show that progression-free survival in patients with treatment-naïve CLL was 96% at 15 months and in relapsed/refractory patients was 87.7% at 18 months." (McCall )
Response even in CLL Bulky disease. An temporary Upsurge in lymphocytosis was reported but soon settles down.
*"Ponatinib is approved for use in patients with chronic myeloid leukemia (CML) and also Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (Ph+ ALL) who have relapsed or are refractory to other therapies. Many of these patients, but not all, have developed a T315I mutation, which makes the disease resistant to the standard treatment with tyrosine kinase inhibitors (TKIs) such as imatinib (Gleevec)."
(Medscape) Watch Amylase and lipase and marrow suppression. READ ORIGINAL ARTICLE BY Z.CHUSTECKA.
*R. NELSON REPORTED ON NEW FDA APPROVAL OF BOSUTINIB!
" Currently, there are no approved therapies available for CML patients who have failed treatment with imatinib (Gleevec, Novartis) and the second-generation products nilotinib (Tasigna, Novartis Oncology) and dasatinib (Sprycel, Bristol-Myers Squibb).
Bosutinib is an oral, once-daily, second-generation inhibitor of Abl and Src family kinases. It is a potent ATP-competitive inhibitor of the BCR-ABL oncogene, and unlike competitors, it has minimal inhibitory activity against c-KIT and PDGFR."
AT THE END YOU NEED PRACTICAL NEWS THANKS TO MEDSCAPE!
about Ibrutinib " Now, updated data show that progression-free survival in patients with treatment-naïve CLL was 96% at 15 months and in relapsed/refractory patients was 87.7% at 18 months." (McCall )
Response even in CLL Bulky disease. An temporary Upsurge in lymphocytosis was reported but soon settles down.
*"Ponatinib is approved for use in patients with chronic myeloid leukemia (CML) and also Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (Ph+ ALL) who have relapsed or are refractory to other therapies. Many of these patients, but not all, have developed a T315I mutation, which makes the disease resistant to the standard treatment with tyrosine kinase inhibitors (TKIs) such as imatinib (Gleevec)."
(Medscape) Watch Amylase and lipase and marrow suppression. READ ORIGINAL ARTICLE BY Z.CHUSTECKA.
*R. NELSON REPORTED ON NEW FDA APPROVAL OF BOSUTINIB!
" Currently, there are no approved therapies available for CML patients who have failed treatment with imatinib (Gleevec, Novartis) and the second-generation products nilotinib (Tasigna, Novartis Oncology) and dasatinib (Sprycel, Bristol-Myers Squibb).
Bosutinib is an oral, once-daily, second-generation inhibitor of Abl and Src family kinases. It is a potent ATP-competitive inhibitor of the BCR-ABL oncogene, and unlike competitors, it has minimal inhibitory activity against c-KIT and PDGFR."
AT THE END YOU NEED PRACTICAL NEWS THANKS TO MEDSCAPE!
Wednesday, July 10, 2013
More news
*SEERS data suggest Stage I colon cancers are better off totally/ resected (radical Resection) than plucked off (Local excision)!
*Remember there is a Metabolic Pancreatic Panel (Xylitol,Glucitol, Inositol, Histidine) keep checking out against the standard CEA and CA19-9! Is it really better in detecting early Pancreatic cancers? more validation needed.
*Esophageal Cancer...NO Cetuximab! (The Oncology Report says so! Read it for a full story!)
*In Vitro Fertilization not associated with Autism rate but association with Mental Retardation was supported in a study by Sandin et al! (of Sweden!)
*Gradual cessation of smoking Vs Abrupt Cessation, no difference in result suggested Per Lindson-Hawley et al! SO DON'T BITE YOUR NAIL ABOUT THIS JUST DO IT, IT'S ALL THE SAME AND LEAD TO RESULT!
*Remember there is a Metabolic Pancreatic Panel (Xylitol,Glucitol, Inositol, Histidine) keep checking out against the standard CEA and CA19-9! Is it really better in detecting early Pancreatic cancers? more validation needed.
*Esophageal Cancer...NO Cetuximab! (The Oncology Report says so! Read it for a full story!)
*In Vitro Fertilization not associated with Autism rate but association with Mental Retardation was supported in a study by Sandin et al! (of Sweden!)
*Gradual cessation of smoking Vs Abrupt Cessation, no difference in result suggested Per Lindson-Hawley et al! SO DON'T BITE YOUR NAIL ABOUT THIS JUST DO IT, IT'S ALL THE SAME AND LEAD TO RESULT!
SO YOU ARE KEPT IN THE LOOP!
*There are more ALK positive agents available. They have ROS-1 Inhibition and some have ANTI-EGFR activity. Response in Brain tumor are noted. It is suggested that SOME of these agents work a little longer (in weeks!). YES most of these agents have wonderful response rates but not long lasting.
*In Glioma, Co-deletion of 1p and 19q announces response to chemotherapy. and Mutation in IDH gene is a good prognosis factor! (Isocitrate De-Hydrogenase). This Mutation is associated with the MGMT promoter of DNA methylation and G-CIMP,TP53, and ATRX. IDH1 mutation is mostly associated with Oligodendroglioma.
*Women with breast cancer which is ER positive not only will receive chemotherapy but now 10 years of Tamoxifen. Some reports suggested only 5% of them have a clear discussion of Fertility preservation issues
and fewer see a Reproductive Endocrinologist. Come ON Oncologists, wake-up and smell the coffee, the law is coming after you!
*Oral Topotecan is a good second line in Metastatic small cell lung cancer, could you add Avastin!? read David R Spigel et al!
*In Glioma, Co-deletion of 1p and 19q announces response to chemotherapy. and Mutation in IDH gene is a good prognosis factor! (Isocitrate De-Hydrogenase). This Mutation is associated with the MGMT promoter of DNA methylation and G-CIMP,TP53, and ATRX. IDH1 mutation is mostly associated with Oligodendroglioma.
*Women with breast cancer which is ER positive not only will receive chemotherapy but now 10 years of Tamoxifen. Some reports suggested only 5% of them have a clear discussion of Fertility preservation issues
and fewer see a Reproductive Endocrinologist. Come ON Oncologists, wake-up and smell the coffee, the law is coming after you!
*Oral Topotecan is a good second line in Metastatic small cell lung cancer, could you add Avastin!? read David R Spigel et al!
Tuesday, July 9, 2013
NEWS ABOUT ACTOS (from medscape)
Doctors Concerned as India Suspends Diabetes Drug Pioglitazone
medscape
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Drug & Reference Information
Diabetologists in India are up in arms following
an unexpected decision by the government there to suspend sales of the
diabetes drug pioglitazone. The ruling came seemingly out of the
blue, and there is much concern among doctors about their patients with
type 2 diabetes who are currently taking this medication.
The government suspended the manufacture, sale, and distribution of pioglitazone at the end of June, citing concerns over adverse effects, particularly bladder cancer, according to a report in BMJ and a number of Indian media outlets.
Vijay Panikar, MD, an endocrinologist from Lilavati Hospital, Bandra, Mumbai, who is also the secretary of the Association for Diabetes Care and Prevention, told Medscape Medical News: "I think it's unfortunate. Pioglitazone should not have been banned. The government could have put some restrictions [on it] but still allowed marketing of the drug because there is no clear-cut indication that it does cause bladder cancer." In fact, he said, "there are new data coming, which are probably in favor of pioglitazone, expected in 2014."
And the secretary general of the Indian Pharmaceutical Alliance, which represents 19 research-based national pharmaceutical companies, Beilib D.G. Shah, said his members are also infuriated by this decision, which he says is wrong on a number of levels.
"First, the due process of law for suspensions was not followed," Shah told Medscape Medical News, adding that normally there is a procedure for this type of legislation, with logical steps, none of which were followed in this case. Second, "the government cites the fact that pioglitazone is banned in France and Germany," but the French ban "was 3 years ago," Shah noted, and in Germany "they have suspended sales to new patients" only, he said.
"This drug has been on the Indian market for 12 years, and there has been no suggestion of a link with bladder cancer. This decision has put 3 million patients on pioglitazone at risk and has come so suddenly. Now they will have to go to their diabetologist or doctor and discuss what therapy to change to. One of their choices now is to move to a new therapy, at 10 times the cost. There is a suspicion that some foreign companies [have pressured for this] to switch patients from safe low-cost treatments to newer therapies such as gliptins," he asserted.
Medscape Medical News tried to speak with a representative of the Indian government. But G.N. Singh, PhD, the drugs controller general of India, was overseas and could not be contacted, and Dr. Arun Panda, of the Ministry of Health and Welfare, could not be reached for comment.
Pioglitazone "Cornerstone of Therapy" in India
The thiazolidinedione drug class, which includes rosiglitazone (Avandia, GlaxoSmithKline) as well as pioglitazone, has never been far from controversy. Rosiglitazone was suspended by the European Union in 2010 and its use severely restricted in the United States because of concerns about a possible increased risk of cardiovascular adverse effects, although this assertion has recently been challenged in the second in a high-profile Food and Drug Administration advisory committee meeting.
Shah told Medscape Medical News that rosiglitazone was removed from the Indian market around the same time as it was suspended in Europe, leaving pioglitazone — originally developed by Takeda Pharmaceuticals and marketed as Actos but now widely available as a generic medication — as the remaining thiazolidinedione. It, too, has been associated with adverse effects, including fractures and fluid retention, but bladder cancer is probably the greatest concern. Although pioglitazone has remained on the market in many countries, some — including France and Germany — have banned it or severely restricted its use.
Indian patients are particularly well suited to pioglitazone, Dr. Panikar told Medscape Medical News, "because they have a lot of insulin resistance, so this drug is ideal for that." In fact, pioglitazone "is the cornerstone of treatment in most patients" in India, he stated.
Most in India are taking pioglitazone in combination with either metformin or a sulfonylurea, with many using fixed-dose combination products. Now that pioglitazone is suddenly unavailable, "the next step is to give gliptins or insulin," he explained. However, gliptins "are probably 10 times the price" of pioglitazone, so "a large number of patients…cannot afford this at all," and they also say, "Why should we take insulin…when all this time we were controlled without insulin?" he observed.
He noted that pioglitazone is used in very low doses in India, 7.5 to 15 mg daily. "If you don't have a contraindication for the use of pioglitazone, it should be used in a low dose," he asserted.
Dr. Panikar and others also stress that pioglitazone remains on the market in the United States, the United Kingdom, and in many other Western nations and that it is endorsed and recommended for diabetes management by many respected organizations, including the American Diabetes Association (ADA), the European Association for the Study of Diabetes (EASD), and the International Diabetes Federation (IDF).
"We are worried, rather than being angry. We are concerned about our patients. We are making appeals to the government to reconsider the decision. Associations are in the process of putting together appeals, which will be presented, and we are hopeful they will reverse this decision," Dr. Panikar said.
Most Indians Cannot Afford Newer Medications
Pioglitazone has been available generically in India for some time, but newer oral type 2 diabetes medications, such as the gliptins (dipeptidyl peptidase-4 [DPP-4] inhibitors), are available only as branded products from Western companies, said Shah, whose organization represents domestic firms, such as Dr. Reddy's Laboratories and Ranbaxy Laboratories. There is 1 exception to this, with the Indian company Glenmark Pharmaceuticals, selling a cheaper version of one of the gliptins, but this is being legally challenged, he noted.
He said that the Indian government ruling on pioglitazone specifically cites that all "drug formulations containing pioglitazone are likely to involve risk to human beings" and states that "safer alternatives to the said drug are available."
While it is true that alternatives are available, many people simply cannot afford them, he maintained. "Around a third" of existing patients could probably afford to switch to newer diabetes medications, but the remainder cannot, he explained.
The market for pioglitazone in India is estimated to be worth about Rs7 billion ($120 million) a year, but the medication is cheap for individual patients, priced as low as Re1 to Rs4 per tablet, according to Indian reports.
But, "We haven't heard the last word yet," Shah asserted. Following "strong protestations" from a number of quarters, the government has now backtracked a little and agreed to a meeting of "technical experts" to discuss the situation, possibly as early as next week, he told Medscape Medical News.
The government suspended the manufacture, sale, and distribution of pioglitazone at the end of June, citing concerns over adverse effects, particularly bladder cancer, according to a report in BMJ and a number of Indian media outlets.
Vijay Panikar, MD, an endocrinologist from Lilavati Hospital, Bandra, Mumbai, who is also the secretary of the Association for Diabetes Care and Prevention, told Medscape Medical News: "I think it's unfortunate. Pioglitazone should not have been banned. The government could have put some restrictions [on it] but still allowed marketing of the drug because there is no clear-cut indication that it does cause bladder cancer." In fact, he said, "there are new data coming, which are probably in favor of pioglitazone, expected in 2014."
And the secretary general of the Indian Pharmaceutical Alliance, which represents 19 research-based national pharmaceutical companies, Beilib D.G. Shah, said his members are also infuriated by this decision, which he says is wrong on a number of levels.
"First, the due process of law for suspensions was not followed," Shah told Medscape Medical News, adding that normally there is a procedure for this type of legislation, with logical steps, none of which were followed in this case. Second, "the government cites the fact that pioglitazone is banned in France and Germany," but the French ban "was 3 years ago," Shah noted, and in Germany "they have suspended sales to new patients" only, he said.
"This drug has been on the Indian market for 12 years, and there has been no suggestion of a link with bladder cancer. This decision has put 3 million patients on pioglitazone at risk and has come so suddenly. Now they will have to go to their diabetologist or doctor and discuss what therapy to change to. One of their choices now is to move to a new therapy, at 10 times the cost. There is a suspicion that some foreign companies [have pressured for this] to switch patients from safe low-cost treatments to newer therapies such as gliptins," he asserted.
Medscape Medical News tried to speak with a representative of the Indian government. But G.N. Singh, PhD, the drugs controller general of India, was overseas and could not be contacted, and Dr. Arun Panda, of the Ministry of Health and Welfare, could not be reached for comment.
Pioglitazone "Cornerstone of Therapy" in India
The thiazolidinedione drug class, which includes rosiglitazone (Avandia, GlaxoSmithKline) as well as pioglitazone, has never been far from controversy. Rosiglitazone was suspended by the European Union in 2010 and its use severely restricted in the United States because of concerns about a possible increased risk of cardiovascular adverse effects, although this assertion has recently been challenged in the second in a high-profile Food and Drug Administration advisory committee meeting.
Shah told Medscape Medical News that rosiglitazone was removed from the Indian market around the same time as it was suspended in Europe, leaving pioglitazone — originally developed by Takeda Pharmaceuticals and marketed as Actos but now widely available as a generic medication — as the remaining thiazolidinedione. It, too, has been associated with adverse effects, including fractures and fluid retention, but bladder cancer is probably the greatest concern. Although pioglitazone has remained on the market in many countries, some — including France and Germany — have banned it or severely restricted its use.
Indian patients are particularly well suited to pioglitazone, Dr. Panikar told Medscape Medical News, "because they have a lot of insulin resistance, so this drug is ideal for that." In fact, pioglitazone "is the cornerstone of treatment in most patients" in India, he stated.
Most in India are taking pioglitazone in combination with either metformin or a sulfonylurea, with many using fixed-dose combination products. Now that pioglitazone is suddenly unavailable, "the next step is to give gliptins or insulin," he explained. However, gliptins "are probably 10 times the price" of pioglitazone, so "a large number of patients…cannot afford this at all," and they also say, "Why should we take insulin…when all this time we were controlled without insulin?" he observed.
He noted that pioglitazone is used in very low doses in India, 7.5 to 15 mg daily. "If you don't have a contraindication for the use of pioglitazone, it should be used in a low dose," he asserted.
Dr. Panikar and others also stress that pioglitazone remains on the market in the United States, the United Kingdom, and in many other Western nations and that it is endorsed and recommended for diabetes management by many respected organizations, including the American Diabetes Association (ADA), the European Association for the Study of Diabetes (EASD), and the International Diabetes Federation (IDF).
"We are worried, rather than being angry. We are concerned about our patients. We are making appeals to the government to reconsider the decision. Associations are in the process of putting together appeals, which will be presented, and we are hopeful they will reverse this decision," Dr. Panikar said.
Most Indians Cannot Afford Newer Medications
Pioglitazone has been available generically in India for some time, but newer oral type 2 diabetes medications, such as the gliptins (dipeptidyl peptidase-4 [DPP-4] inhibitors), are available only as branded products from Western companies, said Shah, whose organization represents domestic firms, such as Dr. Reddy's Laboratories and Ranbaxy Laboratories. There is 1 exception to this, with the Indian company Glenmark Pharmaceuticals, selling a cheaper version of one of the gliptins, but this is being legally challenged, he noted.
He said that the Indian government ruling on pioglitazone specifically cites that all "drug formulations containing pioglitazone are likely to involve risk to human beings" and states that "safer alternatives to the said drug are available."
While it is true that alternatives are available, many people simply cannot afford them, he maintained. "Around a third" of existing patients could probably afford to switch to newer diabetes medications, but the remainder cannot, he explained.
The market for pioglitazone in India is estimated to be worth about Rs7 billion ($120 million) a year, but the medication is cheap for individual patients, priced as low as Re1 to Rs4 per tablet, according to Indian reports.
But, "We haven't heard the last word yet," Shah asserted. Following "strong protestations" from a number of quarters, the government has now backtracked a little and agreed to a meeting of "technical experts" to discuss the situation, possibly as early as next week, he told Medscape Medical News.
AS I REVIEW MELANOMA, MITF COMES UP
MTIF A REGULATOR OF MELANOCYTE DIFFERENTIATION,
AN OLD STORY ON CRBCM
The LysRS-Ap4A-MITF signaling pathway
The LysRS-Ap4A-MITF signaling pathway was first discovered in mast cells, in which , the MAPK pathway is activated upon allergen stimulation. Lysyl-tRNA synthetase (LysRS), which normally resides in the multisynthetase complex with other tRNA sythetases, is phosphorylated on Serine 207 in a MAPK-dependent manner.[30] This phosphorylation causes LysRS to change its conformation, detach from the complex and translocate into the nucleus, where it associates with the MITF-HINT1 inhibitory complex. The conformational change switches LysRS activity from aminoacylation of Lysine tRNA to diadenosine tetraphosphate (Ap4A) production. Ap4A binds to HINT1, which releases MITF from the inhibitory complex, allowing it to transcribe its target genes.[31] Activation of the LysRS-Ap4A-MITF signaling pathway by isoproterenol has been confirmed in cardiomyocytes, where MITF is a major regulator of cardiac growth and hypertrophy.[32][33](wikipedia)
Not only it gives Hypertrophy but epidermolysis goes through this intergrin, it participates in the ERBB pathways. Mark my word this is are critical pathways in pancreatic cancers.
MTIF GIVES YOU MOTIVES TO GO AFTER IT!
MAKING THE ERBIN A PLAUSIBLE TARGET.
MAKING ALSO A STRONGER CASE THAT MEMBRANE CYTOSKELETON SHOULD BE A GOOD TARGET BECAUSE OF THE WAY IT DRIVES ITS PATHWAY NOT THROUGH THE CYTOSOL( ALTHOUGH THERE IS A SECONDARY RAS/MAPK STIMULATION,) BUT THE PATHWAY HERE IS THROUGH THE RETICULUM ENDOTHELIUM DIRECTLY TO THE NUCLEUS! CONCEPTUALLY, AN ANTIBODY TO LAMININ ATTACHED TO A SUBUNIT OF A LIPOLYTIC COMPOUND SHOULD HAVE A THERAPEUTIC OR CHEMICAL EFFECT AT THIS LEVEL. AN INTERESTING APPROACH. CHANCES ARE IT MAY ALSO HAVE A STRONG IMPACT ON THE WNT-PATHWAY WHICH TRAVEL CLOSE BY AND IS IMPORTANT IN BREAST CANCER!
MTA-1: THIS IS A REAL OPPORTUNITY
Here the cell stopped fooling around trying to lie to you. Here the cell says to you this is one of my way to metastatasize. yes this is my gene to mestastasize and I will work like any CBF like molecule by attaching to DNA and make me protein that will have me spread like wild fire! And by the way I will use a growth hormone like Estrogen. no kidding around
"MTA1 has been shown to interact with HDAC1,[4][5] Histone deacetylase 2,[4][6][5] MTA2,[4] Estrogen receptor alpha[7][5] and MNAT1.[8] MTA1 has also been shown to inhibit SMAD7 at the transcriptional level[9]"
IT DOES NEED TGF TO WORK, TGF IS FOR LOCAL GROWTH ANYWAY THAT WHY IT BLOCKS THE SMAD.
SPINT2
Mutation at SPINT2 leads to significant Malignant Ascites and peritoneal invasion, SPINT 2 is a suppressor of this phenomena. On the Intestinal membrane deficiency of SPINT2 leads to sodium induced/containing diarrhea. This is also true in Ovarian cancer or peritoneal based tumors. Targeting this is better then trying Avastin, a blind approach when it comes to effusions management.
MMP11
A metalloproteiase, aimed at breaking down extracellular matrix and be on the move. Targeting MMP for cancer has proven futile. The cell is not stupid, it does not put out things that is going to hunt it! It first builds a strong inhibitor to metalloproteinases. In fact lack of inhibitors has been recognized as the main pathogenesis of TTP. With the ADAMs being the integrins involved! and next is that Inhibitor which is of course expressed in pancreatic cancer.
TIMP1
TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein that is expressed from the several tissues of organisms.
This protein a member of the TIMP family. The glycoprotein is a natural inhibitor of the matrix metalloproteinases (MMPs), a group of peptidases involved in degradation of the extracellular matrix. In addition to its inhibitory role against most of the known MMPs, the encoded protein is able to promote cell proliferation in a wide range of cell types, and may also have an anti-apoptotic function.
==============
PRKCA see PRKCG
Here Phorbol esters, diacylglycerol, and calcium become important for the cell performance of various functions. Did I mention few targets, I truly believe I did!
CDH1 The Cadherin by excellence, not only important as adhesion molecule and role in metastasis. Its role is amplified by what else anchors here such as Vinculin, and others molecules such as Plakoglobins, amplifying the role. Remember even Cytochrome C is anchored at the mitochondrial membrane and its release leads to apoptosis!
The anchors are legitimate targets therefore, and brings to mind NACA1 in the anchoring to Histone deacetyl transferase (SEE OUR LEUKEMIA SECTION) CDH13 THAT'S ANOTHER BALL GAME ALL TOGETHER. THE CELL TWEACKS SOMETHING AND IT IS ANOTHER BALL GAME ALL TOGETHER!
==========================
NOW IN MELANOMA THEY ADD
1. THE C-KIT
2. BRAF
3. NRAS
4. GNAQ/GNA11 FOR UVEAL MELANOMA
5. P16/CDKN2A
6. IF MITF IS THE DRIVER, KNOCK OUT AP4A THEY SAY!
AN OLD STORY ON CRBCM
The LysRS-Ap4A-MITF signaling pathway
The LysRS-Ap4A-MITF signaling pathway was first discovered in mast cells, in which , the MAPK pathway is activated upon allergen stimulation. Lysyl-tRNA synthetase (LysRS), which normally resides in the multisynthetase complex with other tRNA sythetases, is phosphorylated on Serine 207 in a MAPK-dependent manner.[30] This phosphorylation causes LysRS to change its conformation, detach from the complex and translocate into the nucleus, where it associates with the MITF-HINT1 inhibitory complex. The conformational change switches LysRS activity from aminoacylation of Lysine tRNA to diadenosine tetraphosphate (Ap4A) production. Ap4A binds to HINT1, which releases MITF from the inhibitory complex, allowing it to transcribe its target genes.[31] Activation of the LysRS-Ap4A-MITF signaling pathway by isoproterenol has been confirmed in cardiomyocytes, where MITF is a major regulator of cardiac growth and hypertrophy.[32][33](wikipedia)
Not only it gives Hypertrophy but epidermolysis goes through this intergrin, it participates in the ERBB pathways. Mark my word this is are critical pathways in pancreatic cancers.
MTIF GIVES YOU MOTIVES TO GO AFTER IT!
MAKING THE ERBIN A PLAUSIBLE TARGET.
MAKING ALSO A STRONGER CASE THAT MEMBRANE CYTOSKELETON SHOULD BE A GOOD TARGET BECAUSE OF THE WAY IT DRIVES ITS PATHWAY NOT THROUGH THE CYTOSOL( ALTHOUGH THERE IS A SECONDARY RAS/MAPK STIMULATION,) BUT THE PATHWAY HERE IS THROUGH THE RETICULUM ENDOTHELIUM DIRECTLY TO THE NUCLEUS! CONCEPTUALLY, AN ANTIBODY TO LAMININ ATTACHED TO A SUBUNIT OF A LIPOLYTIC COMPOUND SHOULD HAVE A THERAPEUTIC OR CHEMICAL EFFECT AT THIS LEVEL. AN INTERESTING APPROACH. CHANCES ARE IT MAY ALSO HAVE A STRONG IMPACT ON THE WNT-PATHWAY WHICH TRAVEL CLOSE BY AND IS IMPORTANT IN BREAST CANCER!
MTA-1: THIS IS A REAL OPPORTUNITY
Here the cell stopped fooling around trying to lie to you. Here the cell says to you this is one of my way to metastatasize. yes this is my gene to mestastasize and I will work like any CBF like molecule by attaching to DNA and make me protein that will have me spread like wild fire! And by the way I will use a growth hormone like Estrogen. no kidding around
"MTA1 has been shown to interact with HDAC1,[4][5] Histone deacetylase 2,[4][6][5] MTA2,[4] Estrogen receptor alpha[7][5] and MNAT1.[8] MTA1 has also been shown to inhibit SMAD7 at the transcriptional level[9]"
IT DOES NEED TGF TO WORK, TGF IS FOR LOCAL GROWTH ANYWAY THAT WHY IT BLOCKS THE SMAD.
SPINT2
Mutation at SPINT2 leads to significant Malignant Ascites and peritoneal invasion, SPINT 2 is a suppressor of this phenomena. On the Intestinal membrane deficiency of SPINT2 leads to sodium induced/containing diarrhea. This is also true in Ovarian cancer or peritoneal based tumors. Targeting this is better then trying Avastin, a blind approach when it comes to effusions management.
MMP11
A metalloproteiase, aimed at breaking down extracellular matrix and be on the move. Targeting MMP for cancer has proven futile. The cell is not stupid, it does not put out things that is going to hunt it! It first builds a strong inhibitor to metalloproteinases. In fact lack of inhibitors has been recognized as the main pathogenesis of TTP. With the ADAMs being the integrins involved! and next is that Inhibitor which is of course expressed in pancreatic cancer.
TIMP1
TIMP1
From Wikipedia, the free encyclopedia
| TIMP metallopeptidase inhibitor 1 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
 PDB rendering based on 1d2b. |
|||||||||||
|
|||||||||||
| Identifiers | |||||||||||
| Symbols | TIMP1; CLGI; EPA; EPO; HCI; TIMP | ||||||||||
| External IDs | OMIM: 305370 MGI: 98752 HomoloGene: 36321 GeneCards: TIMP1 Gene | ||||||||||
|
|||||||||||
| RNA expression pattern | |||||||||||
 |
|||||||||||
| More reference expression data | |||||||||||
| Orthologs | |||||||||||
| Species | Human | Mouse | |||||||||
| Entrez | 7076 | 21857 | |||||||||
| Ensembl | ENSG00000102265 | ENSMUSG00000001131 | |||||||||
| UniProt | P01033 | P12032 | |||||||||
| RefSeq (mRNA) | NM_003254 | NM_001044384 | |||||||||
| RefSeq (protein) | NP_003245 | NP_001037849 | |||||||||
| Location (UCSC) | Chr X: 47.44 – 47.45 Mb |
Chr X: 20.87 – 20.87 Mb |
|||||||||
| PubMed search | ] | ||||||||||
This protein a member of the TIMP family. The glycoprotein is a natural inhibitor of the matrix metalloproteinases (MMPs), a group of peptidases involved in degradation of the extracellular matrix. In addition to its inhibitory role against most of the known MMPs, the encoded protein is able to promote cell proliferation in a wide range of cell types, and may also have an anti-apoptotic function.
==============
PRKCA see PRKCG
Here Phorbol esters, diacylglycerol, and calcium become important for the cell performance of various functions. Did I mention few targets, I truly believe I did!
CDH1 The Cadherin by excellence, not only important as adhesion molecule and role in metastasis. Its role is amplified by what else anchors here such as Vinculin, and others molecules such as Plakoglobins, amplifying the role. Remember even Cytochrome C is anchored at the mitochondrial membrane and its release leads to apoptosis!
The anchors are legitimate targets therefore, and brings to mind NACA1 in the anchoring to Histone deacetyl transferase (SEE OUR LEUKEMIA SECTION) CDH13 THAT'S ANOTHER BALL GAME ALL TOGETHER. THE CELL TWEACKS SOMETHING AND IT IS ANOTHER BALL GAME ALL TOGETHER!
==========================
NOW IN MELANOMA THEY ADD
1. THE C-KIT
2. BRAF
3. NRAS
4. GNAQ/GNA11 FOR UVEAL MELANOMA
5. P16/CDKN2A
6. IF MITF IS THE DRIVER, KNOCK OUT AP4A THEY SAY!
CELEBRATION 30 YEARS AGO 8/8/1983
EXACTLY 30 YEARS AGO, I GRADUATED IN MEDICINE WITH THESE GUYS
AND ITS SEEMS LIKE YESTERDAY!
Date: Tue, 9 Jul 2013 08:56:23 +0100
From: adrienkisi@yahoo.fr
Subject: Re: Du lundi 08 Août 1983 au lundi 08 Août 2013 : 30 ans en tant que docteur en médecine
To: kymrisgey_poy@hotmail.com; gkapuku@yahoo.com; tnemuandjare2003@yahoo.fr; llukuni@yahoo.fr; nkinsi@care.org; lukemnkinsi@yahoo.com; mdiese@iapac.org.za; kasongo@pathcare.co.za; kapikabongo@yahoo.com; mwanatambwe_milanga/patho2@nms.ac.jp; kiantede_p_nzogu@yahoo.com; mbimabiala@yahoo.fr; kayembe.m.kashalala@gmail.com; gaston.k@usa.net; tnemuanandjare2003@yahoo.fr; theonemuandjare@gmail.com; ezechkalund@yahoo.fr; emuembo@yahoo.fr; bertzinga@yahoo.fr; ilungan75@hotmail.com; pietuy@yahoo.com; prosdibikabi@hotmail.com; pietuy@yahoo.fr; pmuwonga@hotmail.com; david_nku@kin.salvationarmy.org; fatakibombil@gmail.com; ghsalu@yahoo.fr; ggombe@yahoo.uk.com; gslugoma@gmail.com; henbalt@yahoo.fr; jeanmarie.bamvita@douglas.mcgill.ca; floribert.kasende@yahoo.fr; mutombo.kankonde@kp.org; kanko1@yahoo.com; krubguss@yahoo.fr; chmavula@hotmail.com
THESE ARE GOOD GUYS SPREAD NOW ACROSS AND AROUND THE WORLD DOING WHAT WE LIKE FROM JAPAN TO SAHEL! FROM SOUTH AFRICA TO CANADA! WORKING HARD! HAPPY ANNIVERSARY TO ALL! FROM ZIMBABWE TO FRANCE!
AND ITS SEEMS LIKE YESTERDAY!
Date: Tue, 9 Jul 2013 08:56:23 +0100
From: adrienkisi@yahoo.fr
Subject: Re: Du lundi 08 Août 1983 au lundi 08 Août 2013 : 30 ans en tant que docteur en médecine
To: kymrisgey_poy@hotmail.com; gkapuku@yahoo.com; tnemuandjare2003@yahoo.fr; llukuni@yahoo.fr; nkinsi@care.org; lukemnkinsi@yahoo.com; mdiese@iapac.org.za; kasongo@pathcare.co.za; kapikabongo@yahoo.com; mwanatambwe_milanga/patho2@nms.ac.jp; kiantede_p_nzogu@yahoo.com; mbimabiala@yahoo.fr; kayembe.m.kashalala@gmail.com; gaston.k@usa.net; tnemuanandjare2003@yahoo.fr; theonemuandjare@gmail.com; ezechkalund@yahoo.fr; emuembo@yahoo.fr; bertzinga@yahoo.fr; ilungan75@hotmail.com; pietuy@yahoo.com; prosdibikabi@hotmail.com; pietuy@yahoo.fr; pmuwonga@hotmail.com; david_nku@kin.salvationarmy.org; fatakibombil@gmail.com; ghsalu@yahoo.fr; ggombe@yahoo.uk.com; gslugoma@gmail.com; henbalt@yahoo.fr; jeanmarie.bamvita@douglas.mcgill.ca; floribert.kasende@yahoo.fr; mutombo.kankonde@kp.org; kanko1@yahoo.com; krubguss@yahoo.fr; chmavula@hotmail.com
THESE ARE GOOD GUYS SPREAD NOW ACROSS AND AROUND THE WORLD DOING WHAT WE LIKE FROM JAPAN TO SAHEL! FROM SOUTH AFRICA TO CANADA! WORKING HARD! HAPPY ANNIVERSARY TO ALL! FROM ZIMBABWE TO FRANCE!
ASPECTS OF AUTOIMMUNE DISEASES/ FROM MEDSCAPE
Gluten Sensitivity Linked to Autism
A subset of children with autism have increased
immune reactivity to gluten, but the mechanism of this increased
reactivity appears to be distinct from that involved with celiac
disease, new research shows.
The results also indicated an association between elevated antibodies to gluten proteins and the presence of gastrointestinal (GI) symptoms in the affected children.
"There is evidence that immune system abnormalities are associated with symptoms in a substantial number of individuals with autism," senior author Armin Alaedini, PhD, assistant professor of medical sciences in the Department of Medicine and the Institute of Human Nutrition at Columbia University Medical Center, New York City, told Medscape Medical News.
"In addition, several studies have evaluated gastrointestinal symptoms and defects in GI barrier function in affected patients. Some have pointed to higher frequency of celiac disease, family history of celiac disease, or elevated antibody to gluten among autistic children, but these studies have been inconsistent about such associations," Dr. Alaedini said.
The study was published online June 18 in PLoS One.
Growing Popularity of Gluten-Free Diets
Diets that exclude gluten are increasingly popular in the autism community, but their effectiveness has not been proven in controlled and blinded studies.
In the current study, Dr. Alaedini and his team analyzed serologic and genetic markers of celiac disease and gluten sensitivity in 37 children diagnosed with autism according to both the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADI-R) as well as in 27 of their unaffected siblings and 76 age-matched unrelated healthy control individuals.
The blood samples were tested for antibodies to tissue transglutaminase, a sensitive and specific marker of celiac disease, as well as antibodies to gliadin.
The children with autism were also genotyped for celiac disease associated HLA-DQ2 and HLA-DQ8 alleles.
The analysis showed that the children with autism had significantly higher levels of IgG antibody to gliadin compared with unrelated healthy controls individuals (P < .01). The IgG levels were also higher compared with the unaffected siblings but did not reach statistical significance.
The researchers also found that the IgG antigliadin antibody response was significantly greater in the autistic children with GI symptoms in comparison to those without GI symptoms (P < .01).
There was no difference in IgA response to gliadin among the 3 groups.
Additionally, levels of celiac disease–specific serologic markers, for example, antibodies to deamidated gliadin and TG2, did not differ between patients and control individuals.
Nor was an association between increased antigliadin antibody and presence of HLA-DQ2 and -DQ8 observed.
Little Clinical Relevance Yet
The findings have little relevance to bedside practice at the moment, Dr. Alaedini said.
"It would be too early to talk about medical advice or treatment resulting directly from this study. Also, the findings need to be confirmed in larger cohorts."
He added that the observations from this study point to immunologic or intestinal barrier abnormalities and their association with GI symptoms in autism.
"Having a clearer understanding of the immunologic differences in the affected children can give us novel clues about the mechanism of autism, such as the potential involvement of immune-mediated pathways. These clues, in turn, may lead to new treatments that, for example, target those specific immune pathways," Dr. Alaedini noted.
"In addition, characterization of the target gluten molecules in the observed antibody response may offer biomarkers to identify a subset of patients that would respond to certain treatment strategies."
Another Piece of the Puzzle
Commenting on the study, Dan Coury, MD, medical director of the Autism Speaks Autism Treatment Network and professor of pediatrics and psychiatry in the College of Medicine at the Ohio State University, Columbus, said the findings provide additional information to what is currently known about GI problems in autism.
"The investigators found increased levels of an antibody to gluten, but not the abnormalities that are seen with celiac disease which is caused by gluten. They also found these antibodies increased more in those with autism and GI problems than in those with autism alone. These antibodies were significantly increased compared to healthy controls, but not significantly different from unaffected siblings. While the IgG antibodies were higher, the IgA antibodies were not," he told Medscape Medical News.
"In this case," Dr. Coury continued, "IgA antibodies are a sign of immune function of the gut mucosa, while IgG antibodies are a sign of the body having an overall immune response, for example, they can indicate a person's immunity to something such as chickenpox."
The findings pose additional questions, he added.
"The high IgG suggests that without high IgA, what we are seeing may not be related to current GI gluten problems but some past exposure. This would also fit with the fact that there were no abnormalities typically seen in celiac disease.
"It might also mean that this IgG antigliadin antibody isn't actually
an antibody to gliadin. It might be an antibody that reacts with
gliadin but actually is produced by the body to react to something
else," he said.
Dr. Coury noted that because immune abnormalities have been seen in autism, it may be another part of the puzzle that needs to be solved.
"By themselves, antigliadin antibodies do not mean disease. They are part of the whole puzzle. When they occur with other abnormalities and with symptoms, we begin to get a clearer picture. As the authors note, these findings deserve further study. It may be that this will help identify a subgroup of individuals with autism who might benefit from a specific treatment someday, when we have a better understanding of just what is going on here."
The study was funded by the US Department of Defense. Dr. Alaedini and Dr. Coury report no relevant financial relationships.
PLoS One. Published online June 18, 2013. Full article
The results also indicated an association between elevated antibodies to gluten proteins and the presence of gastrointestinal (GI) symptoms in the affected children.
"There is evidence that immune system abnormalities are associated with symptoms in a substantial number of individuals with autism," senior author Armin Alaedini, PhD, assistant professor of medical sciences in the Department of Medicine and the Institute of Human Nutrition at Columbia University Medical Center, New York City, told Medscape Medical News.
"In addition, several studies have evaluated gastrointestinal symptoms and defects in GI barrier function in affected patients. Some have pointed to higher frequency of celiac disease, family history of celiac disease, or elevated antibody to gluten among autistic children, but these studies have been inconsistent about such associations," Dr. Alaedini said.
The study was published online June 18 in PLoS One.
Growing Popularity of Gluten-Free Diets
Diets that exclude gluten are increasingly popular in the autism community, but their effectiveness has not been proven in controlled and blinded studies.
In the current study, Dr. Alaedini and his team analyzed serologic and genetic markers of celiac disease and gluten sensitivity in 37 children diagnosed with autism according to both the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADI-R) as well as in 27 of their unaffected siblings and 76 age-matched unrelated healthy control individuals.
The blood samples were tested for antibodies to tissue transglutaminase, a sensitive and specific marker of celiac disease, as well as antibodies to gliadin.
The children with autism were also genotyped for celiac disease associated HLA-DQ2 and HLA-DQ8 alleles.
The analysis showed that the children with autism had significantly higher levels of IgG antibody to gliadin compared with unrelated healthy controls individuals (P < .01). The IgG levels were also higher compared with the unaffected siblings but did not reach statistical significance.
The researchers also found that the IgG antigliadin antibody response was significantly greater in the autistic children with GI symptoms in comparison to those without GI symptoms (P < .01).
There was no difference in IgA response to gliadin among the 3 groups.
Additionally, levels of celiac disease–specific serologic markers, for example, antibodies to deamidated gliadin and TG2, did not differ between patients and control individuals.
Nor was an association between increased antigliadin antibody and presence of HLA-DQ2 and -DQ8 observed.
Little Clinical Relevance Yet
The findings have little relevance to bedside practice at the moment, Dr. Alaedini said.
"It would be too early to talk about medical advice or treatment resulting directly from this study. Also, the findings need to be confirmed in larger cohorts."
He added that the observations from this study point to immunologic or intestinal barrier abnormalities and their association with GI symptoms in autism.
"Having a clearer understanding of the immunologic differences in the affected children can give us novel clues about the mechanism of autism, such as the potential involvement of immune-mediated pathways. These clues, in turn, may lead to new treatments that, for example, target those specific immune pathways," Dr. Alaedini noted.
"In addition, characterization of the target gluten molecules in the observed antibody response may offer biomarkers to identify a subset of patients that would respond to certain treatment strategies."
Another Piece of the Puzzle
Commenting on the study, Dan Coury, MD, medical director of the Autism Speaks Autism Treatment Network and professor of pediatrics and psychiatry in the College of Medicine at the Ohio State University, Columbus, said the findings provide additional information to what is currently known about GI problems in autism.
"The investigators found increased levels of an antibody to gluten, but not the abnormalities that are seen with celiac disease which is caused by gluten. They also found these antibodies increased more in those with autism and GI problems than in those with autism alone. These antibodies were significantly increased compared to healthy controls, but not significantly different from unaffected siblings. While the IgG antibodies were higher, the IgA antibodies were not," he told Medscape Medical News.
"In this case," Dr. Coury continued, "IgA antibodies are a sign of immune function of the gut mucosa, while IgG antibodies are a sign of the body having an overall immune response, for example, they can indicate a person's immunity to something such as chickenpox."
The findings pose additional questions, he added.
"The high IgG suggests that without high IgA, what we are seeing may not be related to current GI gluten problems but some past exposure. This would also fit with the fact that there were no abnormalities typically seen in celiac disease.
Review summaries of articles on clinical issues in Type 1 Gaucher disease and gain understanding of patient concerns.
Information from Industry
Dr. Coury noted that because immune abnormalities have been seen in autism, it may be another part of the puzzle that needs to be solved.
"By themselves, antigliadin antibodies do not mean disease. They are part of the whole puzzle. When they occur with other abnormalities and with symptoms, we begin to get a clearer picture. As the authors note, these findings deserve further study. It may be that this will help identify a subgroup of individuals with autism who might benefit from a specific treatment someday, when we have a better understanding of just what is going on here."
The study was funded by the US Department of Defense. Dr. Alaedini and Dr. Coury report no relevant financial relationships.
PLoS One. Published online June 18, 2013. Full article
Monday, July 8, 2013
PROGNOSTIC INDICATORS IN AUTOIMMUNE DISEASES.
=============================================
We have focused lately on some of the indicators of Autoimmune diseases, and one may be surprised at this focus but keep in mind there no smoke without a fire. There is no antibody without a gene abnormality. And some if not all autoimmune diseases lead to lymphoproliferative disorders. So it is pertinent to start looking into these factors with a critical look.
Factors in Autoimmune diseases are grouped generally in Diagnostic (leading to specific diagnosis), Acute phase (denoting active disease), chronic (denoting persistent disease), prognosis (inferring persistent destruction of tissue). Remember Auto-immune diseases target Skin, Lung, Liver, the Heart, Central and peripheral Nervous system, the circulatory system (Vasculitis), the joints, kidney and Muscle skeletal systems or in few words "all the systems". That is why we call these disease "SYSTEMIC DISEASES".
FIRST THE LIST OF PROGNOSIS FACTORS,
AND COMMENTS WILL FOLLOW!
1. High level or titer of Rheumatoid Factor
2. Persistent Anti-DNA
3. Presence of Anti-Ribosomal Antibody in lupus- CNS involvement.
4. Anti-CL70 --"Diffuse" Scleroderma
5. Anti-centromere Antibody -CREST, there is suggestion of good prognosis! (unless the kidney, heart and lung fibrosis come into play to change that!)
6. Anti-Jo ---lung involvement
7. Anti-Smith and anti-RNP associated with hign Interferon-1 and diruption of immunity-high rate of infection
8.Anti-phospholipid AB (Cardiolipin) -Thrombosis/including strokes, watch Antibody to Beta 2 -glycoprotein-1 (does the same!)
9.-Anti-M2-directed against nuclear Helicase (Polymyositis)
10- Anti-Synthetase
11. anti-signal recognition
12. Anti-topoisomerase (worse prognosis, poor response to Corticosteroids, )
13. Anti -anti RNA Polymerase III---scleroderma involving the Kidney
14. In Sjogren the change of rheumatoid factor from positive to negative when following polyclonal to oligoclonal cells announces lymphoproliferative transformation-act quick here!
Think of these
Next Acute phase factors.......
=============================================
We have focused lately on some of the indicators of Autoimmune diseases, and one may be surprised at this focus but keep in mind there no smoke without a fire. There is no antibody without a gene abnormality. And some if not all autoimmune diseases lead to lymphoproliferative disorders. So it is pertinent to start looking into these factors with a critical look.
Factors in Autoimmune diseases are grouped generally in Diagnostic (leading to specific diagnosis), Acute phase (denoting active disease), chronic (denoting persistent disease), prognosis (inferring persistent destruction of tissue). Remember Auto-immune diseases target Skin, Lung, Liver, the Heart, Central and peripheral Nervous system, the circulatory system (Vasculitis), the joints, kidney and Muscle skeletal systems or in few words "all the systems". That is why we call these disease "SYSTEMIC DISEASES".
FIRST THE LIST OF PROGNOSIS FACTORS,
AND COMMENTS WILL FOLLOW!
1. High level or titer of Rheumatoid Factor
2. Persistent Anti-DNA
3. Presence of Anti-Ribosomal Antibody in lupus- CNS involvement.
4. Anti-CL70 --"Diffuse" Scleroderma
5. Anti-centromere Antibody -CREST, there is suggestion of good prognosis! (unless the kidney, heart and lung fibrosis come into play to change that!)
6. Anti-Jo ---lung involvement
7. Anti-Smith and anti-RNP associated with hign Interferon-1 and diruption of immunity-high rate of infection
8.Anti-phospholipid AB (Cardiolipin) -Thrombosis/including strokes, watch Antibody to Beta 2 -glycoprotein-1 (does the same!)
9.-Anti-M2-directed against nuclear Helicase (Polymyositis)
10- Anti-Synthetase
11. anti-signal recognition
12. Anti-topoisomerase (worse prognosis, poor response to Corticosteroids, )
13. Anti -anti RNA Polymerase III---scleroderma involving the Kidney
14. In Sjogren the change of rheumatoid factor from positive to negative when following polyclonal to oligoclonal cells announces lymphoproliferative transformation-act quick here!
Think of these
Next Acute phase factors.......
Saturday, July 6, 2013
Controversy in Gastric cancer
As one reflect on the epidemiology of Gastric cancer, one ends up with questions that are technically answered in the main stream scientific reporting but lead to the following questions in the scientific researcher mind.
1. It is generally accepted as a fact that there is a 75% decrease of Gastric Cancer in the United states over the last few decades. The official reason is that there has been a significant improvement in food storage and quality of water. This conclusion is not really clearly based on gene evolution studies or any hard scientific data, it is based on observational evaluation that poor people living in poor countries still have Gastric Cancers. This assertion goes on unchallenged even though statistical evaluation in poor countries are notoriously unreliable or non-existent. The Peculiarity of the incidence of this disease in Japan challenges both the notions that poverty and unhealthy conditions are the dominant forces leading to the disease. Until all aspects are scientifically explored statements such as "gastric cancer is strongly influenced by nutritional, socio-economic, and medical factor rather than dominated by genetic" call for a pause! The mere fact that there are twice as many men with gastric cancer than women partially challenges the statement. And further more incidence variation is seen among the races (and ages).
2.The gastric cancer treated in Japan appears to have a better prognosis. This fact has been "attributed to the superiority of surgical techniques". The non adoption of such techniques elsewhere fly against that perception. There is a lingering feeling that this cancer in the Japanese population is peculiar somehow. That this peculiarity is the true reason of the good prognosis. That is, the surgical technique is not fully the reason. That feeling leaves western surgeons room to continue their current practice. Indeed it would have been legally unacceptable to do less surgery when the more extensive "is better".
3.The use of Aspirin and non steroidal is associated lower cancer of the G-E junction. This is contrary to what one would expect. A medication causing gastric ulcer is in this case protective!
4.H. Pylori has been clearly demonstrated to lead to gastric cancer. However its eradication is now only indicated for those with an Ulcer. Why not eradicate all together, a vaccine campaign for example. Scientist are not sure because "no definitive evidence shows that mass eradication could reduce the incidence" of this disease. A mass Chinese study reportedly did not achieve such an objective .
WE HAVE GOT TO STUDY GENES AND THEIR DISPARITIES IN RACES MORE THOROUGHLY BEFORE MAKING DEFINITIVE BETTER CONCLUSION!
1. It is generally accepted as a fact that there is a 75% decrease of Gastric Cancer in the United states over the last few decades. The official reason is that there has been a significant improvement in food storage and quality of water. This conclusion is not really clearly based on gene evolution studies or any hard scientific data, it is based on observational evaluation that poor people living in poor countries still have Gastric Cancers. This assertion goes on unchallenged even though statistical evaluation in poor countries are notoriously unreliable or non-existent. The Peculiarity of the incidence of this disease in Japan challenges both the notions that poverty and unhealthy conditions are the dominant forces leading to the disease. Until all aspects are scientifically explored statements such as "gastric cancer is strongly influenced by nutritional, socio-economic, and medical factor rather than dominated by genetic" call for a pause! The mere fact that there are twice as many men with gastric cancer than women partially challenges the statement. And further more incidence variation is seen among the races (and ages).
2.The gastric cancer treated in Japan appears to have a better prognosis. This fact has been "attributed to the superiority of surgical techniques". The non adoption of such techniques elsewhere fly against that perception. There is a lingering feeling that this cancer in the Japanese population is peculiar somehow. That this peculiarity is the true reason of the good prognosis. That is, the surgical technique is not fully the reason. That feeling leaves western surgeons room to continue their current practice. Indeed it would have been legally unacceptable to do less surgery when the more extensive "is better".
3.The use of Aspirin and non steroidal is associated lower cancer of the G-E junction. This is contrary to what one would expect. A medication causing gastric ulcer is in this case protective!
4.H. Pylori has been clearly demonstrated to lead to gastric cancer. However its eradication is now only indicated for those with an Ulcer. Why not eradicate all together, a vaccine campaign for example. Scientist are not sure because "no definitive evidence shows that mass eradication could reduce the incidence" of this disease. A mass Chinese study reportedly did not achieve such an objective .
WE HAVE GOT TO STUDY GENES AND THEIR DISPARITIES IN RACES MORE THOROUGHLY BEFORE MAKING DEFINITIVE BETTER CONCLUSION!
Friday, July 5, 2013
keeping you in the festivity of independance day!
To the Inova family,
When
I was in high school, one of the most enjoyable experiences I had was
playing in the concert band. I was a saxophone player, or a baritone
saxophone player to be more precise. I wasn’t very good due to lack of
practice and presumably talent as well, but I had the opportunity
frequently to travel to the “big city” of Asheville, N.C. to audition
for a seat on the all-state band. You see, there are very few baritone
sax players and even if you weren’t very good, you had a chance to be
chosen for this highly selective band due to lack of competition. I
always used to get nervous despite my reasonably good prospects and can
still remember the tension of those auditions as if it were yesterday.
So
it struck a chord when someone recently shared with me the story of an
aspiring French horn player who tried out for a highly coveted spot on a
prestigious symphony orchestra. The player had practiced for endless
hours and had worked with a coach to gain all the fine points of style
and finesse that mark the truly excellent players of the instrument. To
prevent any unintended bias in the selection process, each hopeful had
to play behind a screen to keep their identity hidden. The orchestra’s
other French horn players served as judges to select their new
colleague for the orchestra and they were renowned for having extremely
high standards. Excellence in performance was EVERYTHING to them! So
after hearing over twenty auditioning players, it was a little
surprising that they were unanimous in their choice and selected the
French horn hopeful who had worked so hard.
It
struck me in hearing that story that excellence really does matter.
Being good or even very good is nice but it’s really not what we at
Inova are striving for. As many of you may know, the Medicare program
administrator (CMS) rates each hospital on the quality of its patient
experience. They ask a sample of patients to rate everything from how
clean and quiet their room was to how well the doctors and nurses
answered their questions, managed their pain and helped them understand
what they needed to do to actively help with their own recovery. The
interesting thing is that the way scores are calculated, they place the
highest emphasis on how EXCELLENT the care was. In many respects, it is
the number of patients that rate our care as EXCELLENT that determines
how our scores come out (and, as an aside, how much we get paid!). I
have written often that our highest priorities are embedded in our
“TRUE NORTH” goals of providing the highest quality, the best experience
for our patients and their families, and reducing our costs to make
our care affordable for the most people. Like the orchestra musicians,
quality, experience and affordability are EVERYTHING to us!
And
you know what—nothing but excellent IS acceptable! Like the French
horn player who “made the team”, we must remember “very good” just means
on some occasions, our patients had pain, they were anxious or fearful,
they didn’t understand what was going on, they didn’t understand
their medicines, or the room was loud and they couldn’t sleep. Sadly,
on some occasions we did things that led to longer periods of recovery
and in some instances, caused real harm!
On
July 4, we are reminded that some things count most when they are
measured in absolutes—such as giving one’s life for your country, or
preventing a terrorist bombing, or being there to treat the victims of a
disaster. You either prevail in your efforts or some people may pay
dearly--sometimes people die or lose their freedom. Today we celebrate
our independence and similarly, I would invite you to remember that our
patients depend on us absolutely. In short, they depend upon us for
excellence and nothing less—their very lives may depend upon it.
When
the young French horn player who won the audition walked out from
behind the screen, the judges” jaws dropped. Their new colleague (did I
mention that they were all men?) was a 29 year old, Asian woman—let’s
face it, she didn’t fit the stereotype of what they were expecting at
all. Not by age, not by gender, not by ethnicity – now they had to face
the fact that the old French horn section was going to look and be
quite different in the future. And you know what? It proved to be the
best French horn section that great orchestra ever had. Because nothing
less than EXCELLENT was acceptable to their new colleague. Their true
north was simple excellence, just like it is for our patients and their
families. So as we remember fireworks and cookouts, let’s also remember
that freedom isn’t free; that excellence doesn’t come without
persistent hard work; and that everyone should be judged on their
commitment to true north rather than some outdated stereotype. Our
patients deserve nothing less. Now that’s something we can all
celebrate!!
God bless you all,
Knox
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