TAXOTERE-CISPLATIN SUPERIOR TO TAXOTERE-XELODA IN TRIPLE NEGATIVE BREAST CANCER

In a recent article published in the Annals of Oncology, Researcher published that Taxotere Cisplatin was a better combination for initial therapy in Metastatic triple negative breast cancer:
"Results:

• The median follow-up was 24 months. ORR was higher in the TP group than in the TX group (63.0% versus 15.4%, P = 0.001).
• PFS was more than doubled (10.9 months versus 4.8 months, P < 0.001) and median OS was also greatly improved (32.8 months versus 21.5 months, P = 0.027).
• Toxic effects were not different except G3/4 vomiting and G2/3 hand-foot syndrome.

Read more: http://www.mdlinx.com/oncology/news-article.cfm/4317563"

These results corroborate or tend to support many facts:

1. That triple negative Breast cancer genome was closer to ovarian cancer, a disease in which   Taxol -Carboplatin is still standard of care particularly in metastatic setting.

2.  That Cisplatin alteration of DNA is more likely to induce P53 cell cycle arrest. (1st law)

3.  That adding Taxotere and its disruption of Macrotubules recruits effectively the 2nd law.   This lead to a doubling  of PROGRESSION FREE SURVIVAL.

Again it would be of interest to see what an Anti-kinesin  (anti-Actin) or Velcade addition would mean in a  clinical trial.   Most molecules involved in programmed cell death such as Cytochrome C are attached to membrane within the organel where they reside.  Disrupting that anchor would most likely boost Apoptosis.  Without further determining the nature of that Anchor, we know that the cytoskeleton is most likely Actinic in nature.  Disruption of the the Cytoskeleton could induced Anoikis, and freedom of molecules attached to membranes leading to major disruption including that of signal pathways.

Velcade main additional effect is disruption of DNA replication restarting after P53 arrest by its affect anti-proteasomic.  Protein restarting the replication are generally ubiquitinated making the front and center to proteasome role!  The issue really remains the determination of how much of a Driver this pathway is in solid tumor.  This determination is one of the major challenge oncologist face today! 

Study: 1.3 Million Overdiagnosed Breast Cancers in 30 Years

Study: 1.3 Million Overdiagnosed Breast Cancers in 30 Years

Nick Mulcahy, Nov 21, 2012

In the past 30 years, an estimated 1.3 million American women had breast cancers that were "overdiagnosed," which means their screening-detected tumors would never have led to clinical symptoms, according to a study published in the November 22 issue of the New England Journal of Medicine.
In 2008 alone, breast cancer was overdiagnosed in an estimated 70,000-plus women, which was 31% of all breast cancers diagnosed that year, assert the study authors, Archie Bleyer, MD, from the Oregon Health and Science University in Portland, and H. Gilbert Welch, MD, MPH, from the Geisel School of Medicine at Dartmouth College in Hanover, New Hampshire.
Overall, about one third of all breast cancers detected in the United States are overdiagnosed, they say.
The authors point out that the advent of widespread mammography screening in the United States led to a "substantial increase" in early-stage breast cancer, but only "marginally reduced" the rate of advanced cancers detected. "The imbalance suggests that there is substantial overdiagnosis."
However, breast screening expert Daniel B. Kopans, MD, from Harvard Medical School in Boston, Massachusetts, believes the study is "outrageous" and "should have never passed peer review."

Mammography does not cause 'overdiagnosis'.

"The paper...is another in a long line of scientifically unsupportable attacks on mammography," he told Medscape Medical News.
Dr. Kopans questioned the authors' methodology in his critique of the study. He also dismissed one of its central findings and ideas. "Mammography does not cause 'overdiagnosis'," said Dr. Kopans. "Unfortunately, pathologists are not yet able to distinguish cancers that will be lethal if left untreated from those that do not need treatment."
First Prerequisite Not Met
In their study, Drs. Bleyer and Welch state that "effective" cancer screening programs must increase the incidence of early cancers detected and decrease the incidence of late cancers detected. But mammography screening has not done the latter substantially, they say.
They used Surveillance, Epidemiology, and End Results (SEER) data to examine trends in the incidence of early-stage breast cancer (ductal carcinoma in situ [DCIS] and localized disease) and late-stage breast cancer (regional and distant disease) in women 40 years and older from 1976 to 2008.
They found that the introduction of screening doubled the number of early breast cancers detected annually.
Specifically, the incidence jumped from 112 to 234 cases per 100,000 women — an absolute increase of 122 cases per 100,000 women over the study period.
At the same time, the rate at which women present with late-stage cancer decreased by only a small amount (8%), from 102 to 94 cases per 100,000 women — an absolute decrease of 8 cases per 100,000 women.
However, only 8 of the 122 additional early-stage cancers diagnosed were expected to progress to advanced disease, say Drs. Bleyer and Welch, leaving a large imbalance between detected early-stage and late-stage cancers.
The data suggest that "mammography has largely not met the first prerequisite for screening to reduce cancer-specific mortality — a reduction in the number of women who present with late-stage cancer," the authors state.
The findings suggest that "screening is having, at best, only a small effect on the rate of death from breast cancer," they conclude.

Our study raises serious questions about the value of screening mammography.

"Our study raises serious questions about the value of screening mammography," say Drs. Bleyer and Welch. However, they note that their study does not answer a common question that women ask: "Should I be screened for breast cancer?"
Dr. Kopans suggests that the study delivers the message that screening is not worthwhile. And he sees Dr. Welch as part of a "small group of highly vocal individuals who have decided that they wish to end all screening for breast cancer."
"All responsible groups agree that mammography screening saves lives," said Dr. Kopans, referring to guidelines that recommend screening from major groups such as the US Preventive Services Task Force and the American College of Physicians.
Assumptions Questioned
Drs. Bleyer and Welch chose the 3-year period from 1976 to 1978 to obtain their estimate of the baseline incidence of breast cancer detected without mammography. "During this period, the incidence of breast cancer was stable and few cases of DCIS were detected," they write.
For each year after 1978, the authors calculated the absolute change in the incidence of early- and late-stage cancer relative to the baseline incidence. They then summed the data across the 3 decades.
However, they had a challenge for the years 1990 to 2005, during which many women used breast cancer-causing hormone replacement therapy. To remove the excess breast cancer incidence from that period, they "truncated" or lowered the incidence of the various types of breast cancers.
They estimated the current incidence of breast cancer on the basis of the 3-year period from 2006 to 2008. This was deemed a good time period because it is believed that the effect of hormone-replacement therapy ended at 2006.
Drs. Bleyer and Welch calculated 4 different estimates of the excess detection or "overdiagnosis" of breast cancer for the 30-year period. The estimates varied with regard to the "underlying incidence" of breast cancer, which is an estimate of the number of cases that would be found without mammography detection.
They calculated that the underlying incidence of breast cancer was increasing by 0.25% with each passing year. They describe this as a "best-guess" estimate, and used it as the basis for their conclusion that 1.3 million women had overdetected/overdiagnosed breast cancer. They also had an "extreme-assumption" estimate that assumed a 0.5% annual increase, resulting in an estimated 1.2 million overdiagnosed cases.
Dr. Kopans said that both of these estimates are too low. He explained that there has been an "underlying 1% per year increase in breast cancer incidence...that has been going on since at least 1940."
He also criticized other elements of the calculations. "They also underestimated the effects of lead time and ignored prevalence screening, which adds to incidence every year as new women begin screening. They also combined DCIS with early-invasive lesions in an effort to dilute the results," he noted.
Drs. Bleyer and Welch anticipated most of these criticisms.
"There has been plenty of time for the surplus of diagnoses of early-stage cancer to translate into a reduction in diagnoses of late-stage cancer — thus eliminating concern about lead time," they write.
They acknowledge that their best-guess estimate of the frequency of overdiagnosis — 31% of all breast cancers — did not distinguish between DCIS and invasive breast cancer. However, they say that invasive disease accounted for about half the overdiagnoses in their estimates, and that about 20% of invasive breast cancers were overdiagnosed. "These findings replicate those of other studies," they write.
They state that reliable estimates of overdiagnosis would "ideally" come from long-term follow-up after a randomized trial. One such trial from Sweden with that long-term follow-up supports these new findings, say the authors. "Among the 9 randomized trials of mammography, the lone example of this is the 15-year follow-up after the end of the Malmö Trial, which showed that about a quarter of mammographically detected cancers were overdiagnosed," they write.
Treatment Deserves Credit Too
Over the study period, "the rate of death from breast cancer decreased considerably," they note, citing other research.
They also cite other research to assert that among women 40 years or older, deaths from breast cancer decreased from 71 to 51 deaths per 100,000 women — a 28% decrease.
But screening is not the sole reason for this drop in the death rate, Drs. Bleyer and Welch note.
"This reduction in mortality is probably due to some combination of the effects of screening mammography and better treatment," they write.
The math suggests that early detection from screening is not the biggest reason for the reduction in disease-specific death, they say.
"Because the absolute reduction in deaths (20 deaths per 100,000 women) is larger than the absolute reduction in the number of cases of late-stage cancer (8 cases per 100,000 women), the contribution of early detection to decreasing numbers of deaths must be small," they write, combining incidence data from their study with those from a death rate study.
Better treatment for breast cancer lessens the need for screening, they suggest.
"Ironically, improvements in treatment tend to deteriorate the benefit of screening. As treatment of clinically detected disease (detected by means other than screening) improves, the benefit of screening diminishes. For example, since pneumonia can be treated successfully, no one would suggest that we screen for pneumonia," they argue.
Dr. Kopans also addressed this issue, saying that "early detection is the main reason that the death rate from breast cancer has declined by over 30% since screening became widely available." He noted that "therapy has improved, but therapy saves lives when cancers are found earlier."
The authors have disclosed no relevant financial relationships. Dr. Kopans reports receiving research support from GE Healthcare.
N Engl J Med. 2012;367:1998-2005. Abstract

Latest in Hematology-Oncology

Invitation to celebrate Dr. MLK Jr.

Mutombo --

Four years ago, during his first inauguration, Barack and I were thrilled when thousands of Americans from every corner of the country took part in the National Day of Service honoring Dr. Martin Luther King, Jr.

We were so excited because we knew that the celebrations weren't just about a new president, but about everything that we can accomplish together. And that starts with service.

So this year, as we prepare for another celebration, we're hoping to renew that spirit of service and citizenship -- we're calling on all Americans, including you, to volunteer in your community on Saturday, January 19th, for this year's Day of Service.

Please join us, and commit to serve on January 19th.

Throughout our lives, Barack and I have seen that building a full life isn't about what you can get for yourself -- but what you can give to those around you. It's a value that's been central to our lives together. And as parents, it's something we're trying every day to pass down to our girls.

This inauguration is only possible because of you and all your hard work. Barack and I are so grateful for you, and for everything you've done for us and for our country.

Pledge to join us for the Day of Service at an event near you:

http://action.2013pic.org/Pledge-to-Serve

Thanks,

Michelle

P.S. -- When you commit to serve, you'll be automatically entered for the chance to come out to Washington, D.C. for Barack's inauguration -- flight and hotel covered.

In a recent Article published in the December 15th ASCO POST,  Lina Baumbach-Reardon, PhD discussing Triple Negative Breast cancer reported differences of gene expression in 2 small cohorts of patients, one from Kenya and one from African Americans in the United States.   Given the size of the cohorts reported, no conclusion can really be drawn, but I agree that it is a teaser!

It also brings back to the surface many questions about where the African American population was pulled from originally and what kind of brassage or mix has occurred since then.  Recognition that patterns of Breast cancer mortality observed in African Americans  is similar to that of "Hispanic" populations, raises questions.  The Breast Cancer "incidence-Mortality paradox " is true for both populations.
Suffice is to say that there is more to find out.  Coming from the Congo, the CRBCM would push for this kind of studies if funds were allowed in the future. This brings up this: (from yahoo)
--------------------------------
   Congo-Kinshasa: African Union Holds Talks on 'Neutral Force' Wed, 09 Jan, 2013 02:27 AM PST
[African Union]Addis Ababa -As a follow-up to the recommendations of the consultative meeting on the operationalization of the security arrangements agreed to in Eastern Democratic Republic of Congo (DRC), held in Addis Ababa, on 27 and 28 December 2012, a ministerial meeting of the countries of the region and international partners took place at the African Union (AU) Headquarters, in Addis ...
UN Seeks Surveillance Drones for Eastern Congo
Wed, 09 Jan, 2013 02:12 AM PST
United Nations peacekeepers are asking the Security Council to support the use of surveillance drones in the eastern Democratic Republic of Congo. U.N. peacekeeping chief Herve Ladsous appealed to the council in a closed-door session Tuesday, seeking the drones to help the more than 17,000 peacekeepers in the country. Rebels briefly took control of the eastern city of Goma late last year after ... Rwanda opposes use of drones by the UN in eastern Congo
reuters.com Wed, 09 Jan, 2013 01:02 AM PST
UNITED NATIONS (Reuters) - Rwanda on Tuesday opposed the use of surveillance drones in eastern Congo as proposed by the United Nations until there is a full assessment of their use, saying it did not want Africa to become a laboratory for foreign intelligence devices. Envoys said U.N. peacekeeping chief Herve Ladsous told the Security Council during a closed-door session that the U.N mission in ...

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AND THE FIGHT GOES ON!

 

FOR THE CURE, TIME FOR PARADIGM SHIFT AND A REVOLUTION AGAINST SOME OF OUR LEADERS IN CANCER MEDICINE

Cancer is a disease involving the cell.  Our current understanding is that during the course of our lives, somewhere in our system, a cell's function will be altered enough to transform a normal cell into A CANCER CELL.   Our current understanding is that all cells want to stay alive and for cancer cell multiplication and dissemination it appears to be assurance of a type of cell preservation.  We know that to survive, the cancer cell will escape several mechanisms.  How to stimulate its growth, how to escape detection by the immune system and removal by the Macrophages and related natural measures, how to stay awake by lighting up certain pathways, how to resist against external chemical attacks, how to repair damages caused by attacks, how to survive on their own etc.?

We also know that cancer cells are not the same not only by tissue of origin, but also by pathways driving them.  We know that to escape death, the cancer cell uses redundancies and loopholes in its pathways, that is it may alter or multiply these pathways to overrun incoming inhibitions.  It may amplify measures to block our reach toward programmed death.  The cancer cell knows that once programmed death mechanisms are started, it has to die.  It builds things like Bcl-2 around the Caspase death path.  The cancer cell knows that there are inhibitory forces that need to be altered.  P53 is one of the Major forces. It needs to be altered or mutated.  Flow through a pathway is another force. And altering regulators may be one way to control the flow.  Or leaving a switch on to drive the pathways. etc...

We also know that every major target in pathways has effects downstream toward the nucleus and its DNA, and upstream toward the Membrane.  For some, we have found lateral connections serving as loophole escape.  More than one phenotype of an important Target is meant to provide Resistance to attacks of the main type.
 
With chemotherapy, we have had some success.  Our failures reside in the mechanisms of resistance, in the ability of the cancer cell to repair itself and escape death.  Escaping death appears to be also solely linked to protection against Necrosis and programmed death.

We also know about Driver pathways as well as forces we can use to stop cell migration, division and seeding. We have got to use this knowledge to plan our action for the cure.

The success of target therapy needs to tell us that leaders who continue to push chemotherapy as the only alternative, creating more combinations, need to be more and more left alone, while we switch to Targeting therapy and some combination therapies.

Targeting therapy tells us we got to get better at defining Driver pathways to be effective.  Particularly in solid tumors.  This is the major priority.  HOW DO YOU TELL THIS IS A DRIVER TARGET OR PATHWAY? IS IT BY DOSING REGULATORY MOLECULES, ENZYMES ALONG A PATHWAY, LEVEL OF TRANSCRIPTION GENES, STATUS OF SWITCH TO TARGET MOLECULES, PROMOTER EXPRESSION?  HOW DO YOU SAY THIS IS THE DRIVER PATHWAY?  WITH THIS KNOWLEDGE WE CAN AVOID STUDIES LIKE TAXOTERE & REVLIMID IN PROSTATE CANCER, WHEN TAXOTERE & VELCADE WOULD HAVE BEEN BETTER.

IF WE KNOW HOW TO DO THIS, OUR PATH TO CURE IS ASSURED.

The second question: HOW TO GET THIS CELL TO CASPASE, TO LYSOZOMAL HYDROLASES AND CATHEPSINS, AND OTHER NECROTIC AND AUTOPHAGIC PROCESSES? HOW TO PUSH IT TO PROGRAMMED DEATH?

TIME TO WAKE UP AND SMELL THE COFFEE BEFORE ANOTHER RUN FOR THE CURE! 

MY FIRST NOVEL IS ATTRACTING MOVIE MAKERS:
" A WHITE WOMAN TO THE CONGO" by Mutombo Kankonde
LOOK FOR IT ON AMAZON, BARNES & NOBLE, iBOOK etc as it starts out as E-BOOK!

Kiambote Peggy,

Good to hear from you!

I had a fascinating time in Rwanda. Finally got to see the finished doc recently here in Austin at the Bob Bullock IMAX during AFF. Turned out really well.

DR Congo appears to be a pretty turbulent place, I assume you've been before. How did you find it to be?

I'll check out the book. Has a script been drafted? Shooting a narrative feature there strikes me as pretty ambitious. Have you put one together prior to this?

Please keep me in the loop, I look forward to hearing more about your progress.

Kende malamu,

Sean

This FOA (RFA-CA-12-015), using the R01 funding mechanism, solicits applications for PQs in Group A. The companion FOA for PQs in Group A, using the R21 exploratory/developmental funding mechanism, is RFA-CA-12-016. PQs in this group challenge investigators to seek answers to specific unsolved problems generally related to investigation of changes in behavior and various exposure risks, mechanistic links between cancer risk factors and biological events associated with cancer development, and how we might identify and better understand prevention mechanisms.

Each research project proposed in response to this FOA must be focused on solving one particular research problem defined by one specific PQ selected from the list in Group A. Projects proposed to address specific PQs may use strategies that incorporate ideas and approaches from multiple disciplines, as appropriate. Transdisciplinary projects are encouraged as long as they serve the scientific focus of the specific PQ chosen.

The other three groups of PQs (and their respective FOAs) are:

• Group B covered by RFA-CA-12-017 (R01) and RFA-CA-12-018 (R21) that generally relates to mechanisms of tumor development or recurrence;
• Group C covered by RFA-CA-12-019 (R01) and RFA-CA-12-020 (R21) that generally relates to cancer detection, diagnosis, and prognosis; and
• Group D covered by RFA-CA-12-021 (R01) and RFA-CA-12-022 (R21) that generally relates to cancer therapy and outcomes.

An overview of all PQs FOAs and general guidelines are provided in the NIH Guide Notice NOT-CA-12-014.  Prospective applicants are encouraged to take advantage of this Notice as a tool to facilitate optimal selection among PQs FOAs.

IN A COMMUNICATION TO CPRIT'S EXECUTIVE DIRECTOR, SENATOR WENDY DAVIS
requested copy of all communications between the embattled CPRIT and the CPRIT FOUNDATION, and CPRIT with its OVERSIGHT committee.  The request cites the reason being "for legislative purpose" as she prepares to draft further legislation to tighten CPRIT's functions.  The request is also clearly the latest round of investigations that will certainly unveil new irregularities at CPRIT, we believe.
If an internal investigation brought up one huge gaffe at CPRIT it would be amazing that an outside investigation turned up empty handed.  We are waiting to see just how pervasive back door dealings were at CPRIT.   CPRIT stands accused now, but they say it is not convicted yet.  Let's cross our fingers, bite our nails and wait!
The CRBCM has pulled back its appeal request to stay clear of tensions at CPRIT.  We have a fear of retaliation!  We are only guilty of innocence!

"RESEARCH MISCONDUCT ON THE RISE"

This is the title of a disturbing article published by the Clinical Oncology News, with Victoria Stern reporting.
The report suggested that on average, 2% of scientists surveyed admitted fabricating or falsifying data. And as many as 33% reported to have altered the experiment leading to their conclusion.  This added to our recent report by the CDC that 22 Millions of women reported having had a PAP smear post Hysterectomy.  With a 94% Total Hysterectomies, there is a bunch of  lying going around!

The fascinating thing is this lying is going on in large and small institutions alike.  At Duke University the case reported is that of Anil Potti, MD and Joseph Nevins, PhD.  These two reported scientists told the world they were able to predict patients who would be more likely responding to common chemotherapy using microarray data.  This sensational news was quickly published in a 2006 article in Nature Medicine.
Suffice is to report that following the discovery of this misrepresentation, 11 articles have been retracted, seven corrections have resulted and lawsuits have been filed against the University and the culprit.

And the lying is global.  A dentist by the name of Jon Subdo was also reported to have filed a 100% bogus claim that he followed over 800 patients and concluded that Non steroidal drugs lowered risk of Oral cancer.  The 800 Oslo residents he based on his cavalier conclusion have not been found to this day!

The death of Bone Marrow transplant as way to treat Breast Cancer with high dose therapy was once resurrected by a Brave South African Doctor who reported wonderful results until he was confronted with the truth.  He dreamed up those results we were told!

The question is: why are these things happening?
People want to win it all!  Universities are squeezing their staff?  Or is it the sordid notion that any controversy is good?  Remember though, lies take the elevator, but truth takes the stairs.  So unless the building is being built further, truth always arrive at the top.  Then the liar loses control of the outcome!

To Mr. Douglas H Shulman
Commissioner of the Internal Revenue Services (IRS)
Re: Locator #:17053-158-04004-2

EIN: 45-5275857

Dear Mr. Shulman,


I am writing on behalf of the Coalition for the Reversal of  Breast Cancer Mortality in African American Women (CRBCM) which has been notified 2 days ago that it will not receive 60,000 dollars because of one reason ONLY:  Our inability to produce proof of  Non-Profit 501(c)(3) Tax Exempt Status. You will understand that I truly believe that the IRS, in my mind, is a 100.000 people organization full of either incompetent people or totally unaware of their role and mission.  It is a Red tape Organization distracted and without clear understanding of its Purpose.  We have filed for a tax exemption in June 2012.  By June 18th, 2012, the IRS wrote that after review of our file, we needed to send an additional 100 dollars which was promptly done. We even filed for an "expedited service" knowing that by year end it will be time to submit grants requests.

Suffice is to say that 7 months into the process we still have not heard from the IRS, and there is not even a suggestion that this DARK organization will respond soon!  For a start up organization like the CRBCM, the denial of a grant for cancer education and prevention of $ 60,000 is a huge loss and Job creation is evidently undermined by activity or lack of activity by the IRS.   In low income communities like El Paso, your Organization's inefficiency is crushing people's lives.  The Coalition's cause is to fight Breast cancer and trying to save people's lives.  Your organization is proving to be a large and unplanned impediment.

In developing countries where I originally come from, authorities sit on their hands to solicit bribes.  In the IRS case, I clearly have no idea what could be the reason justifying 7 months of inaction.

Dear Mr. Shulman, I am not sure you planned to start the new year like this, but do something for Godsake!
By February 1st, if we do not have this matter resolved, I will seek reparation from a Court.  I have enclosed the letter from the Susan Komen Organization in El Paso which has led to this outcry!

Sincerely yours!

Mutombo Kankonde, MD


Of Note: We are a Coalition, we will fight for our cause.

KYPROLIS or CARFILZOMIB, A NEW DOOR FOR RESEARCH AT CRBCM!

KYPROLIS, a proteasome inhibitor indicated for refractory Multiple Myeloma after failure of Velcade and an immunomodulator, has opened a new can of worm in research.  We have said that proteasome inhibitors are the most powerful class of drug in this disease in which the cancer cell rely on autocrine growth factors.  Lack of destruction of used proteins by impairing ubiquitination or eliminating ubiquitinated proteins, has a strong inhibitory effect.  This inhibitory effect is as strong as destroying the Nuclear content by an Alkylating agent.  This is why Velcade has been the strongest medication against Myeloma and should be included in any serious initial Therapy.  Kyprolis success is not a surprise, the Velcade story has led the fight!

Any proteasome inhibitor has also a profound disruption of cell division. It disrupts profoundly check point function and initiation of DNA replication.  In fact, this would be of interest, and probably is another major way to check proteasome inhibitor efficacy.  We propose that activity of this new drug be checked by quantitatively measuring Ki 67, ORC and Cdc6 or Cdc28 for that matter.  

This discussion brings up the fact that since we have gotten so good at genome study, we should have by now identified differences in Origin Recognition Complexes between cancer cells Vs normal cell. Because if we do, this could be a major way to electively stop cancer progression by shutting down cell division.

The story of the Silent Information Regulator (Yeast), its relation to Origin Recognition Complex, its now described inhibition of NFkB signaling by a Vanderbilt Team, and its role on the Osteoclastogenesis, put the inhibitor of proteasome center to the treatment of Myeloma and beyond!

QUESTION AT CRBCM?

what is the DRIVER mechanism in Myeloma? This post suggests:

1. Inhibition of Growth factor ubiquitination
2. Inhibition of ubiquitination of  proteins involved with initiation of Replication at check points or interphases.
3. Inhibition of survival pathways or NFkB signaling

You tell me!  We are working hard at CRBCM!
and should Ki 67 and Cdc6 be a way to monitor efficacy of Anti-Proteasome, will speak with the NCI (CPRIT being paralyzed and all!)

*  AFTER A STUDY ON OVER 900 PEOPLE, A DRUG RELEASED BY THE FDA FOR TREATMENT OF ALS FAILED TO SHOW THERAPEUTIC VALUE, BIOGEN IDEC WILL STOP PRODUCTION OF DEXPRAMIPEXOLE BECAUSE OF THIS STUDY. THE STUDY WAS CALLED "EMPOWER" BUT HAS CONCLUDED IN A DISAPPOINTMENT.

* IF THE REPORT BY THE CDC IS TRUE, MAJOR INVESTIGATION FOR WRONG DOING IS NEEDED URGENTLY. THE REPORTS SUGGESTS THAT 22 MILLIONS WOMEN WHO HAVE UNDERGONE HYSTERECTOMIES, CONTINUED TO HAVE PAP SMEAR.  WITH A 94 % RATE OF TOTAL HYSTERECTOMY, IT IS SUSPECTED THAT MILLIONS OF WOMEN WERE DUPED!
THE REPORT WAS GENERATED REPORTEDLY BY PHONE INTERVIEWS CONDUCTED BETWEEN 2000 AND 2010.  SCANDAL IS IN THE AIR!  THE DEFENSE FROM THE MEDICAL COMMUNITY: "PHONE INTERVIEW ARE BIASED".

CRBCM KEEPS ADVANCING!

History at CRBCM has shown that our Blog has reached now over 6000 hits and is being followed internationally.  This a testimony to the efforts we put into the science we discuss here.  We should also recognize that the CPRIT story has attracted people internationally because we have noted a steady following by international readers every time the CPRIT name is mentioned.  CPRIT with its up and down remains a game changer attracting the eyes of the world.  And the CPRIT seal is coveted right here in Texas and of course around the world as companies attracted by the CPRIT emblem are fighting to move to Texas.  CRBCM would also want to merit the CPRIT Seal so it can break free and really fight for the cure.
The fight is ahead, we believe we can win.  At time we, at CRBCM, feel we cannot gather enough political muscle to convince those who review our project.  But every time we remember the mission, every time we look around and remember the dead from cancer, our resolve comes back and we go again banging doors.

Our clinic has been given new wind, so we are not going anywhere but up and in their face until we are heard.  The CRBCM is a Coalition and Coalition by definition fight until those who are resisting this mission get it!  With the cancer Center advancing by the Glory of the almighty, and so his our mission.  We are not backing down.  We have a plan, our knowledge and insufficiencies  can be helped, we will get there! The future is brighter by the day...with every resistance, we double our efforts!   

As of 1/7/2013, ----------------------  United States	5497
Germany	160
United Kingdom	93
Russia	57
France	37
Sweden	24
Latvia	22
South Korea	15
Poland	15
Ukraine	15

Commentary: This information is highly important.
Often patients will arrive with an outside biopsy. The biopsy should be processed for p16 testing and a reflex HPV test if p16+. There are no other molecular markers that are indicated for routine testing yet.

 

HPV-related cancers have some distinct characteristics such as they are caused by high-risk HPV (HPV16), restricted to oropharynx, have distinct molecular markers, usually have "good" prognosis, and patients are typically younger and in general good health (Goon et al, 2009).¹ Tumor HPV testing is now "recommended" by NCCN in 2012,² which changed from being "suggested" in 2011. NCCN recommends either immunohistochemistry for analysis of p16 expression or HPV in situ hybridization (ISH) for HPV DNA detection in tumor cell nuclei. The prognosis of HPV status is defined by RTOG 0129 study that compared accelerated concomitant boost radiotherapy to standard radiotherapy. Of the 323 oropharyngeal tumors that were tested 64% were HPV+ and of those, 96% were HPV16+. P16 is a marker of Rb inactivation (Gillison et al, 2009).³ Another study that assessed HPV positivity was TAX324 study where demographics by HPV status showed that from the 110 patients tested, 50% were HPV+, were younger, higher lymph node burden, smaller primary tumors, and better performance status (Posner et al, 2011).⁴ The survival was significantly different for HPV+ compared to HPV- patients. The HPV+ patients also demonstrated better local regional control (Posner et al, 2011).⁴

 

A recent study is consistent with the detection of HPV16 status using a combination of tests such as in Ned's example where IHC and PCR were used. This study evaluated the importance of accurate testing of HPV16. While the tests were comparable in sensitivity, there were significant disparities in specificity when p16IHC, HR HPV ISH, or DNA qPCR was used independently (Schache et al, 2011).⁵

Marshall R. Posner, MD
Director, Head and Neck Medical Oncology, Division of Hematology/Medical Oncology, Mount Sinai School of Medicine
Professor of Medicine, and Professor of Gene and Cell Medicine, The Tisch Cancer Institute
New York, NY

After the initial workup and additional requests, we asked about the most feasible treatment for Ned: surgery with post-op CRT; CRT only; sequential chemotherapy; or palliative chemotherapy/supportive care.

While surgery could be accomplished initially, it does not address the biology of this disease, which will require post-operative CRT and possesses a high risk of distant metastases. In addition, the functional consequences of the surgery would significantly reduce this patient's quality of life (NCCN, 2012).¹

 

CRT offers a standard of care for this stage of disease, and is associated with improved survival compared to radiotherapy alone (Sharma et al, 2010).² Data from randomized phase III trials supports the use of weekly or bolus cisplatin (Adelstein et al, 2003),³ carboplatin and 5-FU (Denis et al, 2004⁴; Bourhis et al, 2012⁵), or cetuximab (Bonner et al, 2010)⁶ with standard fractionated radiotherapy. IMRT would not offer much in terms of salivary sparing given the extent of disease. Radiation would be delivered over 7 weeks (NCCN, 2012).¹

 

Sequential therapy with TPF followed by CRT also represents a standard of care. Phase III trials have demonstrated that TPF (docetaxel, cisplatin, 5-FU) regimens are well tolerated and improve survival and organ preservation compared to PF (Cisplatin, 5-FU; Van Herpen et al, 2007⁷; Posner et al, 2007⁸). There are no completed trials comparing TPF sequential therapy to CRT (Haddad et al, 2012⁹; Lorch et al, 2012¹⁰). Sequential therapy can reduce tumor volume and improve the functional outcome of subsequent definitive CRT, improve local regional control, reduce the risk of distant metastases, and provide response data to inform later treatment decisions.

 

Palliative/supportive therapy might be considered if the patient is not motivated to undertake an aggressive course of therapy, or has significant psychological barriers to completing and rehabilitating from an aggressive therapeutic course.

 

Statement of Participation
The Postgraduate Institute for Medicine certifies that
Mutombo Kankonde, MD
has participated in the enduring material titled
Ned Visit 1: A 57-year-old Man with Human Papillomavirus (HPV) Negative Oropharynx Cancer
on 07-Jan-13 and is awarded 0.5 AMA PRA Category 1 Credit(s)™.
	The Postgraduate Institute for Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Postgraduate Institute for Medicine 304 Inverness Way South, Suite 100 Englewood, CO 80112 (303) 799-1930 (303) 858-8848 - Fax	Trace Hutchison, PharmD Director of Medical Education Postgraduate Institute for Medicine

 

 

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Downstream from the MAP-Kinase is located the JNK patways with C-JUN as main member. 
This pathway is usually stimulated by stress whether the stress is radiation or a Tumor Necrosis factor.
Antibody to C-jun arrest the cell cycle at G1 to S phase.  Speculation is this how DNA alteration, which is perceived as a stress by the cell, though this pathway, activate P53 and induce cell cycle arrest.  This pathways seems to participate in tissue differentiation.  Formation of the brain is particularly compromised by mutations at C-jun (most likely located at Chromosome One).  C-jun may regulate few promoter gene expression and interact with Cyclin D1.  C-jun is to be tested for mutation in cancer naturally responsive to growth factors and interleukins  (And response to Radiation therapy).  We are digging deeper to clarify some of these assumptions!

Rita Levi-Montalcini Dies

Jan 1, 2013

Rita Levi-Montalcini speaking at the international NGF meeting 2008: Katzir Conference on Life and Death in the Nervous System, at Kfar Blum, ...(from science blog)

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Nobel laureate and pioneer scientist died.she discovered and described Nerve Growth Factor at a time when current evaluation instrument did not exist. Reportedly, even during the war, she continued her work in a makeshift lab at home.  No need for large Biotech companies or large university lab. These are the pioneer that inspires work at CRBCM!  Discovery can be achieved by anyone who believes their cause is right and the problem is here to be solved.  We are inspired by Rita.  May God bless her soul!

Mutombo --

As a Marylander, you probably know all about the huge crowds a presidential inauguration brings.

Every four years, people from across the country come to D.C. and Maryland for inaugural events -- and thousands of amazing people like you step up to be world-class hosts, and make sure everyone has a great time.

This year, I'm asking you to offer that hospitality in an official capacity by lending a hand as an inauguration volunteer. Volunteers will play an important role in making the events before, after, and including the inauguration ceremony a success. We won't be able to do it without you.

Can you volunteer to help out at an event during Inauguration Weekend, or on the big day?

We're going to need a lot of solid people to help make sure we put on an event worthy of the president we'll be swearing in -- and I know we'll be needing some of that Maryland charm, too.

There are a number of events you can be a part of -- take a look, and sign up if you can help out:

http://action.2013pic.org/Volunteer-at-the-Inauguration

Thanks,

Marlon

Marlon Marshall
Senior Adviser
2013 Presidential Inaugural Committee

P.S. -- If you sign up to volunteer, you'll get to be a part of this historic event. More than that though, I guarantee you'll have fun, too.


NOTE:  The Obama Campaign has not realized I moved to El Paso, TX. I am a Texan now!
still own my house in MD waiting for the market to improve a bit!
GO MINERS!

MAP KINASES /ERK
THE MAP KINASES OR MITOGEN ACTIVATED PROTEIN KINASE WHICH WE SPOKE ABOUT RECENTLY AS THEY RELATE TO PANCREATIC, RENAL, AND BRAIN TUMORS,
are downstream from the Epidermal Growth Factor (EGFR) pathways.  When speaking about a pathway,  it is  like a dance where A will dance with B,  A will flirt with B, and B will then leave A and go dance with C and flirt again, and C will the move to D and Flirt and so on.  With each Flirting, there is an exchange of all kinds of things including emotions (and I am not kidding) . Down this pathway is found Molecule involved with Schizoaffective disoders such as bipolar state.  The Actual Pathways is as follow:

EGF--EGFR--GRB2--SOS (My favorite Sons Of the Sevenless) which switch on or excite RAS--RAF--MEK--MAPK (our MITOGEN Activated Protein) which switch a number of Molecules depending on location including MYC and the action goes into the Nucleus to stimulate transcription genes and production of growth proteins.

At each flirt contact, we can intervene and spoil the moment with a Target therapy.
At RAS-RAf we can spoil it by sending Sorafenib or Vemurafenib and treat lung cancer.
At the Raf-MEK, we can send in Selumetinib or Trametinib to inhibit MEK and so on.

At each level, the flirting is actually a chemical reaction mostly involving phosphorylation.  Spoiling the language of phosphorylation is achievable but the challenge is that even normal cells uses this language so it is hard to be selective.  Altering phosphorylation will affect many other normal functions of cells including energy production.  This is an area of intense investigation. It would be a lack of respect if we did not of memtion EGFR inhibition which is the main action in treatment of many important cancer from Head and neck to lung, colon, gastric and so on so forth. And you know the drugs!

ELF5 A NEW PROGNOSIS PREDICTOR OF BREAST CANCER THAT MAY BE SIGNIFICANT IN TRIPLE NEGATIVE BREAST CANCER.  ELF5 IS REPORTED TO BE THE PROTEIN STIMULATING MILK PRODUCTION. IN A BREAST CANCER CELL, IT FAILS TO DO ITS MILK PRODUCTION WORK BUT REPORTEDLY INDUCES GROWTH OF THE CELL PARTICULARLY IN HORMONE RECEPTOR NEGATIVE TUMORS.  POTENTIAL FOR TARGET THERAPY IS INFERRED.  

"CYP2D6 Has Impact on Effectiveness of Tamoxifen

Roxanne Nelson

Dec 31, 2012

Although previous studies have been somewhat inconsistent, a new study shows that breast cancer patients taking tamoxifen who have genetic alterations in CYP2D6 have a higher likelihood of both disease recurrence and death.
Approximately 5% to 7% of European and North American populations are considered to be poor metabolizers of tamoxifen, and there is a simple test that can identify these"
 FROM MEDSCAPE