Welcome to the Clinical Center Grand Rounds,
a weekly series of educational lectures for physicians and
health care professionals broadcast from the Clinical
Center at the National Institutes of Health in
Bethesda, MD.
The NIH Clinical Center is the world's largest hospital totally
dedicated to investigational research and leads the global
effort in training today's investigators and discovering
tomorrow's cures.
Learn more by visiting us online at http://clinicalcenter.nih.gov
TODAY WE ARE HONORED TO HAVE AS
OUR SPEAKER DR. SADHANA JACKSON.
A TENURE TRACK INVESTIGATOR AT
THE SURGICAL NEUROLOGY BRANCH.
SHE RECEIVED HER BACHELOR OF
SCIENCE DEGREE FROM NEW
HAMPSHIRE.
SHE COMPLETED HER TRAINING IN
PEDIATRICS IN ORLANDO, FLORIDA.
FOLLOWING HER FELLOWSHIP SHE
ENTERED INTO A A JOINT
FELLOWSHIP IN PEDIATRIC ONCOLOGY
AT JOHNS HOPKINS UNIVERSITY.
AFTERWARDS IN 2015 DR. JACKSON
JOINED NIH IN THE NEURO ONCOLOGY
BRANCH AND IN 2020 SHE WAS
APPOINTED TO A TENURE TRACK
INVESTIGATOR POSITION IN NINDS
AND NCI.
AS LEAD INVESTIGATOR WITHIN
NINDS DR. JACKSON FOCUSED ON
CHARACTERIZING THE BLOOD BRAIN
BARRIER.
HER LAB STUDIES -- TO THE
ANALYSIS OF THE STRUCTURE OF
FUNCTION AND EXPRESSION WOULD GO
TO TRANSLATE TO OPEN THE BARRIER
AND IMPROVE CHEMO THERAPEUTIC
DELIVERY.
HER TEAMS EAMES TO MODULATE TO
ENHANCE EFFECTIVENESS AND
MAXIMIZE LONG SURVIVAL.
DR. JACKSON IS BOARD CERTIFIED
IN PEDIATRICS AND ONCOLOGY.
SHE IS A LEADER IN THE
COMMUNITY.
AN INITIATIVE TO ADDRESS
STRUCTURAL RACISM.
SHE SERVED AS A COCHAIR OF THE
COMMITTEE AND SERVES AS THE
COMMUNICATION LEAD FOR 8 CHANGES
FOR RACIAL EQUITY.
DR. JACKSON HAS RECEIVED AWARDS
INCLUDING HER WORK FOR AKER.
SHE WAS A 40 UNDER 40 HONOREE IN
2021 AND WAS NOMINATED FOR
SCIENTISTS AND ENGINEERS IN TO
20.
NOW PLEASE JOIN ME IN WELCOMING
TODAY'S GRAND ROUND SPEAKER
DR. SADHANA JACKSON FOR HER
PRESENTATION BLOOD TUMOR BARRIER
AND CLINICAL RELEVANCE.
>>THANK YOU SO MUCH FORGIVING
ME THE OPPORTUNITY FOR ME TO
PRESENT MY RESEARCH TODAY AND I
AGREE THAT BLOOD BRAIN BARRIER
BIOLOGY IS VERY HARD TO SAY OVER
AND OVER.
SO I WILL BE DISCUSSING TODAY
NEW PERSPECTIVES ON DRUG
DELIVERY AND CLINICAL RELEVANCE.
I WILL DISCUSS AN OFF LABEL USE
BUT I'M NOT RECEIVING ANY
FEEDBACK OR MONEY FOR THAT.
WE WILL ENTAIL -- OUTLINING THE
CHALLENGES AND TO EVALUATE
STUDIES AIMED AT ENHANCING
VARIABILITY AND TO EXAMINE THE
ROLE OF NEURO PHARMACOKINETICS
FOR PATIENTS.
WE'RE FOCUSES ON CHILDREN AND
YOUNG ADULTS AND SPELL WITHIN MY
LAB * AND CLINICAL RESEARCH WE
EXPERIENCE THIS AS IT RELATES TO
HIGH GRADE.
THIS IS A YOUNG CHILD OR YOUNG
ADULT WITH WITH HIGH GRADE
GLLOMA.
WHY WE CARE SO MUCH IS THE
SURVIVAL IS SO POOR IN CHILDREN
AND ADOLESCENTS 0-19 YEARS OF
AGE.
YOU CAN SEE THAT JUST STARTING
IN 2004 TO 2017 A TWO-YEAR
SURVIVAL RATE IS LESS THAN 50%.
AROUND 30% AND THERE HAS NOT
BEEN IMPROVEMENT THROUGHOUT ALL
OF THESE DECADES.
SADLY WE PROVIDE EVERYTHING IN
TERMS OF THERAPY FOR THESE
PATIENTS.
WE HAVE THE NEURO SURGEONS THAT
PROVIDE SAFE RESECTION.
WE HAVE RADIATION ONCOLOGIST.
AND THEN MYSELF ONCOLOGIST WE
PROVIDE CHEMOTHERAPY AND STILL
THE SURVIVAL CURVE IS BLEAK AND
DISMAL.
ONE OF THE ROPES FOR WHY THIS IS
SO POOR IS THE BLOOD BRAIN
BARRIER OR BLOOD TUMOR BARRIER.
WHO CARES?
IT'S ALREADY DISRUPTED AND WE
CAN GET THERAPY THERE.
SO THERE IS A YES COMPONENT.
BECAUSE AS YOU LOOK AT THE CORE
OF THE TUMOR YOU CAN SEE THAT
IT'S A PERMEABLE BBB WHERE
REFLECTED HERE IN BLUE ARE THE
DRUG MOLECULES THAT GET OUT TO
THESE AGGRESSIVE PEACH GLLOMA
CELLS.
YOU CAN SEE THAT THE THERAPY
GETS TO THE TUMOR CELLS IN THE
CORE OF THE TUMOR.
IN THE CELLS THAT ARE DISRUPTED
THE PARASITES SEEN HERE IN GREEN
THAT COMMUNICATE AND THEY ARE
ALSO VERY POOR COMMUNICATION AND
THE THERAPY IS ABLE TO GET THERE
AS WELL AS THIS PROCESS THAT
DOES NOT HOLD TIGHT TO KEEP THIS
BLOOD BRAIN BARRIER INTACT.
SO WHILE THIS IS AN ISSUE IN THE
CORE OF THE TUMOR IN THE PERRY
TUMOR AREA WE HAVE MORE OF AN
INTACT BLOOD BRAIN BARRIER WHERE
THE CELLS ARE CLOSER TOGETHER
AND THE PROCESSES HAVE BETTER
COMMUNICATION.
HOWEVER THESE TUMOR CELLS ARE
STILL HIDING OUT HERE IN THE
NORMAL TYPE BRAIN MIXTURE AS
WELL AS WE GO TO THE DISTAL SITE
AREAS OF THE BRAIN WE HAVE AN
IMPERMEABLE BBB.
THIS BECOMES A BIG CHALLENGE.
FOR THERAPIES OF SURGICAL
RESECTION, RADIATION AND
CHEMOTHERAPY THAT USUALLY ONLY
GETS TO THE CORE AND SIX TO 12
MONTHS LATER WE'LL SEE
RECURRENCE.
THAT IS LIKELY BECAUSE OF
THERAPY UNABLE TO GET TO THESE
AREAS THESE TUMOR CELLS ARE ABLE
TO REGROW AND SCOFF AT THE FACT
THAT WE GIVE REPEAT THERAPIES TO
THIS AREA.
SO IT REALLY DRIVES THE REASON
FOR WHY WE HAVE BAD PROGNOSIS
FOR THESE PATIENTS.
WE HAVE THIS HETEROGENEITY OF
THE PERMEABILITY OF THESE DRUGS.
IT MOTIVATES OUR RESEARCH
STUDIES TO FOCUS ON THREE MAIN
AIMS.
OUR ATHAT IS WHAT I CALL KILLINO
BIRDS WITH ONE STONE BUT I DON'T
LIKE TO TALK ABOUT KILLING AS A
VEGETARIAN.
AND THEN 3 WE THINK ABOUT HOW
MUCH DRUG GETS TO THESE AREAS.
SO WE LIKE TO DETERMINE THE
PENETRATION OF CURRENT AGENTS
AND WE USE THIS COOL TOOL.
SO TODAY WE'LL DETAIL A BENCH TO
BEDSIDE BACK TO BENCH
TRANSLATIONAL RESEARCH STUDY
WHERE I'M TALKING ABOUT A DRUG
CALLED REGADENOSON.
RESIGNATION.
-- RESIGNATION.
-- *.
IN MY SENIOR YEAR I TOOK THE
METRO OR THE BUS.
I DIDN'T DRIVE AND I CAME DOWN
TO THE NIH AND I WORKED IN THE
NCI LABS.
SO THAT EXPERIENCE JUST GOT ME
SO EXCITED ABOUT CANCER RESEARCH
AND BEING A CLINICIAN SCIENTISTS
THAT I APPLIED FOR THIS NIH
SCHOLARSHIP PROGRAM.
THAT AFFORDED ME THE A
AVAILABILITY TO RECEIVE MONIES
TO ATTEND HAMPTON UNIVERSITY FOR
THE FIRST TWO YEARS, THEY GAVE
ME ROOM AND BOARD AND I WAS ABLE
TO COME BACK AND WORK DURING THE
SUMMERS AT THE NIH WITHIN NIDCD.
AND I LOVED IT.
SO THE SUMMERS I WAS AN NIH
EMPLOYEE AND I LOVED IT.
NOW ONE OF THE SERVICE
REQUIREMENTS WAS THAT I NEEDED
TO COME BACK AND WORK AT THE NIH
AFTER ALL OF MY TRAINING.
AND SO I KNEW I WANTED TO GO TO
MEDICAL SCHOOL AND BE AN
ONCOLOGIST SO I DID THIS
TRAINING TO BE A PEDIATRIC
ONCOLOGIST AND IN 2015 I
RETURNED TO THE NIH TO NCI AND
I'M EXCITED TO BE HERE AND I
TALK ABOUT THE JOB THAT I HAVE
TODAY I OBTAINED THAT JOB AT THE
AGE OF 17 AND HERE I AM NOW
STILL WORKING HERE AND HAPPY TO
HAVE RECEIVED THE NIH
DISTINGUISHED SCHOLAR BEING PART
OF THE FIRST INAUGURAL CLASS AND
NOW CONTINUED IN 2023.
SO I SAY THAT TO SAY THAT I HAD
THIS CURIOSITY AND PASSION
AROUND CANCER RESEARCH AND
CLINICAL INVESTIGATION AND
LABORATORY INVESTIGATION SINCE
1998 AND PROBABLY EARLIER IF YOU
ASK MY PARENTS AND THAT LEADS
INTO THE CLINICAL AND
TRANSLATIONAL RESEARCH THAT I
HAVE ONGOING IN MY LAB AND WITH
MY PATIENTS.
SO IN THINKING ABOUT THAT I'M
USING -- WE USED A CARDIAC
STRESS DRUG CALLED REGADENOSON.
AND IT SPECIFICALLY WORKS ON THE
A2A RECEPTOR TO AGONIZE THIS
RECEPTOR.
TO INCREASE AMP.
IT INCREASES VASCULAR SMOOTH
RELAXATION AND NET CARDIAC
PROFUSION.
SO ALL THAT MEANS IS WHEN YOU GO
TO THE DOCTOR AND YOU SAY I'M
HAVING SOME CHEST PAIN THEY ARE
ABLE TO HAVE YOU WALK ON A
TREADMILL LIKE THIS INDIVIDUAL
HERE SO THAT THEY CAN SEE WHAT
THE FUNCTION AND THE
PERMEABILITY OF THE VESTIBLES
ARE AROUND YOUR HEART.
IF YOU'RE UNABLE TO WALK ON THE
TREADMILL THEY GIVE YOU THIS
DRUG REGADENOSON.
THIS REGADENOSON AGENT REALLY
WORKS TO SEE ABOUT PERMEABILITY
AND IT CAUSES BASAL DILATION IN
THE VESSELS AROUND THE HEART.
SO INTERESTING ENOUGH THIS FDA
APPROVED DRUG FOR CARDIAC STRESS
TESTING IN 26% OF PATIENTS IT
CAUSES HEADACHESES BECAUSE THE
BASAL DILATION ALSO CAUSES
DILATION IN THE VESSELS OF THE
BRAIN SO THERE WAS A GROUP OUT
OF CORNELL THAT CAPITALIZED ON
THIS INFORMATION AND THEY SAID
IF WE HAVE BASAL DILATION IN THE
BRAIN I BET THERE IS MORE BBB
PERMEABILITY.
SO THEY LOOKED AT RODENTS
NONTUMOR BEARING RATS AND MICE
AND THEY GAVE THEM THIS DRUG AND
THEY FOUND THEY COULD GET A
MOLECULE WITHIN THE BRAIN OF
THESE NONTUMOR BEARING ANIMALS.
SO WE SAID * IF WE CAN GET THIS
LARGE SUGAR PROTEIN IN WHAT IF
WE COULD GET OUR STANDARD
CHEMOTHERAPY TREATMENT.
WE MEASURED AND LOOKED AT WHAT
REGADENOSON COULD DO TO INCREASE
CONCENTRATION IN THE BRAIN OF
RATS AND WHAT WE FOUND IS IN OUR
NONTUMOR BEARING RATS WE COULD
SEE A 60% INCREASE IN BRAIN
CONCENTRATION WHEN WE MEASURED
IT AND WE COULD SEE THAT TWO
HOURS AFTER WE GAVE THIS
COMBINATION THERE WAS A 60%
INCREASE AND BY SIX HOURS THERE
WAS NOT ENOUGH AN EFFECT OF THE
COMBINES THERAPY SHOWING US THIS
WAS JUST A TRANSIENT EFFECT
WHICH IS GOOD IF WE'RE GOING TO
OPEN THE BBB WE WANT TO HAVE IT
COME BACK TOGETHER AND GO BACK
TO NORMAL AS IF WE DID NOTHING.
WE DON'T WANT THAT TO BE OPEN
AND CAUSE MORE PROBLEMS BECAUSE
THE MAIN PROBLEM IS IF YOU'RE
GOING TO OPEN THE BBB IS THAT
GOING TO CAUSE FOR MORE BAD
THINGS TO GET IN.
POTENTIALLY.
SO THAT IS WHY THE INTEREST IS
TO HAVE A TRANSIENT EFFECT.
SO WE WERE EXCITED ABOUT THESE
FINDINGS.
WHAT IF WE LOOKED AT PATIENTS
THAT HAD HIGH GRADE GLLEOMA.
WOULD WE SEE THAT EFFECT FROM
INCREASED -- ON THEIR BRAIN
TUMORS.
TEMPOROMANDIBULAR.
*.
TEMOZOLOMIDE ALONE ON DAY ONE
AND THEN TEMOZOLOMIDE WITH
REGADENOSON ON DAY TWO.
I WAS AT THE BEDSIDE WITH THESE
PATIENTS WHO HAD BRAIN SURGERY
AND REPLACED THESE CATHETERS.
THEY ARE INTELLIGENT TOOLS.
PLASTIC TUBING THAT THE NURSE
SURGEON PLACES AFTER A SURGICAL
RESECTION AND WE'RE ABLE TO
INFUSE ARTIFICIAL CFF.
AT A VERY SLOW INFUSION RATE.
.5 TO ON ONE MICRO LITER PER MIE
AND WE'RE ABLE TO GAIN FLUID AND
MEASURE TEMOZOLOMIDE
CONCENTRATION.
SO THIS TRIAL WAS A SAFETY AND
FEASIBILITY TRIAL TO SEE COULD
WE SAFELY MEASURE CONCENTRATIONS
INTO THE BRAIN AND DID WE SEE AN
EFFECT WHEN WE GAVE REGADENOSON
SO I WAS AT THE BEDSIDE OF THESE
PATIENTS.
8 A DAY AFTER THEY HAD SURGERY
SO I WAS HAVING MY OWN CARDIAC
STRESS TEST.
ALSO OF INTEREST THESE PATIENTS
COULD NOT HAVE ANY CAFFEINE.
THEY ARE GETTING THIS CARDIAC
STRESS TEST AND THEY CANNOT
DRINK COFFEE SO THEY WERE NOT MY
BEST FRIENDS AT THE END OF THIS
TRIAL.
WE LOOKED AT FIVE TOTAL
PATIENTS.
AND WE DID NOT SEE THE 60%
INCREASE THAT WE EXPECTED.
INSTEAD WE ONLY SAW IN PATIENT 2
AND PATIENT 5 AND LOOKING AT
TEMOZOLOMIDE ALONE OR
TEMOZOLOMIDE WITH REGADENOSON IN
RED THAT THERE WAS AN INCREASE
EARLY AND THAT WAS 55% INCREASE
AREA UNDER THE CURVE AND THEN 2%
UNDER THE CURVE.
BUT IN PATIENTS 1, 3 AND 4 WE
DID NOT APPRECIATE A DIFFERENCE
OR INCREASE WITH REGADENOSON
ADMINISTRATION.
SO WE SAID WE DON'T SEE THAT
INCREASE OF 60%.
WHAT ARE WE MISSING?
WHAT MORE CAN WE LEARN FROM
GOING FROM THE BENCH TO THE
BEDSIDE?
AND SO THAT LED US TO THINK
ABOUT WHAT IS HAPPENING ON THE
CELLULAR LEVEL AND WHAT IS GOING
ON WITH THE TIME DEPENDENCE OF
WHEN REGADENOSON IS GIVEN VERSUS
THE EFFECT AND THEN WHAT HAPPENS
LONG-TERM IF YOU GIVE REPEATED
DOSING OF REGADENOSON IN TUMOR
BEARING ANIMALS.
WE WENT BACK TO THE BENCH AND I
HAVE A FORMER POSTDOC WHERE WE
LOOKED AT TUMOR BEARING RATS AND
THEY WERE GIVEN REGADENOSON WITH
TEMOZOLOMIDE.
WHAT HAPPENS ON THE CELLULAR
LEVEL.
THAT ARE TREATED WITH EITHER
TEMOZOLOMIDE OR TEMOZOLOMIDE
WITH REGADENOSON.
WE WANTED TO KNOW WHAT HAPPENS
TO THE JUNCTIONAL EXPRESSION
AMONG THIS.
THIS IS VERY COMMON THAT KEEPS
THESE CELLS ADD CHEESED TO EACH
OTHER.
*.
WE COULD SEE DECREASED CELL TO
CELL ATTACHMENT WITH THIS
JUNCTIONAL PROTEIN WITHIN THE
TUMOR BUT NO DIFFERENCE IN THE
NORMAL BRAIN SO WE SAID HMMM.
THEN WHEN WE LOOKED AT THE
CONCENTRATION OF TEMOZOLOMIDE
THERE WAS A HIGHER CONCENTRATION
OF TEMOZOLOMIDE IN THE TUMOR SO,
THAT IS THE INJECTED SIDE OF THE
BRAIN OF THE ANIMAL BUT NO
INCREASE IN THE NONTUMOR BEARING
SIDE WHICH IS VERY DIFFERENT
THAN THE 60% INCREASE.
SO WE SAID WE SEE A 40% INCREASE
IN THE TUMOR CONCENTRATION.
DECREASED EXPRESSION.
THIS SHOULD TRANSLATE TO
PROLONGED SURVIVAL, RIGHT?
OF COURSE, NOT.
THERE WAS NO PROLONGED MODEL
SURVIVAL WHEN GIVEN TEMOZOLOMIDE
ALONE VERSUS TEMOZOLOMIDE WITH
REGADENOSON.
SO EVEN WITH REPEAT TREATMENT WE
DID NOT SEE THAT PROLONG GOINGS
*.
WHAT WE WERE ABLE TO LEARN THE
THREE MAIN TAKE AWAYS.
THE TIMING OF THE BBB -- BTB
DISRUPTION TRULY MATTERS.
WE SHOULD NOT JUST FOCUS ON
BRAIN ENDOTHELIAL.
AND THAT IT'S REALLY IMPORTANT
TO UNDERSTAND HOW MUCH DRUG GETS
TO THE TUMOR AND NONTUMOR
REGIONS TO SAY IF THE DRUG IS
REALLY EFFECTIVE AND HOW TO GO
FORWARD.
SO THAT LEADS REALLY NICELY INTO
OUR AIM TWO.
BUT LOOKING AT COMMON SIGNALING
PATHWAYS BOTH IN GLEOMA CELLS
AND THE BBB.
SO WHEN YOU THINK ABOUT THE
BRAIN ENDO THEME YUM -- AND A
LOT OF TIMES THEY ARE BUY
CELLULAR OR TRY CELLULAR
JUNCTION PROTEINS.
THEY ARE CLOUD IN 5 AND THAT IS
SEEN HERE IN PURPLE AND THAT
KEEPS THE CELLS TIGHT TOGETHER
BUT THERE ARE TWO OTHER PROTEINS
THAT ARE INTEGRAL.
THOSE ARE TRY CELLULAR SEEN HERE
IN YELLOW AND GREEN.
THERE IS HIGH EXPRESSION FOR
THESE TRY CELLULAR JUNCTIONS.
THIS HELPS TO RECRUIT TRY
CELLULAR TO FORM BBB TYPE
CELLULAR JUNCTIONS.
THIS EXPRESSIONS HIGH WITHIN THE
BRAIN AND WITHIN THE GUT.
AND INTERESTING ENOUGH IS THAT
ANGLIN ONE * -- ALSO IS ANOTHER
NAME IS -- LSR.
SO, IT'S NOT JUST PRESENT IN
THESE CELLS TO CAUSE FOR
INCREASED TYPE JUNCTIONAL
ADHESION BUT ALSO IN THESE
NORMAL CELLS.
SO WHEN WE LOOKED IN THE CCGA
AND THE TCGA THERE WAS HIGH
EXPRESSION ALSO WITHIN HIGH
GRADE GLEOMA SPECIFICALLY GRADE
4 AND HIGH IN YOUNG ADULTS LESS
THAN 47 YEARS OF AGE.
*.
AS YOU CAN SEE HERE THERE IS
HIGHER EXPRESSION IN LESS THAN
47 YEARS OF AGE GENE EXPRESSION,
7.5 IN COMPARISON TO GREATER
THAN 47 YEARS OF AGE.
SO OKAY.
I'M A PEDIATRIC ONCOLOGIST WE'RE
SEEING THIS ANGLIN ONE
EXPRESSION.
IT'S HIGH IN THESE TUMOR CELLS
IN THIS YOUNG ADULT POPULATION.
THIS IS SOMETHING THAT I CAN GO
AFTER.
WHAT IS IN THE LITERATURE AND
WHAT HAS BEEN DONE SO FAR?
THERE WAS A GROUP OUT OF JAPAN
THAT USED OR CREATED AN AGENT
CALLED ANGUBIDIN.
THEY CREATED THIS AMINO ACID
COMPLEX THAT BINDS AND THEY WERE
ABLE TO INHIBIT THE FUNCTION AND
EXPRESSION SO AS TO ALLOW FOR
INCREASED PASSAGE OF THEIR --
NUCLEO TIDE AGAINST CARCINOMA.
* AND DECREASE THE EXPRESSION OF
MALAT-RNA.
THEY COULD SEE A DECREASE IN THE
EXPRESSION AND THEY COULD SEE
THAT IN THE BRAIN AND THE
CERVICAL AND LUMBAR SPINAL CORD.
IT ONLY TOOK TWO HOURS TO SEE A
SIGNIFICANT EFFECT.
SO WE SAID THAT IS INTERESTING.
WHAT IF WE DID THE SAME BUT WE
LOOKED AT IT IN THE CONTEXT OF
OUR CHEMOTHERAPY OF INTEREST.
SO WE HYPOTHESIZED THAT IT WILL
ENHANCE CONCENTRATION AND
THROUGH BBB/BTB CHANGES.
IT'S HIGHLY EXPRESSED IN GLEOMA
CELLS.
WITH THE WORK OF TWO PO POST BAS
IN THE LAB -- * THEY CREATED AND
BIDEN FOR US.
ANGUBINDIN FOR US.
* THIS TIME WE WANTED TO USE AN
AGENT THAT WE KNOW DOES NOT
CROSS INTO THE BLOOD BRAIN
BARRIER VERY WELL AND IT SERVES
AS A SUBSTRATE FOR PROTEIN WHICH
IS A VERY IMPORTANT ABC
TRANSPORTER WITHIN THE BLOOD
BRAIN BARRIER.
SO WE WANTED TO SEE IF WE COULD
OVERCOME THE CHALLENGE OF NOT
JUST BBB PERMEABILITY BUT ALSO
E. FLUX TRANSPORTERS.
THIS SEEN HERE IN BLUE IS THE
DOXIL.
SO AS A CLINICIAN IT'S IMPORTANT
TO THINK ABOUT IF YOU'RE GOING
TO THINK ABOUT A PROTEIN OR GENE
OF INTEREST WHAT CAN YOU LEARN
FROM JUST LOOKING AT SURVIVAL
CURVES IN EXPRESSION FOR
PATIENTS WITH GLIAL BLAST TOMA.
* SO WHAT IS THE SURVIVAL LIKE?
SO I FIRST WAS OH, NO IF
PATIENTS HAVE A HIGH EXPRESSION
WHILE SURVIVAL IS BLEAK IT STILL
LOOKS LIKE THEY DO BETTER IF
THEY HAVE A HIGHER EXPRESSION SO
WHAT DOES IT LOOK LIKE IF I AM
TRYING TO INHIBIT THIS?
IF WE LOOK AT RECURRENT PARENTS
THERE IS NO SURVIVAL DIFFERENCE.
MAYBE WE SHOULD NOT GO THIS PATH
I ALSO THOUGHT ABOUT WELL IF YOU
HAVE HIGH OR LOW EXPRESSION
SPECIFICALLY LOW EXPRESSION
ANGLIN ONE IN THIS BLEAK
SURVIVAL CURVE YOU HAVE TO THINK
ABOUT THE ENDO THEME YUM.
*.
THE TUMOR CELLS HAVE HIGH ANGLIN
1 EXPRESSION.
WE'LL FOCUS ON INHIBIT THE
EXPRESSION IN THE TUMOR CELL AS
WELL AS THE NEURONS AND WE'LL
SEE WHAT HAPPENS.
AND SO WE FIRST WANTED TO LOOK
AT JUST ENDO THIEL YAM.
* AND WE PLATE THESE CELLS IN
SOUTHERN WELLS WHERE IT ALLOWS
US TO LOOK AT THE ELECTRON FLOW.
SO AS WE PLATE THESE CELLS WE'RE
ABLE TO SEE WHAT THE CELL CELL
ATTACHMENT AND ADHESION IS.
WE USE AN ELECTRICAL FLOW.
AS YOU USE MORE CELLS THAT
ATTACH TO EACH OTHER THERE IS
HIGHER CELL CELL INDEX.
AS YOU HAVE THE CELLS COMING
APART YOU HAVE LOWER CELLS INDEX
OR LOWER CELL CELL IMPEDENCE.
WHEN WE MEASURED ADHESION EITHER
TREATED WITH BUY CELLULAR
JUNCTION INHIBITORS OR
TRIINHIBITION YOU CAN SEE A
SIGNIFICANT EFFECT AT THE 4 OR 6
HOUR TIME PERIOD AND THAT THEN
RETURN BACK AT A 12 HOUR TIME
PERIOD.
THE IMPORTANCE TO THINK ABOUT A
TRANSIENT EFFECT OF THIS AGENT.
SO, THAT IS WHAT IS HAPPENING
WITH THE ENDO THIEL YUM BUT WHAT
HAPPENS ON THE PROTEIN?
WE WANTED TO KNOW IF YOU LOOK AT
ANGLIN ONE WHAT HAPPENS TO THE
EXPRESSION AND WE SEE ALSO AT
THAT SAME KIND OF FIVE HOUR TIME
PERIOD THERE IS DECREASED
EXPRESSION AND HIGHER EXPRESSION
ON THE CITO PLATTISM * CITO
FLACH.
SO WE WANTED TO USE ANIMALS SO
WE'RE USING RAT CELLS WHICH ARE
AKIN TO HIGH GRADE GLEOMA CELLS
IN HUMANS AND THE BASELINE IS
HIGH EXPRESSION BUT AFTER YOU
TREAT WE SEE LOWER EXPRESSION
AND BY 48 HOURS THE EFFECT OF
THE AGENT HAS WORN OFF.
KNOWING ALSO THAT WE WERE USING
DOXIL AND KNOWING THAT IS A
SUBSTRATE OF P LIKE OH PROTEIN
-- WE WANTED TO KNOW WHAT EFFECT
AND BIDEN HAD.
WE USED A FLOW ASSAY.
PGP IS PRESENT ON THESE TUMOR
CELLS AND WHEN YOU USE A KNOWN
INHIBITOR OF PGP YOU SHOULD SEE
A SHIFT TO THE RIGHT AND A SHIFT
TO THE RIGHT SIGNALS A HIGHER
FLUORESCENCE OF THESE CELLS.
INTERESTING WE SEE THAT WHEN WE
GAVE AND BIDEN AT THE SAME DOSE
WE SEE A CONTINUED OR PUSH TO
THE RIGHT.
A HIGHER FLUORESCENCE OF THESE
TUMOR CELLS SHOWING THAT IT ALSO
HAS A PGP INHIBITION FUNCTION.
SO WE'RE SAYING OKAY.
WE'RE GOING IN THE RIGHT
DIRECTION.
WE HAVE INHIBITION OF THE CELLS.
WE HAVE PGP INHIBITION.
WHAT CAN WE STEER WRONG?
* AGAIN WE USED IMMUNO COMPETENT
ANIMALS.
WE INJECTED THEM AND ON DAY 7
AND 14 THEY RECEIVED DOXIL ALONR
VEHICLE TREATMENT AND WE WERE
ABLE TO MEASURE DOXIL
CONCENTRATION AS WELL AS THE
SURVIVAL END POINT.
AND WHAT WE FOUND IS THAT WHEN
WE LOOKED AT CONCENTRATION THAT
THERE WAS ONLY INCREASED DOXIL
CONCENTRATION IN THE TUMOR AND
THIS IS NOT A GREAT PERMEABILITY
AGENT WITHIN THE BRAIN BUT WE
COULD SEE A HIGHER INCREASE OR
HIGHER -- CONCENTRATION OF DOXIL
WITHIN THE TREATED ANIMALS
VERSUS THE DOXIL ALONE.
WE'RE GOING IN THE RIGHT
DIRECTION.
WHAT WE FOUND WITH THE HELP OF
TWO OF THE ANIMAL BIOLOGIST IS
THAT WE COULD SEE DECREASED
TUMOR VOLUME HERE.
THESE ARE JUST TWO
REPRESENTATIVE MRI IMAGES WITH
THE VARIOUS TREATMENTS AND YOU
CAN SEE THAT THE TUMOR VOLUME IS
SIGNIFICANTLY SMALLER BUT THEY
WENT THROUGH AND LOOKED AT EACH
OF THE SLICES AND THIS IS A
QUANTIFICATION OF SUCH.
ALSO JUST A SNAPSHOT IMAGE OF A
STAINING.
YOU CAN SEE THAT IN COMBINATION
THE TUMOR SIZES SIGNIFICANTLY
SMALLER IN THE COMBINES VERSUS
ANY OF THE OTHER THREE
TREATMENTS?
DOES THIS TRANSLATE TO SURVIVAL?
AND ACTUALLY IT DOES.
SO IN LOOKING AT VEHICLES SEEN
HERE IN RED OR DOXIL ALONE
COMPARED TO THE COMBINATION
THERE IS A LONGER SURVIVAL WITH
THE COMBINATION THERAPY AND EVEN
MEDIAN SURVIVAL IS IMPACTED.
I DON'T SEE THE ASTERISKS BUT
THERE WERE WITH PROLONGED
SURVIVAL.
THIS COMBINATION THERAPY HAS A
SIGNIFICANT IMPACT ON SURVIVAL.
WHERE DO WE GO FROM HERE IN HOW
DOES THAT TRANSLATE FURTHER?
IT'S NOT LOST ON US THAT THE
BLOOD BRAIN BARRIER IS THE ONLY
CHALLENGE TO PROVIDING EFFECTIVE
THERAPY TO THESE TUMORS.
WE HAVE THE IMMUNE SYSTEM THAT
IS VERY IMPORTANT FOR ALL
TUMORS.
WHEN YOU THINK ABOUT HOW T CELLS
GET TO THE TUMOR OR TO THE
NORMAL BRAIN THERE IS A WAY OF
TRANS CELLULAR MIGRATION.
THIS IS THE GRAPHICAL
ILLUSTRATION.
YOU'LL SEE IN ORDER TO GET INTO
THE BRAIN THEY COME FROM THE
VASCULATURE AND THEY ROLL AND
THEY COME TO THE SITE OF INJURY
OR INFECTION OR TO THE SITE OF A
TUMOR PRESENT.
BUT THE WAY THEY COME ABOUT IT
IS THROUGH PERRY CELLULAR
TRANSPORT THROUGH THESE TIGHT
JUNCTIONS OR TRANS CELLULAR.
THEY CAN COME THROUGH THE
ENDOTHELIAL CELLS.
THERE WAS A GROUP OUT OF
SWITZERLAND -- THEY INHIBITED
PCAM.
IF THEY INHIBITED BUY CELLULAR
JUNCTIONS YOU CAN SEE A HIGHER
MIGRATION OF THESE T CELLS.
THIS IS JUST BUY CELLULAR.
CAN WE SEE INCREASED TRANS
CELLULAR -- MIGRATION OF THESE
CELLS.
IT HAD US TO SAY WHAT IS THE
ROLE OF THE JUNCTIONS WHEN YOU
INHIBIT THEM.
SO WE TOOK -- THESE ARE TC
DEFICIENT.
WE INJECTED THEM WITH TUMOR
CELL.
WE LOOKED AT DAY 7 AND 14 TO
GIVE THE COMBINATION AND WANTED
TO SEE WHAT THEIR SURVIVAL IS.
THERE IS NO SURVIVAL BENEFIT AND
THE ONLY LONG SURVIVAL IS WITH
DOXIL ALONE.
THE T CELLS ARE PRYING A ROLE IN
PROVIDING SURVIVAL.
WE HAVE MORE INVESTIGATIONS TO
DO ON THAT SIDE AS IT RELATES TO
THE IMMUNE SYSTEM.
WE'RE ABLE TO DEDUCE AND
HYPOTHESIZE THAT THIS HALTS
DISEASE PROGRESSION AND WE'VE
BEEN ABLE TO SHOW THAT IT
DISRUPTS ENDO THIEL YUM AND
INCREASED DOXIL CONCENTRATION
WITH LONG SURVIVAL.
WE HAVE PRELIMINARY STUDIES TO
SHOW -- IT'S NOT JUST AKIN TO
RAT GLEE OPENED AFTER CELLS.
WE ALSO SEE IT IN * TUMOR
TISSUE.
WE SEE THAT -- INHIBITION THAT
WE'RE STARTING TO EVALUATE TC
MIGRATION DIFFERENCES AND ALSO
PROVIDING A CLEAN WAY TO INHIBIT
ANGLIN 1 EXPRESSION WITH STUDIES
BOTH ON ENDO THIEL YUM AND THEN
LOOKING TO SEE WHAT THE EFFECT
IS IN VITRO AND THEN EVENTUALLY
ENVY HAVE A.
* AND IN THE FUTURE WE'LL
CONTINUE TO IDENTIFY OTHER DUAL
ROLE AGENTS THAT WORK ON BOTH SO
THAT WE CAN INVESTIGATE INVITRO
TO SEE THE EFFECT.
NOW THIS LEADS INTO THE EFFECT
OF THE PHARMACOLOGY MATTERS.
SO OUR AIM 3 IS TO DETERMINE --
THE PENETRATION OF CURRENTLY
USED CHEMO THERAPEUTIC GAUGE END
INTO MALIGNANT GLEE OMAHAS.
SOMETIMES WE'RE ABLE TO MEASURE
DRUG CONCENTRATION IN THESE
AGGRESSIVE TUMORS.
BUT THAT IS ONLY ONE TIME POINT.
WHEN THESE PATIENTS ARE ON NO
CHEMOTHERAPY BUT STEROID THERAPY
THAT CAN CLOSE THE BBB.
THAT IS ONE TIME POINT THAT
WE'RE ABLE TO SAY THE DRUG GETS
IN OR DOESN'T AND NO LONG-TERM
OF HOW MUCH GETS INTO THE BRAIN.
YOU HAVE THIS BRAIN AND THE
SKULL AND ALL OF THESE LAYERS
AND IT'S NOT LIKE A PERIPHERAL
TUMOR THAT WE CAN CONTINUE TO
BIOPSY.
THE TOOL IS JUST ONE WAY THAT
WE'RE EXPLORING TO BE MORE
UTILIZED IN THE SETTING TO
UNDERSTAND MORE ABOUT THE
PHARMACOLOGY OF THESE TUMORS.
THIS IS ONE AGENT.
FDA APPROVED AND A POTENT
INHIBITOR.
IT WORKS TO INHIBIT -- RETINAL
BLAST STOLEN A GENE AND IMPAIRS
THE * G1.
THERE IS ALSO DISREGULATION --
IN HIGH GRADE GLIOMAS.
AND THIS DRUG SPECIFICALLY HAS
BEEN SHOWN TO PROLONG SURVIVAL
IN NEWLY DIAGNOSED PATIENTS AND
META STATIC BRAIN PATIENTS.
THE ARCHITECTURE IS DIFFERENT.
IN THINKING ABOUT THE MID-LINE
IF YOU THINK ABOUT THE PONDS OF
THE BRAIN THAT IS THE TEXTURE
AND THE SPONGINESS OF THE BRAIN
VERSUS THE MID-LINE STRUCTURES
ARE SIGNIFICANTLY DIFFERENT.
YES.
YOU SEE PROLONGED SURVIVAL WITH
THIS AGENT BUT WHAT TYPE OF
SURVIVAL OR EFFECT AND WHAT TIME
OF PERMEABILITY DO YOU SEE FOR
PATIENTS WITH DIFFUSED MID-LINE
GLEOMA.
I USU-- FOR PHASE 01 TRIAL THATS
AT THE SAFETY AND FEASIBILITY OF
PLACEMENT AND SAMPLING WITH
PATIENTS.
MEASURING BOTH -- AND THEN WE
HAVE THE PHASE I COMPONENT OF
LONG-TERM FOLLOW-UP ONCE THEY
RECEIVE THIS.
AND WE'RE AGAIN USING OUR FANCY
TOOL OF THE CATHETER.
THIS TIME BECAUSE OF THE
LOCATION OF THE TUMOR WE'RE NOT
ABLE TO DO A SURGICAL RESECTION
OF THE TUMOR BUT INSTEAD A
BIOPSY AND A CATHETER IS PLACED
AND THROUGH PASSIVE DIFFUSION
WE'RE ABLE TO GAIN EXTRA
CELLULAR FLUID AND MAKE
MEASUREMENTS.
WITH THE REP OR ASSISTANCE OF
DR. BROWN WHO'S A NEURO SURGICAL
ONCOLOGIST WE ENROLL PATIENTS
WITH RECURRENT HIGH GRADE GLIOMA
OR DIFFUSED MID-LINE GLIOMA AND
PATIENTS TAKE -- AND THEN ON THE
5th DAY THEY HAVE A RESECTION
OR BIOPSY AND THESE CATHETERS
ARE PLACED.
WE'RE ABLE TO DETERMINE -- THE
CONCENTRATIONS.
WE'RE ABLE TO DO STUDIES.
WE'RE ABLE TO DO GENOMIC
PROFILING ON THE TISSUE AND
WE'RE ABLE TO DO PDX MODELING.
WE HAVE THESE CATHETERS IN PLACE
AND WE'RE ABLE TO DO TIMED
SAMPLING OF THE FLUID IN
COMPARISON TO PLASMA
CONCENTRATION AND AT 48 HOURS
THESE CATHETERS ARE REMOVED AT
THE BEDSIDE AND THE FLUID IS
SENT TO THE LAB AND WE'RE ABLE
TO MEASURE FOR 0-48 HOURS.
THIS IS A DIFFERENT TYPE OF
STUDY IN THE FACT THAT WE HAVE A
GO, NO GO COMPONENT.
IF IT'S A CERTAIN CONCENTRATION
GREATER THAN 10 PER LITER OUR
RECOMMENDATION IS TO RESTART.
WE'RE GIVING DRUG BECAUSE WE
THINK IT WILL GET THERE AND HAVE
AN EFFECT.
SO THIS IS A VERY INTELLIGENT
WAY FOR US TO SAY A GO, NO GO
AND NOT JUST BLINDLY PROVIDING
THERAPY.
WITH EVERY THREE MONTHS CHECKING
TO SEE IF THERE IS A CHECK ON
THE TUMOR.
THESE ARE VERY AGGRESSIVE TYPE
TIMERS.
THESE PATIENTS WILL HAVE COME TO
US WITH RECURRENT DISEASE
DEPENDING ON WHAT THERAPIES THEY
HAVE RECEIVED AT THEIR HOME
INSTITUTION.
WE'VE ACCRUED ONE PATIENT TO
THIS STUDY.
CT/MRI OVERLAY.
THIS PATIENT HAD AN AGGRESSIVE
RECURRENT GLIAL BLAST TOMA.
THE * CATHETER WAS PLACED RIGHT
HERE.
YOU CAN SEE THE DIFFERENT WAYS
TO IMAGE FOR THE CATHETER TIP
PLACEMENT.
WHAT WE WERE ABLE TO SEE IS THAT
WE COULD SUCCESSFULLY MEASURE
THE CONCENTRATIONS IN BOTH
PLASMA BRAIN DIALYSIS.
THIS WAS THE TIME AT FIRST
ADMINISTRATION.
IT WENT DOWN OVER THE 72 HOURS
AFTER US DOING REPEAT BLOOD
DRAWS AND AFTER THE CATS
TERRIFIC WAS PLACED * THAT THE
HIGHEST CONCENTRATION WAS ABOUT
6 HOURS IN TERMS OF THE AREA
UNDER THE CURVE AND CLEARANCE
OVER TIME WENT DOWN OVER THE 48
HOUR TIME PERIOD.
IT WAS A THRESHOLD THAT WE WOULD
RECOMMEND FOR RESTART AND FOR
THIS PATIENT THEY MET THE
THRESHOLD.
SO THAT WOULD BE THE
RECOMMENDATION TO RESTART.
WE ADDITIONALLY WANTED TO LOOK
IN THE TUMOR TISSUE AND WE WERE
ABLE TO GET THREE DIFFERENT
TUMOR SPECIMENS.
THEY HAD DIFFERENT
CONCENTRATIONS OF ABEMACICLIB.
A&M OUR TAKE AWAYS.
THIS WILL PREDICT TREATMENT
RESPONSE.
THAT ABEMACICLIB IS SAFE AND
FEASIBLE AND THAT WE HAVE
ONGOING STUDIES.
WE'RE RECRUITING PATIENTS 2-5.
IF YOU HAVE A PATIENT OF
INTEREST PLEASE SEND THEM OUR
WAY.
SO WE CAN POTENTIALLY ENROLL
THEM FOR STUDY FOR THIS STUDY OR
FOR OTHERS.
SIMULTANEOUSLY WE'RE DOING
PRECLINICAL STUDIES LOOKING AT
RODENT MODELS WHERE WE PLACE
CATHETERS IN TUMOR INJECTED
VERSUS NONTUMOR.
I TALKED ABOUT THE GRAPHICAL
ILLUSTRATION OF THE CORE AREAS
AND MORE INFORMATION CAN BE
OBTAINED ABOUT THIS DISTANT SIDE
AREA IF WE'RE ABLE TO PUT A
CATHETER IN THE NONINJECTED
SIDE.
AND THAT THE THE OVER-ALL TAKE
AWAY -- THIS IS A FEASIBLE
ADJUNCT FOR BOTH PRECLINICAL AND
CLINICAL MANAGEMENT.
WE HOPE THAT WE CAN EXPAND THE
USE OF THE TOOL IN MORA DULL THE
-- STUDIES AS WELL * AS
PEDIATRIC TRIALS.
IT COULD HELP TO ADVANCE MORE
ABOUT OUR GO NO GO OR TO BE MORE
INTELLIGENT IF A DRUG WORKS OR
GETTING TO WHERE WE WANT IT TO
GO.
THESE CAN HELP WITH OUR CLINICAL
STUDY INVESTIGATIONS AND OUR
CREATION FOR THESE TRIALS.
SO AS THE ONLY BLACK PEDIATRIC
ONCOLOGIST IN THE COUNTRY IT IS
AN HONOR TO CONDUCT MY RESEARCH
HERE AT THE NIH.
I'M STILL HERE.
AND WE'RE EMPOWERED THAT THESE
STUDIES ARE HELPING TO ADVANCE
OUR FIELD RELATED TO THE TIME
DEPENDENT CHANGES, THE DUE
RECALL ROLE THEN PIECE AND THE
PHARMACOLOGY OF THESE AGGRESSIVE
TUMORS.
AND THEN AS WAS MENTIONED
EARLIER MY WORK IS NOT JUST AT
THE NIH.
IT IS WORLDWIDE AND THESE ARE
JUST A FEW PICTURES OF THE WORK
THAT I'VE DONE AT THE NIH THAT
I'VE DONE GLOBALLY TO HELP
FOSTER MENTORING OUTREACH
INCLUSIVITY AND DIVERSITY AMONG
THE SCIENCES AND STEM.
YOU CAN SEE A PICTURE WITH MY
KIDS.
WITH MY COLLEAGUES.
WOMEN IN NEURO ONCOLOGY AND WHY
IT'S SO IMPORTANT THAT THERE IS
DIVERSITY OF THOUGHT WITHIN THE
ENTIRE BIOMEDICAL ENTERPRISE AND
IT'S HELPED TO FOSTER BOTH MY
PERSONAL AND PROFESSIONAL GROWTH
OVER TIME.
I'M GRATEFUL TO HAVE THESE
OPPORTUNITIES.
SO THANK YOU VERY MUCH FOR YOUR
TIME.
I APPRECIATE YOU BEING
INTENTIONAL ABOUT LISTENING AND
THINKING ABOUT GOOD QUESTIONS
THAT ARE EASY FOR ME TO ANSWER
AT THE END OF THIS PRESENTATION.
I REMIND YOU THAT WE HAVE AN
OPEN POSTDOCTORAL POSITIONS.
WE HAVE TWO.
SO PLEASE SEND PEOPLE MY WAY.
WE WANT TO CONTINUE TO BE ROBUST
IN OUR THINKING AROUND BBB AND
PHARMACOLOGY.
THANK YOU.
>>DR., JACKSON, I WANT TO THANK
YOU FOR YOUR BRILLIANT
PRESENTATION.
AND * WE HAVE A COUPLE OF
QUESTIONS THAT HAVE COME IN.
ONE IS A LOT OF YOUR WORK HAS
BEEN FOCUSED ON THE GROWTH OF
PRIMARY TUMOR.
INHIBITING TUMOR VOLUME AND
REGRESSION.
DO YOU HAVE A SIGNAL ON WHAT IT
MEANS FOR METASTATIC OR
REOCCURRING?
>>THAT IS A GOOD QUESTION.
WE DON'T WORK ON METASTATIC
DISEASE.
A LOT OF THE B-B-B IS ALREADY
PERM ABLE.
THEY HAVE THE OPPOSITE PROBLEM
OF PRIMARY AGREE OMAHA.
-- GLIOMA.A QUESTION ABOUT DISTE
PRIMARY SITE.
SO ONE OF MY FIRST SLIDES WAS
ABOUT THE DIFFERENCE OF THE BBB
HETEROGENEITY.
WE'RE STILL EXAMINING HOW DO WE
IMPROVE DELIVERY COMPARED TO THE
CORE OF THE TUMOR WHERE THERE IS
NO PROBLEM.
THAT KEEPS US WORKING AND BUSY.
>>ANOTHER QUESTION CAME IN
THROUGH THE VIDEO CAST.
VERY NICE TALK ON A TOUGH
PROBLEM.
CAN YOU PLEASE COMMENT ON THE
STATUS OF FOCUS ULTRASOUND IN
CREATING BLOOD BRAIN BARRIER TO
CHEMICAL THERAPY.
>>FOCUS ULTRASOUND.
THEY'VE BEEN ABLE TO SHOW THAT
YOU CAN INCREASE THE BBB AND
INCREASE THERAPY.
SOME OF THE CAVEATS ARE IT CAN
ONLY GO FOR CERTAIN AREAS OR
REGIONS OF THE TUMOR AND IS NOT
GREAT FOR DISTANT AREAS WHERE
TUMOR CELLS ARE HIDING OUT AND
TELLING OTHER NORMAL BRAIN
CELLS, WE'RE NOT HERE.
IT'S HELPFUL FOR ONE SITE OF
DISEASE.
BUT THOSE TUMOR CELLS ARE
INFILTRATE I HAVE AND THE FOCUS
ULTRASOUND ARE NOT HELPFUL FOR
DISEASE THROUGHOUT THE BRAIN.
*
>>DO WE HAVE ANY QUESTIONS FROM
THE AUDIENCE?
>>HI, SADHANA.
THANK YOU FOR A WONDERFUL
PRESENTATION.
I WAS CURIOUS WITH YOUR MICRO
DIALYSIS SET UP ARE YOU ABLE TO
COMBINE SOMETHING WITH
CONVECTION ENHANCED DELIVERY?
>>A LOT OF PEOPLE ASK THAT.
THIS IS JUST A ONE WAY TOOL FOR
US TO LOOK AT OUTPUT FROM THE
BRAIN.
CONVECTION ENHANCED DELIVERY,
THEY PLACE THAT AND THEY CAN
DELIVER THERAPIES TO THE BRAIN.
ONE DISADVANTAGES IS DEPENDING
ON HOW FAST OR HOW MUCH DRUG
VOLUME IS ABLE TO GET TO THE
TUMOR IT ONLY GOES TO THAT ONE
AREA.
WE SEE DISTANT SITE AREAS THAT
HAVE TUMOR CELLS THAT ARE THERE
AND SO THE CONVECTION ENHANCED
DELIVERY TOOL DOES A --
>>QUESTION FOR YOU -- WITH THE
DISCUSSION ABOUT NEW VACCINE
DOES YOUR WORK PLAY A ROLE IN
HELPING TO DELIVER TO TARGET
CELLS?
>>WE HAVE NOT LOOKED AT THAT
JUST YET BUT IT WOULD BE GREAT
TO PAIR WITH A GROUP TO SEE WHAT
THE DISTRIBUTION OF THE VACCINE
THERAPY IS AND WHAT HAPPENS TO
THE ENDO THIEL YUM AT THE TIME
OF JUST INITIAL TREATMENT VERSUS
PROLONG GOINGS OF DISEASE *
PROGRESSION OR IMMUNE SYSTEM
CHANGES.
>>SO IT WOULD BE GREAT.
I JUST TALKED ABOUT IT IN THE
CONTEXT TODAY OF CHEMOTHERAPY.
THERE ARE IMMUNE THERAPIES AND
NONOH CLONAL THERAPIES THAT I
THINK WILL HAVE DIFFERENT
SPLASHES THAT WE HAVE NOT --
>>THANK YOU.
>>I WANT TO SAY THANK YOU VERY
MUCH FOR YOUR WORK.
THANK YOU VERY MUCH.
>>THANK YOU.