1 00:00:11,440 --> 00:00:13,640 Welcome to the Clinical Center Grand Rounds, 2 00:00:13,640 --> 00:00:17,440 a weekly series of educational lectures for physicians and 3 00:00:17,440 --> 00:00:20,080 health care professionals broadcast from the Clinical 4 00:00:20,080 --> 00:00:23,040 Center at the National Institutes of Health in 5 00:00:23,040 --> 00:00:24,840 Bethesda, MD. 6 00:00:24,840 --> 00:00:28,400 The NIH Clinical Center is the world's largest hospital totally 7 00:00:28,400 --> 00:00:32,080 dedicated to investigational research and leads the global 8 00:00:32,080 --> 00:00:35,040 effort in training today's investigators and discovering 9 00:00:35,040 --> 00:00:37,200 tomorrow's cures. 10 00:00:37,200 --> 00:00:46,160 Learn more by visiting us online at http://clinicalcenter.nih.gov 11 00:00:46,160 --> 00:00:48,760 TODAY WE ARE HONORED TO HAVE AS 12 00:00:48,760 --> 00:00:51,200 OUR SPEAKER DR. SADHANA JACKSON. 13 00:00:51,200 --> 00:00:55,000 A TENURE TRACK INVESTIGATOR AT 14 00:00:55,000 --> 00:01:02,120 THE SURGICAL NEUROLOGY BRANCH. 15 00:01:02,120 --> 00:01:05,920 SHE RECEIVED HER BACHELOR OF 16 00:01:05,920 --> 00:01:08,480 SCIENCE DEGREE FROM NEW 17 00:01:08,480 --> 00:01:10,240 HAMPSHIRE. 18 00:01:10,240 --> 00:01:12,920 SHE COMPLETED HER TRAINING IN 19 00:01:12,920 --> 00:01:21,400 PEDIATRICS IN ORLANDO, FLORIDA. 20 00:01:21,400 --> 00:01:23,200 FOLLOWING HER FELLOWSHIP SHE 21 00:01:23,200 --> 00:01:25,560 ENTERED INTO A A JOINT 22 00:01:25,560 --> 00:01:29,280 FELLOWSHIP IN PEDIATRIC ONCOLOGY 23 00:01:29,280 --> 00:01:31,960 AT JOHNS HOPKINS UNIVERSITY. 24 00:01:31,960 --> 00:01:36,880 AFTERWARDS IN 2015 DR. JACKSON 25 00:01:36,880 --> 00:01:39,680 JOINED NIH IN THE NEURO ONCOLOGY 26 00:01:39,680 --> 00:01:41,800 BRANCH AND IN 2020 SHE WAS 27 00:01:41,800 --> 00:01:46,520 APPOINTED TO A TENURE TRACK 28 00:01:46,520 --> 00:01:48,120 INVESTIGATOR POSITION IN NINDS 29 00:01:48,120 --> 00:01:49,920 AND NCI. 30 00:01:49,920 --> 00:01:53,280 AS LEAD INVESTIGATOR WITHIN 31 00:01:53,280 --> 00:01:58,880 NINDS DR. JACKSON FOCUSED ON 32 00:01:58,880 --> 00:02:02,520 CHARACTERIZING THE BLOOD BRAIN 33 00:02:02,520 --> 00:02:02,920 BARRIER. 34 00:02:02,920 --> 00:02:09,560 HER LAB STUDIES -- TO THE 35 00:02:09,560 --> 00:02:10,880 ANALYSIS OF THE STRUCTURE OF 36 00:02:10,880 --> 00:02:12,440 FUNCTION AND EXPRESSION WOULD GO 37 00:02:12,440 --> 00:02:14,600 TO TRANSLATE TO OPEN THE BARRIER 38 00:02:14,600 --> 00:02:17,880 AND IMPROVE CHEMO THERAPEUTIC 39 00:02:17,880 --> 00:02:18,280 DELIVERY. 40 00:02:18,280 --> 00:02:22,320 HER TEAMS EAMES TO MODULATE TO 41 00:02:22,320 --> 00:02:25,480 ENHANCE EFFECTIVENESS AND 42 00:02:25,480 --> 00:02:29,240 MAXIMIZE LONG SURVIVAL. 43 00:02:29,240 --> 00:02:31,600 DR. JACKSON IS BOARD CERTIFIED 44 00:02:31,600 --> 00:02:34,600 IN PEDIATRICS AND ONCOLOGY. 45 00:02:34,600 --> 00:02:36,960 SHE IS A LEADER IN THE 46 00:02:36,960 --> 00:02:38,240 COMMUNITY. 47 00:02:38,240 --> 00:02:40,560 AN INITIATIVE TO ADDRESS 48 00:02:40,560 --> 00:02:42,480 STRUCTURAL RACISM. 49 00:02:42,480 --> 00:02:45,960 SHE SERVED AS A COCHAIR OF THE 50 00:02:45,960 --> 00:02:48,440 COMMITTEE AND SERVES AS THE 51 00:02:48,440 --> 00:02:52,280 COMMUNICATION LEAD FOR 8 CHANGES 52 00:02:52,280 --> 00:03:00,360 FOR RACIAL EQUITY. 53 00:03:00,360 --> 00:03:08,400 DR. JACKSON HAS RECEIVED AWARDS 54 00:03:08,400 --> 00:03:12,240 INCLUDING HER WORK FOR AKER. 55 00:03:12,240 --> 00:03:18,800 SHE WAS A 40 UNDER 40 HONOREE IN 56 00:03:18,800 --> 00:03:22,680 2021 AND WAS NOMINATED FOR 57 00:03:22,680 --> 00:03:24,360 SCIENTISTS AND ENGINEERS IN TO 58 00:03:24,360 --> 00:03:24,800 20. 59 00:03:24,800 --> 00:03:27,520 NOW PLEASE JOIN ME IN WELCOMING 60 00:03:27,520 --> 00:03:29,800 TODAY'S GRAND ROUND SPEAKER 61 00:03:29,800 --> 00:03:32,440 DR. SADHANA JACKSON FOR HER 62 00:03:32,440 --> 00:03:35,040 PRESENTATION BLOOD TUMOR BARRIER 63 00:03:35,040 --> 00:03:39,800 AND CLINICAL RELEVANCE. 64 00:03:39,800 --> 00:03:42,120 >>THANK YOU SO MUCH FORGIVING 65 00:03:42,120 --> 00:03:43,880 ME THE OPPORTUNITY FOR ME TO 66 00:03:43,880 --> 00:03:46,160 PRESENT MY RESEARCH TODAY AND I 67 00:03:46,160 --> 00:03:48,560 AGREE THAT BLOOD BRAIN BARRIER 68 00:03:48,560 --> 00:03:51,880 BIOLOGY IS VERY HARD TO SAY OVER 69 00:03:51,880 --> 00:03:53,280 AND OVER. 70 00:03:53,280 --> 00:03:55,160 SO I WILL BE DISCUSSING TODAY 71 00:03:55,160 --> 00:03:58,680 NEW PERSPECTIVES ON DRUG 72 00:03:58,680 --> 00:04:00,920 DELIVERY AND CLINICAL RELEVANCE. 73 00:04:00,920 --> 00:04:04,000 I WILL DISCUSS AN OFF LABEL USE 74 00:04:04,000 --> 00:04:07,160 BUT I'M NOT RECEIVING ANY 75 00:04:07,160 --> 00:04:10,200 FEEDBACK OR MONEY FOR THAT. 76 00:04:10,200 --> 00:04:15,200 WE WILL ENTAIL -- OUTLINING THE 77 00:04:15,200 --> 00:04:17,720 CHALLENGES AND TO EVALUATE 78 00:04:17,720 --> 00:04:23,040 STUDIES AIMED AT ENHANCING 79 00:04:23,040 --> 00:04:25,880 VARIABILITY AND TO EXAMINE THE 80 00:04:25,880 --> 00:04:30,240 ROLE OF NEURO PHARMACOKINETICS 81 00:04:30,240 --> 00:04:32,800 FOR PATIENTS. 82 00:04:32,800 --> 00:04:36,720 WE'RE FOCUSES ON CHILDREN AND 83 00:04:36,720 --> 00:04:39,880 YOUNG ADULTS AND SPELL WITHIN MY 84 00:04:39,880 --> 00:04:44,760 LAB * AND CLINICAL RESEARCH WE 85 00:04:44,760 --> 00:04:48,960 EXPERIENCE THIS AS IT RELATES TO 86 00:04:48,960 --> 00:04:49,680 HIGH GRADE. 87 00:04:49,680 --> 00:04:53,640 THIS IS A YOUNG CHILD OR YOUNG 88 00:04:53,640 --> 00:05:01,920 ADULT WITH WITH HIGH GRADE 89 00:05:01,920 --> 00:05:03,080 GLLOMA. 90 00:05:03,080 --> 00:05:05,440 WHY WE CARE SO MUCH IS THE 91 00:05:05,440 --> 00:05:07,440 SURVIVAL IS SO POOR IN CHILDREN 92 00:05:07,440 --> 00:05:11,720 AND ADOLESCENTS 0-19 YEARS OF 93 00:05:11,720 --> 00:05:11,880 AGE. 94 00:05:11,880 --> 00:05:15,560 YOU CAN SEE THAT JUST STARTING 95 00:05:15,560 --> 00:05:19,240 IN 2004 TO 2017 A TWO-YEAR 96 00:05:19,240 --> 00:05:22,600 SURVIVAL RATE IS LESS THAN 50%. 97 00:05:22,600 --> 00:05:24,920 AROUND 30% AND THERE HAS NOT 98 00:05:24,920 --> 00:05:26,400 BEEN IMPROVEMENT THROUGHOUT ALL 99 00:05:26,400 --> 00:05:28,000 OF THESE DECADES. 100 00:05:28,000 --> 00:05:29,560 SADLY WE PROVIDE EVERYTHING IN 101 00:05:29,560 --> 00:05:31,880 TERMS OF THERAPY FOR THESE 102 00:05:31,880 --> 00:05:32,120 PATIENTS. 103 00:05:32,120 --> 00:05:36,080 WE HAVE THE NEURO SURGEONS THAT 104 00:05:36,080 --> 00:05:38,120 PROVIDE SAFE RESECTION. 105 00:05:38,120 --> 00:05:42,000 WE HAVE RADIATION ONCOLOGIST. 106 00:05:42,000 --> 00:05:45,880 AND THEN MYSELF ONCOLOGIST WE 107 00:05:45,880 --> 00:05:47,440 PROVIDE CHEMOTHERAPY AND STILL 108 00:05:47,440 --> 00:05:51,520 THE SURVIVAL CURVE IS BLEAK AND 109 00:05:51,520 --> 00:05:51,760 DISMAL. 110 00:05:51,760 --> 00:05:54,160 ONE OF THE ROPES FOR WHY THIS IS 111 00:05:54,160 --> 00:05:57,880 SO POOR IS THE BLOOD BRAIN 112 00:05:57,880 --> 00:06:01,160 BARRIER OR BLOOD TUMOR BARRIER. 113 00:06:01,160 --> 00:06:02,440 WHO CARES? 114 00:06:02,440 --> 00:06:04,080 IT'S ALREADY DISRUPTED AND WE 115 00:06:04,080 --> 00:06:05,680 CAN GET THERAPY THERE. 116 00:06:05,680 --> 00:06:07,640 SO THERE IS A YES COMPONENT. 117 00:06:07,640 --> 00:06:09,160 BECAUSE AS YOU LOOK AT THE CORE 118 00:06:09,160 --> 00:06:11,040 OF THE TUMOR YOU CAN SEE THAT 119 00:06:11,040 --> 00:06:14,680 IT'S A PERMEABLE BBB WHERE 120 00:06:14,680 --> 00:06:17,440 REFLECTED HERE IN BLUE ARE THE 121 00:06:17,440 --> 00:06:19,680 DRUG MOLECULES THAT GET OUT TO 122 00:06:19,680 --> 00:06:24,640 THESE AGGRESSIVE PEACH GLLOMA 123 00:06:24,640 --> 00:06:24,840 CELLS. 124 00:06:24,840 --> 00:06:27,200 YOU CAN SEE THAT THE THERAPY 125 00:06:27,200 --> 00:06:29,760 GETS TO THE TUMOR CELLS IN THE 126 00:06:29,760 --> 00:06:32,960 CORE OF THE TUMOR. 127 00:06:32,960 --> 00:06:35,080 IN THE CELLS THAT ARE DISRUPTED 128 00:06:35,080 --> 00:06:38,200 THE PARASITES SEEN HERE IN GREEN 129 00:06:38,200 --> 00:06:40,280 THAT COMMUNICATE AND THEY ARE 130 00:06:40,280 --> 00:06:42,080 ALSO VERY POOR COMMUNICATION AND 131 00:06:42,080 --> 00:06:44,320 THE THERAPY IS ABLE TO GET THERE 132 00:06:44,320 --> 00:06:47,520 AS WELL AS THIS PROCESS THAT 133 00:06:47,520 --> 00:06:51,960 DOES NOT HOLD TIGHT TO KEEP THIS 134 00:06:51,960 --> 00:06:54,480 BLOOD BRAIN BARRIER INTACT. 135 00:06:54,480 --> 00:06:56,160 SO WHILE THIS IS AN ISSUE IN THE 136 00:06:56,160 --> 00:06:59,360 CORE OF THE TUMOR IN THE PERRY 137 00:06:59,360 --> 00:07:02,680 TUMOR AREA WE HAVE MORE OF AN 138 00:07:02,680 --> 00:07:05,160 INTACT BLOOD BRAIN BARRIER WHERE 139 00:07:05,160 --> 00:07:07,600 THE CELLS ARE CLOSER TOGETHER 140 00:07:07,600 --> 00:07:10,480 AND THE PROCESSES HAVE BETTER 141 00:07:10,480 --> 00:07:10,880 COMMUNICATION. 142 00:07:10,880 --> 00:07:12,920 HOWEVER THESE TUMOR CELLS ARE 143 00:07:12,920 --> 00:07:15,760 STILL HIDING OUT HERE IN THE 144 00:07:15,760 --> 00:07:17,840 NORMAL TYPE BRAIN MIXTURE AS 145 00:07:17,840 --> 00:07:21,440 WELL AS WE GO TO THE DISTAL SITE 146 00:07:21,440 --> 00:07:24,680 AREAS OF THE BRAIN WE HAVE AN 147 00:07:24,680 --> 00:07:26,320 IMPERMEABLE BBB. 148 00:07:26,320 --> 00:07:30,520 THIS BECOMES A BIG CHALLENGE. 149 00:07:30,520 --> 00:07:32,760 FOR THERAPIES OF SURGICAL 150 00:07:32,760 --> 00:07:35,040 RESECTION, RADIATION AND 151 00:07:35,040 --> 00:07:38,240 CHEMOTHERAPY THAT USUALLY ONLY 152 00:07:38,240 --> 00:07:41,240 GETS TO THE CORE AND SIX TO 12 153 00:07:41,240 --> 00:07:44,800 MONTHS LATER WE'LL SEE 154 00:07:44,800 --> 00:07:45,200 RECURRENCE. 155 00:07:45,200 --> 00:07:47,080 THAT IS LIKELY BECAUSE OF 156 00:07:47,080 --> 00:07:50,880 THERAPY UNABLE TO GET TO THESE 157 00:07:50,880 --> 00:07:53,280 AREAS THESE TUMOR CELLS ARE ABLE 158 00:07:53,280 --> 00:07:55,840 TO REGROW AND SCOFF AT THE FACT 159 00:07:55,840 --> 00:07:58,040 THAT WE GIVE REPEAT THERAPIES TO 160 00:07:58,040 --> 00:07:59,200 THIS AREA. 161 00:07:59,200 --> 00:08:02,080 SO IT REALLY DRIVES THE REASON 162 00:08:02,080 --> 00:08:05,800 FOR WHY WE HAVE BAD PROGNOSIS 163 00:08:05,800 --> 00:08:07,080 FOR THESE PATIENTS. 164 00:08:07,080 --> 00:08:11,800 WE HAVE THIS HETEROGENEITY OF 165 00:08:11,800 --> 00:08:15,200 THE PERMEABILITY OF THESE DRUGS. 166 00:08:15,200 --> 00:08:17,880 IT MOTIVATES OUR RESEARCH 167 00:08:17,880 --> 00:08:24,080 STUDIES TO FOCUS ON THREE MAIN 168 00:08:24,080 --> 00:08:27,440 AIMS. 169 00:08:27,440 --> 00:08:38,240 OUR ATHAT IS WHAT I CALL KILLINO 170 00:08:40,040 --> 00:08:42,320 BIRDS WITH ONE STONE BUT I DON'T 171 00:08:42,320 --> 00:08:44,760 LIKE TO TALK ABOUT KILLING AS A 172 00:08:44,760 --> 00:08:47,480 VEGETARIAN. 173 00:08:47,480 --> 00:08:49,640 AND THEN 3 WE THINK ABOUT HOW 174 00:08:49,640 --> 00:08:51,520 MUCH DRUG GETS TO THESE AREAS. 175 00:08:51,520 --> 00:08:55,440 SO WE LIKE TO DETERMINE THE 176 00:08:55,440 --> 00:08:58,080 PENETRATION OF CURRENT AGENTS 177 00:08:58,080 --> 00:09:05,760 AND WE USE THIS COOL TOOL. 178 00:09:05,760 --> 00:09:09,760 SO TODAY WE'LL DETAIL A BENCH TO 179 00:09:09,760 --> 00:09:11,680 BEDSIDE BACK TO BENCH 180 00:09:11,680 --> 00:09:13,440 TRANSLATIONAL RESEARCH STUDY 181 00:09:13,440 --> 00:09:18,280 WHERE I'M TALKING ABOUT A DRUG 182 00:09:18,280 --> 00:09:22,800 CALLED REGADENOSON. 183 00:09:22,800 --> 00:09:33,000 RESIGNATION. 184 00:09:43,680 --> 00:09:53,880 -- RESIGNATION. 185 00:09:58,000 --> 00:10:01,880 -- *. 186 00:10:01,880 --> 00:10:03,960 IN MY SENIOR YEAR I TOOK THE 187 00:10:03,960 --> 00:10:05,760 METRO OR THE BUS. 188 00:10:05,760 --> 00:10:07,320 I DIDN'T DRIVE AND I CAME DOWN 189 00:10:07,320 --> 00:10:10,160 TO THE NIH AND I WORKED IN THE 190 00:10:10,160 --> 00:10:12,400 NCI LABS. 191 00:10:12,400 --> 00:10:14,760 SO THAT EXPERIENCE JUST GOT ME 192 00:10:14,760 --> 00:10:16,640 SO EXCITED ABOUT CANCER RESEARCH 193 00:10:16,640 --> 00:10:19,240 AND BEING A CLINICIAN SCIENTISTS 194 00:10:19,240 --> 00:10:22,560 THAT I APPLIED FOR THIS NIH 195 00:10:22,560 --> 00:10:24,280 SCHOLARSHIP PROGRAM. 196 00:10:24,280 --> 00:10:27,600 THAT AFFORDED ME THE A 197 00:10:27,600 --> 00:10:28,840 AVAILABILITY TO RECEIVE MONIES 198 00:10:28,840 --> 00:10:31,040 TO ATTEND HAMPTON UNIVERSITY FOR 199 00:10:31,040 --> 00:10:33,200 THE FIRST TWO YEARS, THEY GAVE 200 00:10:33,200 --> 00:10:35,600 ME ROOM AND BOARD AND I WAS ABLE 201 00:10:35,600 --> 00:10:37,720 TO COME BACK AND WORK DURING THE 202 00:10:37,720 --> 00:10:44,080 SUMMERS AT THE NIH WITHIN NIDCD. 203 00:10:44,080 --> 00:10:45,320 AND I LOVED IT. 204 00:10:45,320 --> 00:10:50,160 SO THE SUMMERS I WAS AN NIH 205 00:10:50,160 --> 00:10:52,080 EMPLOYEE AND I LOVED IT. 206 00:10:52,080 --> 00:10:54,000 NOW ONE OF THE SERVICE 207 00:10:54,000 --> 00:10:56,080 REQUIREMENTS WAS THAT I NEEDED 208 00:10:56,080 --> 00:10:59,240 TO COME BACK AND WORK AT THE NIH 209 00:10:59,240 --> 00:11:01,240 AFTER ALL OF MY TRAINING. 210 00:11:01,240 --> 00:11:03,640 AND SO I KNEW I WANTED TO GO TO 211 00:11:03,640 --> 00:11:05,560 MEDICAL SCHOOL AND BE AN 212 00:11:05,560 --> 00:11:08,000 ONCOLOGIST SO I DID THIS 213 00:11:08,000 --> 00:11:10,400 TRAINING TO BE A PEDIATRIC 214 00:11:10,400 --> 00:11:12,640 ONCOLOGIST AND IN 2015 I 215 00:11:12,640 --> 00:11:16,160 RETURNED TO THE NIH TO NCI AND 216 00:11:16,160 --> 00:11:18,320 I'M EXCITED TO BE HERE AND I 217 00:11:18,320 --> 00:11:19,560 TALK ABOUT THE JOB THAT I HAVE 218 00:11:19,560 --> 00:11:22,160 TODAY I OBTAINED THAT JOB AT THE 219 00:11:22,160 --> 00:11:24,080 AGE OF 17 AND HERE I AM NOW 220 00:11:24,080 --> 00:11:26,320 STILL WORKING HERE AND HAPPY TO 221 00:11:26,320 --> 00:11:29,000 HAVE RECEIVED THE NIH 222 00:11:29,000 --> 00:11:31,600 DISTINGUISHED SCHOLAR BEING PART 223 00:11:31,600 --> 00:11:34,960 OF THE FIRST INAUGURAL CLASS AND 224 00:11:34,960 --> 00:11:37,440 NOW CONTINUED IN 2023. 225 00:11:37,440 --> 00:11:40,120 SO I SAY THAT TO SAY THAT I HAD 226 00:11:40,120 --> 00:11:42,120 THIS CURIOSITY AND PASSION 227 00:11:42,120 --> 00:11:43,800 AROUND CANCER RESEARCH AND 228 00:11:43,800 --> 00:11:45,280 CLINICAL INVESTIGATION AND 229 00:11:45,280 --> 00:11:46,520 LABORATORY INVESTIGATION SINCE 230 00:11:46,520 --> 00:11:49,160 1998 AND PROBABLY EARLIER IF YOU 231 00:11:49,160 --> 00:11:51,600 ASK MY PARENTS AND THAT LEADS 232 00:11:51,600 --> 00:11:52,960 INTO THE CLINICAL AND 233 00:11:52,960 --> 00:11:53,840 TRANSLATIONAL RESEARCH THAT I 234 00:11:53,840 --> 00:11:56,120 HAVE ONGOING IN MY LAB AND WITH 235 00:11:56,120 --> 00:11:56,920 MY PATIENTS. 236 00:11:56,920 --> 00:11:59,840 SO IN THINKING ABOUT THAT I'M 237 00:11:59,840 --> 00:12:04,000 USING -- WE USED A CARDIAC 238 00:12:04,000 --> 00:12:08,440 STRESS DRUG CALLED REGADENOSON. 239 00:12:08,440 --> 00:12:11,800 AND IT SPECIFICALLY WORKS ON THE 240 00:12:11,800 --> 00:12:15,280 A2A RECEPTOR TO AGONIZE THIS 241 00:12:15,280 --> 00:12:16,680 RECEPTOR. 242 00:12:16,680 --> 00:12:19,200 TO INCREASE AMP. 243 00:12:19,200 --> 00:12:21,920 IT INCREASES VASCULAR SMOOTH 244 00:12:21,920 --> 00:12:23,920 RELAXATION AND NET CARDIAC 245 00:12:23,920 --> 00:12:24,520 PROFUSION. 246 00:12:24,520 --> 00:12:26,160 SO ALL THAT MEANS IS WHEN YOU GO 247 00:12:26,160 --> 00:12:29,440 TO THE DOCTOR AND YOU SAY I'M 248 00:12:29,440 --> 00:12:31,680 HAVING SOME CHEST PAIN THEY ARE 249 00:12:31,680 --> 00:12:33,680 ABLE TO HAVE YOU WALK ON A 250 00:12:33,680 --> 00:12:35,000 TREADMILL LIKE THIS INDIVIDUAL 251 00:12:35,000 --> 00:12:36,680 HERE SO THAT THEY CAN SEE WHAT 252 00:12:36,680 --> 00:12:39,880 THE FUNCTION AND THE 253 00:12:39,880 --> 00:12:40,880 PERMEABILITY OF THE VESTIBLES 254 00:12:40,880 --> 00:12:42,200 ARE AROUND YOUR HEART. 255 00:12:42,200 --> 00:12:44,960 IF YOU'RE UNABLE TO WALK ON THE 256 00:12:44,960 --> 00:12:47,160 TREADMILL THEY GIVE YOU THIS 257 00:12:47,160 --> 00:12:48,800 DRUG REGADENOSON. 258 00:12:48,800 --> 00:12:50,760 THIS REGADENOSON AGENT REALLY 259 00:12:50,760 --> 00:12:53,800 WORKS TO SEE ABOUT PERMEABILITY 260 00:12:53,800 --> 00:12:56,480 AND IT CAUSES BASAL DILATION IN 261 00:12:56,480 --> 00:13:00,680 THE VESSELS AROUND THE HEART. 262 00:13:00,680 --> 00:13:02,720 SO INTERESTING ENOUGH THIS FDA 263 00:13:02,720 --> 00:13:05,240 APPROVED DRUG FOR CARDIAC STRESS 264 00:13:05,240 --> 00:13:08,200 TESTING IN 26% OF PATIENTS IT 265 00:13:08,200 --> 00:13:11,240 CAUSES HEADACHESES BECAUSE THE 266 00:13:11,240 --> 00:13:14,320 BASAL DILATION ALSO CAUSES 267 00:13:14,320 --> 00:13:15,840 DILATION IN THE VESSELS OF THE 268 00:13:15,840 --> 00:13:18,960 BRAIN SO THERE WAS A GROUP OUT 269 00:13:18,960 --> 00:13:20,680 OF CORNELL THAT CAPITALIZED ON 270 00:13:20,680 --> 00:13:22,520 THIS INFORMATION AND THEY SAID 271 00:13:22,520 --> 00:13:24,880 IF WE HAVE BASAL DILATION IN THE 272 00:13:24,880 --> 00:13:28,520 BRAIN I BET THERE IS MORE BBB 273 00:13:28,520 --> 00:13:28,920 PERMEABILITY. 274 00:13:28,920 --> 00:13:31,760 SO THEY LOOKED AT RODENTS 275 00:13:31,760 --> 00:13:34,160 NONTUMOR BEARING RATS AND MICE 276 00:13:34,160 --> 00:13:36,840 AND THEY GAVE THEM THIS DRUG AND 277 00:13:36,840 --> 00:13:39,760 THEY FOUND THEY COULD GET A 278 00:13:39,760 --> 00:13:41,520 MOLECULE WITHIN THE BRAIN OF 279 00:13:41,520 --> 00:13:44,800 THESE NONTUMOR BEARING ANIMALS. 280 00:13:44,800 --> 00:13:48,960 SO WE SAID * IF WE CAN GET THIS 281 00:13:48,960 --> 00:13:51,720 LARGE SUGAR PROTEIN IN WHAT IF 282 00:13:51,720 --> 00:13:54,800 WE COULD GET OUR STANDARD 283 00:13:54,800 --> 00:13:55,760 CHEMOTHERAPY TREATMENT. 284 00:13:55,760 --> 00:13:58,120 WE MEASURED AND LOOKED AT WHAT 285 00:13:58,120 --> 00:14:00,720 REGADENOSON COULD DO TO INCREASE 286 00:14:00,720 --> 00:14:01,960 CONCENTRATION IN THE BRAIN OF 287 00:14:01,960 --> 00:14:05,360 RATS AND WHAT WE FOUND IS IN OUR 288 00:14:05,360 --> 00:14:08,040 NONTUMOR BEARING RATS WE COULD 289 00:14:08,040 --> 00:14:12,160 SEE A 60% INCREASE IN BRAIN 290 00:14:12,160 --> 00:14:14,160 CONCENTRATION WHEN WE MEASURED 291 00:14:14,160 --> 00:14:16,000 IT AND WE COULD SEE THAT TWO 292 00:14:16,000 --> 00:14:18,160 HOURS AFTER WE GAVE THIS 293 00:14:18,160 --> 00:14:20,560 COMBINATION THERE WAS A 60% 294 00:14:20,560 --> 00:14:23,000 INCREASE AND BY SIX HOURS THERE 295 00:14:23,000 --> 00:14:25,440 WAS NOT ENOUGH AN EFFECT OF THE 296 00:14:25,440 --> 00:14:27,800 COMBINES THERAPY SHOWING US THIS 297 00:14:27,800 --> 00:14:29,280 WAS JUST A TRANSIENT EFFECT 298 00:14:29,280 --> 00:14:31,240 WHICH IS GOOD IF WE'RE GOING TO 299 00:14:31,240 --> 00:14:34,320 OPEN THE BBB WE WANT TO HAVE IT 300 00:14:34,320 --> 00:14:35,800 COME BACK TOGETHER AND GO BACK 301 00:14:35,800 --> 00:14:38,040 TO NORMAL AS IF WE DID NOTHING. 302 00:14:38,040 --> 00:14:42,680 WE DON'T WANT THAT TO BE OPEN 303 00:14:42,680 --> 00:14:44,400 AND CAUSE MORE PROBLEMS BECAUSE 304 00:14:44,400 --> 00:14:46,040 THE MAIN PROBLEM IS IF YOU'RE 305 00:14:46,040 --> 00:14:48,560 GOING TO OPEN THE BBB IS THAT 306 00:14:48,560 --> 00:14:50,360 GOING TO CAUSE FOR MORE BAD 307 00:14:50,360 --> 00:14:53,360 THINGS TO GET IN. 308 00:14:53,360 --> 00:14:53,760 POTENTIALLY. 309 00:14:53,760 --> 00:14:56,000 SO THAT IS WHY THE INTEREST IS 310 00:14:56,000 --> 00:14:58,280 TO HAVE A TRANSIENT EFFECT. 311 00:14:58,280 --> 00:15:00,480 SO WE WERE EXCITED ABOUT THESE 312 00:15:00,480 --> 00:15:04,720 FINDINGS. 313 00:15:04,720 --> 00:15:10,520 WHAT IF WE LOOKED AT PATIENTS 314 00:15:10,520 --> 00:15:14,000 THAT HAD HIGH GRADE GLLEOMA. 315 00:15:14,000 --> 00:15:17,640 WOULD WE SEE THAT EFFECT FROM 316 00:15:17,640 --> 00:15:19,680 INCREASED -- ON THEIR BRAIN 317 00:15:19,680 --> 00:15:23,360 TUMORS. 318 00:15:23,360 --> 00:15:32,080 TEMPOROMANDIBULAR. 319 00:15:32,080 --> 00:15:34,840 *. 320 00:15:34,840 --> 00:15:37,320 TEMOZOLOMIDE ALONE ON DAY ONE 321 00:15:37,320 --> 00:15:39,600 AND THEN TEMOZOLOMIDE WITH 322 00:15:39,600 --> 00:15:40,520 REGADENOSON ON DAY TWO. 323 00:15:40,520 --> 00:15:43,960 I WAS AT THE BEDSIDE WITH THESE 324 00:15:43,960 --> 00:15:45,680 PATIENTS WHO HAD BRAIN SURGERY 325 00:15:45,680 --> 00:15:50,200 AND REPLACED THESE CATHETERS. 326 00:15:50,200 --> 00:15:53,600 THEY ARE INTELLIGENT TOOLS. 327 00:15:53,600 --> 00:15:55,560 PLASTIC TUBING THAT THE NURSE 328 00:15:55,560 --> 00:15:57,840 SURGEON PLACES AFTER A SURGICAL 329 00:15:57,840 --> 00:16:00,360 RESECTION AND WE'RE ABLE TO 330 00:16:00,360 --> 00:16:04,480 INFUSE ARTIFICIAL CFF. 331 00:16:04,480 --> 00:16:08,480 AT A VERY SLOW INFUSION RATE. 332 00:16:08,480 --> 00:16:16,080 .5 TO ON ONE MICRO LITER PER MIE 333 00:16:16,080 --> 00:16:23,800 AND WE'RE ABLE TO GAIN FLUID AND 334 00:16:23,800 --> 00:16:25,600 MEASURE TEMOZOLOMIDE 335 00:16:25,600 --> 00:16:27,920 CONCENTRATION. 336 00:16:27,920 --> 00:16:31,240 SO THIS TRIAL WAS A SAFETY AND 337 00:16:31,240 --> 00:16:33,760 FEASIBILITY TRIAL TO SEE COULD 338 00:16:33,760 --> 00:16:37,280 WE SAFELY MEASURE CONCENTRATIONS 339 00:16:37,280 --> 00:16:39,280 INTO THE BRAIN AND DID WE SEE AN 340 00:16:39,280 --> 00:16:41,080 EFFECT WHEN WE GAVE REGADENOSON 341 00:16:41,080 --> 00:16:44,080 SO I WAS AT THE BEDSIDE OF THESE 342 00:16:44,080 --> 00:16:44,600 PATIENTS. 343 00:16:44,600 --> 00:16:47,200 8 A DAY AFTER THEY HAD SURGERY 344 00:16:47,200 --> 00:16:51,760 SO I WAS HAVING MY OWN CARDIAC 345 00:16:51,760 --> 00:16:55,480 STRESS TEST. 346 00:16:55,480 --> 00:17:02,800 ALSO OF INTEREST THESE PATIENTS 347 00:17:02,800 --> 00:17:05,520 COULD NOT HAVE ANY CAFFEINE. 348 00:17:05,520 --> 00:17:07,640 THEY ARE GETTING THIS CARDIAC 349 00:17:07,640 --> 00:17:09,520 STRESS TEST AND THEY CANNOT 350 00:17:09,520 --> 00:17:12,160 DRINK COFFEE SO THEY WERE NOT MY 351 00:17:12,160 --> 00:17:14,400 BEST FRIENDS AT THE END OF THIS 352 00:17:14,400 --> 00:17:14,800 TRIAL. 353 00:17:14,800 --> 00:17:16,760 WE LOOKED AT FIVE TOTAL 354 00:17:16,760 --> 00:17:17,720 PATIENTS. 355 00:17:17,720 --> 00:17:21,200 AND WE DID NOT SEE THE 60% 356 00:17:21,200 --> 00:17:24,520 INCREASE THAT WE EXPECTED. 357 00:17:24,520 --> 00:17:27,600 INSTEAD WE ONLY SAW IN PATIENT 2 358 00:17:27,600 --> 00:17:30,720 AND PATIENT 5 AND LOOKING AT 359 00:17:30,720 --> 00:17:32,480 TEMOZOLOMIDE ALONE OR 360 00:17:32,480 --> 00:17:34,360 TEMOZOLOMIDE WITH REGADENOSON IN 361 00:17:34,360 --> 00:17:40,480 RED THAT THERE WAS AN INCREASE 362 00:17:40,480 --> 00:17:43,880 EARLY AND THAT WAS 55% INCREASE 363 00:17:43,880 --> 00:17:47,840 AREA UNDER THE CURVE AND THEN 2% 364 00:17:47,840 --> 00:17:49,160 UNDER THE CURVE. 365 00:17:49,160 --> 00:17:52,240 BUT IN PATIENTS 1, 3 AND 4 WE 366 00:17:52,240 --> 00:17:54,680 DID NOT APPRECIATE A DIFFERENCE 367 00:17:54,680 --> 00:17:57,120 OR INCREASE WITH REGADENOSON 368 00:17:57,120 --> 00:17:57,520 ADMINISTRATION. 369 00:17:57,520 --> 00:17:59,400 SO WE SAID WE DON'T SEE THAT 370 00:17:59,400 --> 00:18:02,920 INCREASE OF 60%. 371 00:18:02,920 --> 00:18:04,560 WHAT ARE WE MISSING? 372 00:18:04,560 --> 00:18:06,480 WHAT MORE CAN WE LEARN FROM 373 00:18:06,480 --> 00:18:08,080 GOING FROM THE BENCH TO THE 374 00:18:08,080 --> 00:18:08,960 BEDSIDE? 375 00:18:08,960 --> 00:18:10,600 AND SO THAT LED US TO THINK 376 00:18:10,600 --> 00:18:12,560 ABOUT WHAT IS HAPPENING ON THE 377 00:18:12,560 --> 00:18:14,000 CELLULAR LEVEL AND WHAT IS GOING 378 00:18:14,000 --> 00:18:16,720 ON WITH THE TIME DEPENDENCE OF 379 00:18:16,720 --> 00:18:19,080 WHEN REGADENOSON IS GIVEN VERSUS 380 00:18:19,080 --> 00:18:21,280 THE EFFECT AND THEN WHAT HAPPENS 381 00:18:21,280 --> 00:18:22,880 LONG-TERM IF YOU GIVE REPEATED 382 00:18:22,880 --> 00:18:25,640 DOSING OF REGADENOSON IN TUMOR 383 00:18:25,640 --> 00:18:27,120 BEARING ANIMALS. 384 00:18:27,120 --> 00:18:32,120 WE WENT BACK TO THE BENCH AND I 385 00:18:32,120 --> 00:18:34,960 HAVE A FORMER POSTDOC WHERE WE 386 00:18:34,960 --> 00:18:38,120 LOOKED AT TUMOR BEARING RATS AND 387 00:18:38,120 --> 00:18:41,760 THEY WERE GIVEN REGADENOSON WITH 388 00:18:41,760 --> 00:18:42,080 TEMOZOLOMIDE. 389 00:18:42,080 --> 00:18:43,960 WHAT HAPPENS ON THE CELLULAR 390 00:18:43,960 --> 00:18:45,040 LEVEL. 391 00:18:45,040 --> 00:18:46,920 THAT ARE TREATED WITH EITHER 392 00:18:46,920 --> 00:18:48,160 TEMOZOLOMIDE OR TEMOZOLOMIDE 393 00:18:48,160 --> 00:18:49,400 WITH REGADENOSON. 394 00:18:49,400 --> 00:18:51,920 WE WANTED TO KNOW WHAT HAPPENS 395 00:18:51,920 --> 00:18:55,680 TO THE JUNCTIONAL EXPRESSION 396 00:18:55,680 --> 00:18:57,680 AMONG THIS. 397 00:18:57,680 --> 00:19:02,600 THIS IS VERY COMMON THAT KEEPS 398 00:19:02,600 --> 00:19:05,480 THESE CELLS ADD CHEESED TO EACH 399 00:19:05,480 --> 00:19:06,320 OTHER. 400 00:19:06,320 --> 00:19:06,760 *. 401 00:19:06,760 --> 00:19:09,240 WE COULD SEE DECREASED CELL TO 402 00:19:09,240 --> 00:19:12,160 CELL ATTACHMENT WITH THIS 403 00:19:12,160 --> 00:19:14,040 JUNCTIONAL PROTEIN WITHIN THE 404 00:19:14,040 --> 00:19:15,680 TUMOR BUT NO DIFFERENCE IN THE 405 00:19:15,680 --> 00:19:19,840 NORMAL BRAIN SO WE SAID HMMM. 406 00:19:19,840 --> 00:19:22,720 THEN WHEN WE LOOKED AT THE 407 00:19:22,720 --> 00:19:24,840 CONCENTRATION OF TEMOZOLOMIDE 408 00:19:24,840 --> 00:19:26,840 THERE WAS A HIGHER CONCENTRATION 409 00:19:26,840 --> 00:19:28,840 OF TEMOZOLOMIDE IN THE TUMOR SO, 410 00:19:28,840 --> 00:19:31,600 THAT IS THE INJECTED SIDE OF THE 411 00:19:31,600 --> 00:19:33,480 BRAIN OF THE ANIMAL BUT NO 412 00:19:33,480 --> 00:19:36,040 INCREASE IN THE NONTUMOR BEARING 413 00:19:36,040 --> 00:19:37,360 SIDE WHICH IS VERY DIFFERENT 414 00:19:37,360 --> 00:19:40,960 THAN THE 60% INCREASE. 415 00:19:40,960 --> 00:19:44,160 SO WE SAID WE SEE A 40% INCREASE 416 00:19:44,160 --> 00:19:47,760 IN THE TUMOR CONCENTRATION. 417 00:19:47,760 --> 00:19:49,880 DECREASED EXPRESSION. 418 00:19:49,880 --> 00:19:52,040 THIS SHOULD TRANSLATE TO 419 00:19:52,040 --> 00:19:53,840 PROLONGED SURVIVAL, RIGHT? 420 00:19:53,840 --> 00:19:55,160 OF COURSE, NOT. 421 00:19:55,160 --> 00:19:59,240 THERE WAS NO PROLONGED MODEL 422 00:19:59,240 --> 00:20:02,960 SURVIVAL WHEN GIVEN TEMOZOLOMIDE 423 00:20:02,960 --> 00:20:05,120 ALONE VERSUS TEMOZOLOMIDE WITH 424 00:20:05,120 --> 00:20:05,520 REGADENOSON. 425 00:20:05,520 --> 00:20:08,040 SO EVEN WITH REPEAT TREATMENT WE 426 00:20:08,040 --> 00:20:14,960 DID NOT SEE THAT PROLONG GOINGS 427 00:20:14,960 --> 00:20:15,720 *. 428 00:20:15,720 --> 00:20:17,960 WHAT WE WERE ABLE TO LEARN THE 429 00:20:17,960 --> 00:20:19,200 THREE MAIN TAKE AWAYS. 430 00:20:19,200 --> 00:20:25,040 THE TIMING OF THE BBB -- BTB 431 00:20:25,040 --> 00:20:27,760 DISRUPTION TRULY MATTERS. 432 00:20:27,760 --> 00:20:32,680 WE SHOULD NOT JUST FOCUS ON 433 00:20:32,680 --> 00:20:38,160 BRAIN ENDOTHELIAL. 434 00:20:38,160 --> 00:20:40,760 AND THAT IT'S REALLY IMPORTANT 435 00:20:40,760 --> 00:20:42,240 TO UNDERSTAND HOW MUCH DRUG GETS 436 00:20:42,240 --> 00:20:44,520 TO THE TUMOR AND NONTUMOR 437 00:20:44,520 --> 00:20:46,520 REGIONS TO SAY IF THE DRUG IS 438 00:20:46,520 --> 00:20:48,760 REALLY EFFECTIVE AND HOW TO GO 439 00:20:48,760 --> 00:20:49,120 FORWARD. 440 00:20:49,120 --> 00:20:54,880 SO THAT LEADS REALLY NICELY INTO 441 00:20:54,880 --> 00:21:01,280 OUR AIM TWO. 442 00:21:01,280 --> 00:21:05,080 BUT LOOKING AT COMMON SIGNALING 443 00:21:05,080 --> 00:21:09,240 PATHWAYS BOTH IN GLEOMA CELLS 444 00:21:09,240 --> 00:21:12,360 AND THE BBB. 445 00:21:12,360 --> 00:21:16,560 SO WHEN YOU THINK ABOUT THE 446 00:21:16,560 --> 00:21:21,000 BRAIN ENDO THEME YUM -- AND A 447 00:21:21,000 --> 00:21:24,320 LOT OF TIMES THEY ARE BUY 448 00:21:24,320 --> 00:21:27,200 CELLULAR OR TRY CELLULAR 449 00:21:27,200 --> 00:21:31,000 JUNCTION PROTEINS. 450 00:21:31,000 --> 00:21:35,920 THEY ARE CLOUD IN 5 AND THAT IS 451 00:21:35,920 --> 00:21:39,240 SEEN HERE IN PURPLE AND THAT 452 00:21:39,240 --> 00:21:41,120 KEEPS THE CELLS TIGHT TOGETHER 453 00:21:41,120 --> 00:21:45,240 BUT THERE ARE TWO OTHER PROTEINS 454 00:21:45,240 --> 00:21:47,960 THAT ARE INTEGRAL. 455 00:21:47,960 --> 00:21:50,880 THOSE ARE TRY CELLULAR SEEN HERE 456 00:21:50,880 --> 00:21:52,600 IN YELLOW AND GREEN. 457 00:21:52,600 --> 00:21:54,240 THERE IS HIGH EXPRESSION FOR 458 00:21:54,240 --> 00:21:58,280 THESE TRY CELLULAR JUNCTIONS. 459 00:21:58,280 --> 00:22:02,000 THIS HELPS TO RECRUIT TRY 460 00:22:02,000 --> 00:22:05,440 CELLULAR TO FORM BBB TYPE 461 00:22:05,440 --> 00:22:06,600 CELLULAR JUNCTIONS. 462 00:22:06,600 --> 00:22:08,600 THIS EXPRESSIONS HIGH WITHIN THE 463 00:22:08,600 --> 00:22:10,760 BRAIN AND WITHIN THE GUT. 464 00:22:10,760 --> 00:22:19,400 AND INTERESTING ENOUGH IS THAT 465 00:22:19,400 --> 00:22:29,640 ANGLIN ONE * -- ALSO IS ANOTHER 466 00:22:29,640 --> 00:22:39,920 NAME IS -- LSR. 467 00:22:41,480 --> 00:22:44,000 SO, IT'S NOT JUST PRESENT IN 468 00:22:44,000 --> 00:22:46,680 THESE CELLS TO CAUSE FOR 469 00:22:46,680 --> 00:22:48,240 INCREASED TYPE JUNCTIONAL 470 00:22:48,240 --> 00:22:50,040 ADHESION BUT ALSO IN THESE 471 00:22:50,040 --> 00:22:50,880 NORMAL CELLS. 472 00:22:50,880 --> 00:22:54,080 SO WHEN WE LOOKED IN THE CCGA 473 00:22:54,080 --> 00:22:57,520 AND THE TCGA THERE WAS HIGH 474 00:22:57,520 --> 00:22:59,320 EXPRESSION ALSO WITHIN HIGH 475 00:22:59,320 --> 00:23:02,680 GRADE GLEOMA SPECIFICALLY GRADE 476 00:23:02,680 --> 00:23:06,000 4 AND HIGH IN YOUNG ADULTS LESS 477 00:23:06,000 --> 00:23:07,880 THAN 47 YEARS OF AGE. 478 00:23:07,880 --> 00:23:08,280 *. 479 00:23:08,280 --> 00:23:10,520 AS YOU CAN SEE HERE THERE IS 480 00:23:10,520 --> 00:23:12,840 HIGHER EXPRESSION IN LESS THAN 481 00:23:12,840 --> 00:23:16,680 47 YEARS OF AGE GENE EXPRESSION, 482 00:23:16,680 --> 00:23:19,440 7.5 IN COMPARISON TO GREATER 483 00:23:19,440 --> 00:23:20,760 THAN 47 YEARS OF AGE. 484 00:23:20,760 --> 00:23:21,720 SO OKAY. 485 00:23:21,720 --> 00:23:24,840 I'M A PEDIATRIC ONCOLOGIST WE'RE 486 00:23:24,840 --> 00:23:27,080 SEEING THIS ANGLIN ONE 487 00:23:27,080 --> 00:23:27,720 EXPRESSION. 488 00:23:27,720 --> 00:23:30,200 IT'S HIGH IN THESE TUMOR CELLS 489 00:23:30,200 --> 00:23:32,000 IN THIS YOUNG ADULT POPULATION. 490 00:23:32,000 --> 00:23:34,240 THIS IS SOMETHING THAT I CAN GO 491 00:23:34,240 --> 00:23:34,440 AFTER. 492 00:23:34,440 --> 00:23:35,880 WHAT IS IN THE LITERATURE AND 493 00:23:35,880 --> 00:23:38,040 WHAT HAS BEEN DONE SO FAR? 494 00:23:38,040 --> 00:23:40,120 THERE WAS A GROUP OUT OF JAPAN 495 00:23:40,120 --> 00:23:45,320 THAT USED OR CREATED AN AGENT 496 00:23:45,320 --> 00:23:55,640 CALLED ANGUBIDIN. 497 00:23:58,360 --> 00:24:02,840 THEY CREATED THIS AMINO ACID 498 00:24:02,840 --> 00:24:04,320 COMPLEX THAT BINDS AND THEY WERE 499 00:24:04,320 --> 00:24:07,520 ABLE TO INHIBIT THE FUNCTION AND 500 00:24:07,520 --> 00:24:09,840 EXPRESSION SO AS TO ALLOW FOR 501 00:24:09,840 --> 00:24:14,720 INCREASED PASSAGE OF THEIR -- 502 00:24:14,720 --> 00:24:18,680 NUCLEO TIDE AGAINST CARCINOMA. 503 00:24:18,680 --> 00:24:29,280 * AND DECREASE THE EXPRESSION OF 504 00:24:29,920 --> 00:24:30,280 MALAT-RNA. 505 00:24:30,280 --> 00:24:36,240 THEY COULD SEE A DECREASE IN THE 506 00:24:36,240 --> 00:24:38,000 EXPRESSION AND THEY COULD SEE 507 00:24:38,000 --> 00:24:40,560 THAT IN THE BRAIN AND THE 508 00:24:40,560 --> 00:24:44,040 CERVICAL AND LUMBAR SPINAL CORD. 509 00:24:44,040 --> 00:24:46,480 IT ONLY TOOK TWO HOURS TO SEE A 510 00:24:46,480 --> 00:24:47,440 SIGNIFICANT EFFECT. 511 00:24:47,440 --> 00:24:49,320 SO WE SAID THAT IS INTERESTING. 512 00:24:49,320 --> 00:24:51,000 WHAT IF WE DID THE SAME BUT WE 513 00:24:51,000 --> 00:24:55,080 LOOKED AT IT IN THE CONTEXT OF 514 00:24:55,080 --> 00:24:57,440 OUR CHEMOTHERAPY OF INTEREST. 515 00:24:57,440 --> 00:25:01,880 SO WE HYPOTHESIZED THAT IT WILL 516 00:25:01,880 --> 00:25:04,320 ENHANCE CONCENTRATION AND 517 00:25:04,320 --> 00:25:10,720 THROUGH BBB/BTB CHANGES. 518 00:25:10,720 --> 00:25:14,560 IT'S HIGHLY EXPRESSED IN GLEOMA 519 00:25:14,560 --> 00:25:14,760 CELLS. 520 00:25:14,760 --> 00:25:21,880 WITH THE WORK OF TWO PO POST BAS 521 00:25:21,880 --> 00:25:27,880 IN THE LAB -- * THEY CREATED AND 522 00:25:27,880 --> 00:25:33,120 BIDEN FOR US. 523 00:25:33,120 --> 00:25:35,280 ANGUBINDIN FOR US. 524 00:25:35,280 --> 00:25:37,680 * THIS TIME WE WANTED TO USE AN 525 00:25:37,680 --> 00:25:39,600 AGENT THAT WE KNOW DOES NOT 526 00:25:39,600 --> 00:25:42,120 CROSS INTO THE BLOOD BRAIN 527 00:25:42,120 --> 00:25:44,160 BARRIER VERY WELL AND IT SERVES 528 00:25:44,160 --> 00:25:47,800 AS A SUBSTRATE FOR PROTEIN WHICH 529 00:25:47,800 --> 00:25:51,560 IS A VERY IMPORTANT ABC 530 00:25:51,560 --> 00:25:53,120 TRANSPORTER WITHIN THE BLOOD 531 00:25:53,120 --> 00:25:54,080 BRAIN BARRIER. 532 00:25:54,080 --> 00:25:56,200 SO WE WANTED TO SEE IF WE COULD 533 00:25:56,200 --> 00:25:58,640 OVERCOME THE CHALLENGE OF NOT 534 00:25:58,640 --> 00:26:04,480 JUST BBB PERMEABILITY BUT ALSO 535 00:26:04,480 --> 00:26:07,400 E. FLUX TRANSPORTERS. 536 00:26:07,400 --> 00:26:11,200 THIS SEEN HERE IN BLUE IS THE 537 00:26:11,200 --> 00:26:13,600 DOXIL. 538 00:26:13,600 --> 00:26:16,120 SO AS A CLINICIAN IT'S IMPORTANT 539 00:26:16,120 --> 00:26:17,800 TO THINK ABOUT IF YOU'RE GOING 540 00:26:17,800 --> 00:26:20,280 TO THINK ABOUT A PROTEIN OR GENE 541 00:26:20,280 --> 00:26:21,920 OF INTEREST WHAT CAN YOU LEARN 542 00:26:21,920 --> 00:26:24,360 FROM JUST LOOKING AT SURVIVAL 543 00:26:24,360 --> 00:26:26,560 CURVES IN EXPRESSION FOR 544 00:26:26,560 --> 00:26:31,520 PATIENTS WITH GLIAL BLAST TOMA. 545 00:26:31,520 --> 00:26:39,680 * SO WHAT IS THE SURVIVAL LIKE? 546 00:26:39,680 --> 00:26:43,280 SO I FIRST WAS OH, NO IF 547 00:26:43,280 --> 00:26:45,720 PATIENTS HAVE A HIGH EXPRESSION 548 00:26:45,720 --> 00:26:48,280 WHILE SURVIVAL IS BLEAK IT STILL 549 00:26:48,280 --> 00:26:50,320 LOOKS LIKE THEY DO BETTER IF 550 00:26:50,320 --> 00:26:52,240 THEY HAVE A HIGHER EXPRESSION SO 551 00:26:52,240 --> 00:26:54,560 WHAT DOES IT LOOK LIKE IF I AM 552 00:26:54,560 --> 00:27:00,480 TRYING TO INHIBIT THIS? 553 00:27:00,480 --> 00:27:04,160 IF WE LOOK AT RECURRENT PARENTS 554 00:27:04,160 --> 00:27:09,040 THERE IS NO SURVIVAL DIFFERENCE. 555 00:27:09,040 --> 00:27:11,480 MAYBE WE SHOULD NOT GO THIS PATH 556 00:27:11,480 --> 00:27:15,920 I ALSO THOUGHT ABOUT WELL IF YOU 557 00:27:15,920 --> 00:27:19,120 HAVE HIGH OR LOW EXPRESSION 558 00:27:19,120 --> 00:27:22,320 SPECIFICALLY LOW EXPRESSION 559 00:27:22,320 --> 00:27:24,880 ANGLIN ONE IN THIS BLEAK 560 00:27:24,880 --> 00:27:27,560 SURVIVAL CURVE YOU HAVE TO THINK 561 00:27:27,560 --> 00:27:33,400 ABOUT THE ENDO THEME YUM. 562 00:27:33,400 --> 00:27:34,000 *. 563 00:27:34,000 --> 00:27:38,120 THE TUMOR CELLS HAVE HIGH ANGLIN 564 00:27:38,120 --> 00:27:39,080 1 EXPRESSION. 565 00:27:39,080 --> 00:27:43,040 WE'LL FOCUS ON INHIBIT THE 566 00:27:43,040 --> 00:27:45,360 EXPRESSION IN THE TUMOR CELL AS 567 00:27:45,360 --> 00:27:47,600 WELL AS THE NEURONS AND WE'LL 568 00:27:47,600 --> 00:27:49,080 SEE WHAT HAPPENS. 569 00:27:49,080 --> 00:27:52,200 AND SO WE FIRST WANTED TO LOOK 570 00:27:52,200 --> 00:27:56,640 AT JUST ENDO THIEL YAM. 571 00:27:56,640 --> 00:28:01,360 * AND WE PLATE THESE CELLS IN 572 00:28:01,360 --> 00:28:02,960 SOUTHERN WELLS WHERE IT ALLOWS 573 00:28:02,960 --> 00:28:06,400 US TO LOOK AT THE ELECTRON FLOW. 574 00:28:06,400 --> 00:28:09,320 SO AS WE PLATE THESE CELLS WE'RE 575 00:28:09,320 --> 00:28:13,400 ABLE TO SEE WHAT THE CELL CELL 576 00:28:13,400 --> 00:28:15,880 ATTACHMENT AND ADHESION IS. 577 00:28:15,880 --> 00:28:19,120 WE USE AN ELECTRICAL FLOW. 578 00:28:19,120 --> 00:28:21,480 AS YOU USE MORE CELLS THAT 579 00:28:21,480 --> 00:28:24,480 ATTACH TO EACH OTHER THERE IS 580 00:28:24,480 --> 00:28:26,440 HIGHER CELL CELL INDEX. 581 00:28:26,440 --> 00:28:28,320 AS YOU HAVE THE CELLS COMING 582 00:28:28,320 --> 00:28:32,160 APART YOU HAVE LOWER CELLS INDEX 583 00:28:32,160 --> 00:28:36,320 OR LOWER CELL CELL IMPEDENCE. 584 00:28:36,320 --> 00:28:39,640 WHEN WE MEASURED ADHESION EITHER 585 00:28:39,640 --> 00:28:42,320 TREATED WITH BUY CELLULAR 586 00:28:42,320 --> 00:28:48,880 JUNCTION INHIBITORS OR 587 00:28:48,880 --> 00:28:50,400 TRIINHIBITION YOU CAN SEE A 588 00:28:50,400 --> 00:28:54,240 SIGNIFICANT EFFECT AT THE 4 OR 6 589 00:28:54,240 --> 00:28:56,600 HOUR TIME PERIOD AND THAT THEN 590 00:28:56,600 --> 00:28:59,880 RETURN BACK AT A 12 HOUR TIME 591 00:28:59,880 --> 00:29:00,280 PERIOD. 592 00:29:00,280 --> 00:29:02,920 THE IMPORTANCE TO THINK ABOUT A 593 00:29:02,920 --> 00:29:06,720 TRANSIENT EFFECT OF THIS AGENT. 594 00:29:06,720 --> 00:29:08,160 SO, THAT IS WHAT IS HAPPENING 595 00:29:08,160 --> 00:29:12,720 WITH THE ENDO THIEL YUM BUT WHAT 596 00:29:12,720 --> 00:29:14,440 HAPPENS ON THE PROTEIN? 597 00:29:14,440 --> 00:29:19,640 WE WANTED TO KNOW IF YOU LOOK AT 598 00:29:19,640 --> 00:29:22,920 ANGLIN ONE WHAT HAPPENS TO THE 599 00:29:22,920 --> 00:29:25,480 EXPRESSION AND WE SEE ALSO AT 600 00:29:25,480 --> 00:29:27,960 THAT SAME KIND OF FIVE HOUR TIME 601 00:29:27,960 --> 00:29:31,120 PERIOD THERE IS DECREASED 602 00:29:31,120 --> 00:29:33,520 EXPRESSION AND HIGHER EXPRESSION 603 00:29:33,520 --> 00:29:44,040 ON THE CITO PLATTISM * CITO 604 00:29:48,200 --> 00:29:50,960 FLACH. 605 00:29:50,960 --> 00:29:56,800 SO WE WANTED TO USE ANIMALS SO 606 00:29:56,800 --> 00:29:59,880 WE'RE USING RAT CELLS WHICH ARE 607 00:29:59,880 --> 00:30:03,880 AKIN TO HIGH GRADE GLEOMA CELLS 608 00:30:03,880 --> 00:30:08,400 IN HUMANS AND THE BASELINE IS 609 00:30:08,400 --> 00:30:11,600 HIGH EXPRESSION BUT AFTER YOU 610 00:30:11,600 --> 00:30:13,600 TREAT WE SEE LOWER EXPRESSION 611 00:30:13,600 --> 00:30:15,280 AND BY 48 HOURS THE EFFECT OF 612 00:30:15,280 --> 00:30:17,680 THE AGENT HAS WORN OFF. 613 00:30:17,680 --> 00:30:22,320 KNOWING ALSO THAT WE WERE USING 614 00:30:22,320 --> 00:30:27,080 DOXIL AND KNOWING THAT IS A 615 00:30:27,080 --> 00:30:32,320 SUBSTRATE OF P LIKE OH PROTEIN 616 00:30:32,320 --> 00:30:37,680 -- WE WANTED TO KNOW WHAT EFFECT 617 00:30:37,680 --> 00:30:39,160 AND BIDEN HAD. 618 00:30:39,160 --> 00:30:48,320 WE USED A FLOW ASSAY. 619 00:30:48,320 --> 00:30:51,600 PGP IS PRESENT ON THESE TUMOR 620 00:30:51,600 --> 00:30:54,680 CELLS AND WHEN YOU USE A KNOWN 621 00:30:54,680 --> 00:30:58,000 INHIBITOR OF PGP YOU SHOULD SEE 622 00:30:58,000 --> 00:30:59,720 A SHIFT TO THE RIGHT AND A SHIFT 623 00:30:59,720 --> 00:31:03,640 TO THE RIGHT SIGNALS A HIGHER 624 00:31:03,640 --> 00:31:05,880 FLUORESCENCE OF THESE CELLS. 625 00:31:05,880 --> 00:31:08,520 INTERESTING WE SEE THAT WHEN WE 626 00:31:08,520 --> 00:31:13,280 GAVE AND BIDEN AT THE SAME DOSE 627 00:31:13,280 --> 00:31:15,280 WE SEE A CONTINUED OR PUSH TO 628 00:31:15,280 --> 00:31:16,320 THE RIGHT. 629 00:31:16,320 --> 00:31:19,160 A HIGHER FLUORESCENCE OF THESE 630 00:31:19,160 --> 00:31:21,640 TUMOR CELLS SHOWING THAT IT ALSO 631 00:31:21,640 --> 00:31:25,800 HAS A PGP INHIBITION FUNCTION. 632 00:31:25,800 --> 00:31:27,680 SO WE'RE SAYING OKAY. 633 00:31:27,680 --> 00:31:29,080 WE'RE GOING IN THE RIGHT 634 00:31:29,080 --> 00:31:29,360 DIRECTION. 635 00:31:29,360 --> 00:31:33,440 WE HAVE INHIBITION OF THE CELLS. 636 00:31:33,440 --> 00:31:37,000 WE HAVE PGP INHIBITION. 637 00:31:37,000 --> 00:31:41,400 WHAT CAN WE STEER WRONG? 638 00:31:41,400 --> 00:31:47,200 * AGAIN WE USED IMMUNO COMPETENT 639 00:31:47,200 --> 00:31:49,360 ANIMALS. 640 00:31:49,360 --> 00:31:53,040 WE INJECTED THEM AND ON DAY 7 641 00:31:53,040 --> 00:32:00,040 AND 14 THEY RECEIVED DOXIL ALONR 642 00:32:00,040 --> 00:32:01,240 VEHICLE TREATMENT AND WE WERE 643 00:32:01,240 --> 00:32:06,120 ABLE TO MEASURE DOXIL 644 00:32:06,120 --> 00:32:08,440 CONCENTRATION AS WELL AS THE 645 00:32:08,440 --> 00:32:10,080 SURVIVAL END POINT. 646 00:32:10,080 --> 00:32:12,200 AND WHAT WE FOUND IS THAT WHEN 647 00:32:12,200 --> 00:32:16,480 WE LOOKED AT CONCENTRATION THAT 648 00:32:16,480 --> 00:32:20,600 THERE WAS ONLY INCREASED DOXIL 649 00:32:20,600 --> 00:32:21,880 CONCENTRATION IN THE TUMOR AND 650 00:32:21,880 --> 00:32:24,920 THIS IS NOT A GREAT PERMEABILITY 651 00:32:24,920 --> 00:32:27,160 AGENT WITHIN THE BRAIN BUT WE 652 00:32:27,160 --> 00:32:31,240 COULD SEE A HIGHER INCREASE OR 653 00:32:31,240 --> 00:32:36,200 HIGHER -- CONCENTRATION OF DOXIL 654 00:32:36,200 --> 00:32:40,000 WITHIN THE TREATED ANIMALS 655 00:32:40,000 --> 00:32:43,040 VERSUS THE DOXIL ALONE. 656 00:32:43,040 --> 00:32:44,240 WE'RE GOING IN THE RIGHT 657 00:32:44,240 --> 00:32:48,960 DIRECTION. 658 00:32:48,960 --> 00:32:50,840 WHAT WE FOUND WITH THE HELP OF 659 00:32:50,840 --> 00:32:54,040 TWO OF THE ANIMAL BIOLOGIST IS 660 00:32:54,040 --> 00:32:59,440 THAT WE COULD SEE DECREASED 661 00:32:59,440 --> 00:33:01,280 TUMOR VOLUME HERE. 662 00:33:01,280 --> 00:33:03,400 THESE ARE JUST TWO 663 00:33:03,400 --> 00:33:05,480 REPRESENTATIVE MRI IMAGES WITH 664 00:33:05,480 --> 00:33:06,960 THE VARIOUS TREATMENTS AND YOU 665 00:33:06,960 --> 00:33:10,320 CAN SEE THAT THE TUMOR VOLUME IS 666 00:33:10,320 --> 00:33:11,600 SIGNIFICANTLY SMALLER BUT THEY 667 00:33:11,600 --> 00:33:13,240 WENT THROUGH AND LOOKED AT EACH 668 00:33:13,240 --> 00:33:15,800 OF THE SLICES AND THIS IS A 669 00:33:15,800 --> 00:33:17,480 QUANTIFICATION OF SUCH. 670 00:33:17,480 --> 00:33:23,160 ALSO JUST A SNAPSHOT IMAGE OF A 671 00:33:23,160 --> 00:33:23,440 STAINING. 672 00:33:23,440 --> 00:33:25,320 YOU CAN SEE THAT IN COMBINATION 673 00:33:25,320 --> 00:33:28,880 THE TUMOR SIZES SIGNIFICANTLY 674 00:33:28,880 --> 00:33:31,440 SMALLER IN THE COMBINES VERSUS 675 00:33:31,440 --> 00:33:32,920 ANY OF THE OTHER THREE 676 00:33:32,920 --> 00:33:33,360 TREATMENTS? 677 00:33:33,360 --> 00:33:35,920 DOES THIS TRANSLATE TO SURVIVAL? 678 00:33:35,920 --> 00:33:37,760 AND ACTUALLY IT DOES. 679 00:33:37,760 --> 00:33:40,720 SO IN LOOKING AT VEHICLES SEEN 680 00:33:40,720 --> 00:33:48,040 HERE IN RED OR DOXIL ALONE 681 00:33:48,040 --> 00:33:51,600 COMPARED TO THE COMBINATION 682 00:33:51,600 --> 00:33:54,680 THERE IS A LONGER SURVIVAL WITH 683 00:33:54,680 --> 00:33:57,680 THE COMBINATION THERAPY AND EVEN 684 00:33:57,680 --> 00:34:00,160 MEDIAN SURVIVAL IS IMPACTED. 685 00:34:00,160 --> 00:34:05,560 I DON'T SEE THE ASTERISKS BUT 686 00:34:05,560 --> 00:34:08,240 THERE WERE WITH PROLONGED 687 00:34:08,240 --> 00:34:09,600 SURVIVAL. 688 00:34:09,600 --> 00:34:13,320 THIS COMBINATION THERAPY HAS A 689 00:34:13,320 --> 00:34:16,920 SIGNIFICANT IMPACT ON SURVIVAL. 690 00:34:16,920 --> 00:34:19,240 WHERE DO WE GO FROM HERE IN HOW 691 00:34:19,240 --> 00:34:21,840 DOES THAT TRANSLATE FURTHER? 692 00:34:21,840 --> 00:34:24,200 IT'S NOT LOST ON US THAT THE 693 00:34:24,200 --> 00:34:27,160 BLOOD BRAIN BARRIER IS THE ONLY 694 00:34:27,160 --> 00:34:29,800 CHALLENGE TO PROVIDING EFFECTIVE 695 00:34:29,800 --> 00:34:33,000 THERAPY TO THESE TUMORS. 696 00:34:33,000 --> 00:34:35,440 WE HAVE THE IMMUNE SYSTEM THAT 697 00:34:35,440 --> 00:34:37,840 IS VERY IMPORTANT FOR ALL 698 00:34:37,840 --> 00:34:38,280 TUMORS. 699 00:34:38,280 --> 00:34:41,400 WHEN YOU THINK ABOUT HOW T CELLS 700 00:34:41,400 --> 00:34:43,840 GET TO THE TUMOR OR TO THE 701 00:34:43,840 --> 00:34:47,600 NORMAL BRAIN THERE IS A WAY OF 702 00:34:47,600 --> 00:34:50,080 TRANS CELLULAR MIGRATION. 703 00:34:50,080 --> 00:34:54,320 THIS IS THE GRAPHICAL 704 00:34:54,320 --> 00:34:56,080 ILLUSTRATION. 705 00:34:56,080 --> 00:34:57,640 YOU'LL SEE IN ORDER TO GET INTO 706 00:34:57,640 --> 00:35:01,520 THE BRAIN THEY COME FROM THE 707 00:35:01,520 --> 00:35:04,280 VASCULATURE AND THEY ROLL AND 708 00:35:04,280 --> 00:35:06,440 THEY COME TO THE SITE OF INJURY 709 00:35:06,440 --> 00:35:09,880 OR INFECTION OR TO THE SITE OF A 710 00:35:09,880 --> 00:35:10,600 TUMOR PRESENT. 711 00:35:10,600 --> 00:35:13,240 BUT THE WAY THEY COME ABOUT IT 712 00:35:13,240 --> 00:35:16,040 IS THROUGH PERRY CELLULAR 713 00:35:16,040 --> 00:35:20,440 TRANSPORT THROUGH THESE TIGHT 714 00:35:20,440 --> 00:35:22,520 JUNCTIONS OR TRANS CELLULAR. 715 00:35:22,520 --> 00:35:25,600 THEY CAN COME THROUGH THE 716 00:35:25,600 --> 00:35:26,880 ENDOTHELIAL CELLS. 717 00:35:26,880 --> 00:35:32,480 THERE WAS A GROUP OUT OF 718 00:35:32,480 --> 00:35:38,360 SWITZERLAND -- THEY INHIBITED 719 00:35:38,360 --> 00:35:38,760 PCAM. 720 00:35:38,760 --> 00:35:42,160 IF THEY INHIBITED BUY CELLULAR 721 00:35:42,160 --> 00:35:44,960 JUNCTIONS YOU CAN SEE A HIGHER 722 00:35:44,960 --> 00:35:47,000 MIGRATION OF THESE T CELLS. 723 00:35:47,000 --> 00:35:51,280 THIS IS JUST BUY CELLULAR. 724 00:35:51,280 --> 00:35:58,280 CAN WE SEE INCREASED TRANS 725 00:35:58,280 --> 00:36:03,560 CELLULAR -- MIGRATION OF THESE 726 00:36:03,560 --> 00:36:04,720 CELLS. 727 00:36:04,720 --> 00:36:09,800 IT HAD US TO SAY WHAT IS THE 728 00:36:09,800 --> 00:36:13,120 ROLE OF THE JUNCTIONS WHEN YOU 729 00:36:13,120 --> 00:36:16,240 INHIBIT THEM. 730 00:36:16,240 --> 00:36:22,720 SO WE TOOK -- THESE ARE TC 731 00:36:22,720 --> 00:36:23,120 DEFICIENT. 732 00:36:23,120 --> 00:36:25,120 WE INJECTED THEM WITH TUMOR 733 00:36:25,120 --> 00:36:25,520 CELL. 734 00:36:25,520 --> 00:36:30,680 WE LOOKED AT DAY 7 AND 14 TO 735 00:36:30,680 --> 00:36:33,120 GIVE THE COMBINATION AND WANTED 736 00:36:33,120 --> 00:36:37,480 TO SEE WHAT THEIR SURVIVAL IS. 737 00:36:37,480 --> 00:36:44,280 THERE IS NO SURVIVAL BENEFIT AND 738 00:36:44,280 --> 00:36:48,040 THE ONLY LONG SURVIVAL IS WITH 739 00:36:48,040 --> 00:36:50,000 DOXIL ALONE. 740 00:36:50,000 --> 00:36:56,600 THE T CELLS ARE PRYING A ROLE IN 741 00:36:56,600 --> 00:36:59,200 PROVIDING SURVIVAL. 742 00:36:59,200 --> 00:37:00,760 WE HAVE MORE INVESTIGATIONS TO 743 00:37:00,760 --> 00:37:03,720 DO ON THAT SIDE AS IT RELATES TO 744 00:37:03,720 --> 00:37:05,400 THE IMMUNE SYSTEM. 745 00:37:05,400 --> 00:37:10,560 WE'RE ABLE TO DEDUCE AND 746 00:37:10,560 --> 00:37:14,200 HYPOTHESIZE THAT THIS HALTS 747 00:37:14,200 --> 00:37:15,640 DISEASE PROGRESSION AND WE'VE 748 00:37:15,640 --> 00:37:19,840 BEEN ABLE TO SHOW THAT IT 749 00:37:19,840 --> 00:37:23,240 DISRUPTS ENDO THIEL YUM AND 750 00:37:23,240 --> 00:37:26,760 INCREASED DOXIL CONCENTRATION 751 00:37:26,760 --> 00:37:29,560 WITH LONG SURVIVAL. 752 00:37:29,560 --> 00:37:33,600 WE HAVE PRELIMINARY STUDIES TO 753 00:37:33,600 --> 00:37:36,920 SHOW -- IT'S NOT JUST AKIN TO 754 00:37:36,920 --> 00:37:38,760 RAT GLEE OPENED AFTER CELLS. 755 00:37:38,760 --> 00:37:43,480 WE ALSO SEE IT IN * TUMOR 756 00:37:43,480 --> 00:37:44,200 TISSUE. 757 00:37:44,200 --> 00:37:47,280 WE SEE THAT -- INHIBITION THAT 758 00:37:47,280 --> 00:37:50,200 WE'RE STARTING TO EVALUATE TC 759 00:37:50,200 --> 00:37:51,920 MIGRATION DIFFERENCES AND ALSO 760 00:37:51,920 --> 00:37:55,520 PROVIDING A CLEAN WAY TO INHIBIT 761 00:37:55,520 --> 00:37:57,600 ANGLIN 1 EXPRESSION WITH STUDIES 762 00:37:57,600 --> 00:38:01,600 BOTH ON ENDO THIEL YUM AND THEN 763 00:38:01,600 --> 00:38:03,920 LOOKING TO SEE WHAT THE EFFECT 764 00:38:03,920 --> 00:38:09,120 IS IN VITRO AND THEN EVENTUALLY 765 00:38:09,120 --> 00:38:10,800 ENVY HAVE A. 766 00:38:10,800 --> 00:38:15,280 * AND IN THE FUTURE WE'LL 767 00:38:15,280 --> 00:38:19,840 CONTINUE TO IDENTIFY OTHER DUAL 768 00:38:19,840 --> 00:38:24,680 ROLE AGENTS THAT WORK ON BOTH SO 769 00:38:24,680 --> 00:38:29,400 THAT WE CAN INVESTIGATE INVITRO 770 00:38:29,400 --> 00:38:31,120 TO SEE THE EFFECT. 771 00:38:31,120 --> 00:38:33,240 NOW THIS LEADS INTO THE EFFECT 772 00:38:33,240 --> 00:38:36,240 OF THE PHARMACOLOGY MATTERS. 773 00:38:36,240 --> 00:38:46,440 SO OUR AIM 3 IS TO DETERMINE -- 774 00:38:46,440 --> 00:38:48,880 THE PENETRATION OF CURRENTLY 775 00:38:48,880 --> 00:38:52,960 USED CHEMO THERAPEUTIC GAUGE END 776 00:38:52,960 --> 00:39:03,440 INTO MALIGNANT GLEE OMAHAS. 777 00:39:09,360 --> 00:39:10,960 SOMETIMES WE'RE ABLE TO MEASURE 778 00:39:10,960 --> 00:39:13,160 DRUG CONCENTRATION IN THESE 779 00:39:13,160 --> 00:39:14,440 AGGRESSIVE TUMORS. 780 00:39:14,440 --> 00:39:17,360 BUT THAT IS ONLY ONE TIME POINT. 781 00:39:17,360 --> 00:39:21,240 WHEN THESE PATIENTS ARE ON NO 782 00:39:21,240 --> 00:39:25,040 CHEMOTHERAPY BUT STEROID THERAPY 783 00:39:25,040 --> 00:39:27,480 THAT CAN CLOSE THE BBB. 784 00:39:27,480 --> 00:39:29,240 THAT IS ONE TIME POINT THAT 785 00:39:29,240 --> 00:39:31,560 WE'RE ABLE TO SAY THE DRUG GETS 786 00:39:31,560 --> 00:39:35,640 IN OR DOESN'T AND NO LONG-TERM 787 00:39:35,640 --> 00:39:38,120 OF HOW MUCH GETS INTO THE BRAIN. 788 00:39:38,120 --> 00:39:40,080 YOU HAVE THIS BRAIN AND THE 789 00:39:40,080 --> 00:39:42,560 SKULL AND ALL OF THESE LAYERS 790 00:39:42,560 --> 00:39:45,880 AND IT'S NOT LIKE A PERIPHERAL 791 00:39:45,880 --> 00:39:48,160 TUMOR THAT WE CAN CONTINUE TO 792 00:39:48,160 --> 00:39:48,800 BIOPSY. 793 00:39:48,800 --> 00:39:50,600 THE TOOL IS JUST ONE WAY THAT 794 00:39:50,600 --> 00:39:54,640 WE'RE EXPLORING TO BE MORE 795 00:39:54,640 --> 00:39:56,040 UTILIZED IN THE SETTING TO 796 00:39:56,040 --> 00:39:59,680 UNDERSTAND MORE ABOUT THE 797 00:39:59,680 --> 00:40:01,480 PHARMACOLOGY OF THESE TUMORS. 798 00:40:01,480 --> 00:40:04,920 THIS IS ONE AGENT. 799 00:40:04,920 --> 00:40:10,440 FDA APPROVED AND A POTENT 800 00:40:10,440 --> 00:40:11,520 INHIBITOR. 801 00:40:11,520 --> 00:40:20,600 IT WORKS TO INHIBIT -- RETINAL 802 00:40:20,600 --> 00:40:24,840 BLAST STOLEN A GENE AND IMPAIRS 803 00:40:24,840 --> 00:40:28,160 THE * G1. 804 00:40:28,160 --> 00:40:32,120 THERE IS ALSO DISREGULATION -- 805 00:40:32,120 --> 00:40:35,360 IN HIGH GRADE GLIOMAS. 806 00:40:35,360 --> 00:40:37,240 AND THIS DRUG SPECIFICALLY HAS 807 00:40:37,240 --> 00:40:40,920 BEEN SHOWN TO PROLONG SURVIVAL 808 00:40:40,920 --> 00:40:45,720 IN NEWLY DIAGNOSED PATIENTS AND 809 00:40:45,720 --> 00:40:50,480 META STATIC BRAIN PATIENTS. 810 00:40:50,480 --> 00:40:52,480 THE ARCHITECTURE IS DIFFERENT. 811 00:40:52,480 --> 00:40:53,800 IN THINKING ABOUT THE MID-LINE 812 00:40:53,800 --> 00:40:57,640 IF YOU THINK ABOUT THE PONDS OF 813 00:40:57,640 --> 00:41:01,280 THE BRAIN THAT IS THE TEXTURE 814 00:41:01,280 --> 00:41:03,640 AND THE SPONGINESS OF THE BRAIN 815 00:41:03,640 --> 00:41:05,360 VERSUS THE MID-LINE STRUCTURES 816 00:41:05,360 --> 00:41:08,680 ARE SIGNIFICANTLY DIFFERENT. 817 00:41:08,680 --> 00:41:09,280 YES. 818 00:41:09,280 --> 00:41:12,960 YOU SEE PROLONGED SURVIVAL WITH 819 00:41:12,960 --> 00:41:15,960 THIS AGENT BUT WHAT TYPE OF 820 00:41:15,960 --> 00:41:19,080 SURVIVAL OR EFFECT AND WHAT TIME 821 00:41:19,080 --> 00:41:21,520 OF PERMEABILITY DO YOU SEE FOR 822 00:41:21,520 --> 00:41:25,240 PATIENTS WITH DIFFUSED MID-LINE 823 00:41:25,240 --> 00:41:35,400 GLEOMA. 824 00:41:42,080 --> 00:41:52,120 I USU-- FOR PHASE 01 TRIAL THATS 825 00:41:52,120 --> 00:41:54,920 AT THE SAFETY AND FEASIBILITY OF 826 00:41:54,920 --> 00:41:58,680 PLACEMENT AND SAMPLING WITH 827 00:41:58,680 --> 00:42:01,000 PATIENTS. 828 00:42:01,000 --> 00:42:02,920 MEASURING BOTH -- AND THEN WE 829 00:42:02,920 --> 00:42:08,200 HAVE THE PHASE I COMPONENT OF 830 00:42:08,200 --> 00:42:09,560 LONG-TERM FOLLOW-UP ONCE THEY 831 00:42:09,560 --> 00:42:10,600 RECEIVE THIS. 832 00:42:10,600 --> 00:42:14,800 AND WE'RE AGAIN USING OUR FANCY 833 00:42:14,800 --> 00:42:16,720 TOOL OF THE CATHETER. 834 00:42:16,720 --> 00:42:18,600 THIS TIME BECAUSE OF THE 835 00:42:18,600 --> 00:42:20,400 LOCATION OF THE TUMOR WE'RE NOT 836 00:42:20,400 --> 00:42:23,840 ABLE TO DO A SURGICAL RESECTION 837 00:42:23,840 --> 00:42:26,720 OF THE TUMOR BUT INSTEAD A 838 00:42:26,720 --> 00:42:30,800 BIOPSY AND A CATHETER IS PLACED 839 00:42:30,800 --> 00:42:32,920 AND THROUGH PASSIVE DIFFUSION 840 00:42:32,920 --> 00:42:35,800 WE'RE ABLE TO GAIN EXTRA 841 00:42:35,800 --> 00:42:40,080 CELLULAR FLUID AND MAKE 842 00:42:40,080 --> 00:42:42,360 MEASUREMENTS. 843 00:42:42,360 --> 00:42:45,200 WITH THE REP OR ASSISTANCE OF 844 00:42:45,200 --> 00:42:48,280 DR. BROWN WHO'S A NEURO SURGICAL 845 00:42:48,280 --> 00:42:50,200 ONCOLOGIST WE ENROLL PATIENTS 846 00:42:50,200 --> 00:42:55,280 WITH RECURRENT HIGH GRADE GLIOMA 847 00:42:55,280 --> 00:43:02,960 OR DIFFUSED MID-LINE GLIOMA AND 848 00:43:02,960 --> 00:43:05,960 PATIENTS TAKE -- AND THEN ON THE 849 00:43:05,960 --> 00:43:07,960 5th DAY THEY HAVE A RESECTION 850 00:43:07,960 --> 00:43:10,720 OR BIOPSY AND THESE CATHETERS 851 00:43:10,720 --> 00:43:13,400 ARE PLACED. 852 00:43:13,400 --> 00:43:16,640 WE'RE ABLE TO DETERMINE -- THE 853 00:43:16,640 --> 00:43:17,000 CONCENTRATIONS. 854 00:43:17,000 --> 00:43:23,200 WE'RE ABLE TO DO STUDIES. 855 00:43:23,200 --> 00:43:25,880 WE'RE ABLE TO DO GENOMIC 856 00:43:25,880 --> 00:43:27,520 PROFILING ON THE TISSUE AND 857 00:43:27,520 --> 00:43:31,400 WE'RE ABLE TO DO PDX MODELING. 858 00:43:31,400 --> 00:43:33,520 WE HAVE THESE CATHETERS IN PLACE 859 00:43:33,520 --> 00:43:37,160 AND WE'RE ABLE TO DO TIMED 860 00:43:37,160 --> 00:43:39,600 SAMPLING OF THE FLUID IN 861 00:43:39,600 --> 00:43:41,600 COMPARISON TO PLASMA 862 00:43:41,600 --> 00:43:43,960 CONCENTRATION AND AT 48 HOURS 863 00:43:43,960 --> 00:43:45,800 THESE CATHETERS ARE REMOVED AT 864 00:43:45,800 --> 00:43:49,360 THE BEDSIDE AND THE FLUID IS 865 00:43:49,360 --> 00:43:53,320 SENT TO THE LAB AND WE'RE ABLE 866 00:43:53,320 --> 00:43:56,600 TO MEASURE FOR 0-48 HOURS. 867 00:43:56,600 --> 00:43:58,680 THIS IS A DIFFERENT TYPE OF 868 00:43:58,680 --> 00:44:02,400 STUDY IN THE FACT THAT WE HAVE A 869 00:44:02,400 --> 00:44:05,520 GO, NO GO COMPONENT. 870 00:44:05,520 --> 00:44:09,160 IF IT'S A CERTAIN CONCENTRATION 871 00:44:09,160 --> 00:44:11,680 GREATER THAN 10 PER LITER OUR 872 00:44:11,680 --> 00:44:17,280 RECOMMENDATION IS TO RESTART. 873 00:44:17,280 --> 00:44:18,920 WE'RE GIVING DRUG BECAUSE WE 874 00:44:18,920 --> 00:44:20,720 THINK IT WILL GET THERE AND HAVE 875 00:44:20,720 --> 00:44:21,880 AN EFFECT. 876 00:44:21,880 --> 00:44:24,520 SO THIS IS A VERY INTELLIGENT 877 00:44:24,520 --> 00:44:29,800 WAY FOR US TO SAY A GO, NO GO 878 00:44:29,800 --> 00:44:32,280 AND NOT JUST BLINDLY PROVIDING 879 00:44:32,280 --> 00:44:35,280 THERAPY. 880 00:44:35,280 --> 00:44:37,360 WITH EVERY THREE MONTHS CHECKING 881 00:44:37,360 --> 00:44:39,080 TO SEE IF THERE IS A CHECK ON 882 00:44:39,080 --> 00:44:40,960 THE TUMOR. 883 00:44:40,960 --> 00:44:43,560 THESE ARE VERY AGGRESSIVE TYPE 884 00:44:43,560 --> 00:44:43,960 TIMERS. 885 00:44:43,960 --> 00:44:47,200 THESE PATIENTS WILL HAVE COME TO 886 00:44:47,200 --> 00:44:51,040 US WITH RECURRENT DISEASE 887 00:44:51,040 --> 00:44:53,160 DEPENDING ON WHAT THERAPIES THEY 888 00:44:53,160 --> 00:44:55,040 HAVE RECEIVED AT THEIR HOME 889 00:44:55,040 --> 00:44:55,640 INSTITUTION. 890 00:44:55,640 --> 00:44:57,880 WE'VE ACCRUED ONE PATIENT TO 891 00:44:57,880 --> 00:45:03,280 THIS STUDY. 892 00:45:03,280 --> 00:45:04,560 CT/MRI OVERLAY. 893 00:45:04,560 --> 00:45:08,320 THIS PATIENT HAD AN AGGRESSIVE 894 00:45:08,320 --> 00:45:12,720 RECURRENT GLIAL BLAST TOMA. 895 00:45:12,720 --> 00:45:16,200 THE * CATHETER WAS PLACED RIGHT 896 00:45:16,200 --> 00:45:16,400 HERE. 897 00:45:16,400 --> 00:45:18,480 YOU CAN SEE THE DIFFERENT WAYS 898 00:45:18,480 --> 00:45:21,800 TO IMAGE FOR THE CATHETER TIP 899 00:45:21,800 --> 00:45:22,200 PLACEMENT. 900 00:45:22,200 --> 00:45:24,200 WHAT WE WERE ABLE TO SEE IS THAT 901 00:45:24,200 --> 00:45:26,080 WE COULD SUCCESSFULLY MEASURE 902 00:45:26,080 --> 00:45:29,720 THE CONCENTRATIONS IN BOTH 903 00:45:29,720 --> 00:45:32,760 PLASMA BRAIN DIALYSIS. 904 00:45:32,760 --> 00:45:37,680 THIS WAS THE TIME AT FIRST 905 00:45:37,680 --> 00:45:40,720 ADMINISTRATION. 906 00:45:40,720 --> 00:45:45,040 IT WENT DOWN OVER THE 72 HOURS 907 00:45:45,040 --> 00:45:46,480 AFTER US DOING REPEAT BLOOD 908 00:45:46,480 --> 00:45:48,280 DRAWS AND AFTER THE CATS 909 00:45:48,280 --> 00:45:51,040 TERRIFIC WAS PLACED * THAT THE 910 00:45:51,040 --> 00:45:53,120 HIGHEST CONCENTRATION WAS ABOUT 911 00:45:53,120 --> 00:45:55,160 6 HOURS IN TERMS OF THE AREA 912 00:45:55,160 --> 00:45:57,800 UNDER THE CURVE AND CLEARANCE 913 00:45:57,800 --> 00:46:00,840 OVER TIME WENT DOWN OVER THE 48 914 00:46:00,840 --> 00:46:01,720 HOUR TIME PERIOD. 915 00:46:01,720 --> 00:46:06,240 IT WAS A THRESHOLD THAT WE WOULD 916 00:46:06,240 --> 00:46:11,640 RECOMMEND FOR RESTART AND FOR 917 00:46:11,640 --> 00:46:15,280 THIS PATIENT THEY MET THE 918 00:46:15,280 --> 00:46:15,680 THRESHOLD. 919 00:46:15,680 --> 00:46:17,040 SO THAT WOULD BE THE 920 00:46:17,040 --> 00:46:18,840 RECOMMENDATION TO RESTART. 921 00:46:18,840 --> 00:46:21,480 WE ADDITIONALLY WANTED TO LOOK 922 00:46:21,480 --> 00:46:22,960 IN THE TUMOR TISSUE AND WE WERE 923 00:46:22,960 --> 00:46:26,480 ABLE TO GET THREE DIFFERENT 924 00:46:26,480 --> 00:46:28,080 TUMOR SPECIMENS. 925 00:46:28,080 --> 00:46:31,600 THEY HAD DIFFERENT 926 00:46:31,600 --> 00:46:40,520 CONCENTRATIONS OF ABEMACICLIB. 927 00:46:40,520 --> 00:46:50,880 A&M OUR TAKE AWAYS. 928 00:47:02,600 --> 00:47:05,560 THIS WILL PREDICT TREATMENT 929 00:47:05,560 --> 00:47:06,040 RESPONSE. 930 00:47:06,040 --> 00:47:08,040 THAT ABEMACICLIB IS SAFE AND 931 00:47:08,040 --> 00:47:11,800 FEASIBLE AND THAT WE HAVE 932 00:47:11,800 --> 00:47:13,240 ONGOING STUDIES. 933 00:47:13,240 --> 00:47:17,240 WE'RE RECRUITING PATIENTS 2-5. 934 00:47:17,240 --> 00:47:18,560 IF YOU HAVE A PATIENT OF 935 00:47:18,560 --> 00:47:21,400 INTEREST PLEASE SEND THEM OUR 936 00:47:21,400 --> 00:47:21,800 WAY. 937 00:47:21,800 --> 00:47:24,280 SO WE CAN POTENTIALLY ENROLL 938 00:47:24,280 --> 00:47:27,040 THEM FOR STUDY FOR THIS STUDY OR 939 00:47:27,040 --> 00:47:31,040 FOR OTHERS. 940 00:47:31,040 --> 00:47:32,760 SIMULTANEOUSLY WE'RE DOING 941 00:47:32,760 --> 00:47:35,160 PRECLINICAL STUDIES LOOKING AT 942 00:47:35,160 --> 00:47:38,800 RODENT MODELS WHERE WE PLACE 943 00:47:38,800 --> 00:47:44,120 CATHETERS IN TUMOR INJECTED 944 00:47:44,120 --> 00:47:47,720 VERSUS NONTUMOR. 945 00:47:47,720 --> 00:47:51,240 I TALKED ABOUT THE GRAPHICAL 946 00:47:51,240 --> 00:47:53,200 ILLUSTRATION OF THE CORE AREAS 947 00:47:53,200 --> 00:47:55,440 AND MORE INFORMATION CAN BE 948 00:47:55,440 --> 00:47:59,000 OBTAINED ABOUT THIS DISTANT SIDE 949 00:47:59,000 --> 00:48:02,520 AREA IF WE'RE ABLE TO PUT A 950 00:48:02,520 --> 00:48:03,920 CATHETER IN THE NONINJECTED 951 00:48:03,920 --> 00:48:14,040 SIDE. 952 00:48:16,560 --> 00:48:19,640 AND THAT THE THE OVER-ALL TAKE 953 00:48:19,640 --> 00:48:22,880 AWAY -- THIS IS A FEASIBLE 954 00:48:22,880 --> 00:48:25,200 ADJUNCT FOR BOTH PRECLINICAL AND 955 00:48:25,200 --> 00:48:26,280 CLINICAL MANAGEMENT. 956 00:48:26,280 --> 00:48:29,040 WE HOPE THAT WE CAN EXPAND THE 957 00:48:29,040 --> 00:48:33,160 USE OF THE TOOL IN MORA DULL THE 958 00:48:33,160 --> 00:48:39,080 -- STUDIES AS WELL * AS 959 00:48:39,080 --> 00:48:41,160 PEDIATRIC TRIALS. 960 00:48:41,160 --> 00:48:44,200 IT COULD HELP TO ADVANCE MORE 961 00:48:44,200 --> 00:48:47,720 ABOUT OUR GO NO GO OR TO BE MORE 962 00:48:47,720 --> 00:48:49,640 INTELLIGENT IF A DRUG WORKS OR 963 00:48:49,640 --> 00:48:51,840 GETTING TO WHERE WE WANT IT TO 964 00:48:51,840 --> 00:48:52,840 GO. 965 00:48:52,840 --> 00:48:55,200 THESE CAN HELP WITH OUR CLINICAL 966 00:48:55,200 --> 00:48:57,200 STUDY INVESTIGATIONS AND OUR 967 00:48:57,200 --> 00:48:59,960 CREATION FOR THESE TRIALS. 968 00:48:59,960 --> 00:49:04,120 SO AS THE ONLY BLACK PEDIATRIC 969 00:49:04,120 --> 00:49:05,640 ONCOLOGIST IN THE COUNTRY IT IS 970 00:49:05,640 --> 00:49:08,120 AN HONOR TO CONDUCT MY RESEARCH 971 00:49:08,120 --> 00:49:09,200 HERE AT THE NIH. 972 00:49:09,200 --> 00:49:10,560 I'M STILL HERE. 973 00:49:10,560 --> 00:49:12,760 AND WE'RE EMPOWERED THAT THESE 974 00:49:12,760 --> 00:49:14,840 STUDIES ARE HELPING TO ADVANCE 975 00:49:14,840 --> 00:49:17,000 OUR FIELD RELATED TO THE TIME 976 00:49:17,000 --> 00:49:19,360 DEPENDENT CHANGES, THE DUE 977 00:49:19,360 --> 00:49:22,200 RECALL ROLE THEN PIECE AND THE 978 00:49:22,200 --> 00:49:26,120 PHARMACOLOGY OF THESE AGGRESSIVE 979 00:49:26,120 --> 00:49:26,520 TUMORS. 980 00:49:26,520 --> 00:49:28,200 AND THEN AS WAS MENTIONED 981 00:49:28,200 --> 00:49:29,880 EARLIER MY WORK IS NOT JUST AT 982 00:49:29,880 --> 00:49:30,720 THE NIH. 983 00:49:30,720 --> 00:49:33,120 IT IS WORLDWIDE AND THESE ARE 984 00:49:33,120 --> 00:49:34,640 JUST A FEW PICTURES OF THE WORK 985 00:49:34,640 --> 00:49:37,120 THAT I'VE DONE AT THE NIH THAT 986 00:49:37,120 --> 00:49:39,200 I'VE DONE GLOBALLY TO HELP 987 00:49:39,200 --> 00:49:42,840 FOSTER MENTORING OUTREACH 988 00:49:42,840 --> 00:49:44,600 INCLUSIVITY AND DIVERSITY AMONG 989 00:49:44,600 --> 00:49:46,360 THE SCIENCES AND STEM. 990 00:49:46,360 --> 00:49:48,600 YOU CAN SEE A PICTURE WITH MY 991 00:49:48,600 --> 00:49:49,000 KIDS. 992 00:49:49,000 --> 00:49:51,760 WITH MY COLLEAGUES. 993 00:49:51,760 --> 00:49:54,840 WOMEN IN NEURO ONCOLOGY AND WHY 994 00:49:54,840 --> 00:49:56,520 IT'S SO IMPORTANT THAT THERE IS 995 00:49:56,520 --> 00:49:58,760 DIVERSITY OF THOUGHT WITHIN THE 996 00:49:58,760 --> 00:50:01,520 ENTIRE BIOMEDICAL ENTERPRISE AND 997 00:50:01,520 --> 00:50:04,280 IT'S HELPED TO FOSTER BOTH MY 998 00:50:04,280 --> 00:50:06,160 PERSONAL AND PROFESSIONAL GROWTH 999 00:50:06,160 --> 00:50:08,120 OVER TIME. 1000 00:50:08,120 --> 00:50:10,440 I'M GRATEFUL TO HAVE THESE 1001 00:50:10,440 --> 00:50:11,320 OPPORTUNITIES. 1002 00:50:11,320 --> 00:50:13,160 SO THANK YOU VERY MUCH FOR YOUR 1003 00:50:13,160 --> 00:50:14,120 TIME. 1004 00:50:14,120 --> 00:50:15,920 I APPRECIATE YOU BEING 1005 00:50:15,920 --> 00:50:18,120 INTENTIONAL ABOUT LISTENING AND 1006 00:50:18,120 --> 00:50:19,360 THINKING ABOUT GOOD QUESTIONS 1007 00:50:19,360 --> 00:50:21,560 THAT ARE EASY FOR ME TO ANSWER 1008 00:50:21,560 --> 00:50:23,800 AT THE END OF THIS PRESENTATION. 1009 00:50:23,800 --> 00:50:26,600 I REMIND YOU THAT WE HAVE AN 1010 00:50:26,600 --> 00:50:33,040 OPEN POSTDOCTORAL POSITIONS. 1011 00:50:33,040 --> 00:50:36,080 WE HAVE TWO. 1012 00:50:36,080 --> 00:50:38,280 SO PLEASE SEND PEOPLE MY WAY. 1013 00:50:38,280 --> 00:50:40,760 WE WANT TO CONTINUE TO BE ROBUST 1014 00:50:40,760 --> 00:50:45,720 IN OUR THINKING AROUND BBB AND 1015 00:50:45,720 --> 00:50:46,080 PHARMACOLOGY. 1016 00:50:46,080 --> 00:50:52,720 THANK YOU. 1017 00:50:52,720 --> 00:50:54,600 >>DR., JACKSON, I WANT TO THANK 1018 00:50:54,600 --> 00:50:56,160 YOU FOR YOUR BRILLIANT 1019 00:50:56,160 --> 00:50:58,840 PRESENTATION. 1020 00:50:58,840 --> 00:51:01,200 AND * WE HAVE A COUPLE OF 1021 00:51:01,200 --> 00:51:03,320 QUESTIONS THAT HAVE COME IN. 1022 00:51:03,320 --> 00:51:05,080 ONE IS A LOT OF YOUR WORK HAS 1023 00:51:05,080 --> 00:51:07,320 BEEN FOCUSED ON THE GROWTH OF 1024 00:51:07,320 --> 00:51:10,040 PRIMARY TUMOR. 1025 00:51:10,040 --> 00:51:13,040 INHIBITING TUMOR VOLUME AND 1026 00:51:13,040 --> 00:51:13,880 REGRESSION. 1027 00:51:13,880 --> 00:51:16,320 DO YOU HAVE A SIGNAL ON WHAT IT 1028 00:51:16,320 --> 00:51:19,680 MEANS FOR METASTATIC OR 1029 00:51:19,680 --> 00:51:20,120 REOCCURRING? 1030 00:51:20,120 --> 00:51:22,160 >>THAT IS A GOOD QUESTION. 1031 00:51:22,160 --> 00:51:24,400 WE DON'T WORK ON METASTATIC 1032 00:51:24,400 --> 00:51:25,400 DISEASE. 1033 00:51:25,400 --> 00:51:30,920 A LOT OF THE B-B-B IS ALREADY 1034 00:51:30,920 --> 00:51:33,000 PERM ABLE. 1035 00:51:33,000 --> 00:51:35,040 THEY HAVE THE OPPOSITE PROBLEM 1036 00:51:35,040 --> 00:51:39,880 OF PRIMARY AGREE OMAHA. 1037 00:51:39,880 --> 00:51:50,840 -- GLIOMA.A QUESTION ABOUT DISTE 1038 00:51:51,720 --> 00:51:53,200 PRIMARY SITE. 1039 00:51:53,200 --> 00:51:55,360 SO ONE OF MY FIRST SLIDES WAS 1040 00:51:55,360 --> 00:52:02,280 ABOUT THE DIFFERENCE OF THE BBB 1041 00:52:02,280 --> 00:52:03,560 HETEROGENEITY. 1042 00:52:03,560 --> 00:52:07,040 WE'RE STILL EXAMINING HOW DO WE 1043 00:52:07,040 --> 00:52:08,960 IMPROVE DELIVERY COMPARED TO THE 1044 00:52:08,960 --> 00:52:10,880 CORE OF THE TUMOR WHERE THERE IS 1045 00:52:10,880 --> 00:52:11,840 NO PROBLEM. 1046 00:52:11,840 --> 00:52:15,680 THAT KEEPS US WORKING AND BUSY. 1047 00:52:15,680 --> 00:52:16,960 >>ANOTHER QUESTION CAME IN 1048 00:52:16,960 --> 00:52:18,960 THROUGH THE VIDEO CAST. 1049 00:52:18,960 --> 00:52:21,200 VERY NICE TALK ON A TOUGH 1050 00:52:21,200 --> 00:52:21,440 PROBLEM. 1051 00:52:21,440 --> 00:52:22,600 CAN YOU PLEASE COMMENT ON THE 1052 00:52:22,600 --> 00:52:26,800 STATUS OF FOCUS ULTRASOUND IN 1053 00:52:26,800 --> 00:52:36,760 CREATING BLOOD BRAIN BARRIER TO 1054 00:52:36,760 --> 00:52:40,920 CHEMICAL THERAPY. 1055 00:52:40,920 --> 00:52:43,080 >>FOCUS ULTRASOUND. 1056 00:52:43,080 --> 00:52:50,520 THEY'VE BEEN ABLE TO SHOW THAT 1057 00:52:50,520 --> 00:52:53,080 YOU CAN INCREASE THE BBB AND 1058 00:52:53,080 --> 00:52:54,360 INCREASE THERAPY. 1059 00:52:54,360 --> 00:53:00,040 SOME OF THE CAVEATS ARE IT CAN 1060 00:53:00,040 --> 00:53:03,800 ONLY GO FOR CERTAIN AREAS OR 1061 00:53:03,800 --> 00:53:06,560 REGIONS OF THE TUMOR AND IS NOT 1062 00:53:06,560 --> 00:53:10,120 GREAT FOR DISTANT AREAS WHERE 1063 00:53:10,120 --> 00:53:12,360 TUMOR CELLS ARE HIDING OUT AND 1064 00:53:12,360 --> 00:53:15,240 TELLING OTHER NORMAL BRAIN 1065 00:53:15,240 --> 00:53:19,040 CELLS, WE'RE NOT HERE. 1066 00:53:19,040 --> 00:53:25,400 IT'S HELPFUL FOR ONE SITE OF 1067 00:53:25,400 --> 00:53:25,800 DISEASE. 1068 00:53:25,800 --> 00:53:28,920 BUT THOSE TUMOR CELLS ARE 1069 00:53:28,920 --> 00:53:33,960 INFILTRATE I HAVE AND THE FOCUS 1070 00:53:33,960 --> 00:53:36,400 ULTRASOUND ARE NOT HELPFUL FOR 1071 00:53:36,400 --> 00:53:37,880 DISEASE THROUGHOUT THE BRAIN. 1072 00:53:37,880 --> 00:53:40,160 * 1073 00:53:40,160 --> 00:53:41,240 >>DO WE HAVE ANY QUESTIONS FROM 1074 00:53:41,240 --> 00:53:47,760 THE AUDIENCE? 1075 00:53:47,760 --> 00:53:48,880 >>HI, SADHANA. 1076 00:53:48,880 --> 00:53:51,960 THANK YOU FOR A WONDERFUL 1077 00:53:51,960 --> 00:53:52,320 PRESENTATION. 1078 00:53:52,320 --> 00:53:56,680 I WAS CURIOUS WITH YOUR MICRO 1079 00:53:56,680 --> 00:53:59,640 DIALYSIS SET UP ARE YOU ABLE TO 1080 00:53:59,640 --> 00:54:01,840 COMBINE SOMETHING WITH 1081 00:54:01,840 --> 00:54:04,320 CONVECTION ENHANCED DELIVERY? 1082 00:54:04,320 --> 00:54:05,800 >>A LOT OF PEOPLE ASK THAT. 1083 00:54:05,800 --> 00:54:07,800 THIS IS JUST A ONE WAY TOOL FOR 1084 00:54:07,800 --> 00:54:11,120 US TO LOOK AT OUTPUT FROM THE 1085 00:54:11,120 --> 00:54:11,600 BRAIN. 1086 00:54:11,600 --> 00:54:14,280 CONVECTION ENHANCED DELIVERY, 1087 00:54:14,280 --> 00:54:17,040 THEY PLACE THAT AND THEY CAN 1088 00:54:17,040 --> 00:54:20,640 DELIVER THERAPIES TO THE BRAIN. 1089 00:54:20,640 --> 00:54:23,960 ONE DISADVANTAGES IS DEPENDING 1090 00:54:23,960 --> 00:54:26,400 ON HOW FAST OR HOW MUCH DRUG 1091 00:54:26,400 --> 00:54:28,160 VOLUME IS ABLE TO GET TO THE 1092 00:54:28,160 --> 00:54:30,640 TUMOR IT ONLY GOES TO THAT ONE 1093 00:54:30,640 --> 00:54:31,080 AREA. 1094 00:54:31,080 --> 00:54:33,440 WE SEE DISTANT SITE AREAS THAT 1095 00:54:33,440 --> 00:54:34,920 HAVE TUMOR CELLS THAT ARE THERE 1096 00:54:34,920 --> 00:54:37,640 AND SO THE CONVECTION ENHANCED 1097 00:54:37,640 --> 00:54:48,040 DELIVERY TOOL DOES A -- 1098 00:56:20,000 --> 00:56:22,800 >>QUESTION FOR YOU -- WITH THE 1099 00:56:22,800 --> 00:56:24,880 DISCUSSION ABOUT NEW VACCINE 1100 00:56:24,880 --> 00:56:26,960 DOES YOUR WORK PLAY A ROLE IN 1101 00:56:26,960 --> 00:56:29,400 HELPING TO DELIVER TO TARGET 1102 00:56:29,400 --> 00:56:29,600 CELLS? 1103 00:56:29,600 --> 00:56:31,400 >>WE HAVE NOT LOOKED AT THAT 1104 00:56:31,400 --> 00:56:33,520 JUST YET BUT IT WOULD BE GREAT 1105 00:56:33,520 --> 00:56:36,480 TO PAIR WITH A GROUP TO SEE WHAT 1106 00:56:36,480 --> 00:56:38,480 THE DISTRIBUTION OF THE VACCINE 1107 00:56:38,480 --> 00:56:41,680 THERAPY IS AND WHAT HAPPENS TO 1108 00:56:41,680 --> 00:56:44,360 THE ENDO THIEL YUM AT THE TIME 1109 00:56:44,360 --> 00:56:47,560 OF JUST INITIAL TREATMENT VERSUS 1110 00:56:47,560 --> 00:56:51,320 PROLONG GOINGS OF DISEASE * 1111 00:56:51,320 --> 00:56:53,680 PROGRESSION OR IMMUNE SYSTEM 1112 00:56:53,680 --> 00:56:55,200 CHANGES. 1113 00:56:55,200 --> 00:56:57,000 >>SO IT WOULD BE GREAT. 1114 00:56:57,000 --> 00:56:58,760 I JUST TALKED ABOUT IT IN THE 1115 00:56:58,760 --> 00:57:02,040 CONTEXT TODAY OF CHEMOTHERAPY. 1116 00:57:02,040 --> 00:57:06,400 THERE ARE IMMUNE THERAPIES AND 1117 00:57:06,400 --> 00:57:08,920 NONOH CLONAL THERAPIES THAT I 1118 00:57:08,920 --> 00:57:12,200 THINK WILL HAVE DIFFERENT 1119 00:57:12,200 --> 00:57:17,640 SPLASHES THAT WE HAVE NOT -- 1120 00:57:17,640 --> 00:57:23,320 >>THANK YOU. 1121 00:57:23,320 --> 00:57:25,800 >>I WANT TO SAY THANK YOU VERY 1122 00:57:25,800 --> 00:57:28,760 MUCH FOR YOUR WORK. 1123 00:57:28,760 --> 00:57:29,960 THANK YOU VERY MUCH. 1124 00:57:29,960 --> 00:00:00,000 >>THANK YOU.