TriStar Presentation 2011


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TriStar Presentation 2011

  1. 1. Sample Acquisition With Annotated ClinicalInformation: A Critical Success Factor In Biomarker Validation
  2. 2. The Need For Targeted Therapeutics with Companion Diagnostics• Most therapies have been developed based on the histological classification ofthe tumor, as opposed to the molecular profile (including “actionable” drivermutations) that is used to select and stratify CT subjects today• Majority of drugs fail in Phase 2 or 3 trials due to lack of efficacy• Development of targeted therapeutics requires testing in targetedpopulations matched to a drug’s mechanism of action• Evaluation of Trastuzamab in “all comer” breast cancer patients (25% HER+,75% HER2-) would not have shown significant benefit in clinical trials • Early proof of concept in the right patient population • Potentially shorter time to market • Cost-effective healthcare
  3. 3. Unresolved Biologic Questions & Challenges• Tumor heterogeneity• Driver vs passenger mutations• Multiple genes & pathways involved• Molecular evolution of tumors over the course of disease progression & therapyChallenges • Access to tissue • Reliance on solid tissue markers & invasive sampling requirements • Dynamic nature of tumor genotype, phenotype & signaling pathways Sample acquisition with annotated clinical information is a critical success factor in target validation.
  4. 4. Locations Hamburg, GermanyRockville, MD Rome & Catania, Italy Madrid, Spain TMA Repository TMA Repository & Contract Research TMA Repository Array Manufacturing Cancer Stem Cell Research Contract Research Biomarker Research “An emerging unmet need in oncology drug development today is service providers that offer both access to well-annotated specimens and sophisticated molecular analytical capabilities”
  5. 5. Locations TriStar provides: Rockville, MD • Access to 2.5 million archived samples & clinical data Hamburg, Germany • Access to patients (prospective TMA Repository Array Manufacturing Contract Research collection projects) • Fit-for-purpose analytical platforms & services (IHC, FISH, qRT-PCR etc.) Rome & Catania, ItalyTMA Repository & Contract Research • Collaboration for Solid tissue biomarker Cancer Stem Cell Research development Madrid, Spain TMA Repository
  6. 6. ETHICAL CONSIDERATIONS Informed Donor Consent IRB/EC Approval Fully Anonymized Compliant with Current International & EU Regulations Blocks That Are in Excess of Diagnostic Sample Only Team of 17 Pathologists & 5 Oncologists for Clinical Data Review
  7. 7. TriStar PRODUCTS & SERVICESProduct Groups Archived Human Tissue Repository: >2.5 million samples(FFPE & Frozen). 70% Oncology, 30% CNS, GI etc. High-Density Tissue Micro Arrays (>60,000 donor samples)with outcome data Blocks, Large sections, RNA, DNA Outcome Data –Treatment, Response rates, disease –freesurvival (DFS), overall survival (OS) Molecular Data: ER/PR/HER2, p53, BRAF, KRAS, EGFR, PIK3CAetc. Cancer Stem Cell Arrays, Lysates & RNA
  8. 8. TriStar PRODUCTS & SERVICESServices Protein Expression: IHC (Antibody protocol development,automated or manual staining, reading & interpretation) Gene Expression: RT-PCR Gene copy number: FISH/CISH Gene sequencing: DNA sequencing Large-Scale Analysis of Prognostic markers (500-3500 donorsamples) Cross-Reactivity Screening in Normal Tissue (GLP)
  9. 9. QUALITY CONTROL Samples are fixed/frozen within 2 – 10 minutes of Excision OCT embedded sample Snap frozen sample Formalin fixed sample 10% Buffered formalin, 10-12 hrs. fixation time Morphology (H&E) & IHC Markers for immunogenicity RNA & DNA Quality (Agilent 2100 Bioanalyzer) RIN can be checked & provided upon request
  10. 10. Partial list of Equipment ABI3100 sequencer ABI7900 thermal cylcer Roche LightCycler 480 ZEISS MIRAX slide scanner ZEISS PALM Laser Capture micro dissection Eppendorf liquid handling system (robot) QiaCube automated DNA/RNA isolation platform TMA arrayers (3), Fluorescence microscopes (4) Ventana Benchmark XT system (4) Dako Autostainer Plus (3) TMA arrayers (3), Fluorescence microscopes (4) Confocal laser scanning microscope (ZEISS)
  11. 11. Primary Tumors With Matched Mets (Partial List) Primary tumor Matched mets Approx. # Breast Nodal 2000 Distant 20 Bone 200 CRC Nodal 2000 Liver 150 Prostate Nodal 500 Bone 300 Lung (NSCLC) Nodal 300 Bone 100 Pancreatic Nodal 100 Head & Neck Nodal/Soft tissue 100 Gastric Nodal, liver etc 200 Melanoma Nodal 50 Bladder Nodal, colon, lung 100 Esophageal Nodal 200
  12. 12. Samples With Outcome Data (Partial List) Tumor type Data Approx. # Breast 5 yr survival 5000 10 yr. survival 300 400 (responders & Herceptin non-responders) CRC 3-5 yr survival 4000 500 (responders & Bevacizumab, Cetuximab non-responders) Prostate 10 yr survival 5000 Breast, CRC, Ovarian SOC Chemotherapy 1500 (responders & non-responders) Lung (NSCLC) 3-5 yr survival 2000 Docetaxel, Gemcitabine 400 Pancreatic Survival 350 Head & Neck Treatment/survival 200 Gastric Survival 250 NHL Survival 200 Ovarian 3-5 yr. survival 300 Bladder Survival 500
  13. 13. Tissue Microarrays 2. 14. Morphology Formalin Fixed Paraffin Embedded 200. RNA/protein Frozen OCT Embedded DNA
  14. 14. Tissue Micro Arrays To Study Tumor Heterogeneity • The whole tumor is sectioned into 8-10 constituent blocks in a standardized method so that the exact localization of each block is recorded. • Cores are taken from each constituent tumor block and transferred to a TMA. • We believe that this is the "real" way to measure intratumoral heterogeneity rather than taking multiple sample from one block. Our method allows for an overview over the whole tumor. Tumor Type Primary tumors Blocks/tumor Matched Nodal Mets Blocks/met Total TMA Cores NSCLC 146 8 66 4 1432 Breast 147 8 32 4 1304 CRC 140 8 42 4 1288 Prostate 190 10 - - 1900 Bladder 147 8 - - 1176
  15. 15. EGFR Amplification is often Heterogeneous in Lung CancerHeterogeneity found in 7/13 (54%) EGFR amplified NSCLC Different areas Different matched of the primary cancer lymph node metastasesCase#1#2 EGFR FISH Result#3 amplification#4 polysomy#5 normal#6#7 n.a.
  16. 16. ERG Heterogeneity In Prostate Cancer: TMA Resultsn=178; 10 samples per tumor analyzedERG nega v: 75 (42%) 3%ERG posi v: 103 (58%) Interfocal heterogeneity 39% 42% Intrafocal ERG-negative heterogeneity 16% all samples positive
  17. 17. Heterogeneity TMA: Co-analysis Of ERG And PTEN In Prostate Cancer 35 ERG+PTEN 10 PTEN only 4 ERG only  PTEN linked to ERG p<0.0001 31 tumors PTEN+ERG PTEN deletions are late events developing 21 ERG precedes PTEN preferentially in ERG positive prostate 0 PTEN precedes ERG cancers  ERG earlier PTEN + ERG PTEN only ERG only
  18. 18. Prostate Cancer Progression & Prognosis AnalysisFrequency of PTEN deletion is strongly linked to prostate cancer progression (n >2200 donor samples) 50.0 45.0 40.0 p<0.0001 35.0 PTEN homozygous fraction of tumors (%) 30.0 25.0 PTEN hemizygous 20.0 15.0 10.0 5.0 0.0 PIN (n=29) BPH (n=20) pT2 pT3a pT3b pT4 (n=24) HR (n=54) (n=1085) (n=360) (n=227)
  19. 19. Tissue Micro Arrays To Study Tumor Heterogeneity• The level of heterogeneity of therapy target genes maybe relevant for diagnosis and response• HER2 is homogenous in breast cancer butheterogeneous in colon cancer• Tumor heterogeneity is clinically important and can beoptimally addressed by heterogeneity TMAs
  20. 20. Molecular EpidemiologyMost oncology drugs in development are expectedto be active only in sub-sets of patients How frequent is expression in human cancer? Specific cancer subtypes or biological properties? -prognostic relevance What normal tissues do express target? Option 1: Option 2: Review the Perform literature own studies
  21. 21. TriStar: A New Dimension in Tissue Biomarker Analysis
  22. 22. Multi Tumor Analysis Including Less Prevalent Tumor Types Skin: Squamous Cell Carcinoma, Basal Cell Carcinoma, Merkel Cell Carcinoma. Uterine Corpus: Endometrioid Adenocarcinoma, Serous. Parathyroid Gland: Adenoma, Carcinoma. Mammary Gland: Intraductal Carcinoma, Lobular Carcinoma In Situ, Invasive Ductal Carcinoma, Invasiv Lobular Carcinoma, Mucinous Carcinoma, Papillary Carcinoma, Tubular Carcinoma. Kidney: Clear Cell Type, Papillary Type, Chromophobe Cell Type. Urinary Bladder: Non-Invasive Papillary Tumor (Pta), Transitional Cell Carcinoma, Squamous Cell Carcinoma, Adenocarcinoma, Small Cell Carcinoma. Salivary Glands: Mixed Tumor, Adenolymphoma, Adenoma, Mucoepidermoid Carcinoma, Acinic Cell Carcinoma, Adenocarcinoma, Adenoid Cystic Carcinoma. Esophagus: Squamous Cell Carcinoma, Adenocarcinoma. Stomach: Adenocarcinoma Diffuse Type, : Adenocarcinoma Intestinal Type. Adrenal Gland: Adrenal Cortical Adenoma, Adrenal Cortical Carcinoma, Pheochromocytoma. Pancreas: Adenocarcinoma, Adenoma. Mediastinum: Thymoma. Small Intestine: Adenocarcinoma, Carcinoid. Large Intestine: Adenoma, Adenocarcinoma. Appendix: Adenocarcinoma, Carcinoid. Anal: Small Cell Carcinoma. Prostate: Prostatic Adenocarcinoma Untreated, Hormone Refractory Adenocarcinoma Adenocarcinoma, Clear Cell Adenocarcinoma, Atypical Hyperplasia. Cervix: Squamous Cell Carcinoma, Adenocarcinoma. Vagina: Squamous Cell Carcinoma, Adenocarcinoma. Vulva: Squamous Cell Carcinoma. Thyroid Gland: Follicular Carcinoma, Papillary Carcinoma, Anaplastic Carcinoma, Medullary Carcinoma, Adenoma. Lung: Squamous Cell Carcinoma, Adenocarcinoma, Undifferentiated Large Cell Carcinoma, Small Cell Carcinoma, Carcinoid. Testis: Seminoma, Teratoma, Embryonal Carcinoma, Choriocarcinoma, Yolk-Sac-Tumor, Teratocarcinoma. Ovary: Serous Carcinoma, Mucinous Carcinoma, Endometrioid Carcinoma, Brenner Tumor, Germ Cell Tumors. Liver: Hepatocellular Carcinoma, Cholangiocarcinoma. Fibrohistiocytic: Fibrosarcoma, Benign Histiocytoma, Dermatofibrosarcoma Protuberans, Atypical Fibroxanthoma, Malignant Fibrous Hiostiocytoma Lipomatous: Lipoma, Lioposarcoma. Smooth Muscle: Leiomyoma, Leiomyosarcoma, Leiomyoblastoma. Skletal Muscle: Rhabdomyoma, Rhabdomyosarcoma. Blood And Lymph Vessels: Angioma, Epitheloid Hemangioma, Hemangioendothelioma, Angiosarcoma, Kaposi Sarcoma. Perivascular: Glomus Tumor, Hemangiopericytoma. Synovial: Benign Giant Cell Tumor Of Tendon Sheath, Synovial Sarcoma. Mesothelial: Solitary Fibrous Tumor Of Pleura And Peritoneum, Adenomatoidtumor, Malignes Mesothelioma. Neural: Neurofibroma, Neurinoma. Granular Cell Tumor, Malignant Peripheral Nerve Sheath Tumor. Clear Cell Sarcoma. Paraganglioma, Ganglioneuroma. Pnet: Ganglioneuroblastoma, Neuroblastoma, Neuoepithelioma, Extraskelettal Ewings- Sarcoma. Malignant Mesenchymoma. Alveolar Soft Part Sarcoma. Epitheloid Sarcoma. Osseous: Osteoidosteoma, Osteoblastoma, Osteosarcoma. Chondrous: Chondroblastom, Chondrom, Chondrosarcoma, Chordomas. Ewing Sarcoma. Giant Cell Tumor Of The Bone. Brain: Astrocytoma, Glioblastoma Multiforme, Oligodendroglioma, Ependymoma, Medulloblastoma, Medulloepithelioma, Craniopharyngeoma, Esthesioneuroblastoma, Retinoblastoma. Nevus Naevocellularis, Malignant Melanoma, Gastrointestinal Stromatumor, Endometrioid Stromal Sarcoma, Mixed Malignent Mesodermal Tumor, Aml, Cml, Cll, Immunocytic Lymphoma, Plasmocytoma, Centrocytic Lymphoma, Centroblastic Centrocytic Lymphoma, Centroblastic Lymphoma, Immunoblastic Lymphoma, Burkitt Lymphoma, T-Cell Lymphoma Low Grade, T-Cell Lymphoma High Grade, M Hodgkin Lymphocytic Depletion, M Hodgkin Mixed Cell Type, M Hodgkin Nodular Sclerosing etc. All tumors & sub-types are stained. Customer can select and pay for data on specific tumors of interest
  23. 23. HER2 Expression and Amplification in Human CancersTapia et al., Modern Pathology, 20(2), 192–198 (2007) IHC FISH Breast cancer Urinary bladder cancer Stomach cancer Pancreatic cancer Esophageal cancer Endometrial cancer Vulva cancer Gall bladder cancer Lung cancer Ovarian cancer 0.0 5.0 10.0 15.0 20.0 Fraction of HER2-amplified samples (%)
  24. 24. Normal Tissue Analysis 76 tissue types, 532 cell types, 8 donors eachMesenchymal tissues: aorta/intima, aorta/media, heart (left ventricle), sceletal muscle, sceletalmuscle/tongue, myometrium, appendix (muscular wall), esophagus (muscular wall), stomach(muscular wall), ileum (muscular wall), colon descendens (muscular wall), kidney pelvis (muscularwall), urinary bladder (muscular wall), penis (glans/corpus spongiosum), ovary (stroma), fat tissue (white),Surfaces: skin (surface), skin (hairs, sebaceous glands), lip (epithelium), oral cavity, tonsil (surfaceepithelium), anal canal (skin), anal canal (transition epithelium), exocervix, esophagus, kidneypelvis, urinary bladder, amnion/chorion, stomach (antrum), stomach (fundus and corpus), smallintestine, duodenum, small intestine, ileum, appendix, colon descendens, rectum, gallbladder,bronchus, paranasal sinus.Solid organs: lymph node, spleen, thymus, tonsil, liver, pancreas, parotid gland, submandibullarygland, sublingual gland, lip (small salivary gland), duodenum (Brunner gland), kidney cortex, kidneymedulla, prostate, seminal vesicle, epididymis, testis, lung (parenchyma), lung (bronchial glands),breast, endocervix, endometrium (proliferation), endometrium (secretion), fallopian tube,endometrium (early decidua), ovary (stroma), ovary (corpus luteum), ovary (follicular cyst),placenta (first trimenon), placenta (mature), adrenal gland, parathyroid gland, thyroid, cerebellum,cerebrum, pituitary gland (posterior lobe), pituitary gland (anterior lobe) In which normal tissues is the target expressed?
  25. 25. MULTI TUMOR CELL LINE ARRAY (FORMALIN FIXED) 140 Human Cell Lines including NCI 60 To identify tumor cell lines for functional studies/drug screening HCT-116 SNB 19 SR LN-401 GAMG p6 HCT-15 SW-620 UO-31 LN-229 IGR-1(/IGR 1) HEP-G-2 T 47 D 786-O BS 149 CRL-7930 HT29 A 498 MEL HO (P4) TK 10 172 COLO-849 IGR-OV1 U 251 ACHN COS-1 ECV-304 K-562 UACC-257 BT-549 HS-766-T CAKI-2 LOX-IMVI UACC-62 CAKI 1 HUT 12 RT-112 MCF-7 CCRF-CEM HUVEC A 549 293 COLO-205 IMR 90 MDA-MB- MDA-MB-435 A 375 UI-38 Mb(/U- 231 (S) EKVX MBC-5/MRC- 138) NCI(/L)- MOLT 4 HCC(/L)- 5 U-87 MB(/U 87 MG) H226 NCI-H23 2998 SM WS-1 NCI-H460 NCI-H322 (M) HOP 62 BT-474(/BT- HS-68 PC-3 HOP 92 747) NCI-H522 MCF-10A EAL 29 RPMI-8226 OVCAR-3 HS-578T RT 112(/RT II2 SJCRH- RXF 393 OVCAR-4 KM 12 D2I) 30WCB MDA-HER-2 SF 268 OVCAR-5 M-14 IM 9 SK-MEL-2 MALME-3M MDANEO OVCAR-8 VM-CUB 1 KRIB CAL-62 SK-MEL-28 SF 295 HELA DBTRG SK-MEL-5 SF 539 T-98-G HACAT HBL-100(WBC) SK-OV-3 SNB 75 U-343-MG KU-19-19 SN 12C Partial list
  26. 26. CANCER STEM CELL(CSC) LINE ARRAY (FORMALIN FIXED) Cytospins from 33 CSC Lines Tissue cores from 11 matched & 2 unmatched xenografts Core diameter: 1.0mm Thyroid Cores per donor block: 2 Type Donors Cores GBM 8 16 Breast 1 2 Melanoma Thyroid 5 10 Colon 7 14 Lung 5 10 Melanoma 7 14 Matched Lung xenografts: Colon 4 8 Lung 3 6 Breast 1 2 Colon Melanoma 3 6 Unmatched xenografts Breast 2 4 Glioblastoma Total cores 92
  27. 27. Validation PlatformTriStar Breast Cancer Prognosis Array pT stage pN stage 2,200 Breast Cancers with Number of nodes examined 5 yr.follow-up information Number of positive nodes Tumor diameter BRE grade Polymorphy Tubulus formation Mitoses Survival months (99%) Survival tumor specific (40%) Some therapy information (40%) Molecular parameters: FISH: HER2, EGFR, MDM2, CCND1, MYC IHC: ER, PR, p53, Cytokeratins, EGFR, HER2, CD117, others
  28. 28. Breast Cancer Prognosis TMA AnalysisESR1 amplification (FISH) ESR1 Amplification* in 358/1739 (21%) of Breast Cancers Holst, Simon et al, Nat Gen (39), 655-660, 2007
  29. 29. ESR1 amplification and anti ER treatment175 Patients Treated With Tamoxifen Monotherapy 1.0 ESR1 amplification (n=43) 0.9 0.8 0.7 ER IHC positive (n=109) 0.6 Surviving 0.5 ER IHC negative(n=23) 0.4 0.3 0.2 0.1 p<0.0001 0.0 0 20 40 60 80 100 months surv Holst, Simon et al, Nat Gen (39), 655-660, 2007ESR1 amplification may predict response to tamoxifen
  30. 30. Study: TPD52 mRNA Expression Analysis of 1,000 Tumor Samples & Normal Tissues ABI7900 based qRT-PCR, TPD52 vs GAPDH Skin 2 Pancreas 1 Lymph node 2 Stomach 2 Lung 2 Kidney 2 Oral cavitiy 2 Prostate 2 Normal tissues Breast 1 Testis 3 Endometrium 2 Bladder 2 Ovar 2 Thyroid gland 2 Vulvar 2 Brain 2 Myometrium 2 Skeletal muscle 2 Liver 3 Fat tissue 2 Malignant melanoma 11 Liver cancer 50 Larynx carcinoma 39 Pancreatic cancer 38 Lung cancer 134 Stomach cancer 50 Oral cavity cancer 56 Renal cell cancer 59 Breast cancer 53 Prostate cancer 48 Cancers Endometrial cancer 31 Testis cancer 59 Ovarian cancer 33 Urinary bladder cancer 55 Uterus cervix carcinoma 28 Thyroid gland cancer 40 Vulvar cancer 39 Leiomyosarcoma 42 Colon cancer 50 Liposarcoma 36 Esophageal cancer 48
  31. 31. Study: TPD52 mRNA Expression Analysis In 1,000 Tumor Samples & Normal Tissues Frequency of TPD52 expression ≥2 fold down-regulated ≥2 fold up-regulated Lung, small cell Oral cavity Thyroid gland Renal, clear cell Renal, papillary Leiomyosarcoma Lung, adeno Liposarcoma Pancreas Vulvar Liver Lung, large cell Melanoma Lung, squamous Endometrium Stomach Prostate Cervix* Ovar Larynx* Colon* Esophagus squamous* Mamma, lobular Mamma, ductal Esophagus adeno* Bladder , non-invasive Seminoma Bladder, invasive Non-Seminoma100 80 60 40 20 0 20 40 60 80 100 UKE data % of samples showing TPD52 overexpression / downregulation
  32. 32. Study: TPD52 mRNA Expression Analysis In 1,000 Tumor Samples & Normal Tissues TPD52 expression levels Renal, papillary Leiomyosarcoma Renal, clear cell Liposarcoma down-regulated Lung, small cell Lung, adeno Oral cavity Vulvar Pancreas Thyroid gland Liver Lung, large cell Melanoma Endometrium Lung, squamous Stomach Prostate Larynx* Cervix* up-regulated Esophagus squamous* Colon* Esophagus adeno* Bladder , non-invasive Ovar Bladder, invasive Mamma, lobular Mamma, ductal Seminoma Non-Seminoma-4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 UKE data avr. TPD52 expression level (log2)
  33. 33. Study: Sequencing Of All 10 PTEN Exons In 100 Prostate Cancer Samples a) c.1067_1070del c) c.1623G>T e) c.352C>T GCAGAAACAAAAGG GATGTTTGAAACTAT GCTTTGTCAAGATCA b) c.2007G>A d) c.1981_1984del - 5% Mutations - Mutation Unrelated To Deletion GCAACATGATTGTCA TAAAGTAAGTACTAG n PTEN not PTENABI3100, 16 capillaries mutated mutated p value analyzableEppendorf pipetting robot PTEN notLaser capture micro dissection deleted 65 95.4% 4.6% 0.3096*(if necessary) PTEN hemizygous 17 88.2% 11.8% deleted FISH not 18 100.0% 0.0% UKE data analyzable
  34. 34. SAMPLE DATA FIELDS Breast Cancer with Herceptin Treatment & Response Information LOCALISATION REF# ORGAN UNIQUE ID AGE DATE OF SURGERY DIAGNOSIS M (TIME METS POST SURGERY GRADE T N STAGE HER2 ER (%) PR (%) SITE OF MET. METS DIAGNOSIS BY 0) (MONTHS) PREV. START TREAT 1 END START TREAT 2 END FOLLOW FOLLOW FOLLOW SURVIVA SETTINGCHEMOTH. TREAT 1 DETAILS TREAT 1 TREAT 2 DETAILS TREAT 2 UP 1 UP 2 UP 3 L Diffused Large B Cell Lymphoma (DLBCL) Performance Date of Diagnosis CD20 CD10 BCL2 Age SITE* Status diagnosis International Bone Extranodal Symptoms Stage Bulky Epo Prognostic GCSF marrow Location Index Maintainance Treatment Treatment Therapy Response Rituximab Cycles Radiotherapy therapy with start schedule reduction to therapy Rituximab ? Date of Second Response Due to Follow up D.O.D. Note relapse treatment to therapy lymphoma
  35. 35. SAMPLE PROSPECTIVE COLLECTION PROJECTs Prospective collection of formalin fixed samples of mantle cell lymphoma from lymph node sites only with 5-10ug matching RNA per sample Prospective collection of Frozen OCT & FFPE samples of IBD & Ulcerative Colitis, recently diagnosed, diseased + adjacent normal. Matched Serum & Whole Blood with Clinical Labs Prospective collection of formalin fixed & OCT samples of metastatic NSCLC (adenocarcinoma & SCC) with matched nodal mets, serum & RNA Prospective collection of formalin fixed & OCT samples of esophageal adenocarcinoma, serum & RNA
  36. 36. CNS Samples Overview • Alzheimer’s Disease • Parkinson’s Disease • Dementia • StrokeMorphology: Molecular Neuropathology: Clinical Samples:Special stains Genetic investigations FFPE & frozen blocksImmunostains Proteomics RNA, DNA & SerumUltra structure Tissue Micro ArraysMorphometry Contract Research Large sections Animal Models Analysis of model organisms
  37. 37. Overview For validation of targets in neurodegenerative diseases we suggest an approach whereby we focus on the central nervous system to verify targets in patients suffering from a wide range of dementing diseases. Here the sample size is not that crucial. Once we have found the right candidate for the right disease we could increase the sample size and include non-demented control patients to check for specificity.
  38. 38. CNS Tissue Micro Arrays Specified Regions/Disease n= Patient Cores DatasetAlzheimer’s Disease 24 3 576 Age/Gender/ Histopathology/ CognitionStroke 12 4 76 Age/Gender/ Histopathology/ CognitionMulti-Dementia 12 3 144 Age/Gender/ Histopathology/ Cognition
  39. 39. Partial List of Clinical Samples in Alzheimer’s Disease
  40. 40. Partial List of Clinical Samples in Alzheimer’s Disease
  41. 41. TriStar Technology Group, LLCSummary 9700 Great Seneca Highway Rockville, MD 20850 U.S.A Complexity of translational biomarker research supporting drug & diagnostic development increasingly requires knowledge-based services/partnerships that go beyond the traditional fee-for-service model Service providers must offer a range of services, histology labs, analytical platforms, top academic opinion leaders etc. TriStar’s service platform is sustainable, scalable, flexible & cost- effective Very large product offering, standardized QC, top-notch scientific capabilities