bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S2 from Development and Validation of Machine Learning–based Model for the Prediction of Malignancy in Multiple Pulmonary Nodules: Analysis from Multicentric Cohorts
Authors: Chen Kezhong , Nie Yuntao , Park Samina , Zhang Kai , Zhang Yangming , Liu Yuan , Hui Bengang , Zhou Lixin , Wang Xun , Qi Qingyi , Li Hao , Kang Guannan , Huang Yuqing , Chen Yingtai , Liu Jiabao , Cui Jian , Li Mingru , Park In Kyu , Kang Chang Hyun , Shen Haifeng , Yang Yingshun , Guan Tian , Zhang Yaxiao , Yang Fan , Kim Young Tae , Wang Jun
Published: April 2023

Comparison of AUCs between PKU-M model, Brock model, PKU model, Mayo model, and VA model in subgroups
Supplementary Table 1 from Phase Ib/II Study of Cetuximab plus Pembrolizumab in Patients with Advanced RAS Wild-Type Colorectal Cancer
Authors: Fountzilas Christos , Bajor David L. , Mukherjee Sarbajit , Saltzman Joel , Witkiewicz Agnieszka K. , Maguire Orla , Minderman Hans , Nambiar Ram , Rosenheck Hanna R. , Knudsen Erik S. , Muhitch Jason B. , Abrams Scott I. , Wang Chong , Hutson Alan D. , Attwood Kristopher , Hicks Karen A. , Jurcevic Jennifer A. , Kalinski Pawel , Iyer Renuka , Boland Patrick M.
Published: April 2023

Adverse events with maximum grade seen
Supplementary Data from Safety and Efficacy of Pembrolizumab in Combination with Acalabrutinib in Advanced Head and Neck Squamous Cell Carcinoma: Phase 2 Proof-of-Concept Study
Authors: Taylor Matthew H. , Betts Courtney B. , Maloney Lauren , Nadler Eric , Algazi Alain , Guarino Michael J. , Nemunaitis John , Jimeno Antonio , Patel Priti , Munugalavadla Veerendra , Tao Lin , Adkins Douglas , Goldschmidt Jerome H. , Cohen Ezra E.W. , Coussens Lisa M.
Published: April 2023

Supplementary Data from Safety and Efficacy of Pembrolizumab in Combination with Acalabrutinib in Advanced Head and Neck Squamous Cell Carcinoma: Phase 2 Proof-of-Concept Study
Supplementary Data from Gene Expression–Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial
Authors: Edlund Karolina , Madjar Katrin , Lebrecht Antje , Aktas Bahriye , Pilch Henryk , Hoffmann Gerald , Hofmann Manfred , Kolberg Hans-Christian , Boehm Daniel , Battista Marco , Seehase Martina , Stewen Kathrin , Gebhard Susanne , Cadenas Cristina , Marchan Rosemarie , Brenner Walburgis , Hasenburg Annette , Koelbl Heinz , Solbach Christine , Gehrmann Mathias , Tanner Berno , Weber Karsten E. , Loibl Sibylle , Sachinidis Agapios , Rahnenführer Jörg , Schmidt Marcus , Hengstler Jan G.
Published: April 2023

Detailed description of all experimental and biostatistical techniques
Figure S1 from Comprehensive Molecular Analysis of Inflammatory Myofibroblastic Tumors Reveals Diverse Genomic Landscape and Potential Predictive Markers for Response to Crizotinib
Authors: Lee Che-Jui , Schöffski Patrick , Modave Elodie , van Wezel Tom , Boeckx Bram , Sufliarsky Jozef , Gelderblom Hans , Blay Jean-Yves , Debiec-Rychter Maria , Sciot Raf , Bovée Judith V.M.G. , Lambrechts Diether , Wozniak Agnieszka
Published: April 2023

The IMFT case with ETV6-NTRK Fusion (SeqID88), presenting characteristic morphology on H&E staining (A), with split ETV6 signal by FISH shown with arrows (B), TRK immunopositivity with pan-TRK antibody (C). On (D) a schematic presentation of the ETV6-NTRK fusion detected by Archer CTL Fusion Panel.
Appendix from Randomized Phase II Study of PARP Inhibitor ABT-888 (Veliparib) with Modified FOLFIRI versus FOLFIRI as Second-line Treatment of Metastatic Pancreatic Cancer: SWOG S1513
Authors: Chiorean E. Gabriela , Guthrie Katherine A. , Philip Philip A. , Swisher Elizabeth M. , Jalikis Florencia , Pishvaian Michael J. , Berlin Jordan , Noel Marcus S. , Suga Jennifer M. , Garrido-Laguna Ignacio , Cardin Dana Backlund , Radke Marc R. , Duong Mai , Bellasea Shay , Lowy Andrew M. , Hochster Howard S.
Published: April 2023

Protocol
Supplementary Figure S4 from Targeting DNA Damage Repair Functions of Two Histone Deacetylases, HDAC8 and SIRT6, Sensitizes Acute Myeloid Leukemia to NAMPT Inhibition
Authors: Zhang Pu , Brinton Lindsey T. , Williams Katie , Sher Steven , Orwick Shelley , Tzung-Huei Lai , Mims Alice S. , Coss Christopher C. , Kulp Samuel K. , Youssef Youssef , Chan Wing Keung , Mitchell Shaneice , Mustonen Allison , Cannon Matthew , Phillips Hannah , Lehman Amy M. , Kauffman Tierney , Beaver Larry , Canfield Daniel , Grieselhuber Nicole R. , Alinari Lapo , Sampath Deepa , Yan Pearlly , Byrd John C. , Blachly James S. , Lapalombella Rosa
Published: April 2023

Mutant IDH1/2 enhances AR-42/KPT-9274 combination sensitivity in a 2-HG-dependent manner.
Supplementary Table S5 from Cell Type–specific Adaptive Signaling Responses to KRASG12C Inhibition
Authors: Solanki Hitendra S. , Welsh Eric A. , Fang Bin , Izumi Victoria , Darville Lancia , Stone Brandon , Franzese Ryan , Chavan Sandip , Kinose Fumi , Imbody Denis , Koomen John M. , Rix Uwe , Haura Eric B.
Published: April 2023

Supplementary Table S5. The complete list of identified proteins after TMT-based quantitative proteomic analysis in KRASG12C mutant lung cancer cell lines (n=8) with mean-centered log abundance values.
Supplementary Data from Phase Ib Dose Expansion and Translational Analyses of Olaparib in Combination with Capivasertib in Recurrent Endometrial, Triple-Negative Breast, and Ovarian Cancer
Authors: Westin Shannon N. , Labrie Marilyne , Litton Jennifer K. , Blucher Aurora , Fang Yong , Vellano Christopher P. , Marszalek Joseph R. , Feng Ningping , Ma XiaoYan , Creason Allison , Fellman Bryan , Yuan Ying , Lee Sanghoon , Kim Tae-Beom , Liu Jinsong , Chelariu-Raicu Anca , Chen Tsun Hsuan , Kabil Nashwa , Soliman Pamela T. , Frumovitz Michael , Schmeler Katheleen M. , Jazaeri Amir , Lu Karen H. , Murthy Rashmi , Meyer Larissa A. , Sun Charlotte C. , Sood Anil K. , Coleman Robert L. , Mills Gordon B.
Published: April 2023

Supplementary Figures Legends
Supplementary Data from Adavosertib with Chemotherapy in Patients with Primary Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer: An Open-Label, Four-Arm, Phase II Study
Authors: Moore Kathleen N. , Chambers Setsuko K. , Hamilton Erika P. , Chen Lee-may , Oza Amit M. , Ghamande Sharad A. , Konecny Gottfried E. , Plaxe Steven C. , Spitz Daniel L. , Geenen Jill J.J. , Troso-Sandoval Tiffany A. , Cragun Janiel M. , Rodrigo Imedio Esteban , Kumar Sanjeev , Mugundu Ganesh M. , Lai Zhongwu , Chmielecki Juliann , Jones Suzanne F. , Spigel David R. , Cadoo Karen A.
Published: April 2023

Supplementary tables S1-S3 and Supplementary figures S1-Se
Figure S5 from Safety and Efficacy of Intraventricular Immunovirotherapy with Oncolytic HSV-1 for CNS Cancers
Authors: Kang Kyung-Don , Bernstock Joshua D. , Totsch Stacie K. , Gary Sam E. , Rocco Abbey , Nan Li , Li Rong , Etminan Tina , Han Xiaosi , Beierle Elizabeth A. , Eisemann Tanja , Wechsler-Reya Robert J. , Bae Sejong , Whitley Richard , Gillespie G. Yancey , Markert James M. , Friedman Gregory K.
Published: April 2023

Comparison of the protective effect of different pretreatment low doses of IVT oHSV from toxicity after a subsequent treatment dose.
Supplementary Data from Combined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus–Driven Cancers
Authors: Ghosh Soma , Mazumdar Tuhina , Xu Wei , Powell Reid T. , Stephan Clifford , Shen Li , Shah Pooja A. , Pickering Curtis R. , Myers Jeffery N. , Wang Jing , Frederick Mitchell J. , Johnson Faye M.
Published: April 2023

Supplementary Data from Combined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus–Driven Cancers
Supplementary Tables S1-S10 from Triple-Negative PAM50 Non-Basal Breast Cancer Subtype Predicts Benefit from Extended Adjuvant Capecitabine
Authors: Asleh Karama , Lluch Ana , Goytain Angela , Barrios Carlos , Wang Xue Q. , Torrecillas Laura , Gao Dongxia , Ruiz-Borrego Manuel , Leung Samuel , Bines José , Guerrero-Zotano Ángel , García-Sáenz Jose Ángel , Cejalvo Juan Miguel , Herranz Jesus , Torres Roberto , Haba-Rodriguez Juan de la , Ayala Francisco , Gómez Henry , Rojo Federico , Nielsen Torsten O. , Martin Miguel
Published: April 2023

Supplementary Table S1 shows the gene list for the NanoString custom nCounter codeset included in the study. Supplementary Table S2 shows patient characteristics in the GEICAM/CIBOMA translational study cohort versus the original trial. Supplementary Table S3 shows the distribution of PAM50 intrinsic subtypes in the GEICAM/CIBOMA translational study cohort. Supplementary Table S4 shows the differential gene expression analysis performed on the 164 genes included in the custom codeset comparing PAM50 non-basal vs. basal-like subtype and their biological processes. Supplementary Table S5 shows multivariate survival analysis and interaction tests for the four genes and metagenes included in the prespecified hypotheses testing their association with DFS. Supplementary Table S6 shows multivariate survival analysis and interaction tests for the continuous expression of the 38 individual genes included in the prespecified hypotheses testing their association with DRFS. Supplementary Table S7 shows multivariate survival analysis and interaction tests for the continuous expression of the 38 individual genes included in the prespecified hypotheses testing their association with OS. Supplementary Table S8 shows multivariate survival analysis and interaction tests for the continuous expression of the 38 individual genes included in the prespecified hypotheses testing their association with DFS. Supplementary Table S9 shows multivariate survival analysis and interaction tests restricted to the PAM50 non-basal subgroup. Supplementary Table S10 shows Exploratory analysis for the prognostic capacity of the continuous expression of genes and metagenes restricted to the PAM50 non-basal subgroup.
Supplementary Table S3 from Circulating Exosomal PD-L1 at Initial Diagnosis Predicts Outcome and Survival of Patients with Osteosarcoma
Authors: Wang Jun , Guo Wei , Wang Xiaofang , Tang Xiaodong , Sun Xin , Ren Tingting
Published: April 2023

Data file
Supplementary Data from Rb Tumor Suppressor in Small Cell Lung Cancer: Combined Genomic and IHC Analysis with a Description of a Distinct Rb-Proficient Subset
Authors: Febres-Aldana Christopher A. , Chang Jason C. , Ptashkin Ryan , Wang Yuhan , Gedvilaite Erika , Baine Marina K. , Travis William D. , Ventura Katia , Bodd Francis , Yu Helena A. , Quintanal-Villalonga Alvaro , Lai W. Victoria , Egger Jacklynn V. , Offin Michael , Ladanyi Marc , Rudin Charles M. , Rekhtman Natasha
Published: April 2023

Supplementary Data from Rb Tumor Suppressor in Small Cell Lung Cancer: Combined Genomic and IHC Analysis with a Description of a Distinct Rb-Proficient Subset
Supplementary Data from A Phase II Study of Nivolumab plus Gemcitabine in Patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (KCSG HN17–11)
Authors: Jung Hyun Ae , Park Keon-Uk , Cho Sanghee , Lim Jinyeong , Lee Keun-Wook , Hong Min Hee , Yun Tak , An Ho Jung , Park Woong-Yang , Pereira Sergio , Ock Chan-Young , Keam Bhumsuk
Published: April 2023

Supplementary Data from A Phase II Study of Nivolumab plus Gemcitabine in Patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (KCSG HN17–11)
Figure S3 from NBN Pathogenic Germline Variants are Associated with Pan-Cancer Susceptibility and In Vitro DNA Damage Response Defects
Authors: Belhadj Sami , Khurram Aliya , Bandlamudi Chaitanya , Palou-Márquez Guillermo , Ravichandran Vignesh , Steinsnyder Zoe , Wildman Temima , Catchings Amanda , Kemel Yelena , Mukherjee Semanti , Fesko Benjamin , Arora Kanika , Mehine Miika , Dandiker Sita , Izhar Aalin , Petrini John , Domchek Susan , Nathanson Katherine L. , Brower Jamie , Couch Fergus , Stadler Zsofia , Robson Mark , Walsh Michael , Vijai Joseph , Berger Michael , Supek Fran , Karam Rachid , Topka Sabine , Offit Kenneth
Published: April 2023

Supplementary Figure S3. Rates of somatic loss of heterozygosity (LOH) stratified by cancer type. NSCLC: NonSmall Cell Lung Cancer, CRC: Colorectal Cancer.
Supplementary Appendix S1 from Fibroblast Activation Protein Triggers Release of Drug Payload from Non-internalizing Small Molecule Drug Conjugates in Solid Tumors
Authors: Zana Aureliano , Galbiati Andrea , Gilardoni Ettore , Bocci Matilde , Millul Jacopo , Sturm Theo , Stucchi Riccardo , Elsayed Abdullah , Nadal Lisa , Cirillo Martina , Roll Wolfgang , Stegger Lars , Asmus Inga , Backhaus Philipp , Schäfers Michael , Neri Dario , Cazzamalli Samuele
Published: April 2023

Supplementary Information
Supplementary Table 1 from Single-Nucleotide Variants and Epimutations Induce Proteasome Inhibitor Resistance in Multiple Myeloma
Authors: Haertle Larissa , Barrio Santiago , Munawar Umair , Han Seungbin , Zhou Xiang , Simicek Michal , Vogt Cornelia , Truger Marietta , Fernandez Rafael Alonso , Steinhardt Maximilian , Weingart Julia , Snaurova Renata , Nerreter Silvia , Teufel Eva , Garitano-Trojaola Andoni , Da Viá Matteo , Ruiz-Heredia Yanira , Rosenwald Andreas , Bolli Niccolò , Hajek Roman , Raab Peter , Raab Marc S. , Weinhold Niels , Haferlach Claudia , Haaf Thomas , Martinez-Lopez Joaquin , Einsele Hermann , Rasche Leo , Kortüm K. Martin
Published: April 2023

Genetic variants in the Würzburg dataset.
Supplementary Figure 3 from Single-Nucleotide Variants and Epimutations Induce Proteasome Inhibitor Resistance in Multiple Myeloma
Authors: Haertle Larissa , Barrio Santiago , Munawar Umair , Han Seungbin , Zhou Xiang , Simicek Michal , Vogt Cornelia , Truger Marietta , Fernandez Rafael Alonso , Steinhardt Maximilian , Weingart Julia , Snaurova Renata , Nerreter Silvia , Teufel Eva , Garitano-Trojaola Andoni , Da Viá Matteo , Ruiz-Heredia Yanira , Rosenwald Andreas , Bolli Niccolò , Hajek Roman , Raab Peter , Raab Marc S. , Weinhold Niels , Haferlach Claudia , Haaf Thomas , Martinez-Lopez Joaquin , Einsele Hermann , Rasche Leo , Kortüm K. Martin
Published: April 2023

DNA promoter methylation of a subset of proteasome subunit genes.
Heatmap comparing methylation pattern of 35 MM patients and 30 PBMC samples. The methylation degree is given by a color code: red – methylated state, blue – unmethylated state. Each line represents an individual sample, each column a single CpG. The methylation degree is encoded by color with blue for an unmethylated and red for a methylated state. Artificially methylated controls were included. For PSMD5, hypermethylation was only present in MM cells, not in PBMCs. For PSMC2, hypermethylation occurred in both, MM cells and PBMCs, indicating a physiological state probably independent of disease development and progression. In the remaining proteasome subunit genes, no aberrant promoter methylation was detected.
Supplementary Figure 7 from Molecular Clusters and Tumor-Immune Drivers of IgM Monoclonal Gammopathies
Authors: Mondello Patrizia , Paludo Jonas , Novak Joseph P. , Wenzl Kerstin , Yang Zhi-Zhang , Jalali Shahrzad , Krull Jordan E. , Braggio Esteban , Dasari Surendra , Manske Michelle K. , Abeykoon Jithma A. , Sarangi Vivekananda , Kapoor Prashant , Paulus Aneel , Reeder Craig B. , Ailawadhi Sikander , Chanan-Khan Asher A. , Kyle Robert A. , Gertz Morie A. , Novak Anne J. , Ansell Stephen M.
Published: April 2023

Supplementary Figure 7 A. Heat map of Spearman's correlation coefficients among paired metabolites in the bone marrow (BM) supernatant and peripheral blood (PB) serum of 12 patients with WM. Positive correlations are shown in red, whereas negative correlations are indicated in blue. B. Heat map showing different expression of 44 metabolites in the BM supernatant among the three molecular clusters. The left bar shows correlation coefficients between BM and PB metabolites. Gray squares indicate non significance.
Supplementary Table 3 from Genomic Complexity Predicts Resistance to Endocrine Therapy and CDK4/6 Inhibition in Hormone Receptor–Positive (HR+)/HER2-Negative Metastatic Breast Cancer
Authors: Davis Andrew A. , Luo Jingqin , Zheng Tiantian , Dai Chao , Dong Xiaoxi , Tan Lu , Suresh Rama , Ademuyiwa Foluso O. , Rigden Caron , Rearden Timothy P. , Clifton Katherine , Weilbaecher Katherine , Frith Ashley , Tandra Pavan K. , Summa Tracy , Haas Brittney , Thomas Shana , Hernandez-Aya Leonel F. , Peterson Lindsay L. , Wang Xiaohong , Luo Shujun J. , Zhou Kemin , Du Pan , Jia Shidong , King Bonnie L. , Krishnamurthy Jairam , Ma Cynthia X.
Published: April 2023

Gene alterations associated with shorter PFS.
Figure S1 from Five-Year Clinical Outcomes after Neoadjuvant Nivolumab in Resectable Non–Small Cell Lung Cancer
Authors: Rosner Samuel , Reuss Joshua E. , Zahurak Marianna , Zhang Jiajia , Zeng Zhen , Taube Janis , Anagnostou Valsamo , Smith Kellie N. , Riemer Joanne , Illei Peter B. , Broderick Stephen R. , Jones David R. , Topalian Suzanne L. , Pardoll Drew M. , Brahmer Julie R. , Chaft Jamie E. , Forde Patrick M.
Published: April 2023

Recurrence per PDL1 and MPR
Supplementary Table S5 from Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial
Authors: Elía Andrés , Saldain Leo , Vanzulli Silvia I. , Helguero Luisa A. , Lamb Caroline A. , Fabris Victoria , Pataccini Gabriela , Martínez-Vazquez Paula , Burruchaga Javier , Caillet-Bois Ines , Spengler Eunice , Acosta Haab Gabriela , Liguori Marcos , Castets Alejandra , Lovisi Silvia , Abascal María F. , Novaro Virginia , Sánchez Jana , Muñoz Javier , Belizán José M. , Abba Martín C. , Gass Hugo , Rojas Paola , Lanari Claudia
Published: April 2023

RNA-Seq Variant calling
Supplementary Figure S1 from Prediction of Response to Lenvatinib Monotherapy for Unresectable Hepatocellular Carcinoma by Machine Learning Radiomics: A Multicenter Cohort Study
Authors: Bo Zhiyuan , Chen Bo , Zhao Zhengxiao , He Qikuan , Mao Yicheng , Yang Yunjun , Yao Fei , Yang Yi , Chen Ziyan , Yang Jinhuan , Yu Haitao , Ma Jun , Wu Lijun , Chen Kaiyu , Wang Luhui , Wang Mingxun , Shi Zhehao , Yao Xinfei , Dong Yulong , Shi Xintong , Shan Yunfeng , Yu Zhengping , Wang Yi , Chen Gang
Published: April 2023

Kaplan–Meier curves analysis between responders and nonresponders with unresectable HCC treated with lenvatinib monotherapy. (A) Kaplan–Meier curves of overall survival between responders and nonresponders; (B) Kaplan–Meier curves of progression-free survival between responders and nonresponders. Abbreviations: HCC, hepatocellular carcinoma; HR, hazard ratio.
Supplementary Table S2 from Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial
Authors: Elía Andrés , Saldain Leo , Vanzulli Silvia I. , Helguero Luisa A. , Lamb Caroline A. , Fabris Victoria , Pataccini Gabriela , Martínez-Vazquez Paula , Burruchaga Javier , Caillet-Bois Ines , Spengler Eunice , Acosta Haab Gabriela , Liguori Marcos , Castets Alejandra , Lovisi Silvia , Abascal María F. , Novaro Virginia , Sánchez Jana , Muñoz Javier , Belizán José M. , Abba Martín C. , Gass Hugo , Rojas Paola , Lanari Claudia
Published: April 2023

Evaluation of Ki67 expression in paired samples before and after mifepristone treatment by two independent pathologists, and time elapsed between core needle biopsy and surgery.
Supplementary Figure S2 from Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial
Authors: Elía Andrés , Saldain Leo , Vanzulli Silvia I. , Helguero Luisa A. , Lamb Caroline A. , Fabris Victoria , Pataccini Gabriela , Martínez-Vazquez Paula , Burruchaga Javier , Caillet-Bois Ines , Spengler Eunice , Acosta Haab Gabriela , Liguori Marcos , Castets Alejandra , Lovisi Silvia , Abascal María F. , Novaro Virginia , Sánchez Jana , Muñoz Javier , Belizán José M. , Abba Martín C. , Gass Hugo , Rojas Paola , Lanari Claudia
Published: April 2023

Morphological features after mifepristone treatment. A-D, Images illustrating increased stromal tissue (A), thin and scarce collagen fibers, and increased stromal matrix (arrow; B), an area of tissue remodeling (C), and an area of increased differentiation (D) observed in the surgical samples (S) compared to the respective core needle biopsies (CNB). E, Image illustrates an area of necrosis (dotted arrow) together with a differentiated structure (black arrow) in a surgical sample. F, Cells with Alcian blue+ (left), PAS+ (middle) and MUC-1+ (immunohistochemistry; right) vacuoles observed in a mifepristone-treated tumor. Inset: High power field of a differentiated gland/duct.
Supplementary Figure S1 from Synthetic Lethal Interaction with BCL-XL Blockade Deepens Response to Cetuximab in Patient-Derived Models of Metastatic Colorectal Cancer
Authors: Leto Simonetta M. , Ferri Martina , Sassi Francesco , Zanella Eugenia R. , Cottino Francesca , Vurchio Valentina , Catalano Irene , Ferrero Alessandro , Zingaretti Caterina C. , Marchiò Caterina , Grassi Elena , Trusolino Livio , Bertotti Andrea
Published: April 2023

Preferential binding of upregulated BIM to BCL-XL in EGFR-inhibited mCRC organoids.
Supplementary Table S1: Clinical Trials of ENPP1 inhibitors from ENPP1 Immunobiology as a Therapeutic Target
Authors: Ruiz-Fernández de Córdoba Borja , Martínez-Monge Rafael , Lecanda Fernando
Published: April 2023

Clinical Trials of ENPP1 inhibitors
Supplementary Figure S5 from Human Effectors of Acute and Chronic GVHD Overexpress CD83 and Predict Mortality
Authors: Holtan Shernan G. , Savid-Frontera Constanza , Walton Kelly , Eaton Anne A. , Demorest Connor , Hoeschen Andrea , Zhang Ling , Reid Kayla , Kurian Tony , Sayegh Zena , Julia Estefania , Maakaron Joseph , Bachanova Veronika , Jurdi Najla El , MacMillan Margaret L. , Weisdorf Daniel J. , Felices Martin , Miller Jeffrey S. , Blazar Bruce R. , Davila Marco L. , Betts Brian C.
Published: April 2023

CD83 CAR T does not impair human hematopoiesis in vivo
Supplementary Figure S4 from Human Effectors of Acute and Chronic GVHD Overexpress CD83 and Predict Mortality
Authors: Holtan Shernan G. , Savid-Frontera Constanza , Walton Kelly , Eaton Anne A. , Demorest Connor , Hoeschen Andrea , Zhang Ling , Reid Kayla , Kurian Tony , Sayegh Zena , Julia Estefania , Maakaron Joseph , Bachanova Veronika , Jurdi Najla El , MacMillan Margaret L. , Weisdorf Daniel J. , Felices Martin , Miller Jeffrey S. , Blazar Bruce R. , Davila Marco L. , Betts Brian C.
Published: April 2023

Human CD83 cell surface tissue microarray (TMA)
Supplementary Figure S2 from Human Effectors of Acute and Chronic GVHD Overexpress CD83 and Predict Mortality
Authors: Holtan Shernan G. , Savid-Frontera Constanza , Walton Kelly , Eaton Anne A. , Demorest Connor , Hoeschen Andrea , Zhang Ling , Reid Kayla , Kurian Tony , Sayegh Zena , Julia Estefania , Maakaron Joseph , Bachanova Veronika , Jurdi Najla El , MacMillan Margaret L. , Weisdorf Daniel J. , Felices Martin , Miller Jeffrey S. , Blazar Bruce R. , Davila Marco L. , Betts Brian C.
Published: April 2023

Clinical outcomes based on grade II-IV acute GVHD or frequency of circulating CD83, CD4 T cells
Supplemental Table 2 from Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit
Authors: Mascarella Marco A. , Olonisakin Tolani F. , Rumde Purva , Vendra Varun , Nance Melonie A. , Kim Seungwon , Kubik Mark W. , Sridharan Shaum S. , Ferris Robert L. , Fenton Moon J. , Clayburgh Daniel R. , Ohr James P. , Joyce Sonali C. , Sen Malabika , Herman James G. , Grandis Jennifer R. , Zandberg Dan P. , Duvvuri Umamaheswar
Published: April 2023

Patient characteristics of control group
Supplementary Figure S1 from Human Effectors of Acute and Chronic GVHD Overexpress CD83 and Predict Mortality
Authors: Holtan Shernan G. , Savid-Frontera Constanza , Walton Kelly , Eaton Anne A. , Demorest Connor , Hoeschen Andrea , Zhang Ling , Reid Kayla , Kurian Tony , Sayegh Zena , Julia Estefania , Maakaron Joseph , Bachanova Veronika , Jurdi Najla El , MacMillan Margaret L. , Weisdorf Daniel J. , Felices Martin , Miller Jeffrey S. , Blazar Bruce R. , Davila Marco L. , Betts Brian C.
Published: April 2023

Increased CD4 T cell CD83 expression is associated with earlier acute GVHD diagnosis
Supplemental Table 1 from Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit
Authors: Mascarella Marco A. , Olonisakin Tolani F. , Rumde Purva , Vendra Varun , Nance Melonie A. , Kim Seungwon , Kubik Mark W. , Sridharan Shaum S. , Ferris Robert L. , Fenton Moon J. , Clayburgh Daniel R. , Ohr James P. , Joyce Sonali C. , Sen Malabika , Herman James G. , Grandis Jennifer R. , Zandberg Dan P. , Duvvuri Umamaheswar
Published: April 2023

Comparison of clinical to pathologic stage migration between patients enrolled in 1 of 4 window trials compared to a control group
Supplementary Methodology 1 from Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial
Authors: Morgan Robert D. , Clamp Andrew R. , White Daniel J. , Price Marcus , Burghel George J. , Ryder W. David J. , Mahmood Reem D. , Murphy Alexander D. , Hasan Jurjees , Mitchell Claire L. , Salih Zena , Wheeler Chelsey , Buckley Emma , Truelove Joanna , King Georgia , Ainaoui Yasmina , Bhaskar Sanjeev S. , Shaw Joseph , Evans D. Gareth R. , Kilerci Bedirhan , Pearce Simon P. , Brady Gerard , Dive Caroline , O'Connor James P.B. , Wallace Andrew J. , Rothwell Dominic G. , Edmondson Richard J. , Jayson Gordon C.
Published: April 2023

Supplementary Methodology.
Supplementary Table S7 from A Phase II Window of Opportunity Study of Neoadjuvant PD-L1 versus PD-L1 plus CTLA-4 Blockade for Patients with Malignant Pleural Mesothelioma
Authors: Lee Hyun-Sung , Jang Hee-Jin , Ramineni Maheshwari , Wang Daniel Y. , Ramos Daniela , Choi Jong Min , Splawn Taylor , Espinoza Monica , Almarez Michelle , Hosey Leandria , Jo Eunji , Hilsenbeck Susan , Amos Christopher I. , Ripley R. Taylor , Burt Bryan M.
Published: April 2023

Supplementary Table 7. CyTOF antibody panel for PBMC, BMMC, and tumor-infiltrating immune cells, relevant to Figure 4 and Figure 5.
Supplementary Table S3 from A Phase II Window of Opportunity Study of Neoadjuvant PD-L1 versus PD-L1 plus CTLA-4 Blockade for Patients with Malignant Pleural Mesothelioma
Authors: Lee Hyun-Sung , Jang Hee-Jin , Ramineni Maheshwari , Wang Daniel Y. , Ramos Daniela , Choi Jong Min , Splawn Taylor , Espinoza Monica , Almarez Michelle , Hosey Leandria , Jo Eunji , Hilsenbeck Susan , Amos Christopher I. , Ripley R. Taylor , Burt Bryan M.
Published: April 2023

Supplementary Table 3. Postoperative 30-day adverse events (AEs) observed after surgery.
Supplementary Figure S7 from A Phase II Window of Opportunity Study of Neoadjuvant PD-L1 versus PD-L1 plus CTLA-4 Blockade for Patients with Malignant Pleural Mesothelioma
Authors: Lee Hyun-Sung , Jang Hee-Jin , Ramineni Maheshwari , Wang Daniel Y. , Ramos Daniela , Choi Jong Min , Splawn Taylor , Espinoza Monica , Almarez Michelle , Hosey Leandria , Jo Eunji , Hilsenbeck Susan , Amos Christopher I. , Ripley R. Taylor , Burt Bryan M.
Published: April 2023

Supplementary Figure 7. Characterization of CD57+ T cell populations in tumor and PBMCs
from MPM patients.
Supplementary Figure S4 from A Phase II Window of Opportunity Study of Neoadjuvant PD-L1 versus PD-L1 plus CTLA-4 Blockade for Patients with Malignant Pleural Mesothelioma
Authors: Lee Hyun-Sung , Jang Hee-Jin , Ramineni Maheshwari , Wang Daniel Y. , Ramos Daniela , Choi Jong Min , Splawn Taylor , Espinoza Monica , Almarez Michelle , Hosey Leandria , Jo Eunji , Hilsenbeck Susan , Amos Christopher I. , Ripley R. Taylor , Burt Bryan M.
Published: April 2023

Supplementary Figure 4. Frequencies of other immune and stromal cell compositions before and
after ICB.
Supplementary Figure S4 from Molecular Subtypes of Head and Neck Cancer in Patients of African Ancestry
Authors: Mezghani Nadia , Yao Alexandria , Vasilyeva Daria , Kaplan Nicole , Shackelford Austin , Yoon Angela , Phillipone Elizabeth , Dubey Sunil , Schwartz Gary K. , Taylor Alison M. , Momen-Heravi Fatemeh
Published: April 2023

Advanced HNC differential mutations and gene expression by race
Supplementary Figure S2 from Molecular Subtypes of Head and Neck Cancer in Patients of African Ancestry
Authors: Mezghani Nadia , Yao Alexandria , Vasilyeva Daria , Kaplan Nicole , Shackelford Austin , Yoon Angela , Phillipone Elizabeth , Dubey Sunil , Schwartz Gary K. , Taylor Alison M. , Momen-Heravi Fatemeh
Published: April 2023

Differential DNA methylation by race
Supplementary Table S1 from Functional Homologous Recombination Assay on FFPE Specimens of Advanced High-Grade Serous Ovarian Cancer Predicts Clinical Outcomes
Authors: Pikkusaari Sanna , Tumiati Manuela , Virtanen Anni , Oikkonen Jaana , Li Yilin , Perez-Villatoro Fernando , Muranen Taru , Salko Matilda , Huhtinen Kaisa , Kanerva Anna , Koskela Heidi , Tapper Johanna , Koivisto-Korander Riitta , Joutsiniemi Titta , Haltia Ulla-Maija , Lassus Heini , Hautaniemi Sampsa , Färkkilä Anniina , Hynninen Johanna , Hietanen Sakari , Carpén Olli , Kauppi Liisa
Published: April 2023

HRR gene mutations found in WGS/WES or clinical BRCA1/2 mutational testing.
Supplementary Figure S8 from Functional Homologous Recombination Assay on FFPE Specimens of Advanced High-Grade Serous Ovarian Cancer Predicts Clinical Outcomes
Authors: Pikkusaari Sanna , Tumiati Manuela , Virtanen Anni , Oikkonen Jaana , Li Yilin , Perez-Villatoro Fernando , Muranen Taru , Salko Matilda , Huhtinen Kaisa , Kanerva Anna , Koskela Heidi , Tapper Johanna , Koivisto-Korander Riitta , Joutsiniemi Titta , Haltia Ulla-Maija , Lassus Heini , Hautaniemi Sampsa , Färkkilä Anniina , Hynninen Johanna , Hietanen Sakari , Carpén Olli , Kauppi Liisa
Published: April 2023

A. PFS-based survival curves shown separately for discovery and validation cohorts. B. Response to second-line platinum therapy. C. PFS-based survival curves excluding BRCAmut fHRD patients.
Supplementary Figure S1 from Functional Homologous Recombination Assay on FFPE Specimens of Advanced High-Grade Serous Ovarian Cancer Predicts Clinical Outcomes
Authors: Pikkusaari Sanna , Tumiati Manuela , Virtanen Anni , Oikkonen Jaana , Li Yilin , Perez-Villatoro Fernando , Muranen Taru , Salko Matilda , Huhtinen Kaisa , Kanerva Anna , Koskela Heidi , Tapper Johanna , Koivisto-Korander Riitta , Joutsiniemi Titta , Haltia Ulla-Maija , Lassus Heini , Hautaniemi Sampsa , Färkkilä Anniina , Hynninen Johanna , Hietanen Sakari , Carpén Olli , Kauppi Liisa
Published: April 2023

The effects of long time-to-fixation on DNA damage markers
Supplemental Figure S4 from Favorable Activity and Safety Profile of Memory-Enriched CD19-Targeted Chimeric Antigen Receptor T-Cell Therapy in Adults with High-Risk Relapsed/Refractory ALL
Authors: Aldoss Ibrahim , Khaled Samer K. , Wang Xiuli , Palmer Joycelynne , Wang Yan , Wagner Jamie R. , Clark Mary C. , Simpson Jennifer , Paul Jinny , Vyas Vibhuti , Chien Sheng-Hsuan , Stein Anthony , Pullarkat Vinod , Salhotra Amandeep , Al Malki Monzr M. , Aribi Ahmed , Sandhu Karamjeet , Thomas Sandra H. , Budde Lihua E. , Marcucci Guido , Brown Christine E. , Forman Stephen J.
Published: April 2023

Toxicity management algorithms
Figure S5 from LAMC2 Regulates Key Transcriptional and Targetable Effectors to Support Pancreatic Cancer Growth
Authors: Erice Oihane , Narayanan Shruthi , Feliu Iker , Entrialgo-Cadierno Rodrigo , Malinova Antonia , Vicentini Caterina , Guruceaga Elizabeth , Delfino Pietro , Trajkovic-Arsic Marija , Moreno Haritz , Valencia Karmele , Blanco Ester , Macaya Irati , Öhlund Daniel , Khatri Purvesh , Lecanda Fernando , Scarpa Aldo , Siveke Jens T. , Corbo Vincenzo , Ponz-Sarvise Mariano , Vicent Silve
Published: April 2023

Suppl. Figure 5. A. RNA expression of KRAS, AREG, DUSP6 and FOSL1 in PATU8902 and HPAFII cells expressing a TET-inducible KRAS shRNA or a control shRNA. B. Box and whiskers plot showing Mean Fluorescence Intensity (MFI) of Areg, Dusp6, Fosl1 upon KRas inactivation in iKRAS GEM. Error bars correspond to s.d. C. Heat map of downregulated genes in HPAFII cells expressing a tet-inducible LAMC2 shRNA compared to control group (shRNA GFP). D. LAMC2 and FOSL1 mRNA expression in PATU8902 and HPAFII cells expressing a tet-inducible LAMC2 shRNA or a control shRNA. Error bars correspond to s.d. E. mRNA expression of overlapping LAMC2 and FOSL1 downregulated genes (LAMC2 -ctrl-, FGFBP1, HMGA1, AURKA, HMMR, PLK1, SNAI2 and PITPNC1) in PATU8902 and HPAFII cells expressing a TET-inducible LAMC2 shRNA or a control shRNA. F. Protein expression of phospho-ERK, ERK. Phospho-EGFR, EGFR in PATU8902 and HPAFII cells expressing a TETinducible LAMC2 shRNAs or a control shRNA. Quantification: pEGFR levels normalized to total EGFR levels and housekeeping protein levels. G. Fosl1 and AXL protein expression in PATU8902 and HPAFII cells treated with AKTi (10μM) and vehicle control. Quantification: AXL and FOSL1 levels normalized to housekeeping protein levels.
Data from Overexpression of Prostate-Specific TMPRSS2(exon 0)-ERG Fusion Transcripts Corresponds with Favorable Prognosis of Prostate Cancer
Authors: Hermans Karin G. , Boormans Joost L. , Gasi Delila , van Leenders Geert J.H.L. , Jenster Guido , Verhagen Paul C.M.S. , Trapman Jan
Published: April 2023

Abstract
Purpose: To gain insight in the mechanism and clinical relevance of TMPRSS2-ERG expression in prostate cancer, we determined the specific characteristics of fusion transcripts starting at TMPRSS2 exon 1 and at a more upstream and less characterized exon 0.

Experimental Design: We used quantitative PCR analysis to investigate expression of wild-type TMPRSS2(exon 0) and TMPRSS2(exon 1) and of ERG fusion transcripts. Expression was tested in normal tissue samples, in prostate cancer cell lines and xenografts, and in fresh-frozen clinical prostate cancer samples (primary tumors and recurrences). Expression in clinical samples was correlated with disease progression.

Results: TMPRSS2(exon 0) and TMPRSS2(exon 1) transcripts were similarly androgen regulated in prostate cancer cell lines, but the expression levels of TMPRSS2(exon 1) were much higher. Comparison of expression in different tissues showed TMPRSS2(exon 0) expression to be much more prostate specific. In androgen receptor–positive prostate cancer xenografts, TMPRSS2(exon 1) transcripts were expressed at similar levels, but TMPRSS2(exon 0) transcripts were expressed at very variable levels. The same phenomenon was observed for TMPRSS2-ERG fusion transcripts. In clinical prostate cancers, the expression of TMPRSS2(exon 0)-ERG was even more variable. Expression of TMPRSS2(exon 0)-ERG transcripts was detected in 55% (24 of 44) of gene fusion–positive primary tumors but only in 15% (4 of 27) of gene fusion–positive recurrences and at much lower levels. Furthermore, in primary tumors, expression of TMPRSS2(exon 0)-ERG transcripts was an independent predictor of biochemical progression-free survival.

Conclusion: The expression of TMPRSS2(exon 0)-ERG fusion transcripts in prostate cancer is associated with a less-aggressive biological behavior. (Clin Cancer Res 2009;15(20):6398–403)
Data from Increased Ectonucleotidase Expression and Activity in Regulatory T Cells of Patients with Head and Neck Cancer
Authors: Mandapathil Magis , Szczepanski Miroslaw J. , Szajnik Marta , Ren Jin , Lenzner Diana E. , Jackson Edwin K. , Gorelik Elieser , Lang Stephan , Johnson Jonas T. , Whiteside Theresa L.
Published: April 2023

Abstract
Purpose: Regulatory T cell (Treg) frequency and activity are increased in cancer patients and play a major role in tumor escape. Although disease progression is favored by the presence of Treg, mechanisms used by Treg to suppress antitumor immunity are unknown. The ectonucleotidases CD39 and CD73 are expressed in Treg and convert ATP into immunosuppressive adenosine. In this study, the involvement of the adenosinergic pathway in Treg-mediated suppression in head and neck squamous cell carcinoma (HNSCC) patients was evaluated.

Experimental Design: HNSCC patients with an active disease (n = 19) and patients with no evident disease after therapy (n = 14) were studied. Ectonucleotidase expression on CD4+ T cells and CD4+CD25high Treg was evaluated by flow cytometry and compared with normal controls. Ectonucleotidase activity was also compared within these three groups. The data were analyzed for associations of ectonucleotidase expression/function with disease stage.

Results: The percentages and expression levels of CD39 and CD73 in CD4+ T cells and Treg were greater in HNSCC than in normal controls and highest in patients with no evident disease. Patients' Treg hydrolyzed ATP at higher rates and produced higher levels of adenosine than normal controls' Treg. The increased frequency and enzymatic activity of CD4+CD39+ cells corresponded to increased adenosine-mediated suppression of effector T cells, which was partly inhibited by ARL67156, an ectonucleotidase inhibitor, and by ZM241385, a selective A2a/A2b receptor antagonist.

Conclusions: CD39+ Treg frequency and adenosine-mediated suppression are significantly increased in HNSCC patients. The adenosinergic pathway is involved in Treg-mediated immunosuppression in cancer and its attenuation could be a promising immunotherapeutic strategy for patients with HNSCC. (Clin Cancer Res 2009;15(20):6348–57)
Data from Preclinical Characterization of SGN-70, a Humanized Antibody Directed against CD70
Authors: McEarchern Julie A. , Smith Leia M. , McDonagh Charlotte F. , Klussman Kerry , Gordon Kristine A. , Morris-Tilden Carol A. , Duniho Steven , Ryan Maureen , Boursalian Tamar E. , Carter Paul J. , Grewal Iqbal S. , Law Che-Leung
Published: April 2023

Abstract
Purpose: CD70 (CD27L) is a member of the tumor necrosis factor family aberrantly expressed on a number of hematologic malignancies and some carcinomas. CD70 expression on malignant cells coupled with its highly restricted expression on normal cells makes CD70 an attractive target for monoclonal antibody (mAb)–based therapies. We developed a humanized anti-CD70 antibody, SGN-70, and herein describe the antitumor activities of this mAb.

Experimental Design: CD70 expression on primary tumors was evaluated by immunohistochemical staining of Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, and renal cell carcinoma tissue microarrays. The CD70-binding and cytotoxic activities of SGN-70 were tested in vitro using a number of cell-based assays. The in vivo antitumor properties of SGN-70 were tested in severe combined immunodeficient mice bearing disseminated lymphoma and multiple myeloma xenografts. Mechanism-of-action studies were conducted using SGN-70v, a variant mAb with equivalent target-binding activity but impaired Fcγ receptor binding compared with SGN-70.

Results: Immunohistochemical analysis identified CD70 expression on ∼40% of multiple myeloma isolates and confirmed CD70 expression on a high percentage of Hodgkin lymphoma Reed-Sternberg cells, non-Hodgkin lymphoma, and renal cell carcinoma tumors. SGN-70 lysed CD70+ tumor cells via Fc-dependent functions, including antibody-dependent cellular cytotoxicity and phagocytosis and complement fixation. In vivo, SGN-70 treatment significantly decreased tumor burden and prolonged survival of tumor-bearing mice.

Conclusions: SGN-70 is a novel humanized IgG1 mAb undergoing clinical development for the treatment of CD70+ cancers. SGN-70 possesses Fc-dependent antibody effector functions and mediates antitumor activity in vivo.
Data from A Phase I Trial of Enzastaurin in Patients with Recurrent Gliomas
Authors: Kreisl Teri N. , Kim Lyndon , Moore Kraig , Duic Paul , Kotliarova Svetlana , Walling Jennifer , Musib Luna , Thornton Donald , Albert Paul S. , Fine Howard A.
Published: April 2023

Abstract
Purpose: Enzastaurin is a selective inhibitor of protein kinase C β. Prior phase I studies did not show increased drug exposures with escalating once daily administration. Limits from gastrointestinal absorption may be overcome by twice daily dosing, potentially improving antitumor effects.

Experimental Design: We conducted a phase I dose escalation study in 26 patients with recurrent malignant glioma, stratified by use of enzyme-inducing antiepileptic drugs, to investigate whether divided twice daily dosing results in higher exposures compared with once daily dosing. Phosphorylated glycogen synthase 3 β was analyzed as a potential biomarker of enzastaurin activity.

Results: Enzastaurin was poorly tolerated at all dose levels evaluated (500, 800, and 1,000 mg total daily), with thrombocytopenia and prolonged QTc as dose-limiting toxicities. The average drug concentration of enzastaurin under steady-state conditions was doubled by twice daily dosing compared with daily dosing [1.990; 90% confidence interval (CI), 1.450-2.730]. Additionally, geometric mean ratios doubled with 800 versus 500 mg dosing for both daily (2.687; 90% CI, 1.232-5.860) and twice daily regimens (1.852; 90% CI, 0.799-4.292). Two patients achieved long-term benefit (over 150 weeks progression free).

Conclusions: Higher and more frequent dosing of enzastaurin resulted in improved drug exposure but with unacceptable toxicity at the doses tested. Phosphorylated glycogen synthase 3 β may be a useful biomarker of the biological activity of enzastaurin. Enzastaurin has activity in a subset of malignant glioma patients and warrants continued study in combination with other agents using a maximal once daily dose of 500 mg.
Data from Clinical and Pharmacologic Study of the Novel Prodrug Delimotecan (MEN 4901/T-0128) in Patients with Solid Tumors
Authors: Veltkamp Stephan A. , Witteveen Els O. , Capriati Angela , Crea Attilio , Animati Fabio , Voogel-Fuchs Marja , van den Heuvel Ingeborg J.G.M. , Beijnen Jos H. , Voest Emile E. , Schellens Jan H.M.
Published: April 2023

Abstract
Purpose: To investigate i.v. administration of delimotecan (MEN 4901/T-0128), a carboxymethyldextran polymer prodrug of the active camptothecin derivative T-2513, and to assess the maximum tolerated dose, safety profile, clinical pharmacology, and antitumor activity of delimotecan and metabolites.

Experimental Design: Patients with solid tumors refractory to standard therapy received i.v. delimotecan as 3-hour infusion once every 6 weeks. The starting dose was 150 mg/m2, followed by an accelerated dose escalation with at least one patient per dose level. The pharmacokinetics of delimotecan, T-2513, and its metabolites, SN-38, SN-38G, T-1335, T-0055, and T-3921, were assessed in plasma and urine, and their pharmacodynamics were determined by measuring the effect of the treatment on hematologic and nonhematologic toxicity.

Results: Twenty-two patients received 35 courses. Dose-limiting toxicities were observed at 5,400 mg/m2 (n = 1), 3,600 mg/m2 (n = 1), and 2,400 mg/m2 (n = 2). The dose level of 1,800 mg/m2 was determined as maximum tolerated dose. Two partial responses were observed in patients with anal cancer (1800 mg/m2) and head and neck cancer (2400 mg/m2). Delimotecan had a long terminal half-life of 109 h, and relatively high exposures to T-2513 and SN-38 were obtained. The percentage decrease in WBC and absolute neutrophil count significantly correlated with the dose of delimotecan.

Conclusions: Based on its preliminary antitumor activity, safety profile, and pharmacokinetic profile, we recommend to evaluate delimotecan given as 3-hour infusion once every 6 weeks at a dose level of 1,800 mg/m2 in a phase II study.
Data from SCG3 Transcript in Peripheral Blood Is a Prognostic Biomarker for REST-Deficient Small Cell Lung Cancer
Authors: Moss Adrian C. , Jacobson Gregory M. , Walker Lauren E. , Blake Neil W. , Marshall Ernie , Coulson Judy M.
Published: April 2023

Abstract
Purpose: Specific markers of circulating tumor cells may be informative in managing lung cancer. Because the RE-1 silencing transcription factor (REST/NRSF) is a transcriptional repressor that is inactivated in neuroendocrine lung cancer, we identified REST-regulated transcripts (CHGA, CHGB, SCG3, VGF, and PCSK1) for evaluation as biomarkers in peripheral blood.

Experimental Design: Transcripts were screened across lung cancer and normal cell lines. Candidates were assessed by reverse transcription-PCR and hybridization of RNA extracted from the peripheral blood of 111 lung cancer patients obtained at clinical presentation and from 27 cancer-free individuals.

Results: Expression profiling revealed multiple chromogranin transcripts were readily induced on REST depletion, most notably SCG3 was induced >500-fold. The SCG3 transcript was also overexpressed by 12,000-fold in neuroendocrine compared with nonneuroendocrine lung cancer cells. In peripheral blood of lung cancer patients and cancer-free individuals, we found that SCG3 was more tumor-specific and more sensitive than other chromogranin transcripts as a biomarker of circulating tumor cells. Overall, 36% of small cell lung cancer (SCLC) and 16% of non-SCLC patients scored positively for normalized SCG3 transcript. This correlated with worse survival among SCLC patients with limited disease (n = 33; P = 0.022) but not extensive disease (n = 29; P = 0.459). Interestingly, the subcohort of 6 SCLC patients with resistance to platinum/etoposide chemotherapy all scored positively for peripheral blood SCG3 transcript (P = 0.022).

Conclusions: SCG3 mRNA, a component of the REST-dependent neurosecretory transcriptional profile, provides a sensitive prognostic biomarker for noninvasive monitoring of neuroendocrine lung cancer.
Data from Heat Shock Protein 90 Overexpression Independently Predicts Inferior Disease-Free Survival with Differential Expression of the α and β Isoforms in Gastrointestinal Stromal Tumors
Authors: Li Chien-Feng , Huang Wen-Wei , Wu Jing-Mei , Yu Shih-Chen , Hu Tsung-Hui , Uen Yih-Huei , Tian Yu-Fang , Lin Ching-Nan , Lu David , Fang Fu-Min , Huang Hsuan-Ying
Published: April 2023

Abstract
Purpose: Most gastrointestinal stromal tumors harbor a mutated KIT or PDGFRA receptor tyrosine kinase (RTK). Heat shock protein 90 (Hsp90) is a chaperone mediating the folding and stabilization of many oncoproteins, including KIT. An Hsp90 inhibitor, 17-AAG, can attenuate KIT activation and proliferation of gastrointestinal stromal tumor cell lines. We further evaluated Hsp90 immunoexpression and the difference between α and β isoforms in gastrointestinal stromal tumor specimens.

Experimental Design: Hsp90 immunostain was assessable in 306 cases on tissue microarrays of primary gastrointestinal stromal tumors and correlated with various variables and disease-free survival (DFS). RTK mutation variants, confirmed in 142 cases by sequencing with or without precedent denaturing high pressure liquid chromatography screening, were dichotomized into two prognostically different groups. Differential expression of transcript and protein isoforms was measured by real-time reverse transcription-PCR and Western blotting in 16 and 6 cases, respectively.

Results: Hsp90 overexpression (55%) significantly correlated with larger size, nongastric location, higher mitotic count and NIH risk level, Ki-67 overexpression (all P ≤ 0.001), and unfavorable RTK genotypes (P = 0.020). It strongly portended inferior DFS univariately (P < 0.0001) and remained independent in multivariate analysis (P = 0.031; risk ratio, 2.44), along with high-risk category, Ki-67 overexpression, and old age. For both mRNA and protein, Hsp90β was more abundant than Hsp90α, whereas the latter was significantly higher in high-risk cases.

Conclusions: Hsp90 overexpression represents a poor prognosticator that correlates with several adverse parameters, highlighting its role in disease progression and alternative therapy for high-risk, imatinib-resistant gastrointestinal stromal tumors. Hsp90α seems more relevant to the intrinsic aggressiveness of gastrointestinal stromal tumors, albeit less abundant than Hsp90β.