bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S1 from Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy
Authors: Martín Miguel , Yoder Rachel , Salgado Roberto , del Monte-Millán María , Álvarez Enrique L. , Echavarría Isabel , Staley Joshua M. , O'Dea Anne P. , Nye Lauren E. , Stecklein Shane R. , Bueno Coralia , Jerez Yolanda , Cebollero María , Bueno Oscar , García Saenz José Ángel , Moreno Fernando , Bohn Uriel , Gómez Henry , Massarrah Tatiana , Khan Qamar J. , Godwin Andrew K. , López-Tarruella Sara , Sharma Priyanka
Published: May 2024

CONSORT diagram
Supplementary Figure S2 from Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair
Authors: Ballout Farah , Lu Heng , Bhat Nadeem , Chen Lei , Peng Dunfa , Chen Zheng , Chen Steven , Sun Xiaodian , Giordano Silvia , Corso Simona , Zaika Alexander , McDonald Oliver , Livingstone Alan S. , El-Rifai Wael
Published: May 2024

Supplementary Figure 2. SMAD3 mediates resistance to oxaliplatin by regulating DNA damage/repair.
Supplementary Figure S4 from The Irreversible FGFR Inhibitor KIN-3248 Overcomes FGFR2 Kinase Domain Mutations
Authors: Balasooriya Eranga R. , Wu Qibiao , Ellis Haley , Zhen Yuanli , Norden Bryanna L. , Corcoran Ryan B. , Mohan Adithi , Martin Eric , Franovic Aleksandra , Tyhonas John , Lardy Matthew , Grandinetti Kathryn B. , Pelham Robert , Soroceanu Liliana , Silveira Vanessa S. , Bardeesy Nabeel
Published: May 2024

Supplementary Figure S4. KIN-3248 efficacy is potentiated by MEK inhibitor treatment. Mice bearing the ICC-21 CDX model were treated daily with vehicle, trametinib 0.1 mg/kg, KIN-3248 5 mg/kg, KIN-3248 15 mg/kg or the combination. A. Serial measurements of tumor volume. n = 8 mice per group. Two-way ANOVA multiple comparisons with Tukey correction were used to analyze the data. ****, P < 0.0001. Data are shown as mean ± SD. B. MSD analysis of phosphoERK was performed after the last dose (3-days treatment) at indicated timepoints (1-24 hours). C. Body weight of animals in the ICC-21 xenograft model dosed KIN-3248, trametinib or the combination is well-tolerated. Data are shown as mean ± SD.
Supplementary Material 1 from Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma
Authors: Schreck Karisa C. , Strowd Roy E. , Nabors Louis B. , Ellingson Benjamin M. , Chang Michael , Tan Sze K. , Abdullaev Zied , Turakulov Rust , Aldape Kenneth , Danda Neeraja , Desideri Serena , Fisher Joy , Iacoboni Michaella , Surakus Trisha , Rudek Michelle A. , Bettegowda Chetan , Grossman Stuart A. , Ye Xiaobu
Published: May 2024

Supplementary Material: Clinical Trial Protocol.
Supplementary Figure S3 from Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma
Authors: Schreck Karisa C. , Strowd Roy E. , Nabors Louis B. , Ellingson Benjamin M. , Chang Michael , Tan Sze K. , Abdullaev Zied , Turakulov Rust , Aldape Kenneth , Danda Neeraja , Desideri Serena , Fisher Joy , Iacoboni Michaella , Surakus Trisha , Rudek Michelle A. , Bettegowda Chetan , Grossman Stuart A. , Ye Xiaobu
Published: May 2024

Supplementary Figure S3: Enhancing tumor volume.
Supplementary Figure S2 from Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma
Authors: Schreck Karisa C. , Strowd Roy E. , Nabors Louis B. , Ellingson Benjamin M. , Chang Michael , Tan Sze K. , Abdullaev Zied , Turakulov Rust , Aldape Kenneth , Danda Neeraja , Desideri Serena , Fisher Joy , Iacoboni Michaella , Surakus Trisha , Rudek Michelle A. , Bettegowda Chetan , Grossman Stuart A. , Ye Xiaobu
Published: May 2024

Supplementary Figure S2: CNV signatures for all tumor samples.
Supplementary Table S4 from FDA Approval Summary: Enfortumab Vedotin plus Pembrolizumab for Cisplatin-Ineligible Locally Advanced or Metastatic Urothelial Carcinoma
Authors: Maguire William F. , Lee Daniel , Weinstock Chana , Gao Xin , Bulik Catharine C. , Agrawal Sundeep , Chang Elaine , Hamed Salaheldin S. , Bloomquist Erik W. , Tang Shenghui , Pazdur Richard , Kluetz Paul G. , Amiri-Kordestani Laleh , Suzman Daniel L.
Published: May 2024

Table S4 shows incidence of new peripheral neuropathy over time in EV monotherapy pooled data
Supplemental Table 3 from A Phase 0/I Pharmacokinetic and Pharmacodynamics and Safety and Tolerability Study of Letrozole in Combination with Standard Therapy in Recurrent High-Grade Gliomas
Authors: Desai Pankaj B. , Karve Aniruddha S. , Zawit Misam , Arora Priyanka , Dave Nimita , Awosika Joy , Li Ningjing , Fuhrman Bethany , Medvedovic Mario , Sallans Larry , Kendler Ady , DasGupta Biplab , Plas David , Curry Richard , Zuccarello Mario , Chaudhary Rekha , Sengupta Soma , Wise-Draper Trisha M.
Published: May 2024

Supplemental Table 3: Patient Survival and Mutation Characteristics
Supplemental Table 2 from A Phase 0/I Pharmacokinetic and Pharmacodynamics and Safety and Tolerability Study of Letrozole in Combination with Standard Therapy in Recurrent High-Grade Gliomas
Authors: Desai Pankaj B. , Karve Aniruddha S. , Zawit Misam , Arora Priyanka , Dave Nimita , Awosika Joy , Li Ningjing , Fuhrman Bethany , Medvedovic Mario , Sallans Larry , Kendler Ady , DasGupta Biplab , Plas David , Curry Richard , Zuccarello Mario , Chaudhary Rekha , Sengupta Soma , Wise-Draper Trisha M.
Published: May 2024

Supplemental Table 2: Representativeness of Study Participants
Supplementary Table S4 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Reported trials on neoadjuvant immunotherapy in head and neck squamous cell carcinoma.
Supplementary Figure S8 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Dynamic changes in PD-L1 combined positive score (CPS) in response to the treatment administered.
Supplementary Figure S7 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Tornado plot for immune-related adverse events.
Supplementary Table S1 from First-in-Human Study of the Ataxia Telangiectasia and Rad3-Related (ATR) Inhibitor Tuvusertib (M1774) as Monotherapy in Patients with Solid Tumors
Authors: Yap Timothy A. , Tolcher Anthony W. , Plummer Ruth , Mukker Jatinder Kaur , Enderlin Marta , Hicking Christine , Grombacher Thomas , Locatelli Giuseppe , Szucs Zoltan , Gounaris Ioannis , de Bono Johann S.
Published: May 2024

Table S1. Representativeness of study participants
Supplementary Figure S5 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Pathologic tumor regression according to baseline characteristics and treatment.
Supplementary Figure S3 from First-in-Human Study of the Ataxia Telangiectasia and Rad3-Related (ATR) Inhibitor Tuvusertib (M1774) as Monotherapy in Patients with Solid Tumors
Authors: Yap Timothy A. , Tolcher Anthony W. , Plummer Ruth , Mukker Jatinder Kaur , Enderlin Marta , Hicking Christine , Grombacher Thomas , Locatelli Giuseppe , Szucs Zoltan , Gounaris Ioannis , de Bono Johann S.
Published: May 2024

Figure S3. CT scans showing partial response to tuvusertib treatment in one patient with platinum- and PARP inhibitor-resistant BRCAwt ovarian cancer, receiving a dose of tuvusertib 150 mg BID 4 days on/3 days off.
Supplementary Figure S3 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Clinical outcome of trial according to treatment and human papilloma virus (HPV) status.
Supplementary Figure S19 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Dynamic changes in the composition of regulatory CD4+ T cells in response to the treatment administered.
Supplementary Figure S15 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Dynamic changes in the composition of CD8+ T cells in response to the treatment administered.
Supplementary Figure S11 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Comparison of immune phenotypes between baseline and surgical resection in patients treated with neoadjuvant cytotoxic chemotherapy.
Supplementary Figure S10 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Representative immunofluorescence staining for tumor-infiltrating T cells. T cells were stained with CD8 (blue), CD4 (green), and FoxP3 (red).
Supplementary Figure S1 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Trial scheme.
Supplementary Figure S4 from Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: May 2024

Figure 4. ARI0002h peak magnitude according to baseline tumor burden measured as proportion of bone marrow plasma cells and soluble BCMA.
Supplementary Figure S14 from Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: May 2024

Figure 14. Progression-free survival according to involved serum free-light chain levels below the lower limit of normality (green) on (A) days 28 and (B) 100.
Supplementary Figure S6 from Circulating microRNA Analysis in a Prospective Co-clinical Trial Identifies MIR652–3p as a Response Biomarker and Driver of Regorafenib Resistance Mechanisms in Colorectal Cancer
Authors: Hedayat Somaieh , Cascione Luciano , Cunningham David , Schirripa Marta , Lampis Andrea , Hahne Jens C. , Tunariu Nina , Hong Sung Pil , Marchetti Silvia , Khan Khurum , Fontana Elisa , Angerilli Valentina , Delrieux Mia , Nava Rodrigues Daniel , Procaccio Letizia , Rao Sheela , Watkins David , Starling Naureen , Chau Ian , Braconi Chiara , Fotiadis Nicos , Begum Ruwaida , Guppy Naomy , Howell Louise , Valenti Melanie , Cribbes Scott , Kolozsvari Bernadett , Kirkin Vladimir , Lonardi Sara , Ghidini Michele , Passalacqua Rodolfo , Elghadi Raghad , Magnani Luca , Pinato David J. , Di Maggio Federica , Ghelardi Filippo , Sottotetti Elisa , Vetere Guglielmo , Ciracì Paolo , Vlachogiannis Georgios , Pietrantonio Filippo , Cremolini Chiara , Cortellini Alessio , Loupakis Fotios , Fassan Matteo , Valeri Nicola
Published: May 2024

Supplementary Figure S6. MIR652-3p targets PSAT1 and ANGPT1
Supplementary Figure S12 from Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: May 2024

Figure 12. Time from measurable residual disease positivity to overt relapse
Supplementary Figure S4 from Circulating microRNA Analysis in a Prospective Co-clinical Trial Identifies MIR652–3p as a Response Biomarker and Driver of Regorafenib Resistance Mechanisms in Colorectal Cancer
Authors: Hedayat Somaieh , Cascione Luciano , Cunningham David , Schirripa Marta , Lampis Andrea , Hahne Jens C. , Tunariu Nina , Hong Sung Pil , Marchetti Silvia , Khan Khurum , Fontana Elisa , Angerilli Valentina , Delrieux Mia , Nava Rodrigues Daniel , Procaccio Letizia , Rao Sheela , Watkins David , Starling Naureen , Chau Ian , Braconi Chiara , Fotiadis Nicos , Begum Ruwaida , Guppy Naomy , Howell Louise , Valenti Melanie , Cribbes Scott , Kolozsvari Bernadett , Kirkin Vladimir , Lonardi Sara , Ghidini Michele , Passalacqua Rodolfo , Elghadi Raghad , Magnani Luca , Pinato David J. , Di Maggio Federica , Ghelardi Filippo , Sottotetti Elisa , Vetere Guglielmo , Ciracì Paolo , Vlachogiannis Georgios , Pietrantonio Filippo , Cremolini Chiara , Cortellini Alessio , Loupakis Fotios , Fassan Matteo , Valeri Nicola
Published: May 2024

Supplementary Figure S4. MIR652-3p modulation and in vivo regorafenib efficacy
Supplementary Figure S3 from Circulating microRNA Analysis in a Prospective Co-clinical Trial Identifies MIR652–3p as a Response Biomarker and Driver of Regorafenib Resistance Mechanisms in Colorectal Cancer
Authors: Hedayat Somaieh , Cascione Luciano , Cunningham David , Schirripa Marta , Lampis Andrea , Hahne Jens C. , Tunariu Nina , Hong Sung Pil , Marchetti Silvia , Khan Khurum , Fontana Elisa , Angerilli Valentina , Delrieux Mia , Nava Rodrigues Daniel , Procaccio Letizia , Rao Sheela , Watkins David , Starling Naureen , Chau Ian , Braconi Chiara , Fotiadis Nicos , Begum Ruwaida , Guppy Naomy , Howell Louise , Valenti Melanie , Cribbes Scott , Kolozsvari Bernadett , Kirkin Vladimir , Lonardi Sara , Ghidini Michele , Passalacqua Rodolfo , Elghadi Raghad , Magnani Luca , Pinato David J. , Di Maggio Federica , Ghelardi Filippo , Sottotetti Elisa , Vetere Guglielmo , Ciracì Paolo , Vlachogiannis Georgios , Pietrantonio Filippo , Cremolini Chiara , Cortellini Alessio , Loupakis Fotios , Fassan Matteo , Valeri Nicola
Published: May 2024

Supplementary Figure S3. MIR652-3p modulation and cancer phenotype in cell lines and PDOs
Supplementary Figure S1 from Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: May 2024

Figure 1. Design of the study. Timeline of lymphodepletion, ARI0002h fractionated infusion and booster dose.
Supplementary Table S6 from Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
Authors: Anselmino Nicolas , Labanca Estefania , Shepherd Peter D.A. , Dong Jiabin , Yang Jun , Song Xiaofei , Nandakumar Subhiksha , Kundra Ritika , Lee Cindy , Schultz Nikolaus , Zhang Jianhua , Araujo John C. , Aparicio Ana M. , Subudhi Sumit K. , Corn Paul G. , Pisters Louis L. , Ward John F. , Davis John W. , Vazquez Elba S. , Gueron Geraldine , Logothetis Christopher J. , Futreal Andrew , Troncoso Patricia , Chen Yu , Navone Nora M.
Published: May 2024

STR Profiling of samples derived from the same patient
Supplementary Table S2 from Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
Authors: Anselmino Nicolas , Labanca Estefania , Shepherd Peter D.A. , Dong Jiabin , Yang Jun , Song Xiaofei , Nandakumar Subhiksha , Kundra Ritika , Lee Cindy , Schultz Nikolaus , Zhang Jianhua , Araujo John C. , Aparicio Ana M. , Subudhi Sumit K. , Corn Paul G. , Pisters Louis L. , Ward John F. , Davis John W. , Vazquez Elba S. , Gueron Geraldine , Logothetis Christopher J. , Futreal Andrew , Troncoso Patricia , Chen Yu , Navone Nora M.
Published: May 2024

T200.1 panel: genes implicated in the pathogenesis of solid cancers
Supplementary Table S1 from Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
Authors: Anselmino Nicolas , Labanca Estefania , Shepherd Peter D.A. , Dong Jiabin , Yang Jun , Song Xiaofei , Nandakumar Subhiksha , Kundra Ritika , Lee Cindy , Schultz Nikolaus , Zhang Jianhua , Araujo John C. , Aparicio Ana M. , Subudhi Sumit K. , Corn Paul G. , Pisters Louis L. , Ward John F. , Davis John W. , Vazquez Elba S. , Gueron Geraldine , Logothetis Christopher J. , Futreal Andrew , Troncoso Patricia , Chen Yu , Navone Nora M.
Published: May 2024

Clinical and morphological features of 44 MDA PCa PDX
Supplementary Figure S3 from Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
Authors: Anselmino Nicolas , Labanca Estefania , Shepherd Peter D.A. , Dong Jiabin , Yang Jun , Song Xiaofei , Nandakumar Subhiksha , Kundra Ritika , Lee Cindy , Schultz Nikolaus , Zhang Jianhua , Araujo John C. , Aparicio Ana M. , Subudhi Sumit K. , Corn Paul G. , Pisters Louis L. , Ward John F. , Davis John W. , Vazquez Elba S. , Gueron Geraldine , Logothetis Christopher J. , Futreal Andrew , Troncoso Patricia , Chen Yu , Navone Nora M.
Published: May 2024

Fusion genes expression levels. CNV details on TMPRSS2-ERG fusion and AR enhancer region. Putative PCa drivers in models lacking alterations in four major genes
Supplementary Figure S2 from Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
Authors: Anselmino Nicolas , Labanca Estefania , Shepherd Peter D.A. , Dong Jiabin , Yang Jun , Song Xiaofei , Nandakumar Subhiksha , Kundra Ritika , Lee Cindy , Schultz Nikolaus , Zhang Jianhua , Araujo John C. , Aparicio Ana M. , Subudhi Sumit K. , Corn Paul G. , Pisters Louis L. , Ward John F. , Davis John W. , Vazquez Elba S. , Gueron Geraldine , Logothetis Christopher J. , Futreal Andrew , Troncoso Patricia , Chen Yu , Navone Nora M.
Published: May 2024

General copy number profile and association with expresion for PTEN and RB1
Supplementary Figure S1 from Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
Authors: Anselmino Nicolas , Labanca Estefania , Shepherd Peter D.A. , Dong Jiabin , Yang Jun , Song Xiaofei , Nandakumar Subhiksha , Kundra Ritika , Lee Cindy , Schultz Nikolaus , Zhang Jianhua , Araujo John C. , Aparicio Ana M. , Subudhi Sumit K. , Corn Paul G. , Pisters Louis L. , Ward John F. , Davis John W. , Vazquez Elba S. , Gueron Geraldine , Logothetis Christopher J. , Futreal Andrew , Troncoso Patricia , Chen Yu , Navone Nora M.
Published: May 2024

MDA PCa PDX-derived organoids
Data from Xevinapant Combined with Pembrolizumab in Patients with Advanced, Pretreated, Colorectal and Pancreatic Cancer: Results of the Phase Ib/II CATRIPCA Trial
Authors: Voisin Allison , Terret Catherine , Schiffler Camille , Bidaux Anne-Sophie , Vanacker Hélène , Perrin-Niquet Marlène , Barbery Maud , Vinceneux Armelle , Eberst Lauriane , Stéphan Pierre , Garin Gwenaële , Spaggiari Dany , Pérol David , Grinberg-Bleyer Yenkel , Cassier Philippe A.
Published: May 2024

AbstractPurpose:
Xevinapant is an orally available inhibitor of apoptosis proteins (IAP) inhibitor. Preclinical data suggest that IAP antagonism may synergize with immune checkpoint blockers by modulating the NFκB pathway in immune cells.
Patients and Methods:
Adult patients with non–high microsatellite instability advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) or colorectal cancer were enrolled in this phase Ib/II study and received pembrolizumab 200 mg every 3 weeks intravenously, and ascending doses of oral xevinapant (100, 150, and 200 mg daily for 14 days on/7 days off). Dose escalation followed a 3+3 design with a 21-day dose-limiting toxicity (DLT) evaluation period. Following the determination of the recommended phase II dose (RP2D), 14 patients with PDAC and 14 patients with colorectal cancer were enrolled in expansion cohorts to assess preliminary efficacy.
Results:
Forty-one patients (26 males) with a median age of 64 years were enrolled: 13 in the dose escalation and 28 in the two expansion cohorts. No DLT was observed during dose escalation. The RP2D was identified as xevinapant 200 mg/day + pembrolizumab 200 mg every 3 weeks. The most common adverse events (AE) were fatigue (37%), gastrointestinal AE (decreased appetite in 37%, nausea in 24%, stomatitis in 12%, and diarrhea and vomiting in 10% each), and cutaneous AE (pruritus, dry skin, and rash seen in 20%, 15%, and 15% of patients, respectively). The best overall response according to RECIST1.1 was partial response (confirmed) in 1 (3%), stable disease in 4 (10%), and progressive disease in 35 (88%).
Conclusions:
Xevinapant combined with pembrolizumab was well tolerated with no unexpected AEs. However, antitumor activity was low.
Data from A Pre-Leukemic DNA Methylation Signature in Healthy Individuals at Higher Risk for Developing Myeloid Malignancy
Authors: Lao Zhentang , Ding Ling-Wen , Sun Qiao-Yang , Jia Li , Yan Benedict , Ng Alvin Yu-Jin , Capinpin Sharah Mae , Wang Renwei , Ying Li , Chng Wee Joo , Koeffler H. Phillip , Koh Woon-Puay , Yuan Jian-Min , Yang Henry , Goh Yeow Tee , Grigoropoulos Nicholas
Published: May 2024

AbstractPurpose:
DNA methylation alterations are widespread in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), some of which appear to have evolved independently of somatic mutations in epigenetic regulators. Although the presence of somatic mutations in peripheral blood can predict the risk of development of AML and MDS, its accuracy remains unsatisfactory.
Experimental Design:
We performed global DNA methylation profiling in a case control study nested within the Singapore Chinese Health Study to evaluate whether DNA methylation alterations were associated with AML/MDS development. Targeted deep sequencing and methylated DNA immunoprecipitation sequencing (MeDIP-seq) were performed on peripheral blood collected a median of 9.9 years before diagnosis of AML or MDS, together with age-matched still-healthy individuals as controls.
Results:
Sixty-six individuals who developed AML or MDS displayed significant DNA methylation changes in the peripheral blood compared with 167 age- and gender-matched controls who did not develop AML/MDS during the follow-up period. Alterations in methylation in the differentially methylation regions were associated with increased odds of developing AML/MDS.
Conclusions:
The epigenetic changes may be acquired independently and before somatic mutations that are relevant for AML/MDS development. The association between methylation changes and the risk of pre-AML/MDS in these individuals was considerably stronger than somatic mutations, suggesting that methylation changes could be used as biomarkers for pre-AML/MDS screening.
Data from Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy
Authors: Martín Miguel , Yoder Rachel , Salgado Roberto , del Monte-Millán María , Álvarez Enrique L. , Echavarría Isabel , Staley Joshua M. , O'Dea Anne P. , Nye Lauren E. , Stecklein Shane R. , Bueno Coralia , Jerez Yolanda , Cebollero María , Bueno Oscar , García Saenz José Ángel , Moreno Fernando , Bohn Uriel , Gómez Henry , Massarrah Tatiana , Khan Qamar J. , Godwin Andrew K. , López-Tarruella Sara , Sharma Priyanka
Published: May 2024

AbstractPurpose:
Stromal tumor-infiltrating lymphocytes (sTIL) are associated with pathologic complete response (pCR) and long-term outcomes for triple-negative breast cancer (TNBC) in the setting of anthracycline-based chemotherapy. The impact of sTILs on refining outcomes beyond prognostic information provided by pCR in anthracycline-free neoadjuvant chemotherapy (NAC) is not known.
Experimental Design:
This is a pooled analysis of two studies where patients with stage I (T>1 cm)–III TNBC received carboplatin (AUC 6) plus docetaxel (75 mg/m2; CbD) NAC. sTILs were evaluated centrally on pre-treatment hematoxylin and eosin slides using standard criteria. Cox regression analysis was used to examine the effect of variables on event-free survival (EFS) and overall survival (OS).
Results:
Among 474 patients, 44% had node-positive disease. Median sTILs were 5% (range, 1%–95%), and 32% of patients had ≥30% sTILs. pCR rate was 51%. On multivariable analysis, T stage (OR, 2.08; P = 0.007), nodal status (OR, 1.64; P = 0.035), and sTILs (OR, 1.10; P = 0.011) were associated with pCR. On multivariate analysis, nodal status (HR, 0.46; P = 0.008), pCR (HR, 0.20; P < 0.001), and sTILs (HR, 0.95; P = 0.049) were associated with OS. At 30% cut-point, sTILs stratified outcomes in stage III disease, with 5-year OS 86% versus 57% in ≥30% versus <30% sTILs (HR, 0.29; P = 0.014), and numeric trend in stage II, with 5-year OS 93% versus 89% in ≥30% versus <30% sTILs (HR, 0.55; P = 0.179). Among stage II–III patients with pCR, EFS was better in those with ≥30% sTILs (HR, 0.16; P, 0.047).
Conclusions:
sTILs density was an independent predictor of OS beyond clinicopathologic features and pathologic response in patients with TNBC treated with anthracycline-free CbD chemotherapy. Notably, sTILs density stratified outcomes beyond tumor–node–metastasis (TNM) stage and pathologic response. These findings highlight the role of sTILs in patient selection and stratification for neo/adjuvant escalation and de-escalation strategies.
Data from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

AbstractPurpose:
Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored.
Patients and Methods:
Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiotherapy based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)–powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses.
Results:
Of the 48 patients enrolled (D, 24 patients; D+T, 24 patients), 45 underwent surgical resection per protocol (D, 21 patients; D+T, 24 patients). D±T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast with the D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T-cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T.
Conclusions:
Preoperative D±T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.
Data from First-in-Human Study of the Ataxia Telangiectasia and Rad3-Related (ATR) Inhibitor Tuvusertib (M1774) as Monotherapy in Patients with Solid Tumors
Authors: Yap Timothy A. , Tolcher Anthony W. , Plummer Ruth , Mukker Jatinder Kaur , Enderlin Marta , Hicking Christine , Grombacher Thomas , Locatelli Giuseppe , Szucs Zoltan , Gounaris Ioannis , de Bono Johann S.
Published: May 2024

AbstractPurpose:
Tuvusertib (M1774) is a potent, selective, orally administered ataxia telangiectasia and Rad3-related (ATR) protein kinase inhibitor. This first-in-human study (NCT04170153) evaluated safety, tolerability, maximum tolerated dose (MTD), recommended dose for expansion (RDE), pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of tuvusertib monotherapy.
Patients and Methods:
Ascending tuvusertib doses were evaluated in 55 patients with metastatic or locally advanced unresectable solid tumors. A safety monitoring committee determined dose escalation based on PK, PD, and safety data guided by a Bayesian 2-parameter logistic regression model. Molecular responses (MR) were assessed in circulating tumor DNA samples.
Results:
Most common grade ≥3 treatment-emergent adverse events were anemia (36%), neutropenia, and lymphopenia (both 7%). Eleven patients experienced dose-limiting toxicities, most commonly grade 2 (n = 2) or 3 (n = 8) anemia. No persistent effects on blood immune cell populations were observed. The RDE was 180 mg tuvusertib QD (once daily), 2 weeks on/1 week off treatment, which was better tolerated than the MTD (180 mg QD continuously). Tuvusertib median time to peak plasma concentration ranged from 0.5 to 3.5 hours and mean elimination half-life from 1.2 to 5.6 hours. Exposure-related PD analysis suggested maximum target engagement at ≥130 mg tuvusertib QD. Tuvusertib induced frequent MRs in the predicted efficacious dose range; MRs were enriched in patients with radiological disease stabilization, and complete MRs were detected for mutations in ARID1A, ATRX, and DAXX. One patient with platinum- and PARP inhibitor–resistant BRCA wild-type ovarian cancer achieved an unconfirmed RECIST v1.1 partial response.
Conclusions:
Tuvusertib demonstrated manageable safety and exposure-related target engagement. Further clinical evaluation of tuvusertib is ongoing.
Data from Ataxia-Telangiectasia Mutated Loss-of-Function Displays Variant and Tissue-Specific Differences across Tumor Types
Authors: Pilié Patrick G. , Giuliani Virginia , Wang Wei-Lien , McGrail Daniel J. , Bristow Christopher A. , Ngoi Natalie Y.L. , Kyewalabye Keith , Wani Khalida M. , Le Hung , Campbell Erick , Sanchez Nora S. , Yang Dong , Gheeya Jinesh S. , Goswamy Rohit Vivek , Holla Vijaykumar , Shaw Kenna Rael , Meric-Bernstam Funda , Liu Chiu-Yi , Ma XiaoYan , Feng Ningping , Machado Annette A. , Bardenhagen Jennifer P. , Vellano Christopher P. , Marszalek Joseph R. , Rajendra Eeson , Piscitello Desiree , Johnson Timothy I. , Likhatcheva Maria , Elinati Elias , Majithiya Jayesh , Neves Joana , Grinkevich Vera , Ranzani Marco , Luzarraga Marina Roy , Boursier Marie , Armstrong Lucy , Geo Lerin , Lillo Giorgia , Tse Wai Yiu , Lazar Alexander J. , Kopetz Scott E. , Geck Do Mary K. , Lively Sarah , Johnson Michael G. , Robinson Helen M.R. , Smith Graeme C.M. , Carroll Christopher L. , Di Francesco M. Emilia , Jones Philip , Heffernan Timothy P. , Yap Timothy A.
Published: May 2024

AbstractPurpose:
Mutations in the ATM gene are common in multiple cancers, but clinical studies of therapies targeting ATM-aberrant cancers have yielded mixed results. Refinement of ATM loss of function (LOF) as a predictive biomarker of response is urgently needed.
Experimental Design:
We present the first disclosure and preclinical development of a novel, selective ATR inhibitor, ART0380, and test its antitumor activity in multiple preclinical cancer models. To refine ATM LOF as a predictive biomarker, we performed a comprehensive pan-cancer analysis of ATM variants in patient tumors and then assessed the ATM variant-to-protein relationship. Finally, we assessed a novel ATM LOF biomarker approach in retrospective clinical data sets of patients treated with platinum-based chemotherapy or ATR inhibition.
Results:
ART0380 had potent, selective antitumor activity in a range of preclinical cancer models with differing degrees of ATM LOF. Pan-cancer analysis identified 10,609 ATM variants in 8,587 patient tumors. Cancer lineage–specific differences were seen in the prevalence of deleterious (Tier 1) versus unknown/benign (Tier 2) variants, selective pressure for loss of heterozygosity, and concordance between a deleterious variant and ATM loss of protein (LOP). A novel ATM LOF biomarker approach that accounts for variant classification, relationship to ATM LOP, and tissue-specific penetrance significantly enriched for patients who benefited from platinum-based chemotherapy or ATR inhibition.
Conclusions:
These data help to better define ATM LOF across tumor types in order to optimize patient selection and improve molecularly targeted therapeutic approaches for patients with ATM LOF cancers.
Data from Infiltrative Vessel Co-optive Growth Pattern Induced by IQGAP3 Overexpression Promotes Microvascular Invasion in Hepatocellular Carcinoma
Authors: Tang Miaoling , Zhang Shuxia , Yang Meisongzhu , Feng Rongni , Lin Jinbin , Chen Xiaohong , Xu Yingru , Yu Ruyuan , Liao Xinyi , Li Ziwen , Li Xincheng , Li Man , Zhang Qiliang , Chen Suwen , Qian Wanying , Liu Yuanji , Song Libing , Li Jun
Published: May 2024

AbstractPurpose:
Microvascular invasion (MVI) is a major unfavorable prognostic factor for intrahepatic metastasis and postoperative recurrence of hepatocellular carcinoma (HCC). However, the intervention and preoperative prediction for MVI remain clinical challenges due to the absent precise mechanism and molecular marker(s). Herein, we aimed to investigate the mechanisms underlying vascular invasion that can be applied to clinical intervention for MVI in HCC.
Experimental Design:
The histopathologic characteristics of clinical MVI+/HCC specimens were analyzed using multiplex immunofluorescence staining. The liver orthotopic xenograft mouse model and mechanistic experiments on human patient-derived HCC cell lines, including coculture modeling, RNA-sequencing, and proteomic analysis, were used to investigate MVI-related genes and mechanisms.
Results:
IQGAP3 overexpression was correlated significantly with MVI status and reduced survival in HCC. Upregulation of IQGAP3 promoted MVI+-HCC cells to adopt an infiltrative vessel co-optive growth pattern and accessed blood capillaries by inducing detachment of activated hepatic stellate cells (HSC) from the endothelium. Mechanically, IQGAP3 overexpression contributed to HCC vascular invasion via a dual mechanism, in which IQGAP3 induced HSC activation and disruption of the HSC–endothelial interaction via upregulation of multiple cytokines and enhanced the trans-endothelial migration of MVI+-HCC cells by remodeling the cytoskeleton by sustaining GTPase Rac1 activity. Importantly, systemic delivery of IQGAP3-targeting small-interfering RNA nanoparticles disrupted the infiltrative vessel co-optive growth pattern and reduced the MVI of HCC.
Conclusions:
Our results revealed a plausible mechanism underlying IQGAP3-mediated microvascular invasion in HCC, and provided a potential target to develop therapeutic strategies to treat HCC with MVI.
Supplementary Data S2 from Mutant RAS-driven Secretome Causes Skeletal Muscle Defects in Breast Cancer
Authors: Wang Ruizhong , Khatpe Aditi S. , Kumar Brijesh , Mang Henry Elmer , Batic Katie , Adebayo Adedeji K. , Nakshatri Harikrishna
Published: May 2024

Raw values of the each cytokine measured in plasma of control and tumor bearing mice.
FIGURE 7 from Mutant RAS-driven Secretome Causes Skeletal Muscle Defects in Breast Cancer
Authors: Wang Ruizhong , Khatpe Aditi S. , Kumar Brijesh , Mang Henry Elmer , Batic Katie , Adebayo Adedeji K. , Nakshatri Harikrishna
Published: May 2024

Circulating cytokine profile in plasma of control and tumor-bearing NSG mice. A, Increased circulating CXCL1 in mice bearing tumors from TKTB34-RAS and TKTB6-RAS cell lines compared with control mice. B–J, Elevated circulating cytokine levels of CCL11, GCSF, GMCSF, MCSF, TNFα, and IL12(70) in mice bearing tumors from TKTB34-RAS cell line. Differences in circulating IL6, IL13, and CCL5 did not reach statistical significance. K and L, Circulating CXCL5 and TGFβ were not affected in tumor-bearing mice.
FIGURE 5 from Mutant RAS-driven Secretome Causes Skeletal Muscle Defects in Breast Cancer
Authors: Wang Ruizhong , Khatpe Aditi S. , Kumar Brijesh , Mang Henry Elmer , Batic Katie , Adebayo Adedeji K. , Nakshatri Harikrishna
Published: May 2024

Molecular changes in plasma and skeletal muscles of mice bearing tumors initiated from transformed cell lines. A, Plasma miR-486 levels. B, Skeletal muscle miR-486 levels. C, Skeletal muscle Pax7 mRNA levels. D, Skeletal muscle Myh1 mRNA levels. E, Skeletal muscle p53 mRNA levels. F, Skeletal muscle Pdk4 mRNA levels. G, Skeletal muscle phosphorylated AKT levels. H, Total AKT levels. I, PTEN levels. J, Phosphorylated p-38 levels. K, Total p-38 levels. Quantification of Western blotting was performed using NIH ImageJ software 1.X. Note that in case of TKTB34-PIK3CA, the same blot was probed for AKT and pp38 and, therefore, one Ponceau S blot is shown. Similarly, the same TKTB34-RAS and TKTB6-RAS blot was probed with AKT and p-38 antibodies and one Ponceau S blot is shown.
Resting-State Functional Connectivity of the Primary Visual Cortex in Children with Anisometropia Amblyopia
Authors: Yu Xueliang , Zhao Feng , Li Xiujuan , Lu Weizhao , Zhao Lisheng , Li Dandan , Chen Di , Wang Yi , Wang Baojian
Published: May 2024

Introduction: This study aimed to explore the functional connectivity of the primary visual cortex (V1) in children with anisometropic amblyopia by using the resting-state functional connectivity analysis method and determine whether anisometropic amblyopia is associated with changes in brain function. Methods: Functional magnetic resonance imaging (fMRI) data were obtained from 16 children with anisometropia amblyopia (CAA group) and 12 healthy children (HC group) during the resting state. The Brodmann area 17 (BA17) was used as the region of interest, and the functional connection (FC) of V1 was analyzed in both groups. A two-sample t test was used to analyze the FC value between the two groups. Pearson’s correlation was used to analyze the correlation between the mean FC value in the brain function change area of the CAA group and the best corrected visual acuity (BCVA) of amblyopia. p < 0.05 was considered statistically significant. Results: There were no significant differences in age and sex between the CAA and HC groups (p > 0.05). Compared to the HC group, the CAA group showed lower FC values in BA17 and the left medial frontal gyrus, as well as BA17 and the left triangle inferior frontal gyrus. Conversely, the CAA group showed higher FC values in BA17 and the left central posterior gyrus. Notably, BCVA in amblyopia did not correlate with the area of change in mean FC in the brain function of the CAA group. Conclusion: Resting-state fMRI-based functional connectivity analysis indicates a significant alteration in V1 of children with anisometropic amblyopia. These findings contribute additional insights into the neuropathological mechanisms underlying visual impairment in anisometropic amblyopia.