bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplemental table ST1: Sample collection and culture conditions from Expanding the Prostate Cancer Cell Line Repertoire with ACRJ-PC28, an AR-negative Neuroendocrine Cell Line Derived From an African-Caribbean Patient
Authors: Valentine Henkel , Aiken William , Morrison Belinda , Zhao Ziran , Fowle Holly , Wasserman Jason S. , Thompson Elon , Chin Warren , Young Mark , Clarke Shannique , Gibbs Denise , Harrison Sharon , McLaughlin Wayne , Kwok Tim , Jin Fang , Campbell Kerry S. , Horvath Anelia , Thompson Rory , Lee Norman H. , Zhou Yan , Graña Xavier , Ragin Camille , Badal Simone
Published: April 2023

In these prior attempts, culture conditions such as media, extra-cellular matrices and culture flasks were varied to determine the optimal culture conditions for generation of prostate cancer explants.
Supplementary Figure 1 from Suppressed Cellular Senescence Mediated by T-box3 in Aged Gastric Epithelial Cells may Contribute to Aging-related Carcinogenesis
Authors: Takeuchi Akio , Asano Naoki , Imatani Akira , Saito Masashi , Jin Xiaoyi , Saito Masahiro , Kanno Takeshi , Hatta Waku , Uno Kaname , Koike Tomoyuki , Masamune Atsushi
Published: April 2023

Supplementary Figure 1. TBX3 suppresses senescence and enhances proliferation. (A) Western blot for TBX3 and b-actin of HEK cells transfected with empty vector or TBX3-expressing plasmid. (B) MTS assay for TBX3- overexpressing HEK cells (n=3). (C) Representative images of SABG assay for TBX3-overexpressing HEK cells. Scale bar: 50μm. (D) The ratio of senescent cells in TBX3-overexpressing HEK cells assessed by SABG assay (n=3). **:P<0.01.
Supplementary Figure S3 from Real-world Studies Link NSAID Use to Improved Overall Lung Cancer Survival
Authors: Roszik Jason , Lee J. Jack , Wu Yi-Hung , Liu Xi , Kawakami Masanori , Kurie Jonathan M. , Belouali Anas , Boca Simina M. , Gupta Samir , Beckman Robert A. , Madhavan Subha , Dmitrovsky Ethan
Published: April 2023

Supplemental Figure 3. Landmark analysis of the MD Anderson Cancer Center lung cancer cases.
Supporting Information S2 from An Informatics Bridge to Improve the Design and Efficiency of Phase I Clinical Trials for Anticancer Drug Combinations
Authors: Wang Lei , Wei Lai , Zhang Shijun , Cheng Lijun , Shendre Aditi , Carson Williams , Chen James L. , Owen Dwight , Gregory Megan , Li Lang
Published: April 2023

Supporting Information S2 provides classification results offor cancer drug combination phase I clinical trials in clinicaltrials.gov (01 January through 31 December 2018)using the designed approach in the paper.
Supporting Infomation S1 from An Informatics Bridge to Improve the Design and Efficiency of Phase I Clinical Trials for Anticancer Drug Combinations
Authors: Wang Lei , Wei Lai , Zhang Shijun , Cheng Lijun , Shendre Aditi , Carson Williams , Chen James L. , Owen Dwight , Gregory Megan , Li Lang
Published: April 2023

Supporting Infomation S1 provides an overview of data source for drug combination Phase I trial design
Extended Dataset 1 from DDR2 Coordinates EMT and Metabolic Reprogramming as a Shared Effector of FOXQ1 and SNAI1
Authors: Mitchell Allison V. , Wu Jason , Meng Fanyan , Dong Lun , Block C. James , Song Won-min , Zhang Bin , Li Jing , Wu Guojun
Published: April 2023

Common deregulated genes between HMLE_FOXQ1 and HMLE_SNAIL1 cell lines
Table S1 from Pharmacologic Inhibition of SHP2 Blocks Both PI3K and MEK Signaling in Low-epiregulin HNSCC via GAB1
Authors: Kurupi Richard , Floros Konstantinos V. , Jacob Sheeba , Chawla Ayesha T. , Cai Jinyang , Hu Bin , Puchalapalli Madhavi , Coon Colin M. , Khatri Rishabh , Crowther Giovanna Stein , Egan Regina K. , Murchie Ellen , Greninger Patricia , Dalton Krista M. , Ghotra Maninderjit S. , Boikos Sosipatros A. , Koblinski Jennifer E. , Harada Hisashi , Sun Yue , Morgan Iain M. , Basu Devraj , Dozmorov Mikhail G. , Benes Cyril H. , Faber Anthony C.
Published: April 2023

Cell line information and SHP099 screen data
Figure S6 from Pharmacologic Inhibition of SHP2 Blocks Both PI3K and MEK Signaling in Low-epiregulin HNSCC via GAB1
Authors: Kurupi Richard , Floros Konstantinos V. , Jacob Sheeba , Chawla Ayesha T. , Cai Jinyang , Hu Bin , Puchalapalli Madhavi , Coon Colin M. , Khatri Rishabh , Crowther Giovanna Stein , Egan Regina K. , Murchie Ellen , Greninger Patricia , Dalton Krista M. , Ghotra Maninderjit S. , Boikos Sosipatros A. , Koblinski Jennifer E. , Harada Hisashi , Sun Yue , Morgan Iain M. , Basu Devraj , Dozmorov Mikhail G. , Benes Cyril H. , Faber Anthony C.
Published: April 2023

Weight profiles of xenograft models treated with SHP099
Figure S3 from Pharmacologic Inhibition of SHP2 Blocks Both PI3K and MEK Signaling in Low-epiregulin HNSCC via GAB1
Authors: Kurupi Richard , Floros Konstantinos V. , Jacob Sheeba , Chawla Ayesha T. , Cai Jinyang , Hu Bin , Puchalapalli Madhavi , Coon Colin M. , Khatri Rishabh , Crowther Giovanna Stein , Egan Regina K. , Murchie Ellen , Greninger Patricia , Dalton Krista M. , Ghotra Maninderjit S. , Boikos Sosipatros A. , Koblinski Jennifer E. , Harada Hisashi , Sun Yue , Morgan Iain M. , Basu Devraj , Dozmorov Mikhail G. , Benes Cyril H. , Faber Anthony C.
Published: April 2023

Three- and five-day western blot analysis of SHP099-sensitive and - resistant HNSCC cell lines
Figure S9 from Real-world Validation of TMB and Microsatellite Instability as Predictive Biomarkers of Immune Checkpoint Inhibitor Effectiveness in Advanced Gastroesophageal Cancer
Authors: Graf Ryon P. , Fisher Virginia , Creeden James , Schrock Alexa B. , Ross Jeffrey S. , Nimeiri Halla , Oxnard Geoffrey R. , Klempner Samuel J.
Published: April 2023

1st line treatment-TMB interaction models from Figure 5. The (A) TTNT and (B) OS interaction models are shown for for propensity adjusted analyses in Figure 5.
Fig. S7 from Targeting Lymphoma-associated Macrophage Expansion via CSF1R/JAK Inhibition is a Therapeutic Vulnerability in Peripheral T-cell Lymphomas
Authors: Gao Xin , Kady Nermin , Wang Chenguang , Abdelrahman Suhaib , Gann Peter , Sverdlov Maria , Wolfe Ashley , Brown Noah , Reneau John , Robida Aaron M. , Murga-Zamalloa Carlos , Wilcox Ryan A.
Published: April 2023

Identification of dual CSF-1R/JAK inhibitors in high-throughput screen
Table S1-S7 from Structures of Cancer Antigen Mesothelin and Its Complexes with Therapeutic Antibodies
Authors: Zhan Jingyu , Lin Dong , Watson Nathan , Esser Lothar , Tang Wai Kwan , Zhang Alex , Liu Xiufen , Hassan Raffit , Gleinich Anne , Shajahan Asif , Azadi Parastoo , Pastan Ira , Xia Di
Published: April 2023

Table S1: Plasmids and primers used for protein expression.

Table S2: Characterization of MSLN expression constructs.

Table S3: Structural alignments of MSLN models.

Table S4: Lists of interactions.

Table S5: Buried surface area for three MSLN-Fab complexes.

Table S6: Observed saccharide attachments at predicted glycosylation sites.

Table S7: Dali search result.
Table S1 from Combination Chemotherapy of Multidrug-resistant Early-stage Colon Cancer: Determining Optimal Dose Schedules by High-performance Computer Simulation
Authors: Cockrell Chase , Axelrod David E.
Published: April 2023

The 913 different dose schedules that cured all cancer cells in 100% of 50 simulation runs while retaining crypt function.
Figure S7 from Nanoparticle STING Agonist Reprograms the Bone Marrow to an Antitumor Phenotype and Protects Against Bone Destruction
Authors: Florian David C. , Bennett Natalie E. , Odziomek Mateusz , Baljon Jessalyn J. , Wehbe Mohamed , Merkel Alyssa R. , Fischer Melissa A. , Savona Michael R. , Rhoades Julie A. , Guelcher Scott A. , Wilson John T.
Published: April 2023

Supplementary Figure 7: Systemic effects of STING-NP on circulating myeloid cells.
Supplementary Figure 5 from The Splicing Factor PTBP1 Represses TP63 γ Isoform Production in Squamous Cell Carcinoma
Authors: Taylor William , Deschamps Stéphane , Reboutier David , Paillard Luc , Méreau Agnès , Audic Yann
Published: April 2023

PTBP1 controls TP63 splicing in HNSCC, additional RTqPCR
Supplementary Figure 3 from The Splicing Factor PTBP1 Represses TP63 γ Isoform Production in Squamous Cell Carcinoma
Authors: Taylor William , Deschamps Stéphane , Reboutier David , Paillard Luc , Méreau Agnès , Audic Yann
Published: April 2023

Alternative junction usage for TP63 in GTEX data
Figure S1 from Small-molecule PTPN2 Inhibitors Sensitize Resistant Melanoma to Anti-PD-1 Immunotherapy
Authors: Zhu Zhouting , Tang Rachel , Huff Sarah , Kummetha Indrasena Reddy , Wang Lingling , Li Na , Rana Tariq M.
Published: April 2023

Supplementary Figure S1
Supplementary Protocol SP1 from Novel Paired Normal Prostate and Prostate Cancer Model Cell Systems Derived from African American Patients
Authors: Jung Mira , Kowalczyk Keith , Hankins Ryan , Bandi Gaurav , Kallakury Bhaskar , Carrasquilla Michael A. , Banerjee Partha P. , Grindrod Scott , Dritschilo Anatoly
Published: April 2023

Material and methods of cell culture and CRC protocol
Supplementary Figure SF3. from Novel Paired Normal Prostate and Prostate Cancer Model Cell Systems Derived from African American Patients
Authors: Jung Mira , Kowalczyk Keith , Hankins Ryan , Bandi Gaurav , Kallakury Bhaskar , Carrasquilla Michael A. , Banerjee Partha P. , Grindrod Scott , Dritschilo Anatoly
Published: April 2023

Figure S3: Immunocytochemistry analysis of normal (N) and tumor (T)- derived paired cell cultures of AP4 and AP10. Normal and tumor cells from AP4 and AP10 were stained with indicated antibodies. DAPI (bottom in blue) stained the nucleus. CK8, HMW CK, and TOPK were mainly located in the cytoplasm.
Supplementary Figure SF2. from Novel Paired Normal Prostate and Prostate Cancer Model Cell Systems Derived from African American Patients
Authors: Jung Mira , Kowalczyk Keith , Hankins Ryan , Bandi Gaurav , Kallakury Bhaskar , Carrasquilla Michael A. , Banerjee Partha P. , Grindrod Scott , Dritschilo Anatoly
Published: April 2023

Figure S2. Western analysis of AR and p53. Cells were examined for expression levels of AR and p53 in a set of cell cultures. LNCaP (AR-dependent and p53+) and PC3 (AR-independent and p53 null) cells were used as controls for AR and p53 expression. Actin was used as the loading control.
Supplementary Figure S12 from The WAVE2/miR-29/Integrin-β1 Oncogenic Signaling Axis Promotes Tumor Growth and Metastasis in Triple-negative Breast Cancer
Authors: Rana Priyanka S. , Wang Wei , Markovic Vesna , Szpendyk Justin , Chan Ernest Ricky , Sossey-Alaoui Khalid
Published: April 2023

Immunofluorescence and Western Blot analyses of WAVE2 distribution between the cytoplasmic and the nuclear compartments of MDA-MB-231 cells.
Supplementary Figure S10 from The WAVE2/miR-29/Integrin-β1 Oncogenic Signaling Axis Promotes Tumor Growth and Metastasis in Triple-negative Breast Cancer
Authors: Rana Priyanka S. , Wang Wei , Markovic Vesna , Szpendyk Justin , Chan Ernest Ricky , Sossey-Alaoui Khalid
Published: April 2023

Volcano plot from the RNA-seq analysis of the differentially expressed genes between CTRL and W2-KO MDA-MB-231 cells.
Supplementary Data S1 from Mechanistic Modeling of the Interplay Between Host Immune System, IL-7 and UCART19 Allogeneic CAR-T Cells in Adult B-cell Acute Lymphoblastic Leukemia
Authors: Derippe Thibaud , Fouliard Sylvain , Marchiq Ibtissam , Dupouy Sandra , Almena-Carrasco Maria , Geronimi Julia , Declèves Xavier , Chenel Marylore , Mager Donald E.
Published: April 2023

Supplementary Data
Supplemental Figure SF3 from Incorporating RNA-based Risk Scores for Genomic Instability to Predict Breast Cancer Recurrence and Immunogenicity in a Diverse Population
Authors: Hamilton Alina M. , Van Alsten Sarah C. , Gao Xiaohua , Nsonwu-Farley Joseph , Calhoun Benjamin C. , Love Michael I. , Troester Melissa A. , Hoadley Katherine A.
Published: April 2023

Supplemental figure 3 shows the distribution of immune classes, PD-L1 and CD8 T-cell categories by AGI status in ER-positive and ER-negative tumors in TCGA and METABRIC.
Supplementary Data File S3 from Multiregional Sequencing Analysis Reveals Extensive Genetic Heterogeneity in Gastric Tumors from Latinos
Authors: Toal Ted W. , Estrada-Florez Ana P. , Polanco-Echeverry Guadalupe M. , Sahasrabudhe Ruta M. , Lott Paul C. , Suarez-Olaya John J. , Guevara-Tique Alix A. , Rocha Sienna , Morales-Arana Alexa , Castro-Valencia Fabian , Urayama Shiro , Kirane Amanda , Wei Dongguang , Rios-Sarabia Nora , Medrano Rafael , Mantilla Alejandra , Echeverry de Polanco Magdalena , Torres Javier , Bohorquez-Lozano Mabel E. , Carvajal-Carmona Luis G.
Published: April 2023

Spreadsheet of counts of patients with SNV/indel mutations in each gene
Supplemental Figure SF1 from Incorporating RNA-based Risk Scores for Genomic Instability to Predict Breast Cancer Recurrence and Immunogenicity in a Diverse Population
Authors: Hamilton Alina M. , Van Alsten Sarah C. , Gao Xiaohua , Nsonwu-Farley Joseph , Calhoun Benjamin C. , Love Michael I. , Troester Melissa A. , Hoadley Katherine A.
Published: April 2023

Supplemental Figure 1 shows differential expression analysis of immune scores according to TP53 and HRD status, stratified by estrogen receptor status in CBCS.
Supplementary Data File S1 from Multiregional Sequencing Analysis Reveals Extensive Genetic Heterogeneity in Gastric Tumors from Latinos
Authors: Toal Ted W. , Estrada-Florez Ana P. , Polanco-Echeverry Guadalupe M. , Sahasrabudhe Ruta M. , Lott Paul C. , Suarez-Olaya John J. , Guevara-Tique Alix A. , Rocha Sienna , Morales-Arana Alexa , Castro-Valencia Fabian , Urayama Shiro , Kirane Amanda , Wei Dongguang , Rios-Sarabia Nora , Medrano Rafael , Mantilla Alejandra , Echeverry de Polanco Magdalena , Torres Javier , Bohorquez-Lozano Mabel E. , Carvajal-Carmona Luis G.
Published: April 2023

Spreadsheet of pan-cancer panel gene composition, with citation codes
Table TS5 from Combination of a New Oral Demethylating Agent, OR2100, and Venetoclax for Treatment of Acute Myeloid Leukemia
Authors: Kamachi Kazuharu , Ureshino Hiroshi , Watanabe Tatsuro , Yoshida-Sakai Nao , Fukuda-Kurahashi Yuki , Kawasoe Kazunori , Hoshiko Toshimi , Yamamoto Yuta , Kurahashi Yuki , Kimura Shinya
Published: April 2023

The transcripts per million (TPM) values of ten upregulated genes
Table TS2 from Combination of a New Oral Demethylating Agent, OR2100, and Venetoclax for Treatment of Acute Myeloid Leukemia
Authors: Kamachi Kazuharu , Ureshino Hiroshi , Watanabe Tatsuro , Yoshida-Sakai Nao , Fukuda-Kurahashi Yuki , Kawasoe Kazunori , Hoshiko Toshimi , Yamamoto Yuta , Kurahashi Yuki , Kimura Shinya
Published: April 2023

The Bliss score in combination of venetoclax
Figure S7 from Combination of a New Oral Demethylating Agent, OR2100, and Venetoclax for Treatment of Acute Myeloid Leukemia
Authors: Kamachi Kazuharu , Ureshino Hiroshi , Watanabe Tatsuro , Yoshida-Sakai Nao , Fukuda-Kurahashi Yuki , Kawasoe Kazunori , Hoshiko Toshimi , Yamamoto Yuta , Kurahashi Yuki , Kimura Shinya
Published: April 2023

Figure S7. OR21 increases ROS levels by suppressing Ven-induced mitophagy
Figure S4 from Combination of a New Oral Demethylating Agent, OR2100, and Venetoclax for Treatment of Acute Myeloid Leukemia
Authors: Kamachi Kazuharu , Ureshino Hiroshi , Watanabe Tatsuro , Yoshida-Sakai Nao , Fukuda-Kurahashi Yuki , Kawasoe Kazunori , Hoshiko Toshimi , Yamamoto Yuta , Kurahashi Yuki , Kimura Shinya
Published: April 2023

Figure S4. HL and KG1a cells were exposed to vehicle (Cont), 1.0 mM of OR21 (OR 1), 0.1 μM (HL60) or 0.5 μM (KG1a) of venetoclax (Ven) and OR21 plus venetoclax (OR+Ven). Then mitochondrial membrane potential (MMP) was measured by flow cytometry. Venetoclax decreased MMP levels in HL60 and KG1a, while OR21 did not affect MMP levels in both monotherapy and combination. *p<0.05. n.s. indicated not significant.
Figure S3 from Combination of a New Oral Demethylating Agent, OR2100, and Venetoclax for Treatment of Acute Myeloid Leukemia
Authors: Kamachi Kazuharu , Ureshino Hiroshi , Watanabe Tatsuro , Yoshida-Sakai Nao , Fukuda-Kurahashi Yuki , Kawasoe Kazunori , Hoshiko Toshimi , Yamamoto Yuta , Kurahashi Yuki , Kimura Shinya
Published: April 2023

Figure S3. BCL2 and BCL-xL levels in HL60 and KG1a following Vehicle (Cont), 1.0 mM of OR21 (OR1), 0.1 mM (HL60) or 0.5 mM (KG1a) of venetoclax and OR21 and venetoclax (OR+Ven) combination treatment. n.s. indicated not significant.
Supplementary Figure SF3 from Mouse IgG2a Isotype Therapeutic Antibodies Elicit Superior Tumor Growth Control Compared with mIgG1 or mIgE
Authors: Vukovic Natasa , Segués Aina , Huang Shuyu , Waterfall Martin , Sijts Alice J.A.M. , Zaiss Dietmar M.
Published: April 2023

Confirmation of OT-1 cells activation by flow cytometry.
Supplementary Figure SF2 from Mouse IgG2a Isotype Therapeutic Antibodies Elicit Superior Tumor Growth Control Compared with mIgG1 or mIgE
Authors: Vukovic Natasa , Segués Aina , Huang Shuyu , Waterfall Martin , Sijts Alice J.A.M. , Zaiss Dietmar M.
Published: April 2023

Flow cytometry data used for ADCC.
Supplementary Figure S7 from IL9 Polarizes Macrophages to M1 and Induces the Infiltration of Antitumor Immune Cells via MIP-1 and CXCR3 Chemokines
Authors: Do-Thi Van Anh , Park Sang Min , Park Song Mi , Jeong Hye Jin , Cho Geunyoung , An Hyun-Jung , Kim Young Sang , Lee Hayyoung , Lee Jie-Oh
Published: April 2023

FACS gating strategy used for tumor-infiltrating immune cell analysis
Supplementary Figure S2 from IL9 Polarizes Macrophages to M1 and Induces the Infiltration of Antitumor Immune Cells via MIP-1 and CXCR3 Chemokines
Authors: Do-Thi Van Anh , Park Sang Min , Park Song Mi , Jeong Hye Jin , Cho Geunyoung , An Hyun-Jung , Kim Young Sang , Lee Hayyoung , Lee Jie-Oh
Published: April 2023

Treatment with IL-9 induces STAT1 and STAT3 phosphorylation in RAW 264.7 cells
Supplementary Figure S1 from IL9 Polarizes Macrophages to M1 and Induces the Infiltration of Antitumor Immune Cells via MIP-1 and CXCR3 Chemokines
Authors: Do-Thi Van Anh , Park Sang Min , Park Song Mi , Jeong Hye Jin , Cho Geunyoung , An Hyun-Jung , Kim Young Sang , Lee Hayyoung , Lee Jie-Oh
Published: April 2023

Generation of sorted bone marrow-derived macrophages (BMDMs)
Figure S4 from Detection of MET polysomy by next-generation sequencing and its clinical relevance for MET inhibitors
Authors: Sun Boyang , Qiu Tian , Zeng Xiaoling , Duan Jianchun , Bai Hua , Xu Jiachen , Li Jin , Li Junling , Hao Xuezhi , Liu Yutao , Lin Lin , Wang Hongyu , Zhang Xin , Zhong Jia , Wang Jie , Ying Jianming , Wang Zhijie
Published: April 2023

One MET-FISH polysomy tumor was classified as negative using the NGS assay.
Supplemental Table 15 from Association Between Recreational Physical Activity and mTOR Signaling Pathway Protein Expression in Breast Tumor Tissue
Authors: Cheng Ting-Yuan David , Zhang Runzhi , Gong Zhihong , Qin Bo , Cannioto Rikki A. , Datta Susmita , Zhang Weizhou , Omilian Angela R. , Yao Song , Khoury Thaer , Hong Chi-Chen , Bandera Elisa V. , Ambrosone Christine B.
Published: April 2023

Supplemental Table 15 reported stratified analysis for lymph node positive status and lymph node negative status.
Supplemental Table 12 from Association Between Recreational Physical Activity and mTOR Signaling Pathway Protein Expression in Breast Tumor Tissue
Authors: Cheng Ting-Yuan David , Zhang Runzhi , Gong Zhihong , Qin Bo , Cannioto Rikki A. , Datta Susmita , Zhang Weizhou , Omilian Angela R. , Yao Song , Khoury Thaer , Hong Chi-Chen , Bandera Elisa V. , Ambrosone Christine B.
Published: April 2023

Supplemental Table 12 reported stratified analysis for low/intermediate-grade tumors and high-grade tumors.
Supplementary Figure SF5 from Analysis of N-linked Glycan Alterations in Tissue and Serum Reveals Promising Biomarkers for Intrahepatic Cholangiocarcinoma
Authors: Ochoa-Rios Shaaron , Blaschke Calvin R.K. , Wang Mengjun , Peterson Kendell D. , DelaCourt Andrew , Grauzam Stéphane Elie , Lewin David , Angel Peggi , Roberts Lewis R. , Drake Richard , Mehta Anand S.
Published: April 2023

Relative intensity quantification of all N-glycans identified in serum (left row) and tissue (right row) analysis. Red font labeling for N-glycans follows the same trend between serum and tissue.
Supplementary Table TS1 from Quantitative, Spatially Defined Expression of Leukocyte-associated Immunoglobulin-like Receptor in Non–small Cell Lung Cancer
Authors: Aung Thazin N. , Gavrielatou Niki , Vathiotis Ioannis A. , Fernandez Aileen I. , Shafi Saba , Yaghoobi Vesal , Burela Sneha , MacNeil Tyler , Ahmed Fahad Shabbir , Myint Han , Flies Dallas B. , Langermann Solomon , Rimm David L.
Published: April 2023

Clinicopathological characteristics of NSCLC validation cohort (YTMA-250).
Supplementary Figure SF3 from Analysis of N-linked Glycan Alterations in Tissue and Serum Reveals Promising Biomarkers for Intrahepatic Cholangiocarcinoma
Authors: Ochoa-Rios Shaaron , Blaschke Calvin R.K. , Wang Mengjun , Peterson Kendell D. , DelaCourt Andrew , Grauzam Stéphane Elie , Lewin David , Angel Peggi , Roberts Lewis R. , Drake Richard , Mehta Anand S.
Published: April 2023

A. Relative contribution of each serum-glycan (left) and TMA-glycan (right) in the first and second principal components. The size and color of the circle represent a higher contribution of the glycan to the respective Dim. (Dimension). B. Three N-glycans in TMA and serum were identified after optimization. C. Relative intensity quantification for both TMAs of the respective N-glycan based on small and large duct classification. D. Two common N-glycans were identified between datasets. LOOCV (Leave-One-Out Cross-Validation). AUC (Area Under the Curve). E. Quantification of the relative contribution of N-glycans (left), table of N-glycans, and proposed structure with importance values (top) when removing N-glycan at 1339 m/z from the analysis. F. ROC (Receiving Operator Characteristic) curve classification for serum (left) ROC curve LOOCV (right) of N-glycans in E. G. List combinations of N-glycan as possible biomarkers to differentiate iCCA from PSC. For N-glycans, red triangle, fucose; blue square, N-acetylglucosamine; green circles, mannose; yellow circles, galactose.
Supplementary Figure FS2 from Quantitative, Spatially Defined Expression of Leukocyte-associated Immunoglobulin-like Receptor in Non–small Cell Lung Cancer
Authors: Aung Thazin N. , Gavrielatou Niki , Vathiotis Ioannis A. , Fernandez Aileen I. , Shafi Saba , Yaghoobi Vesal , Burela Sneha , MacNeil Tyler , Ahmed Fahad Shabbir , Myint Han , Flies Dallas B. , Langermann Solomon , Rimm David L.
Published: April 2023

Representative figures of staining by different antibody clones. Representative QIF images of different LAIR-1 clones staining targeting non-overlapping epitopes in a lung test array (YTMA–295) containing 35 lung tumor cores stained by (A) E7X61 clone, (B) NKT25 clone, (C) 1A10 clone and (D) 1E4 clone. (E) The staining quantification of the four LAIR-1 clones. CK: green, LAIR-1: red, DAPI: blue. The fluorescent channels where each marker was acquired were shown in brackets.
Table TS2 from Tumor-derived GCSF Alters Tumor and Systemic Immune System Cell Subset Composition and Signaling
Authors: Matos Israel , Barvalia Maunish , Chehal Manreet K. , Robertson A. Gordon , Kulic Iva , Silva Jessica A.F.D. , Ranganathan Abhinandan , Short Amy , Huang Yu-Hsuan , Long Erin , Priatel John J. , Dhanji Salim , Nelson Brad H. , Krebs Danielle L. , Harder Kenneth W.
Published: April 2023

Flow cytometry antibodies
Figure S4 from Tumor-derived GCSF Alters Tumor and Systemic Immune System Cell Subset Composition and Signaling
Authors: Matos Israel , Barvalia Maunish , Chehal Manreet K. , Robertson A. Gordon , Kulic Iva , Silva Jessica A.F.D. , Ranganathan Abhinandan , Short Amy , Huang Yu-Hsuan , Long Erin , Priatel John J. , Dhanji Salim , Nelson Brad H. , Krebs Danielle L. , Harder Kenneth W.
Published: April 2023

Supplementary Figure S4 shows that G-CSF and G-CSFR signaling inhibit DC development and activation, in DCs derived in a OP9-DLL1 co-culture system.
Figure S6 from S100A8/S100A9 Promote Progression of Multiple Myeloma via Expansion of Megakaryocytes
Authors: Lin Cindy , Garcia-Gerique Laura , Bonner Erin E. , Mastio Jerome , Rosenwasser Matthew , Cruz Zachary , Lawler Michael , Bernabei Luca , Muthumani Kar , Liu Qin , Poncz Mortimer , Vogl Thomas , Törngren Marie , Eriksson Helena , Vogl Dan T. , Gabrilovich Dmitry I. , Nefedova Yulia
Published: April 2023

Mechanism of S100A9 effect on MK differentiation.
Figure S5 from S100A8/S100A9 Promote Progression of Multiple Myeloma via Expansion of Megakaryocytes
Authors: Lin Cindy , Garcia-Gerique Laura , Bonner Erin E. , Mastio Jerome , Rosenwasser Matthew , Cruz Zachary , Lawler Michael , Bernabei Luca , Muthumani Kar , Liu Qin , Poncz Mortimer , Vogl Thomas , Törngren Marie , Eriksson Helena , Vogl Dan T. , Gabrilovich Dmitry I. , Nefedova Yulia
Published: April 2023

BM angiogenesis in tumor-free and MM-bearing mice treated with TQ.
Figure S4 from S100A8/S100A9 Promote Progression of Multiple Myeloma via Expansion of Megakaryocytes
Authors: Lin Cindy , Garcia-Gerique Laura , Bonner Erin E. , Mastio Jerome , Rosenwasser Matthew , Cruz Zachary , Lawler Michael , Bernabei Luca , Muthumani Kar , Liu Qin , Poncz Mortimer , Vogl Thomas , Törngren Marie , Eriksson Helena , Vogl Dan T. , Gabrilovich Dmitry I. , Nefedova Yulia
Published: April 2023

Effect of S100A9 protein on mouse MKs.
Figure S2 from S100A8/S100A9 Promote Progression of Multiple Myeloma via Expansion of Megakaryocytes
Authors: Lin Cindy , Garcia-Gerique Laura , Bonner Erin E. , Mastio Jerome , Rosenwasser Matthew , Cruz Zachary , Lawler Michael , Bernabei Luca , Muthumani Kar , Liu Qin , Poncz Mortimer , Vogl Thomas , Törngren Marie , Eriksson Helena , Vogl Dan T. , Gabrilovich Dmitry I. , Nefedova Yulia
Published: April 2023

Expression of S100A8 and S100A9 proteins using in vivo electroporation technique.
Supplemental Table 2 from Digital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma
Authors: Gavrielatou Niki , Vathiotis Ioannis A. , Aung Thazin Nwe , Shafi Saba , Burela Sneha , Fernandez Aileen I. , Moutafi Myrto , Burtness Barbara A. , Economopoulou Panagiota , Anastasiou Maria , Foukas Periklis , Psyrri Amanda , Rimm David L.
Published: April 2023

Target-protein panels included in the GeoMxTM Immuno-Oncology Human Protein Assay
Figure S4 from IOA-244 is a non-ATP-competitive, highly selective, tolerable phosphoinositide 3-kinase delta inhibitor that targets solid tumors and breaks immune tolerance
Authors: Johnson Zoë , Tarantelli Chiara , Civanelli Elisa , Cascione Luciano , Spriano Filippo , Fraser Amy , Shah Pritom , Nomanbhoy Tyzoon , Napoli Sara , Rinaldi Andrea , Niewola-Staszkowska Karolina , Lahn Michael , Perrin Dominique , Wenes Mathias , Migliorini Denis , Bertoni Francesco , van der Veen Lars , Di Conza Giusy
Published: April 2023

Tumor experiments showing monotherapy testing of IOA-244
Figure S3 from IOA-244 is a non-ATP-competitive, highly selective, tolerable phosphoinositide 3-kinase delta inhibitor that targets solid tumors and breaks immune tolerance
Authors: Johnson Zoë , Tarantelli Chiara , Civanelli Elisa , Cascione Luciano , Spriano Filippo , Fraser Amy , Shah Pritom , Nomanbhoy Tyzoon , Napoli Sara , Rinaldi Andrea , Niewola-Staszkowska Karolina , Lahn Michael , Perrin Dominique , Wenes Mathias , Migliorini Denis , Bertoni Francesco , van der Veen Lars , Di Conza Giusy
Published: April 2023

Correlation analysis of PI3Kd levels and the response to IOA-244 and Idelalisib
Figure S1 from IOA-244 is a non-ATP-competitive, highly selective, tolerable phosphoinositide 3-kinase delta inhibitor that targets solid tumors and breaks immune tolerance
Authors: Johnson Zoë , Tarantelli Chiara , Civanelli Elisa , Cascione Luciano , Spriano Filippo , Fraser Amy , Shah Pritom , Nomanbhoy Tyzoon , Napoli Sara , Rinaldi Andrea , Niewola-Staszkowska Karolina , Lahn Michael , Perrin Dominique , Wenes Mathias , Migliorini Denis , Bertoni Francesco , van der Veen Lars , Di Conza Giusy
Published: April 2023

IC50 curve of the ATP competitive assay and pie chart of the Kinativ assay
Supplementary Figure S4 from Whole-genome and epigenomic landscapes of malignant gastrointestinal stromal tumors harboring KIT exon 11 557–558 deletion mutations
Authors: Ohshima Keiichi , Nagashima Takeshi , Fujiya Keiichi , Hatakeyama Keiichi , Watanabe Yuko , Morimoto Kimiko , Kamada Fukumi , Shimoda Yuji , Ohnami Sumiko , Naruoka Akane , Serizawa Masakuni , Ohnami Shumpei , Kenmotsu Hirotsugu , Shiomi Akio , Tsubosa Yasuhiro , Bando Etsuro , Sugiura Teiichi , Sugino Takashi , Terashima Masanori , Uesaka Katsuhiko , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken
Published: April 2023

Comparison of somatic mutational landscape between malignant and less malignant GISTs with and without KIT Δ557–558.
Supplementary Figure S4 from Toll-like Receptor Signaling–deficient Cells Enhance Antitumor Activity of Cell-based Immunotherapy by Increasing Tumor Homing
Authors: Morales-Molina Alvaro , Rodriguez-Milla Miguel Ángel , Gambera Stefano , Cejalvo Teresa , de Andrés Belén , Gaspar María-Luisa , García-Castro Javier
Published: April 2023

OAd-MSC TLR4−/− induces changes in tumor-infiltration of innate and adaptive immune cells
Supplementary Figure S8 from Structurally complex osteosarcoma genomes exhibit limited heterogeneity within individual tumors and across evolutionary time
Authors: Rajan Sanjana , Zaccaria Simone , Cannon Matthew , Cam Maren , Gross Amy C , Raphael Benjamin J , Roberts Ryan D.
Published: April 2023

Bulk data genome SCNA plots by patient
Data from Tumor Purity in Preclinical Mouse Tumor Models
Authors: Qian Wubin , Chen Xiaobo , Sheng Yanghui , Zhang Likun , Wang Jingjing , Song Zhenzhen , Li Qi-Xiang , Guo Sheng
Published: April 2023

Tumor biology is determined not only by immortal cancer cells but also by the tumor microenvironment consisting of noncancerous cells and extracellular matrix, together they dictate the pathogenesis and response to treatments. Tumor purity is the proportion of cancer cells in a tumor. It is a fundamental property of cancer and is associated with many clinical features and outcomes. Here we report the first systematic study of tumor purity in patient-derived xenograft (PDX) and syngeneic tumor models using next-generation sequencing data from >9,000 tumors. We found that tumor purity in PDX models is cancer specific and mimics patient tumors, with variation in stromal content and immune infiltration influenced by immune systems of host mice. After the initial engraftment, human stroma in a PDX tumor is quickly replaced by mouse stroma, and tumor purity then stays stable in subsequent transplantations and increases only slightly by passage. Similarly, in syngeneic mouse cancer cell line models, tumor purity also turns out to be an intrinsic property with model and cancer specificities. Computational and pathology analysis confirmed the impact on tumor purity by the diverse stromal and immune profiles. Our study deepens the understanding of mouse tumor models, which will enable their better and novel uses in developing cancer therapeutics, especially ones targeting tumor microenvironment.
Significance:
PDX models are an ideal experimental system to study tumor purity because of its distinct separation of human tumor cells and mouse stromal and immune cells. This study provides a comprehensive view of tumor purity in 27 cancers in PDX models. It also investigates tumor purity in 19 syngeneic models based on unambiguously identified somatic mutations. It will facilitate tumor microenvironment research and drug development in mouse tumor models.
Data from Conduit CAR: Redirecting CAR T-Cell Specificity with A Universal and Adaptable Bispecific Antibody Platform
Authors: Borrok M. Jack , Li Yonghai , Harvilla Paul B. , Vellalore Maruthachalam Bharathikumar , Tamot Ninkka , Prokopowitz Christine , Chen Jun , Venkataramani Sathya , Grewal Iqbal S. , Ganesan Rajkumar , Singh Sanjaya
Published: April 2023

The success of chimeric antigen receptor (CAR) T-cell therapy against hematologic malignancies has altered the treatment paradigm for patients with these diseases. Nevertheless, the occurrence of relapse due to antigen escape or heterogeneous antigen expression on tumors remains a challenge for first-generation CAR T-cell therapies as only a single tumor antigen can be targeted. To address this limitation and to add a further level of tunability and control to CAR T-cell therapies, adapter or universal CAR T-cell approaches use a soluble mediator to bridge CAR T cells with tumor cells. Adapter CARs allow simultaneous or sequential targeting of multiple tumor antigens, control of immune synapse geometry, dose control, and the potential for improved safety. Herein, we described a novel CAR T-cell adapter platform that relies on a bispecific antibody (BsAb) targeting both a tumor antigen and the GGGGS (G4S) linker commonly used in single-chain Fv (ScFv) domains expressed on CAR T-cell surfaces. We demonstrated that the BsAb can bridge CAR T cells to tumor cells and potentiate CAR T-cell activation, proliferation, and tumor cell cytolysis. The cytolytic activity of CAR T-cells was redirected to different tumor antigens by changing the BsAb in a dose-dependent manner. This study highlights the potential of G4S-displaying CAR T cells to be redirected to engage alternative tumor-associated antigens (TAA).
Significance:
New approaches are needed to address relapsed/refractory disease and manage potential toxicities associated with CAR T-cell therapy. We describe an adapter CAR approach to redirect CAR T cells to engage novel TAA-expressing cells via a BsAb targeting a linker present on many clinical CAR T-cell therapeutics. We anticipate the use of such adapters could increase CAR T-cell efficacy and reduce potential CAR-associated toxicities.
Data from A Phenogenetic Axis that Modulates Clinical Manifestation and Predicts Treatment Outcome in Primary Myeloid Neoplasms
Authors: Shen Qiujin , Feng Yahui , Gong Xiaowen , Jia Yujiao , Gao Qingyan , Jiao Xiaokang , Qi Saibing , Liu Xueou , Wei Hui , Huang Bingqing , Zhao Ningning , Song Xiaoqiang , Ma Yueshen , Liang Shihao , Zhang Donglei , Qin Li , Wang Ying , Qu Shiqiang , Zou Yao , Chen Yumei , Guo Ye , Yi Shuhua , An Gang , Jiao Zengtao , Zhang Song , Li Linfeng , Yan Jun , Wang Huijun , Song Zhen , Mi Yingchang , Qiu Lugui , Zhu Xiaofan , Wang Jianxiang , Xiao Zhijian , Chen Junren
Published: April 2023

Although the concept of “myeloid neoplasm continuum” has long been proposed, few comparative genomics studies directly tested this hypothesis. Here we report a multi-modal data analysis of 730 consecutive newly diagnosed patients with primary myeloid neoplasm, along with 462 lymphoid neoplasm cases serving as the outgroup. Our study identified a “Pan-Myeloid Axis” along which patients, genes, and phenotypic features were all aligned in sequential order. Utilizing relational information of gene mutations along the Pan-Myeloid Axis improved prognostic accuracy for complete remission and overall survival in adult patients of de novo acute myeloid leukemia and for complete remission in adult patients of myelodysplastic syndromes with excess blasts. We submit that better understanding of the myeloid neoplasm continuum might shed light on how treatment should be tailored to individual diseases.
Significance:
The current criteria for disease diagnosis treat myeloid neoplasms as a group of distinct, separate diseases. This work provides genomics evidence for a “myeloid neoplasm continuum” and suggests that boundaries between myeloid neoplastic diseases are much more blurred than previously thought.
Data from WEE1 Inhibition Augments CDC7 (DDK) Inhibitor–induced Cell Death in Ewing Sarcoma by Forcing Premature Mitotic Entry and Mitotic Catastrophe
Authors: Martin Jeffrey C. , Sims Jennie R. , Gupta Ajay , Bakin Andrei V. , Ohm Joyce Ellen
Published: April 2023

Ewing sarcoma is an aggressive childhood cancer for which treatment options remain limited and toxic. There is an urgent need for the identification of novel therapeutic strategies. Our group has recently shown that Ewing cells rely on the S-phase kinase cell division cycle 7 (CDC7) DBF4-dependent kinase (DDK) to maintain replication rates and cell viability and that DDK inhibition causes an increase in the phosphorylation of CDK1 and a significant delay in mitotic entry. Here, we expand on our previous findings and show that DDK inhibitor–induced mitotic entry delay is dependent upon WEE1 kinase. Specifically, WEE1 phosphorylates CDK1 and prevents mitotic entry upon DDK inhibition due to the presence of underreplicated DNA, potentially limiting the cytotoxic effects of DDK inhibition. To overcome this, we combined the inhibition of DDK with the inhibition of WEE1 and found that this results in elevated levels of premature mitotic entry, mitotic catastrophe, and apoptosis. Importantly, we have found that DDK and WEE1 inhibitors display a synergistic relationship with regards to reducing cell viability of Ewing sarcoma cells. Interestingly, the cytotoxic nature of this combination can be suppressed by the inhibition of CDK1 or microtubule polymerization, indicating that mitotic progression is required to elicit the cytotoxic effects. This is the first study to display the potential of utilizing the combined inhibition of DDK and WEE1 for the treatment of cancer. We believe this will offer a potential therapeutic strategy for the treatment of Ewing sarcoma as well as other tumor types that display sensitivity to DDK inhibitors.
Significance:
Ewing sarcoma is an aggressive pediatric cancer for which chemotherapy is very intense and often results in acute toxicities. Here, we have found that the combined inhibition of CDC7 kinase (DDK) and WEE1 kinase forces high levels of mitotic errors and synergistic cell death, specifically in Ewing sarcoma cells. This combination has the potential to provide a highly efficacious and minimally toxic treatment strategy for patients with Ewing sarcoma.
Data from A Phase I Study of Pelabresib (CPI-0610), a Small-Molecule Inhibitor of BET Proteins, in Patients with Relapsed or Refractory Lymphoma
Authors: Blum Kristie A. , Supko Jeffrey G. , Maris Michael B. , Flinn Ian W. , Goy Andre , Younes Anas , Bobba Suresh , Senderowicz Adrian M. , Efuni Sergey , Rippley Ronda , Colak Gozde , Trojer Patrick , Abramson Jeremy S.
Published: April 2023

Purpose:
NF-κB, a transcription factor essential for inflammatory responses, is constitutively activated in many lymphomas. In preclinical studies, pelabresib (CPI-0610), an investigational (BET) bromodomain inhibitor, downregulated NF-κB signaling and demonstrated antitumor activity in vitro. Here we report the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity from the first-in-human phase I study of pelabresib in patients with relapsed/refractory lymphomas (NCT01949883).
Experimental Design:
Sixty-four patients with relapsed/refractory lymphoma (median of 4 prior lines of therapy) were treated with either capsule (6, 12, 24, 48, 80, 120, 170, 230, 300 mg) or tablet (125, 225 mg) doses of pelabresib orally once daily on a 14 days on, 7 days off schedule.
Results:
The MTD was determined as the 225 mg tablet daily. The most frequent adverse events were fatigue, nausea, and decreased appetite. Thrombocytopenia, a class effect for all BET inhibitors, was dose-dependent, reversible, and noncumulative. Pelabresib exhibited dose-proportional increases in systemic exposure, rapid absorption, and a half-life of approximately 15 hours (supporting once daily dosing). The bioavailability of the tablet formulation was 60% greater than the capsules. Pelabresib suppressed IL8 and CCR1 mRNA at doses above 120 and 170 mg, respectively. Four patients (6.2%) had an objective response (2 complete response and 2 partial response) and 5 patients had prolonged stable disease.
Conclusions/Discussion:
Pelabresib is capable of BET target gene suppression in an exposure-dependent manner with an acceptable safety profile leading to the recommended phase II dose of the 125 mg tablet once daily.
Significance:
BET proteins inhibition can potentially modify the pathogenic pathways which contribute to many diseases including malignancies. Pelabresib (CPI-0610), a potent and selective small molecule BET proteins inhibitor, has a MTD of 225 mg once daily for 14 days with a 7-day break, clear pharmacokinetic/pharmacodynamic relationship, and manageable clinical safety profile. These findings are part of the foundation for the ongoing pivotal study of pelabresib in patients with myelofibrosis.
Data from ZL-1211 Exhibits Robust Antitumor Activity by Enhancing ADCC and Activating NK Cell–mediated Inflammation in CLDN18.2-High and -Low Expressing Gastric Cancer Models
Authors: Konno Hiroyasu , Lin Tracey , Wu Renyi , Dai Xinchuan , Li Shou , Wang Grace , Chen Min , Li Wenying , Wang Lina , Sun Bee-Chun , Luo Zhen , Huang Tom , Chen Yuping , Zhang John , Ye Qiuping , Bellovin David , Wan Bing , Kang Lishan , Szeto Christopher , Hsu Karl , Kabbarah Omar
Published: April 2023

CLDN18.2 (Claudin18.2)-targeting therapeutic antibodies have shown promising clinical efficacy in approximately 30% of gastric cancers expressing high levels of CLDN18.2 and less pronounced activity in low expressing malignancies. Here, we report that ZL-1211 is a mAb targeting CLDN18.2 engineered to promote enhanced antibody-dependent cellular cytotoxicity (ADCC) with the goal of achieving more potent activity in a wider spectrum of high- and low-CLDN18.2 expressing tumors. ZL-1211 demonstrated more robust in vitro ADCC activity than clinical benchmark not only in CLDN18.2-high but also CLDN18.2-low expressing gastric tumor cell lines. Greater antitumor efficacy was also observed in mouse xenograft models. Natural killer (NK) cell played critical roles in ZL-1211 efficacy and NK-cell depletion abrogated ZL-1211–mediated ADCC activity in vitro. ZL-1211 efficacy in vivo was also dependent on the presence of an NK compartment. Strikingly, NK cells strongly induced an inflammatory response in response to ZL-1211 treatment, including increased IFNγ, TNFα, and IL6 production, and were recruited into tumor microenvironment in patient-derived gastric tumors expressing CLDN18.2 upon ZL-1211 treatment to lyse the tumor cells. Taken together, our data suggest that ZL-1211 more effectively targets CLDN18.2-high gastric cancers as well as -low expressing malignancies that may not be eligible for treatment with the leading clinical benchmark by inducing enhanced ADCC response and activating NK cells with robust inflammation to enhance antitumor efficacy. Clinical activity of ZL-1211 is currently under evaluation in a phase I clinical trial (NCT05065710).
Significance:
ZL-1211, anti-CLDN18.2 therapeutic antibody can target CLDN18.2-high as well as -low gastric cancers that may not be eligible for treatment with clinical benchmark. ZL-1211 treatment induces NK-cell activation with robust inflammation to further activate antitumor immunity in tumor microenvironment.
Data from Smoking-associated Downregulation of FILIP1L Enhances Lung Adenocarcinoma Progression Through Mucin Production, Inflammation, and Fibrosis
Authors: Kwon Mijung , Rubio Genesaret , Wang Haitao , Riedlinger Gregory , Adem Asha , Zhong Hua , Slegowski Daniel , Post-Zwicker Louisa , Chidananda Anshruta , Schrump David S. , Pine Sharon R. , Libutti Steven K.
Published: April 2023

Lung adenocarcinoma (LUAD) is the major subtype in lung cancer, and cigarette smoking is essentially linked to its pathogenesis. We show that downregulation of Filamin A interacting protein 1-like (FILIP1L) is a driver of LUAD progression. Cigarette smoking causes its downregulation by promoter methylation in LUAD. Loss of FILIP1L increases xenograft growth, and, in lung-specific knockout mice, induces lung adenoma formation and mucin secretion. In syngeneic allograft tumors, reduction of FILIP1L and subsequent increase in its binding partner, prefoldin 1 (PFDN1) increases mucin secretion, proliferation, inflammation, and fibrosis. Importantly, from the RNA-sequencing analysis of these tumors, reduction of FILIP1L is associated with upregulated Wnt/β-catenin signaling, which has been implicated in proliferation of cancer cells as well as inflammation and fibrosis within the tumor microenvironment. Overall, these findings suggest that down-regulation of FILIP1L is clinically relevant in LUAD, and warrant further efforts to evaluate pharmacologic regimens that either directly or indirectly restore FILIP1L-mediated gene regulation for the treatment of these neoplasms.
Significance:
This study identifies FILIP1L as a tumor suppressor in LUADs and demonstrates that downregulation of FILIP1L is a clinically relevant event in the pathogenesis and clinical course of these neoplasms.
Methodology and Baseline Data of a Comparative Exploratory Double-Blinded Randomized Study of Intravenous Iron on Fibroblast Growth Factor 23 and Phosphate in Chronic Kidney Disease
Authors: Kassianides Xenophon , Bhandari Sunil
Published: April 2023

Modern intravenous iron compounds (e.g., ferric carboxymaltose [FCM] and ferric derisomaltose [FDI]) are utilized in the treatment of iron deficiency anemia in non-dialysis-dependent chronic kidney disease (ND-CKD). Product-specific alterations in the metabolism of fibroblast growth factor 23 (FGF-23) leading to hypophosphatemia have been described for certain intravenous iron compounds, such as FCM, with potential effects on bone and cardiovascular health and quality of life. No prior head-to-head comparison between FCM and FDI exists in ND-CKD. This single-center exploratory double-blind randomized controlled trial primarily aimed to investigate the differential impact of FCM and FDI on FGF-23 and phosphate in patients with iron deficiency +/− anemia and ND-CKD (stages 3a–5 – serum ferritin <200 μg/L or serum ferritin 200–299 μg/L and transferrin saturation <20%). Patients were randomized (1:1) to receive either FCM or FDI over two infusions (1 month apart). Follow-up was 3 months. Measurements of serum intact FGF-23, phosphate, vitamin D metabolites, parathyroid hormone, other bone metabolism, cardiovascular, and quality of life markers were monitored. 168 patients were prescreened. Thirty-five patients were screened; 26 patients were randomized. The mean (standard deviation) age was 67.9 (12.4) years and 17 participants were male. Most participants had stage 4 CKD (median [interquartile range] estimated glomerular filtration rate [eGFR]: 18.0 [11.3] mL/min/1.73 m2). A higher than normal median (interquartile range) level of intact FGF-23 (212.1 [116.4] pg/mL) was noted. Serum phosphate was within normal range, while parathyroid hormone was higher and 1,25 (OH)2 vitamin D lower than the normal range. The “Iron and Phosphaturia – ExplorIRON-CKD” trial will provide important information regarding the differential effect of intravenous iron products in terms of FGF-23, phosphate, and other markers of bone and cardiovascular metabolism, alongside patient-reported outcome measures in patients with ND-CKD.
Unilateral Suprainguinal Ectopic Scrotum: Case Report and Literature Review
Authors: Wang Hengyou , Tang Daxing , Yan Xiang
Published: April 2023

Ectopic scrotum is an infrequent congenital scrotal anomaly. Different surgical methods of correcting ectopic scrotum have been used, but none have produced optimal cosmetic results for all types. We describe a case of left ectopic suprainguinal scrotum in a 14-month-old boy who had an undescended left testicle and a left-sided scrotal skin tag. Single-stage rotational flap scrotoplasty and unilateral orchiopexy were performed; however, we modified the surgical technique of scrotal rotation by excising the intervening longitudinal skin. Eight months after surgery, the repositioned scrotum had a better appearance, and the affected testicle was similar in size to the contralateral one. In comparison with other surgical methods, pedicle flap rotation of the ectopic scrotal skin with excision of the intervening longitudinal skin may produce a better cosmetic outcome.