bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S5 from The Methyltransferases METTL7A and METTL7B Confer Resistance to Thiol-Based Histone Deacetylase Inhibitors
Authors: Robey Robert W. , Fitzsimmons Christina M. , Guiblet Wilfried M. , Frye William J.E. , González Dalmasy José M. , Wang Li , Russell Drake A. , Huff Lyn M. , Perciaccante Andrew J. , Ali-Rahmani Fatima , Lipsey Crystal C. , Wade Heidi M. , Mitchell Allison V. , Maligireddy Siddhardha S. , Terrero David , Butcher Donna , Edmondson Elijah F. , Jenkins Lisa M. , Nikitina Tatiana , Zhurkin Victor B. , Tiwari Amit K. , Piscopio Anthony D. , Totah Rheem A. , Bates Susan E. , Arda H. Efsun , Gottesman Michael M. , Batista Pedro J.
Published: April 2024

Figure S5 contains cycle cycle analysis of MCF7 DpVp300 cells following knockdown of METTL7A.
Figure S1 from The Methyltransferases METTL7A and METTL7B Confer Resistance to Thiol-Based Histone Deacetylase Inhibitors
Authors: Robey Robert W. , Fitzsimmons Christina M. , Guiblet Wilfried M. , Frye William J.E. , González Dalmasy José M. , Wang Li , Russell Drake A. , Huff Lyn M. , Perciaccante Andrew J. , Ali-Rahmani Fatima , Lipsey Crystal C. , Wade Heidi M. , Mitchell Allison V. , Maligireddy Siddhardha S. , Terrero David , Butcher Donna , Edmondson Elijah F. , Jenkins Lisa M. , Nikitina Tatiana , Zhurkin Victor B. , Tiwari Amit K. , Piscopio Anthony D. , Totah Rheem A. , Bates Susan E. , Arda H. Efsun , Gottesman Michael M. , Batista Pedro J.
Published: April 2024

Figure S1 contains chemical structures of select HDAC inhibitors
Figure S1 from Development of a Novel DNA Mono-alkylator Platform for Antibody–Drug Conjugates
Authors: Thomas Joshua D. , Yurkovetskiy Aleksandr V. , Yin Mao , Bodyak Natalya D. , Tang Shuyi , Protopopova Marina , Kelleher Eugene , Jones Brian , Yang Liping , Custar Daniel , Catcott Kalli C. , Demady Damon R. , Collins Scott D. , Xu Ling , Bu Charlie , Qin LiuLiang , Ter-Ovanesyan Elena , Damelin Marc , Toader Dorin , Lowinger Timothy B.
Published: April 2024

Structures of PBD Platform 5 and AF-HPA Platform 7 (known as Dolaflexin)
Data from TAS0313 plus Pembrolizumab for Post-Chemotherapy Immune Checkpoint Inhibitor—Naïve Locally Advanced or Metastatic Urothelial Carcinoma
Authors: Nishiyama Hiroyuki , Yonese Junji , Kawahara Takashi , Matsumoto Ryuji , Miyake Hideaki , Matsubara Nobuaki , Uemura Hiroji , Eto Masatoshi , Azuma Haruhito , Obara Wataru , Terai Akito , Fukasawa Satoshi , Suekane Shigetaka
Published: April 2024

Abstract
We evaluated the efficacy and safety of TAS0313, a multi-epitope long peptide vaccine, plus pembrolizumab in post-chemotherapy immune checkpoint inhibitor—naïve patients with locally advanced/metastatic urothelial carcinoma (la/mUC). TAS0313 9 mg was administered subcutaneously followed by pembrolizumab 200 mg on Day 1, and as monotherapy on Day 8 and 15 of Cycles 1 and 2, and Day 1 of subsequent cycles in 21-day cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Biomarkers of response were assessed. In 36 patients enrolled, the ORR was 33.3% (complete response: 7 patients; partial response: 5 patients). Median PFS was 5.0 months; 6- and 12-month progression-free rates were 46.4% and 36.5%, respectively. Median OS was not reached; 6-, 12-, and 24-month OS rates were 83.3%, 72.2%, and 55.1%, respectively. In post hoc analysis, patients with a tumor infiltrating CD8+ lymphocyte (CD8+ TIL) count ≥99 and/or programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥50 and lymphocyte count >1,380 cells/μL had higher ORRs and prolonged PFS versus patients with a CD8+ TIL count <99, PD-L1 CPS <50, and lymphocyte count ≤1,380 cells/μL. Thirty-four (94.4%) patients receiving combination therapy experienced treatment-related adverse events (AE), with pyrexia (n = 15, 41.7%), injection-site reactions (n = 15, 41.7%), injection-site induration (n = 6, 16.7%), and malaise (n = 6, 16.7%) the most common. No grade ≥3 treatment-related AEs occurred in ≥10% of patients. TAS0313 plus pembrolizumab combination therapy showed promising efficacy and manageable safety in la/mUC.

Clinical Trial Registration: JapicCTI-183824.
Data from Combination Therapy with EGFR Tyrosine Kinase Inhibitors and TEAD Inhibitor Increases Tumor Suppression Effects in EGFR Mutation–positive Lung Cancer
Authors: Ogimoto Tatsuya , Ozasa Hiroaki , Tsuji Takahiro , Funazo Tomoko , Yamazoe Masatoshi , Hashimoto Kentaro , Yoshida Hiroshi , Hosoya Kazutaka , Ajimizu Hitomi , Nomizo Takashi , Yoshida Hironori , Hamaji Masatsugu , Menju Toshi , Yoshizawa Akihiko , Date Hiroshi , Hirai Toyohiro
Published: April 2024

Abstract
EGFR-tyrosine kinase inhibitors (TKI) are the first-line therapies for EGFR mutation–positive lung cancer. EGFR-TKIs have favorable therapeutic effects. However, a large proportion of patients with EGFR mutation–positive lung cancer subsequently relapse. Some cancer cells survive the initial treatment with EGFR-TKIs, and this initial survival may be associated with subsequent recurrence. Therefore, we aimed to overcome the initial survival against EGFR-TKIs. We hypothesized that yes-associated protein 1 (YAP1) is involved in the initial survival against EGFR-TKIs, and we confirmed the combined effect of EGFR-TKIs and a YAP1–TEAD pathway inhibitor. The KTOR27 (EGFR kinase domain duplication) lung cancer cell lines established from a patient with EGFR mutation–positive lung cancer and commercially available PC-9 and HCC827 (EGFR exon 19 deletions) lung cancer cell lines were used. These cells were used to evaluate the in vitro and in vivo effects of VT104, a TEAD inhibitor. In addition, YAP1 involvement was investigated in pathologic specimens. YAP1 was activated by short-term EGFR-TKI treatment in EGFR mutation–positive lung cancer cells. In addition, inhibiting YAP1 function using siRNA increased the sensitivity to EGFR-TKIs. Combination therapy with VT104 and EGFR-TKIs showed better tumor-suppressive effects than EGFR-TKIs alone, in vitro and in vivo. Moreover, the combined effect of VT104 and EGFR-TKIs was observed regardless of the localization status of YAP1 before EGFR-TKI exposure. These results suggest that combination therapy with the TEAD inhibitor and EGFR-TKIs may improve the prognosis of patients with EGFR mutation–positive lung cancer.
Data from ADCT-602, a Novel PBD Dimer–containing Antibody–Drug Conjugate for Treating CD22-positive Hematologic Malignancies
Authors: Zammarchi Francesca , Havenith Karin E. , Sachini Nikoleta , Janghra Narinder , Chivers Simon , Idusogie Esohe , Gaudio Eugenio , Tarantelli Chiara , Bertelli Francois , Santos Kathleen , Tyrer Peter , Corbett Simon , Spriano Filippo , Golino Gaetanina , Cascione Luciano , Bertoni Francesco , Hartley John A. , van Berkel Patrick H.
Published: April 2024

Abstract
Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and lymphomas have poor patient outcomes; novel therapies are needed. CD22 is an attractive target for antibody–drug conjugates (ADCs), being highly expressed in R/R B-ALL with rapid internalization kinetics. ADCT-602 is a novel CD22-targeting ADC, consisting of humanized mAb hLL2-C220, site specifically conjugated to the pyrrolobenzodiazepine dimer–based payload tesirine. In preclinical studies, ADCT-602 demonstrated potent, specific cytotoxicity in CD22-positive lymphomas and leukemias. ADCT-602 was specifically bound, internalized, and trafficked to lysosomes in CD22-positive tumor cells; after cytotoxin release, DNA interstrand crosslink formation persisted for 48 hours. In the presence of CD22-positive tumor cells, ADCT-602 caused bystander killing of CD22-negative tumor cells. A single ADCT-602 dose led to potent, dose-dependent, in vivo antitumor activity in subcutaneous and disseminated human lymphoma/leukemia models. Pharmacokinetic analyses (rat and cynomolgus monkey) showed excellent stability and tolerability of ADCT-602. Cynomolgus monkey B cells were efficiently depleted from circulation after one dose. Gene signature association analysis revealed IRAK1 as a potential marker for ADCT-602 resistance. Combining ADCT-602 + pacritinib was beneficial in ADCT-602–resistant cells. Chidamide increased CD22 expression on B-cell tumor surfaces, increasing ADCT-602 activity. These data support clinical testing of ADCT-602 in R/R B-ALL (NCT03698552) and CD22-positive hematologic cancers.
Data from Development of a Novel DNA Mono-alkylator Platform for Antibody–Drug Conjugates
Authors: Thomas Joshua D. , Yurkovetskiy Aleksandr V. , Yin Mao , Bodyak Natalya D. , Tang Shuyi , Protopopova Marina , Kelleher Eugene , Jones Brian , Yang Liping , Custar Daniel , Catcott Kalli C. , Demady Damon R. , Collins Scott D. , Xu Ling , Bu Charlie , Qin LiuLiang , Ter-Ovanesyan Elena , Damelin Marc , Toader Dorin , Lowinger Timothy B.
Published: April 2024

Abstract
Although microtubule inhibitors (MTI) remain a therapeutically valuable payload option for antibody–drug conjugates (ADC), some cancers do not respond to MTI-based ADCs. Efforts to fill this therapeutic gap have led to a recent expansion of the ADC payload “toolbox” to include payloads with novel mechanisms of action such as topoisomerase inhibition and DNA cross-linking. We present here the development of a novel DNA mono-alkylator ADC platform that exhibits sustained tumor growth suppression at single doses in MTI-resistant tumors and is well tolerated in the rat upon repeat dosing. A phosphoramidate prodrug of the payload enables low ADC aggregation even at drug-to-antibody ratios of 5:1 while still delivering a bystander-capable payload that is effective in multidrug resistant (MDR)-overexpressing cell lines. The platform was comparable in xenograft studies to the clinical benchmark DNA mono-alkylator ADC platform DGN459 but with a significantly better tolerability profile in rats. Thus, the activity and tolerability profile of this new platform make it a viable option for the development of ADCs.
Targeting CD33+ Acute Myeloid Leukemia with GLK-33, a Lintuzumab–Auristatin Conjugate with a Wide Therapeutic Window
Authors: Satomaa Tero , Pynnönen Henna , Aitio Olli , Hiltunen Jukka O. , Pitkänen Virve , Lähteenmäki Tuula , Kotiranta Titta , Heiskanen Annamari , Hänninen Anna-Liisa , Niemelä Ritva , Helin Jari , Kuusanmäki Heikki , Vänttinen Ida , Rathod Ramji , Nieminen Anni I. , Yatkin Emrah , Heckman Caroline A. , Kontro Mika , Saarinen Juhani
Published: April 2024

CD33 (Siglec-3) is a cell surface receptor expressed in approximately 90% of acute myeloid leukemia (AML) blasts, making it an attractive target for therapy of AML. Although previous CD33-targeting antibody–drug conjugates (ADC) like gemtuzumab ozogamicin (GO, Mylotarg) have shown efficacy in AML treatment, they have suffered from toxicity and narrow therapeutic window. This study aimed to develop a novelADCwith improved tolerability and a wider therapeutic window. GLK-33 consists of the anti-CD33 antibody lintuzumab and eight mavg-MMAU auristatin linkerpayloads per antibody. The experimental methods included testing in cell cultures, patient-derived samples, mouse xenograft models, and rat toxicology studies. GLK-33 exhibited remarkable efficacy in reducing cell viability within CD33-positive leukemia cell lines and primary AML samples. Notably, GLK-33 demonstrated antitumor activity at single dose as low as 300 mg/kg in mice, while maintaining tolerability at single dose of 20 to 30 mg/kg in rats. In contrast with both GO and lintuzumab vedotin, GLK-33 exhibited a wide therapeutic window and activity against multidrug-resistant cells. The development of GLK-33 addresses the limitations of previous ADCs, offering a wider therapeutic window, improved tolerability, and activity against drug-resistant leukemia cells. These findings encourage further exploration of GLK-33 in AML through clinical trials.
Supplementary Table 3 from Identification of Colorectal Cancer Cell Stemness from Single-Cell RNA Sequencing
Authors: Lin Kangyu , Chowdhury Saikat , Zeineddine Mohammad A. , Zeineddine Fadl A. , Hornstein Nicholas J. , Villarreal Oscar E. , Maru Dipen M. , Haymaker Cara L. , Vauthey Jean-Nicolas , Chang George J. , Bogatenkova Elena , Menter David , Kopetz Scott , Shen John Paul
Published: April 2024

Gene list of single-cell stemness signature.
Supplementary Table 2 from Identification of Colorectal Cancer Cell Stemness from Single-Cell RNA Sequencing
Authors: Lin Kangyu , Chowdhury Saikat , Zeineddine Mohammad A. , Zeineddine Fadl A. , Hornstein Nicholas J. , Villarreal Oscar E. , Maru Dipen M. , Haymaker Cara L. , Vauthey Jean-Nicolas , Chang George J. , Bogatenkova Elena , Menter David , Kopetz Scott , Shen John Paul
Published: April 2024

The quality matrix of single-cell RNAseq data by sample.
Figure S7 from miR-217 Regulates Normal and Tumor Cell Fate Following Induction of Endoplasmic Reticulum Stress
Authors: Dey Neekkan , Koumenis Costas , Ruggero Davide , Fuchs Serge Y. , Diehl J. Alan
Published: April 2024

S7. Model depicting the molecular mechanisms by which PERK responsive microRNAs, specifically miR-211 (green) and miR-217 (orange) orchestrate cell fate determination under acute ER stress.
Supplementary Figure Legends from NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth
Authors: Cai Chufan , Tu Jiayi , Najarro Jeronimo , Zhang Rukang , Fan Hao , Zhang Freya Q. , Li Jiacheng , Xie Zhicheng , Su Rui , Dong Lei , Arellano Nicole , Ciboddo Michele , Elf Shannon E. , Gao Xue , Chen Jing , Wu Rong
Published: April 2024

Supplementary Figure Legends
Figure S9 from NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth
Authors: Cai Chufan , Tu Jiayi , Najarro Jeronimo , Zhang Rukang , Fan Hao , Zhang Freya Q. , Li Jiacheng , Xie Zhicheng , Su Rui , Dong Lei , Arellano Nicole , Ciboddo Michele , Elf Shannon E. , Gao Xue , Chen Jing , Wu Rong
Published: April 2024

Supplementary Figure 9. RT-qPCR validates key up/downregulated target genes from gene sets related to cell proliferation from RNA-seq.
Figure S7 from NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth
Authors: Cai Chufan , Tu Jiayi , Najarro Jeronimo , Zhang Rukang , Fan Hao , Zhang Freya Q. , Li Jiacheng , Xie Zhicheng , Su Rui , Dong Lei , Arellano Nicole , Ciboddo Michele , Elf Shannon E. , Gao Xue , Chen Jing , Wu Rong
Published: April 2024

Supplementary Figure 7. AHCYL1 deficiency attenuates cell proliferation, decreases ER calcium levels, and activates the UPR.
Figure S5 from NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth
Authors: Cai Chufan , Tu Jiayi , Najarro Jeronimo , Zhang Rukang , Fan Hao , Zhang Freya Q. , Li Jiacheng , Xie Zhicheng , Su Rui , Dong Lei , Arellano Nicole , Ciboddo Michele , Elf Shannon E. , Gao Xue , Chen Jing , Wu Rong
Published: April 2024

Supplementary Figure 5. IP3R deficiency doesn’t change AHCYL1 protein level in the whole cell lysates.
Figure S3 from NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth
Authors: Cai Chufan , Tu Jiayi , Najarro Jeronimo , Zhang Rukang , Fan Hao , Zhang Freya Q. , Li Jiacheng , Xie Zhicheng , Su Rui , Dong Lei , Arellano Nicole , Ciboddo Michele , Elf Shannon E. , Gao Xue , Chen Jing , Wu Rong
Published: April 2024

Supplementary Figure 3. AHCYL2 does not overexpress and is not critical in human NRAS-mutated melanoma as AHCYL1.
Figure S1 from NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth
Authors: Cai Chufan , Tu Jiayi , Najarro Jeronimo , Zhang Rukang , Fan Hao , Zhang Freya Q. , Li Jiacheng , Xie Zhicheng , Su Rui , Dong Lei , Arellano Nicole , Ciboddo Michele , Elf Shannon E. , Gao Xue , Chen Jing , Wu Rong
Published: April 2024

Supplementary Figure 1. AHCYL1 is selectively critical for NRAS-mutated but not for BRAF-mutated human melanoma cells.
Supplementary Tables 1 and 2 from Semi-Supervised, Attention-Based Deep Learning for Predicting TMPRSS2:ERG Fusion Status in Prostate Cancer Using Whole Slide Images
Authors: Omar Mohamed , Xu Zhuoran , Rand Sophie B. , Alexanderani Mohammad K. , Salles Daniela C. , Valencia Itzel , Schaeffer Edward M. , Robinson Brian D. , Lotan Tamara L. , Loda Massimo , Marchionni Luigi
Published: April 2024

Supplementary Table 1. Performance metrics for the ERG prediction model in the TCGA testing cohort. The table shows the model’s performance in the TCGA testing cohort consisting of 59 whole slide images using different thresholds derived from the training data. PPV: positive predictive value; NPV: negative predictive value; MCC: Matthews Correlation Coefficient.
Supplementary Table 2. Performance metrics for the ERG prediction model in the natural history cohort. The table shows the model’s performance in the natural history cohort consisting of 314 whole slide images using different thresholds derived from the training data. PPV: positive predictive value; NPV: negative predictive value; MCC: Matthews Correlation Coefficient.
Supplementary Figure 2 from Semi-Supervised, Attention-Based Deep Learning for Predicting TMPRSS2:ERG Fusion Status in Prostate Cancer Using Whole Slide Images
Authors: Omar Mohamed , Xu Zhuoran , Rand Sophie B. , Alexanderani Mohammad K. , Salles Daniela C. , Valencia Itzel , Schaeffer Edward M. , Robinson Brian D. , Lotan Tamara L. , Loda Massimo , Marchionni Luigi
Published: April 2024

Supplementary Figure 2. Comparison of Cellular Composition by TMPRSS2:ERG Fusion Status and Gleason Score in the TCGA Cohort. The average immune, neoplastic, and stroma to neoplastic ratios across two categories of TMPRSS2:ERG fusion status (Negative and Positive) stratified by Gleason score (<8 and >=8). The immune ratio panel shows the proportion of immune cells, the neoplastic ratio panel displays the proportion of neoplastic cells, and the stroma to neoplastic ratio panel depicts the relative abundance of stromal to neoplastic cells within the analyzed tissue sections. Red bars represent cases with a Gleason score of less than 8, while blue bars represent cases with a Gleason score of 8 or higher.
Data from NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth
Authors: Cai Chufan , Tu Jiayi , Najarro Jeronimo , Zhang Rukang , Fan Hao , Zhang Freya Q. , Li Jiacheng , Xie Zhicheng , Su Rui , Dong Lei , Arellano Nicole , Ciboddo Michele , Elf Shannon E. , Gao Xue , Chen Jing , Wu Rong
Published: April 2024

Abstract
Calcium homeostasis is critical for cell proliferation, and emerging evidence shows that cancer cells exhibit altered calcium signals to fulfill their need for proliferation. However, it remains unclear whether there are oncogene-specific calcium homeostasis regulations that can expose novel therapeutic targets. Here, from RNAi screen, we report that adenosylhomocysteinase like protein 1 (AHCYL1), a suppressor of the endoplasmic reticulum (ER) calcium channel protein inositol trisphosphate receptor (IP3R), is selectively upregulated and critical for cell proliferation and tumor growth potential of human NRAS-mutated melanoma, but not for melanoma expressing BRAF V600E. Mechanistically, AHCYL1 deficiency results in decreased ER calcium levels, activates the unfolded protein response (UPR), and triggers downstream apoptosis. In addition, we show that AHCYL1 transcription is regulated by activating transcription factor 2 (ATF2) in NRAS-mutated melanoma. Our work provides evidence for oncogene-specific calcium regulations and suggests AHCYL1 as a novel therapeutic target for RAS mutant-expressing human cancers, including melanoma.
Implications:
Our findings suggest that targeting the AHCYL1–IP3R axis presents a novel therapeutic approach for NRAS-mutated melanomas, with potential applicability to all cancers harboring RAS mutations, such as KRAS-mutated human colorectal cancers.
Supplementary Figure S2 from The Effects of Black Raspberry as a Whole Food–Based Approach on Biomarkers of Oxidative Stress in Buccal Cells and Urine of Smokers
Authors: Chen Kun-Ming , Sun Yuan-Wan , Krebs Nicolle M. , Reinhart Lisa , Sun Dongxiao , Liao Jiangang , Cook Rachel , Bond Paige Elizabeth , Mallery Susan R. , El-Bayoumy Karam
Published: April 2024

Supplementary Figure S2: The results demonstrate that cotinine levels in each participant differ across the various time points suggesting a modulation of tobacco consumption.
Supplemental Table 3 from Differences in Serum miRNA Profiles by Race, Ethnicity, and Socioeconomic Status: Implications for Developing an Equitable Ovarian Cancer Screening Test
Authors: Alimena Stephanie , Stephenson Briana Joy K. , Webber James W. , Wollborn Laura , Sussman Chad B. , Packard Daniel George , Williams Marta , Comrie Cameron Elizabeth , Wang Joyce Y. , Markert Tahireh , Spiegel Julia , Rodriguez Carmen B. , Lightfoot Maya , Graye Amia , O'Connor Sean , Elias Kevin M.
Published: April 2024

Supplemental Table 3 shows the ratio of non-white mean fluorescence units (MFI) to white MFI for the eight miRNA associated with ovarian cancer risk. MFI for non-white patients were on average higher for these race-associated miRNA compared to white patients (significance denoted with an asterisk).
Supplementary Table S1 from Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti–PD-1 Therapy
Authors: Chen Jiang , Amoozgar Zohreh , Liu Xin , Aoki Shuichi , Liu Zelong , Shin Sarah M. , Matsui Aya , Hernandez Alexei , Pu Zhangya , Halvorsen Stefan , Lei Pin-Ji , Datta Meenal , Zhu Lingling , Ruan Zhiping , Shi Lei , Staiculescu Daniel , Inoue Koetsu , Munn Lance L. , Fukumura Dai , Huang Peigen , Sassi Slim , Bardeesy Nabeel , Ho Won Jin , Jain Rakesh K. , Duda Dan G.
Published: April 2024

Supplementary Table S1: Antibody list.
Supplementary Table 1 from The Immune Suppressor IGSF1 as a Potential Target for Cancer Immunotherapy
Authors: Koh Dong-In , Lee Minki , Park Yoon Sun , Shin Jae-Sik , Kim Joseph , Ryu Yea Seong , Lee Jun Hyung , Bae Seunggeon , Lee Mi So , Hong Jun Ki , Jeong Hong-Rae , Choi Mingee , Hong Seung-Woo , Kim Dong Kwan , Lee Hyun-kyung , Kim Bomi , Yoon Yoo Sang , Jin Dong-Hoon
Published: April 2024

Primers and RNAs used in the experiments.
Supplementary Figure 3 from The Immune Suppressor IGSF1 as a Potential Target for Cancer Immunotherapy
Authors: Koh Dong-In , Lee Minki , Park Yoon Sun , Shin Jae-Sik , Kim Joseph , Ryu Yea Seong , Lee Jun Hyung , Bae Seunggeon , Lee Mi So , Hong Jun Ki , Jeong Hong-Rae , Choi Mingee , Hong Seung-Woo , Kim Dong Kwan , Lee Hyun-kyung , Kim Bomi , Yoon Yoo Sang , Jin Dong-Hoon
Published: April 2024

Cytokine profile released from PBMCs co-cultured with NCI-H292-IGSF1 O/E cancer cell line.
Supplementary Figure 1 from The Immune Suppressor IGSF1 as a Potential Target for Cancer Immunotherapy
Authors: Koh Dong-In , Lee Minki , Park Yoon Sun , Shin Jae-Sik , Kim Joseph , Ryu Yea Seong , Lee Jun Hyung , Bae Seunggeon , Lee Mi So , Hong Jun Ki , Jeong Hong-Rae , Choi Mingee , Hong Seung-Woo , Kim Dong Kwan , Lee Hyun-kyung , Kim Bomi , Yoon Yoo Sang , Jin Dong-Hoon
Published: April 2024

IGSF1 targeting antibody is developed and characterized by various methods
Supplementary Figure 2 from Tumor Burden Dictates the Neoantigen Features Required to Generate an Effective Cancer Vaccine
Authors: Garzia Irene , Nocchi Linda , Avalle Lidia , Troise Fulvia , Leoni Guido , Seclì Laura , Antonucci Laura , Cotugno Gabriella , Allocca Simona , Romano Giuseppina , Conti Laura , Caiazza Carmen , Mallardo Massimo , Poli Valeria , Scarselli Elisa , D'Alise Anna Morena
Published: April 2024

Generation of CT26 #5KO and CT26 #23KO cells using CRISPR-Cas9 technology. A) CRISPR/Cas9 strategy used for the generation of CT26 cells lacking of nAg #5. Red arrows represent forward and reverse primers used for PCR. Blue lines 1 and 2 indicate 2 sgRNAs designed for Cas9-mediating genome editing, within exon 10, harboring #5 mutation (blue star). The position of the 2 sgRNAs is also indicated. B) Left panel: representative agarose gel of PCR screening on cDNA showing homozygous deletions of 74nt in the genomic region encoding nAg#5 (E2f8 gene). Right panel: representative sequenced region of E2f8 gene and the relative chromatogram. In red, PAM sequences are indicated. The deleted region is underlined. The mutated nucleotide of nAg#5 is in black bold. Red arrow indicates Cas9 cut site. C) CRISPR/Cas9 strategy used for the generation of CT26 cells lacking of nAg #23. Red arrows represent forward and reverse primers used for PCR. Blue lines indicate the 2 sgRNAs designed for Cas9-mediating genome editing. Exon 12 harbors #23 mutation (green star). The position of the 2 sgRNAs is also indicated. D) Left panel: representative agarose gel of PCR screening on genomic DNA showing homozygous deletions of 116nt in the genomic region encoding nAg#23 (Mtch1 gene). Right panel: representative sequenced region of Mtch1 gene and relative chromatogram. In red, PAM sequences are indicated. The deleted region is underlined. The mutated nucleotide of nAg#23 is in black bold. Red arrow indicates Cas9 cut site.
Supplementary Figure 1 from Immune Modulation with RANKL Blockade through Denosumab Treatment in Patients with Cancer
Authors: Chang Hewitt , Marquez Jaqueline , Chen Brandon K. , Kim Daniel M. , Cheng Michael L. , Liu Eric V. , Yang Hai , Zhang Li , Sinha Meenal , Cheung Alexander , Kwek Serena S. , Chow Eric D. , Bridge Mark , Aggarwal Rahul R. , Friedlander Terence W. , Small Eric J. , Anderson Mark , Fong Lawrence
Published: April 2024

Supplementary Figure 1: Manual gating strategy A representative patient sample was used to illustrate the gating strategy on Cytobank to create pre-determined landmark nodes for scaffold analysis and clustering.
Supplementary Figure 6 from Gut Mycobiota Dysbiosis Is Associated with Melanoma and Response to Anti–PD-1 Therapy
Authors: Szóstak Natalia , Handschuh Luiza , Samelak-Czajka Anna , Tomela Katarzyna , Pietrzak Bernadeta , Schmidt Marcin , Galus Łukasz , Mackiewicz Jacek , Mackiewicz Andrzej , Kozlowski Piotr , Philips Anna
Published: April 2024

Supplementary Figure 6. Gut microbiota richness.
Supplementary Figure 2 from Gut Mycobiota Dysbiosis Is Associated with Melanoma and Response to Anti–PD-1 Therapy
Authors: Szóstak Natalia , Handschuh Luiza , Samelak-Czajka Anna , Tomela Katarzyna , Pietrzak Bernadeta , Schmidt Marcin , Galus Łukasz , Mackiewicz Jacek , Mackiewicz Andrzej , Kozlowski Piotr , Philips Anna
Published: April 2024

Supplementary Figure 2. (A) Shannon diversity of patients with normal (n=102) and elevated level of serum LDH (n=16). Kruskal–Wallis test was performed to compare groups, p<0.05. Horizontal line shows median. The lower and upper hinges correspond to the first and third quartiles. The upper and the lower whiskers extend from the hinge to the largest and smallest value, respectively, no further than 1.5 * IQR from the hinge (where IQR is the inter-quartile range, or distance between the first and third quartiles). Dots represent potential outliers. (B) Relative abundance of Neurospora crassa and Sugiyamaella lignohabitans in patients with normal serum LDH level (n=102) and patients with elevated level of serum LDH (LDH>1.5x, what corresponds to >375 U/L, n=16). Welch Two Sample t-test was performed to compare groups, padj<0.05 (FDR). Horizontal line shows median. Red dot shows mean. Dots represent individual samples.
Supplementary Table 2 from Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells
Authors: Carnevale Silvia , Ponzetta Andrea , Rigatelli Anna , Carriero Roberta , Puccio Simone , Supino Domenico , Grieco Giovanna , Molisso Piera , Di Ceglie Irene , Scavello Francesco , Perucchini Chiara , Pasqualini Fabio , Recordati Camilla , Tripodo Claudio , Belmonte Beatrice , Mariancini Andrea , Kunderfranco Paolo , Sciumè Giuseppe , Lugli Enrico , Bonavita Eduardo , Magrini Elena , Garlanda Cecilia , Mantovani Alberto , Jaillon Sebastien
Published: April 2024

Supplementary Table 2. List of critical reagents and antibodies used.
Figure S3. from High-Specificity CRISPR-Mediated Genome Engineering in Anti-BCMA Allogeneic CAR T Cells Suppresses Allograft Rejection in Preclinical Models
Authors: Degagné Émilie , Donohoue Paul D. , Roy Suparna , Scherer Jessica , Fowler Tristan W. , Davis Ryan T. , Reyes Gustavo A. , Kwong George , Stanaway Morena , Larroca Vicena Vanina , Mutha Devin , Guo Raymond , Edwards Leslie , Schilling Benjamin , Shaw McKay , Smith Stephen C. , Kohrs Bryan , Kufeldt Heinrich J. , Churchward Glen , Ruan Finey , Nyer David B. , McSweeney Kyle , Irby Matthew J. , Fuller Christopher K. , Banh Lynda , Toh Mckenzi S. , Thompson Matthew , Owen Arthur L.G. , An Zili , Gradia Scott , Skoble Justin , Bryan Mara , Garner Elizabeth , Kanner Steven B.
Published: April 2024

CB-011 cells exhibit in vitro antitumor activity against PBMCs from patients with multiple myeloma.
Supplementary Figure S7 from Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells
Authors: Carnevale Silvia , Ponzetta Andrea , Rigatelli Anna , Carriero Roberta , Puccio Simone , Supino Domenico , Grieco Giovanna , Molisso Piera , Di Ceglie Irene , Scavello Francesco , Perucchini Chiara , Pasqualini Fabio , Recordati Camilla , Tripodo Claudio , Belmonte Beatrice , Mariancini Andrea , Kunderfranco Paolo , Sciumè Giuseppe , Lugli Enrico , Bonavita Eduardo , Magrini Elena , Garlanda Cecilia , Mantovani Alberto , Jaillon Sebastien
Published: April 2024

Figure S7.
A) Frequency of CD4+ Foxp3+ regulatory T cells in colon LP of DSS-treated Csf3r+/+ and Csf3r-/-. Unpaired Student’s t-Test. Data are mean ± SEM. ns: not significant.
Figure S1. from High-Specificity CRISPR-Mediated Genome Engineering in Anti-BCMA Allogeneic CAR T Cells Suppresses Allograft Rejection in Preclinical Models
Authors: Degagné Émilie , Donohoue Paul D. , Roy Suparna , Scherer Jessica , Fowler Tristan W. , Davis Ryan T. , Reyes Gustavo A. , Kwong George , Stanaway Morena , Larroca Vicena Vanina , Mutha Devin , Guo Raymond , Edwards Leslie , Schilling Benjamin , Shaw McKay , Smith Stephen C. , Kohrs Bryan , Kufeldt Heinrich J. , Churchward Glen , Ruan Finey , Nyer David B. , McSweeney Kyle , Irby Matthew J. , Fuller Christopher K. , Banh Lynda , Toh Mckenzi S. , Thompson Matthew , Owen Arthur L.G. , An Zili , Gradia Scott , Skoble Justin , Bryan Mara , Garner Elizabeth , Kanner Steven B.
Published: April 2024

chRDNA-mediated gene editing did not result in any off-target editing above the limit of detection.
Supplementary Figure S4 from Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells
Authors: Carnevale Silvia , Ponzetta Andrea , Rigatelli Anna , Carriero Roberta , Puccio Simone , Supino Domenico , Grieco Giovanna , Molisso Piera , Di Ceglie Irene , Scavello Francesco , Perucchini Chiara , Pasqualini Fabio , Recordati Camilla , Tripodo Claudio , Belmonte Beatrice , Mariancini Andrea , Kunderfranco Paolo , Sciumè Giuseppe , Lugli Enrico , Bonavita Eduardo , Magrini Elena , Garlanda Cecilia , Mantovani Alberto , Jaillon Sebastien
Published: April 2024

Figure S4. Neutrophil deficiency is associated with decreased expression of IL-22 by γδ T cells. Related to Figure 4-5.
A-C) Representative gating strategy used to gate myeloid population (A), lymphoid population (B) and innate lymphoid cells (ILC) (C) in colon LP. UTC: unconventional T cells (TCRβ+, CD8-, CD4-). D) IL-22 expression in myeloid cells derived from DSS-treated Csf3r+/+(n=3), Csf3r-/-(n=3) stimulated 4 hours with IL-23 analyzed by FACS. E-F) Expression of IL-22 by lymphoid cells derived from DSS-treated Csf3r+/+(n=4), Csf3r-/- (n=4) stimulated 4 hours with IL-23 plus IL-1β (E) and PMA plus ionomycin (F) analyzed by FACS. A-F) Representative data of three independent experiments. D-F) Multiple t-test. Data are mean ± SEM. *** p < 0.001 ** p < 0.01 * p < 0.05.
Supplementary Figure S3 from Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells
Authors: Carnevale Silvia , Ponzetta Andrea , Rigatelli Anna , Carriero Roberta , Puccio Simone , Supino Domenico , Grieco Giovanna , Molisso Piera , Di Ceglie Irene , Scavello Francesco , Perucchini Chiara , Pasqualini Fabio , Recordati Camilla , Tripodo Claudio , Belmonte Beatrice , Mariancini Andrea , Kunderfranco Paolo , Sciumè Giuseppe , Lugli Enrico , Bonavita Eduardo , Magrini Elena , Garlanda Cecilia , Mantovani Alberto , Jaillon Sebastien
Published: April 2024

Figure S3. Neutrophils drive the expression of IL-23 by BMDMs. Related to Figure 3.
A) Total number of ulcers in the colon of DSS-treated Csfr3+/+ (n=6) and Csf3r-/- (n=7) mice. B) IL-23 levels detected by ELISA in supernatants of BMDMs, neutrophils (NΦ) and BMDM-NΦ co-cultures after stimulation with GM-CSF+CpG. In indicated conditions neutrophils were pre-treated with diphenyleneiodonium (DPI) (10µM) or BMDM-NΦ were cultured in transwells (for all conditions n=6). C) Percentage of viable neutrophils (AnnexinV-/PI-) cultured alone or after co-culture with BMDMs. D) Schematic representation of the treatment schedule for anti-IL-22 treatment and neutrophil adoptive cell transfer during acute colitis. Days of treatment are indicated by red arrows. E) Percentage of body weight loss during DSS-induced acute colitis in Csf3r+/+(n=4), Csf3r-/-(n=4) and Csf3r-/- mice upon adoptive transfer of neutrophils treated with anti-IL-22 or isotype control (50µg/mouse) via i.p. injection (Csf3r-/- mice+Isotype n=3; Csf3r-/-+anti-IL-22 n=3). A) Representative data of five independent experiments. B) Representative data of three independent experiments. C) Representative of two independent experiments. E) One experiment. A) Unpaired Student’s t-Test. B-C) Multiple Student’s t-Test. E) Wilcoxon matched-pairs signed rank test. Data are mean ± SEM. *** p < 0.001 ** p < 0.01 * p < 0.05.
Supplementary Fig. S4 from Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti–PD-1 Therapy
Authors: Chen Jiang , Amoozgar Zohreh , Liu Xin , Aoki Shuichi , Liu Zelong , Shin Sarah M. , Matsui Aya , Hernandez Alexei , Pu Zhangya , Halvorsen Stefan , Lei Pin-Ji , Datta Meenal , Zhu Lingling , Ruan Zhiping , Shi Lei , Staiculescu Daniel , Inoue Koetsu , Munn Lance L. , Fukumura Dai , Huang Peigen , Sassi Slim , Bardeesy Nabeel , Ho Won Jin , Jain Rakesh K. , Duda Dan G.
Published: April 2024

Supplementary Fig. S4: IMC analysis of ICC after GC-based therapies in orthotopic murine 425-ICC model.
Supplementary Fig. S2 from Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti–PD-1 Therapy
Authors: Chen Jiang , Amoozgar Zohreh , Liu Xin , Aoki Shuichi , Liu Zelong , Shin Sarah M. , Matsui Aya , Hernandez Alexei , Pu Zhangya , Halvorsen Stefan , Lei Pin-Ji , Datta Meenal , Zhu Lingling , Ruan Zhiping , Shi Lei , Staiculescu Daniel , Inoue Koetsu , Munn Lance L. , Fukumura Dai , Huang Peigen , Sassi Slim , Bardeesy Nabeel , Ho Won Jin , Jain Rakesh K. , Duda Dan G.
Published: April 2024

Supplementary Fig. S2: Standard chemotherapy converts ICB-resistant ICCs to ICB-responsive tumors, significantly delays tumor progression and increases survival in mice.
Supplementary Fig. S11 from Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti–PD-1 Therapy
Authors: Chen Jiang , Amoozgar Zohreh , Liu Xin , Aoki Shuichi , Liu Zelong , Shin Sarah M. , Matsui Aya , Hernandez Alexei , Pu Zhangya , Halvorsen Stefan , Lei Pin-Ji , Datta Meenal , Zhu Lingling , Ruan Zhiping , Shi Lei , Staiculescu Daniel , Inoue Koetsu , Munn Lance L. , Fukumura Dai , Huang Peigen , Sassi Slim , Bardeesy Nabeel , Ho Won Jin , Jain Rakesh K. , Duda Dan G.
Published: April 2024

Supplementary Fig. S11: Cxcr3 in CD8 T cells mediates the benefit of GC/ICB combination therapy in orthotopic murine 425-ICC model.
Data from Immune Modulation with RANKL Blockade through Denosumab Treatment in Patients with Cancer
Authors: Chang Hewitt , Marquez Jaqueline , Chen Brandon K. , Kim Daniel M. , Cheng Michael L. , Liu Eric V. , Yang Hai , Zhang Li , Sinha Meenal , Cheung Alexander , Kwek Serena S. , Chow Eric D. , Bridge Mark , Aggarwal Rahul R. , Friedlander Terence W. , Small Eric J. , Anderson Mark , Fong Lawrence
Published: April 2024

Abstract
Denosumab is a fully human mAb that binds receptor activator of NFκB ligand (RANKL). It is routinely administered to patients with cancer to reduce the incidence of new bone metastasis. RANK–RANKL interactions regulate bone turnover by controlling osteoclast recruitment, development, and activity. However, these interactions also can regulate immune cells including dendritic cells and medullary thymic epithelial cells. Inhibition of the latter results in reduced thymic negative selection of T cells and could enhance the generation of tumor-specific T cells. We examined whether administering denosumab could modify modulate circulating immune cells in patients with cancer. Blood was collected from 23 patients with prostate cancer and 3 patients with renal cell carcinoma, all of whom had advanced disease and were receiving denosumab, prior to and during denosumab treatment. Using high-dimensional mass cytometry, we found that denosumab treatment by itself induced modest effects on circulating immune cell frequency and activation. We also found minimal changes in the circulating T-cell repertoire and the frequency of new thymic emigrants with denosumab treatment. However, when we stratified patients by whether they were receiving chemotherapy and/or steroids, patients receiving these concomitant treatments showed significantly greater immune modulation, including an increase in the frequency of natural killer cells early and classical monocytes later. We also saw broad induction of CTLA-4 and TIM3 expression in circulating lymphocytes and some monocyte populations. These findings suggest that denosumab treatment by itself has modest immunomodulatory effects, but when combined with conventional cancer treatments, can lead to the induction of immunologic checkpoints.

See related Spotlight by Nasrollahi and Davar, p. 383.
Data from NCI Resources for Cancer Immunoprevention Research
Authors: Sei Shizuko , Srivastava Sudhir , Kelly Halonna R. , Miller Mark Steven , Leitner Wolfgang W. , Shoemaker Robert H. , Szabo Eva , Castle Philip E.
Published: April 2024

Abstract
Cancer prevention and early detection, the first two of the eight primary goals of the National Cancer Plan released in April 2023, are at the forefront of the nation's strategic efforts to reduce cancer incidence and mortality. The Division of Cancer Prevention (DCP) of the NCI is the federal government's principal component devoted to promoting and supporting innovative cancer prevention research. Recent advances in tumor immunology, cancer immunotherapy, and vaccinology strongly suggest that the host immune system can be effectively harnessed to elicit protective immunity against the development of cancer, that is, cancer immunoprevention. Cancer immunoprevention may be most effective if the intervention is given before or early in the carcinogenic process while the immune system remains relatively uncompromised. DCP has increased the emphasis on immunoprevention research in recent years and continues to expand program resources and interagency collaborations designed to facilitate research in the immunoprevention field. These resources support a wide array of basic, translational, and clinical research activities, including discovery, development, and validation of biomarkers for cancer risk assessment and early detection (Early Detection Research Network), elucidation of biological and pathophysiological mechanistic determinants of precancer growth and its control (Translational and Basic Science Research in Early Lesions), spatiotemporal multiomics characterization of precancerous lesions (Human Tumor Atlas Network/Pre-Cancer Atlas), discovery of immunoprevention pathways and immune targets (Cancer Immunoprevention Network), and preclinical and clinical development of novel agents for immunoprevention and interception (Cancer Prevention-Interception Targeted Agent Discovery Program, PREVENT Cancer Preclinical Drug Development Program, and Cancer Prevention Clinical Trials Network).
Data from Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells
Authors: Carnevale Silvia , Ponzetta Andrea , Rigatelli Anna , Carriero Roberta , Puccio Simone , Supino Domenico , Grieco Giovanna , Molisso Piera , Di Ceglie Irene , Scavello Francesco , Perucchini Chiara , Pasqualini Fabio , Recordati Camilla , Tripodo Claudio , Belmonte Beatrice , Mariancini Andrea , Kunderfranco Paolo , Sciumè Giuseppe , Lugli Enrico , Bonavita Eduardo , Magrini Elena , Garlanda Cecilia , Mantovani Alberto , Jaillon Sebastien
Published: April 2024

Abstract
Neutrophils are the most abundant leukocytes in human blood and play a primary role in resistance against invading microorganisms and in the acute inflammatory response. However, their role in colitis and colitis-associated colorectal cancer is still under debate. This study aims to dissect the role of neutrophils in these pathologic contexts by using a rigorous genetic approach. Neutrophil-deficient mice (Csf3r−/− mice) were used in classic models of colitis and colitis-associated colorectal cancer and the role of neutrophils was assessed by histologic, cellular, and molecular analyses coupled with adoptive cell transfer. We also performed correlative analyses using human datasets. Csf3r−/− mice showed increased susceptibility to colitis and colitis-associated colorectal cancer compared with control Csf3r+/+ mice and adoptive transfer of neutrophils in Csf3r−/− mice reverted the phenotype. In colitis, Csf3r−/− mice showed increased bacterial invasion and a reduced number of healing ulcers in the colon, indicating a compromised regenerative capacity of epithelial cells. Neutrophils were essential for γδ T-cell polarization and IL22 production. In patients with ulcerative colitis, expression of CSF3R was positively correlated with IL22 and IL23 expression. Moreover, gene signatures associated with epithelial-cell development, proliferation, and antimicrobial response were enriched in CSF3Rhigh patients. Our data support a model where neutrophils mediate protection against intestinal inflammation and colitis-associated colorectal cancer by controlling the intestinal microbiota and driving the activation of an IL22-dependent tissue repair pathway.
Figure S1 from Identification of Enhanced Vaccine Mimotopes for the p15E Murine Cancer Antigen
Authors: Zhou Shiqi , Song Yiting , Luo Yuan , Quinn Breandan , Jiao Yang , Long Mark D. , Abrams Scott I. , Lovell Jonathan F.
Published: April 2024

Flow cytometry cell gating strategy
FIGURE 1 from Identification of Enhanced Vaccine Mimotopes for the p15E Murine Cancer Antigen
Authors: Zhou Shiqi , Song Yiting , Luo Yuan , Quinn Breandan , Jiao Yang , Long Mark D. , Abrams Scott I. , Lovell Jonathan F.
Published: April 2024

The wild-type p15E short peptide is poorly immunogenic and does not inhibit tumor growth. C57BL/6 mice were vaccinated intramuscularly with 2 μg of E7 or p15E peptide displayed on CPQ liposomes (along with 8 μg CoPoP, 3.2 μg PHAD and 3.2 μg QS-21) on day 0 and 7; then blood was collected for Ag-specific CD8+ T-cell tetramer staining on day 14 and E7 vaccinated mice were challenged with 1 × 105 TC-1 cells and p15E vaccinated mice were challenged with 1 × 106 MC38 cells. (A) Ag-specific CD8+ T-cell percentages in CD8+ T cells in blood. TC-1 (B) and MC38 (C) tumor volume in non-vaccinated control (Ctrl) mice, or mice immunized with the E7 or p15E (wild-type) peptides. Statistical analysis shows unpaired t test. ****, P < 0.0001. Error bars show mean + SD for 3 mice per group.
Synchronous Papillary Thyroid Cancer and Colorectal Cancer in a Young Patient with a CHEK2 Mutation
Authors: Hoskins Sydney Brooke , Torgerson Leslie
Published: April 2024

Introduction: Mutations of CHEK2 are usually inherited and have been implicated in breast cancers, colorectal cancers, thyroid cancers, kidney cancers, and prostate cancers. The CHEK2 gene codes for checkpoint kinase 2 protein which is an effector in the ATM-CHEK2-p53 pathway and responds to DNA double-strand breaks. Case Presentation: We describe a unique case of a 29-year-old Canadian female who presented with synchronous papillary thyroid carcinoma and rectal adenocarcinoma who was subsequently found to have a sporadic CHEK2 (checkpoint kinase 2) mutation. She presented with an 8-month history of bright red blood per rectum and saw two different physicians who diagnosed hemorrhoids and possible rectal ulcers, respectively. When the symptoms continued, the patient pursued a colonoscopy exam which found a large rectal tumor. Subsequent clinical staging diagnosed a rectal adenocarcinoma and a synchronous papillary thyroid carcinoma. Due to her synchronous tumors, a genetic panel was performed, which revealed a low-risk CHEK2 mutation. Our patient had a full response to neoadjuvant brachytherapy of the rectum and surgical treatment of her cancers. Conclusion: This is the first case report, to our knowledge, of a patient with a CHEK2 mutation who presented with synchronous papillary thyroid carcinoma and invasive colonic adenocarcinoma. The incidence of colorectal cancers and papillary thyroid cancers in those under 30 with no family history is very low, which signifies the rarity of their simultaneous occurrence at such a young age.
Impact of Shelf-Life Extension on Platelet Availability: Results from an Inventory Management Modeling Study
Authors: Brixner Veronika , Cardoso Marcia , Spaepen Erik , Seifried Erhard
Published: April 2024

Introduction: In Germany, demand for platelet transfusion is maintained or even increasing, despite a decrease in whole blood donations observed in the last decade. The shelf-life of platelet concentrates (PCs) in Germany is 4 days, which can be extended to 5 days if appropriate safety measures are used. This short shelf-life leads to decreased PC availability. Methods: We investigated the impact of PC shelf-life extension on PC shortage, using a mathematical simulation model based on the PC production and delivery statistics of the Frankfurt Institute of the German Red Cross Transfusion Service of Baden-Württemberg-Hessen. We used a 2.2-year dataset for PC production and delivery as input data for a Monte Carlo inventory management simulation, focusing on PC shortage. The model generated the daily stock (expressed as mean number of PC units ± standard deviation), mean PC age at release, mean number of expired PC units, and shortage rates (i.e., requiring the release of more PCs than available), overall and by PC blood group. Results: Over 2.2 years, a total of 74,322 PC units were produced and 62,178 units were released at the Frankfurt Institute; the overall overproduction rate was 19.5%. Shortage rates decrease with an increase in PC shelf-life and/or increase in overproduction rates. At an overproduction rate of 20%, shortage rates would be reduced from 2.8% for a 4-day shelf-life to 0.7%, 0.3%, and 0.2%, for shelf-life lengths of 5, 6, and 7 days, respectively. Extending the PC shelf-life to 6 or 7 days would eliminate shortages almost entirely, including for rare bloods. Conclusion: These results can inform blood services and regulatory authorities on the potential medical and economic impact of extending PC shelf-life to 6 or 7 days.
A Medeia de Nelson Rodrigues: Desamparo freudiano em Álbum de família, de Nelson Rodrigues
Authors: Tavares José Luiz Cordeiro Dias , Cardoso Elizabeth da Penha
Published: April 2024

Neste artigo propomos a Hilflosigkeit freudiana como a principal condutora dos recursos estéticos em Álbum de família, de Nelson Rodrigues. Revisitamos este conceito e sua perspectiva metapsicológica para pensarmos o percurso de sofrimento da protagonista Senhorinha nessa obra. Neste caminho encontramos Medeia. Ambas atuaram, em gesto, o que na linguagem se fez ausência.