bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Ipatasertib plus Paclitaxel for Patients with PIK3CA/AKT1/PTEN-Altered Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer in the IPATunity130 Phase III Trial
Authors: Dent Rebecca A. , Kim Sung-Bae , Oliveira Mafalda , Barrios Carlos , O’Shaughnessy Joyce , Isakoff Steven J. , Saji Shigehira , Freitas-Junior Ruffo , Philco Manuel , Bondarenko Igor , Lian Qinshu , Bradley Denise , Hinton Heather , Wongchenko Matthew J. , Reilly Sarah-Jayne , Turner Nicholas
Published: October 2024

AbstractPurpose:
In the randomized phase II LOTUS trial, combining ipatasertib with first-line paclitaxel for triple-negative breast cancer (TNBC) improved progression-free survival (PFS), particularly in patients with PIK3CA/AKT1/PTEN-altered tumors. We aimed to validate these findings in a biomarker-selected TNBC population.
Patients and Methods:
In Cohort A of the randomized double-blind placebo-controlled phase III IPATunity130 trial, taxane-eligible patients with PIK3CA/AKT1/PTEN-altered measurable advanced TNBC and no prior chemotherapy for advanced disease were randomized 2:1 to ipatasertib (400 mg, days 1–21) or placebo, both plus paclitaxel (80 mg/m2, days 1, 8, and 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS.
Results:
Between February 2018 and April 2020, 255 patients were randomized (168 to ipatasertib, 87 to placebo). At the primary analysis, there was no significant difference between treatment arms in PFS [hazard ratio 1.02, 95% confidence interval (CI), 0.71–1.45; median 7.4 months with ipatasertib vs. 6.1 months with placebo]. The final analysis showed no difference in overall survival between treatment arms (hazard ratio 1.08, 95% CI, 0.73–1.58; median 24.4 vs. 24.9 months, respectively). Ipatasertib was associated with more grade ≥3 diarrhea (9% vs. 2%) and adverse events leading to dose reduction (39% vs. 14%) but similar incidences of grade ≥3 adverse events (51% vs. 46%). Exploratory subgroup analyses by PAM50 and Burstein gene expression showed inconsistent results.
Conclusions:
Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered advanced TNBC. Biomarkers for benefit from PI3K/AKT pathway inhibition in TNBC remain poorly understood.
Supplementary Figure S8 from Anti-Claudin-2 Antibody–Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis
Authors: Tabariès Sébastien , Robert Alma , Marcil Anne , Ling Binbing , Acchione Mauro , Lippens Julie , Pagé Martine , Fortin Annie , Meury Luc , Coutu Mathieu , Annis Matthew G. , Girondel Charlotte , Navarre Julie , Jaramillo Maria , Moraitis Anna N. , Siegel Peter M.
Published: October 2024

Supplementary Figure S8
Supplementary Figure S14 from Anti-Claudin-2 Antibody–Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis
Authors: Tabariès Sébastien , Robert Alma , Marcil Anne , Ling Binbing , Acchione Mauro , Lippens Julie , Pagé Martine , Fortin Annie , Meury Luc , Coutu Mathieu , Annis Matthew G. , Girondel Charlotte , Navarre Julie , Jaramillo Maria , Moraitis Anna N. , Siegel Peter M.
Published: October 2024

Supplementary Figure S14
Supplementary Figure S13 from Anti-Claudin-2 Antibody–Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis
Authors: Tabariès Sébastien , Robert Alma , Marcil Anne , Ling Binbing , Acchione Mauro , Lippens Julie , Pagé Martine , Fortin Annie , Meury Luc , Coutu Mathieu , Annis Matthew G. , Girondel Charlotte , Navarre Julie , Jaramillo Maria , Moraitis Anna N. , Siegel Peter M.
Published: October 2024

Supplementary Figure S14
Supplementary Figure S10 from Anti-Claudin-2 Antibody–Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis
Authors: Tabariès Sébastien , Robert Alma , Marcil Anne , Ling Binbing , Acchione Mauro , Lippens Julie , Pagé Martine , Fortin Annie , Meury Luc , Coutu Mathieu , Annis Matthew G. , Girondel Charlotte , Navarre Julie , Jaramillo Maria , Moraitis Anna N. , Siegel Peter M.
Published: October 2024

Supplementary Figure S10
Supplementary Tables from Characterization of AB598, a CD39 Enzymatic Inhibitory Antibody for the Treatment of Solid Tumors
Authors: Anderson Amy E. , Parashar Kaustubh , Jin Ke , Clor Julie , Stagnaro Carlo E. , Vani Urvi , Singh Jaskirat , Chen Ada , Guan Yihong , Talukdar Priyanka , Sathishkumar Pavithra , Juat Damie J. , Singh Hema , Kushwaha Ritu , Zhao Xiaoning , Kaplan Angelo , Seitz Lisa , Walters Matthew J. , Fernandez-Salas Ester , Walker Nigel P.C. , Bowman Christine E.
Published: October 2024

Supplementary Tables
Figure S7 from Characterization of AB598, a CD39 Enzymatic Inhibitory Antibody for the Treatment of Solid Tumors
Authors: Anderson Amy E. , Parashar Kaustubh , Jin Ke , Clor Julie , Stagnaro Carlo E. , Vani Urvi , Singh Jaskirat , Chen Ada , Guan Yihong , Talukdar Priyanka , Sathishkumar Pavithra , Juat Damie J. , Singh Hema , Kushwaha Ritu , Zhao Xiaoning , Kaplan Angelo , Seitz Lisa , Walters Matthew J. , Fernandez-Salas Ester , Walker Nigel P.C. , Bowman Christine E.
Published: October 2024

Figure S7
Extended Methods from Characterization of AB598, a CD39 Enzymatic Inhibitory Antibody for the Treatment of Solid Tumors
Authors: Anderson Amy E. , Parashar Kaustubh , Jin Ke , Clor Julie , Stagnaro Carlo E. , Vani Urvi , Singh Jaskirat , Chen Ada , Guan Yihong , Talukdar Priyanka , Sathishkumar Pavithra , Juat Damie J. , Singh Hema , Kushwaha Ritu , Zhao Xiaoning , Kaplan Angelo , Seitz Lisa , Walters Matthew J. , Fernandez-Salas Ester , Walker Nigel P.C. , Bowman Christine E.
Published: October 2024

Supplementary Methods
Figure S5 from FZ-AD005, a Novel DLL3-Targeted Antibody–Drug Conjugate with Topoisomerase I Inhibitor, Shows Potent Antitumor Activity in Preclinical Models
Authors: Guo Qingsong , Gao Bei , Song Ruiwen , Li Weinan , Zhu Shulei , Xie Qian , Lou Sensen , Wang Lei , Shen Jiafei , Zhao Teng , Zhang Yifan , Wu Jinsong , Lu Wei , Yang Tong
Published: October 2024

Supplementary Fig.S5
Figure S6 from PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer
Authors: Chen Anran , Kim Beom-Jun , Mitra Aparna , Vollert Craig T. , Lei Jonathan T. , Fandino Diana , Anurag Meenakshi , Holt Matthew V. , Gou Xuxu , Pilcher Jacob B. , Goetz Matthew P. , Northfelt Donald W. , Hilsenbeck Susan G. , Marshall C. Gary , Hyer Marc L. , Papp Robert , Yin Shou-Yun , De Angelis Carmine , Schiff Rachel , Fuqua Suzanne A.W. , Ma Cynthia X. , Foulds Charles E. , Ellis Matthew J.
Published: October 2024

Correlation of PKMYT1 protein levels with Hallmark scores in ER+ breast cancer PDXs
Figure S18 from PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer
Authors: Chen Anran , Kim Beom-Jun , Mitra Aparna , Vollert Craig T. , Lei Jonathan T. , Fandino Diana , Anurag Meenakshi , Holt Matthew V. , Gou Xuxu , Pilcher Jacob B. , Goetz Matthew P. , Northfelt Donald W. , Hilsenbeck Susan G. , Marshall C. Gary , Hyer Marc L. , Papp Robert , Yin Shou-Yun , De Angelis Carmine , Schiff Rachel , Fuqua Suzanne A.W. , Ma Cynthia X. , Foulds Charles E. , Ellis Matthew J.
Published: October 2024

The combination of RP-6306 and gemcitabine increases apoptosis and activates DNA damage signaling in palbociclib-resistant T47D cells
Supplementary Table S3 from Blocking M2-Like Macrophage Polarization Using Decoy Oligodeoxynucleotide-Based Gene Therapy Prevents Immune Evasion for Pancreatic Cancer Treatment
Authors: Chen Chang-Jung , Wang Hao-Chen , Hou Ya-Chin , Wu Yi-Ying , Shieh Chi-Chang , Shan Yan-Shen
Published: October 2024

Supplementary Table S3. Clinical parameters of the 100 pancreatic cancer patients for RNA sequencing
Supplementary Figure S6 from Blocking M2-Like Macrophage Polarization Using Decoy Oligodeoxynucleotide-Based Gene Therapy Prevents Immune Evasion for Pancreatic Cancer Treatment
Authors: Chen Chang-Jung , Wang Hao-Chen , Hou Ya-Chin , Wu Yi-Ying , Shieh Chi-Chang , Shan Yan-Shen
Published: October 2024

Supplementary Figure S6. Inhibiting SATA6 and HDAC restores IL-4-mediated reduction of CYBB expression in U937 cells. U937 cells were pre-treated with or without the STAT6 inhibitor AS1517499 (AS, 250 nM), the Pan-HDAC inhibitors TSA (10 µM) and LBH589 (LBH, 50 µM) for 24 h, and then were treated with 20 ng/ml IL-4 for 1 h. RT-qPCR analysis was performed to measure HDAC2 and CYBB mRNA expression. The bar graphs depict relative mRNA expression. ***, p < 0.001, compared with the control group. Data represent the mean of 3 independent experiments.
Supplementary Figure S3 from Blocking M2-Like Macrophage Polarization Using Decoy Oligodeoxynucleotide-Based Gene Therapy Prevents Immune Evasion for Pancreatic Cancer Treatment
Authors: Chen Chang-Jung , Wang Hao-Chen , Hou Ya-Chin , Wu Yi-Ying , Shieh Chi-Chang , Shan Yan-Shen
Published: October 2024

Supplementary Figure S3. Expression of MRC1 and ARG1 mRNAs in U937 cells or THP-1 cells cocultured with PANC-1 cells was inhibited by IL-4 neutralization. A, U937, and B, THP-1 cells were cocultured with PANC-1 cells and simultaneously treated with IL-4 neutralizing antibodies. After 72 h of incubation, U937 and THP-1 cells were collected for RT-qPCR to measure MRC1, ARG1, and CYBB gene expression. The bar graphs depict relative protein expression. ***, p < 0.001, significant differences between groups. Data represent the mean of 3 independent experiments.
Supplementary Figure S13 from Blocking M2-Like Macrophage Polarization Using Decoy Oligodeoxynucleotide-Based Gene Therapy Prevents Immune Evasion for Pancreatic Cancer Treatment
Authors: Chen Chang-Jung , Wang Hao-Chen , Hou Ya-Chin , Wu Yi-Ying , Shieh Chi-Chang , Shan Yan-Shen
Published: October 2024

Supplementary Figure S13. Treatment with STAT6-CYBB ODNs reduces the proliferation of stromal or epithelial-type tumor cells. A, IF staining for Ki67 and the stromal marker αSMA was performed in KPC tumors from the scrambled ODN, mutated ODN, and STAT6-CYBB ODN-treated mice. Each of the images are representative of a field of immuno-stained cells, taken using a ×20 objective with the Olympus BX53 platform. Each composite image includes the nuclear marker DAPI in blue. B, The Bar graph shows the αSMA (left) and Ki67 (right) positive cells relative to the DAPI-stained nuclei in cells in mouse tumor tissue. ***, p < 0.001, compared to mouse tumors treated with the scrambled-ODN. The random of five fields of 3 random sections from each mouse were used to quantify the positive cells. C, IF staining for Ki67 and the epithelial marker CK7 was performed in KPC tumors from the scrambled ODN, mutated ODN, and STAT6-CYBB ODN-treated mice. Each of the images are representative of a field of immuno-stained cells, taken using a ×20 objective with the Olympus BX53 platform. Each composite image includes the nuclear marker DAPI in blue. D, The Bar graph shows the CK7 (left) and Ki67 (right) positive cells relative to the DAPI-stained nuclei in cells in mouse tumor tissue. ***, p < 0.001, compared to mouse tumors treated with the scrambled-ODN. The random of five fields of 3 random sections from each mouse were used to quantify the positive cells.
Supplementary Figure S12 from Blocking M2-Like Macrophage Polarization Using Decoy Oligodeoxynucleotide-Based Gene Therapy Prevents Immune Evasion for Pancreatic Cancer Treatment
Authors: Chen Chang-Jung , Wang Hao-Chen , Hou Ya-Chin , Wu Yi-Ying , Shieh Chi-Chang , Shan Yan-Shen
Published: October 2024

Supplementary Figure S12. STAT6-CYBB ODNs upregulate CYBB expression in mouse pancreatic tumors. A, IHC staining for CYBB was performed in KPC tumors from the scrambled ODN, mutated ODN, and STAT6-CYBB ODN-treated mice. B, The bar graph depicts the average numbers of CYBB positive cells per field. ***, p < 0.001, compared to the scrambled ODN treatment group. Five random fields of 3 random sections from each mouse were used to quantify the positive cells.
Table S2 from AKT Inhibition Sensitizes to Polo-Like Kinase 1 Inhibitor Onvansertib in Prostate Cancer
Authors: Nouri Mannan , Varkaris Andreas , Ridinger Maya , Dalrymple Susan L. , Dennehy Christopher M. , Isaacs John T. , Einstein David J. , Brennen W.N. , Balk Steven P.
Published: October 2024

Table S2 (% Control)
Figure S7 from AKT Inhibition Sensitizes to Polo-Like Kinase 1 Inhibitor Onvansertib in Prostate Cancer
Authors: Nouri Mannan , Varkaris Andreas , Ridinger Maya , Dalrymple Susan L. , Dennehy Christopher M. , Isaacs John T. , Einstein David J. , Brennen W.N. , Balk Steven P.
Published: October 2024

Ipatasertib and onvansertib treatment in in vivo models demonstrates no significant toxicity.
Figure S1 from AKT Inhibition Sensitizes to Polo-Like Kinase 1 Inhibitor Onvansertib in Prostate Cancer
Authors: Nouri Mannan , Varkaris Andreas , Ridinger Maya , Dalrymple Susan L. , Dennehy Christopher M. , Isaacs John T. , Einstein David J. , Brennen W.N. , Balk Steven P.
Published: October 2024

PLK1 is increased with tumor progression and correlates with genes associated with G2-M transition
Supplementary Table S3 from Discovery of Monovalent Direct Degraders of BRD4 that Act via the Recruitment of DCAF11
Authors: Parker Gregory S. , Toth Julia I. , Fish Sarah , Blanco Gabrielle , Kampert Taylor , Li Xiaoming , Yang Linette , Stumpf Craig R. , Steadman Kenneth , Jamborcic Aleksandar , Chien Stephen , Daniele Elizabeth , Dearie Alejandro , Leriche Geoffray , Bailey Simon , Thompson Peggy A.
Published: October 2024

Supplemental Table S3 shows the protein expression plasmids used in these studies
Supplementary Table S2 from Discovery of Monovalent Direct Degraders of BRD4 that Act via the Recruitment of DCAF11
Authors: Parker Gregory S. , Toth Julia I. , Fish Sarah , Blanco Gabrielle , Kampert Taylor , Li Xiaoming , Yang Linette , Stumpf Craig R. , Steadman Kenneth , Jamborcic Aleksandar , Chien Stephen , Daniele Elizabeth , Dearie Alejandro , Leriche Geoffray , Bailey Simon , Thompson Peggy A.
Published: October 2024

Supplementary Table S2 show anti-proliferative activity in AML cell lines (n = 2)
Supplementary Table S3 from The SOS1 Inhibitor MRTX0902 Blocks KRAS Activation and Demonstrates Antitumor Activity in Cancers Dependent on KRAS Nucleotide Loading
Authors: Sudhakar Niranjan , Yan Larry , Qiryaqos Fadia , Engstrom Lars D. , Laguer Jade , Calinisan Andrew , Hebbert Allan , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Ketcham John M. , Ivetac Anthony , Smith Christopher R. , Lawson J. David , Rahbaek Lisa , Clarine Jeffrey , Nguyen Natalie , Saechao Barbara , Parker Cody , Elliott Adam J. , Vanderpool Darin , He Leo , Hover Laura D. , Fernandez-Banet Julio , Coma Silvia , Pachter Jonathan A. , Hallin Jill , Marx Matthew A. , Briere David M. , Christensen James G. , Olson Peter , Haling Jacob , Khare Shilpi
Published: October 2024

Supplementary Table S3 displays the various genetic co-alterations present in human KRAS G12C-mutant tumor cell line-derived and patient-derived xenograft models evaluated.
Supplementary Figure S8 from The SOS1 Inhibitor MRTX0902 Blocks KRAS Activation and Demonstrates Antitumor Activity in Cancers Dependent on KRAS Nucleotide Loading
Authors: Sudhakar Niranjan , Yan Larry , Qiryaqos Fadia , Engstrom Lars D. , Laguer Jade , Calinisan Andrew , Hebbert Allan , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Ketcham John M. , Ivetac Anthony , Smith Christopher R. , Lawson J. David , Rahbaek Lisa , Clarine Jeffrey , Nguyen Natalie , Saechao Barbara , Parker Cody , Elliott Adam J. , Vanderpool Darin , He Leo , Hover Laura D. , Fernandez-Banet Julio , Coma Silvia , Pachter Jonathan A. , Hallin Jill , Marx Matthew A. , Briere David M. , Christensen James G. , Olson Peter , Haling Jacob , Khare Shilpi
Published: October 2024

Supplementary Figure S8 details the antitumor effects associated with coadministration of MRTX0902 and adagrasib in the MIA PaCa-2 (KRAS G12C-mutant) model.
Supplementary Figure S5 from The SOS1 Inhibitor MRTX0902 Blocks KRAS Activation and Demonstrates Antitumor Activity in Cancers Dependent on KRAS Nucleotide Loading
Authors: Sudhakar Niranjan , Yan Larry , Qiryaqos Fadia , Engstrom Lars D. , Laguer Jade , Calinisan Andrew , Hebbert Allan , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Ketcham John M. , Ivetac Anthony , Smith Christopher R. , Lawson J. David , Rahbaek Lisa , Clarine Jeffrey , Nguyen Natalie , Saechao Barbara , Parker Cody , Elliott Adam J. , Vanderpool Darin , He Leo , Hover Laura D. , Fernandez-Banet Julio , Coma Silvia , Pachter Jonathan A. , Hallin Jill , Marx Matthew A. , Briere David M. , Christensen James G. , Olson Peter , Haling Jacob , Khare Shilpi
Published: October 2024

Supplementary Figure S5 shows levels of KRAS-MAPK pathway modulation associated with coadministration of MRTX0902 and adagrasib in the murine CT26 (KRAS G12C-mutant) model.
Supplementary Figure S2 from The SOS1 Inhibitor MRTX0902 Blocks KRAS Activation and Demonstrates Antitumor Activity in Cancers Dependent on KRAS Nucleotide Loading
Authors: Sudhakar Niranjan , Yan Larry , Qiryaqos Fadia , Engstrom Lars D. , Laguer Jade , Calinisan Andrew , Hebbert Allan , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Ketcham John M. , Ivetac Anthony , Smith Christopher R. , Lawson J. David , Rahbaek Lisa , Clarine Jeffrey , Nguyen Natalie , Saechao Barbara , Parker Cody , Elliott Adam J. , Vanderpool Darin , He Leo , Hover Laura D. , Fernandez-Banet Julio , Coma Silvia , Pachter Jonathan A. , Hallin Jill , Marx Matthew A. , Briere David M. , Christensen James G. , Olson Peter , Haling Jacob , Khare Shilpi
Published: October 2024

Supplementary Figure S2 shows the antitumor activity of MRTX0902 in the LN229 (PTPN11 A72S-mutant) model, with tumor growth inhibition data displayed in Figure S2A and ERK phosphorylation graphed in Figure S2B.
Data from PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer
Authors: Chen Anran , Kim Beom-Jun , Mitra Aparna , Vollert Craig T. , Lei Jonathan T. , Fandino Diana , Anurag Meenakshi , Holt Matthew V. , Gou Xuxu , Pilcher Jacob B. , Goetz Matthew P. , Northfelt Donald W. , Hilsenbeck Susan G. , Marshall C. Gary , Hyer Marc L. , Papp Robert , Yin Shou-Yun , De Angelis Carmine , Schiff Rachel , Fuqua Suzanne A.W. , Ma Cynthia X. , Foulds Charles E. , Ellis Matthew J.
Published: October 2024

Abstract
Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast cancer cells without functional p53. In vitro the combination increased DNA damage and apoptosis. In palbociclib-resistant, TP53 mutant PDX-derived organoids and PDXs, RP-6306 with low-dose gemcitabine induced greater tumor volume reduction compared to treatment with either single agent. Our study demonstrates the clinical potential of RP-6306 in combination with gemcitabine for ET and CDK4/6 inhibitor resistant TP53 mutant ER+ breast cancer.
Data from The SOS1 Inhibitor MRTX0902 Blocks KRAS Activation and Demonstrates Antitumor Activity in Cancers Dependent on KRAS Nucleotide Loading
Authors: Sudhakar Niranjan , Yan Larry , Qiryaqos Fadia , Engstrom Lars D. , Laguer Jade , Calinisan Andrew , Hebbert Allan , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Ketcham John M. , Ivetac Anthony , Smith Christopher R. , Lawson J. David , Rahbaek Lisa , Clarine Jeffrey , Nguyen Natalie , Saechao Barbara , Parker Cody , Elliott Adam J. , Vanderpool Darin , He Leo , Hover Laura D. , Fernandez-Banet Julio , Coma Silvia , Pachter Jonathan A. , Hallin Jill , Marx Matthew A. , Briere David M. , Christensen James G. , Olson Peter , Haling Jacob , Khare Shilpi
Published: October 2024

Abstract
KRAS is the most frequently mutated oncogene in human cancer and facilitates uncontrolled growth through hyperactivation of the receptor tyrosine kinase (RTK)/mitogen-activated protein kinase (MAPK) pathway. The Son of Sevenless homolog 1 (SOS1) protein functions as a guanine nucleotide exchange factor (GEF) for the RAS subfamily of small GTPases and represents a druggable target in the pathway. Using a structure-based drug discovery approach, MRTX0902 was identified as a selective and potent SOS1 inhibitor that disrupts the KRAS:SOS1 protein–protein interaction to prevent SOS1-mediated nucleotide exchange on KRAS and translates into an anti-proliferative effect in cancer cell lines with genetic alterations of the KRAS–MAPK pathway. MRTX0902 augmented the antitumor activity of the KRAS G12C inhibitor adagrasib when dosed in combination in eight out of 12 KRAS G12C–mutant human non–small cell lung cancer and colorectal cancer xenograft models. Pharmacogenomic profiling in preclinical models identified cell cycle genes and the SOS2 homolog as genetic co-dependencies and implicated tumor suppressor genes (NF1 and PTEN) in resistance following combination treatment. Lastly, combined vertical inhibition of RTK/MAPK pathway signaling by MRTX0902 with inhibitors of EGFR or RAF/MEK led to greater downregulation of pathway signaling and improved antitumor responses in KRAS–MAPK pathway–mutant models. These studies demonstrate the potential clinical application of dual inhibition of SOS1 and KRAS G12C and additional SOS1 combination strategies that will aide in the understanding of SOS1 and RTK/MAPK biology in targeted cancer therapy.
Gram-Negative Microflora Dysbiosis Facilitates Tumor Progression and Immune Evasion by Activating the CCL3/CCL5–CCR1–MAPK–PD-L1 Pathway in Esophageal Squamous Cell Carcinoma
Authors: Yang Huiqin , Cai Jiahao , Huang Xiaolong , Zhan Cheng , Lu Chunlai , Gu Jie , Ma Teng , Zhang Hongyu , Cheng Tao , Xu Fengkai , Ge Di
Published: October 2024

Gram-negative (G−) microflora dysbiosis occurs in multiple digestive tumors and is found to be the dominant microflora in the esophageal squamous cell carcinoma (ESCC) microenvironment. The continuous stimulation of G− bacterium metabolites may cause tumorigenesis and reshape the microimmune environment in ESCC. However, the mechanism of G− bacilli causing immune evasion in ESCC remains underexplored. We identified CC chemokine receptor 1 (CCR1) as a tumor-indicating gene in ESCC. Interestingly, expression levels of CCR1 and PD-L1 were mutually upregulated after G− bacilli metabolite lipopolysaccharide stimulation. First, we found that CCR1 high expression levels were associated with poor overall survival in ESCC. Importantly, we found that high levels of CCR1 expression upregulated PD-L1 expression by activating MAPK phosphorylation in ESCC and induced tumor malignant behavior. Finally, we found that T-cell exhaustion and cytotoxicity suppression were associated with CCR1 expression in ESCC, which were decreased after CCR1 inhibiting. Our work identifies CCR1 as a potential immune check point regulator of PD-L1 and may cause T-cell exhaustion and cytotoxicity suppression in ESCC microenvironment and highlights the potential value of CCR1 as a therapeutic target of immunotherapy.

Implications: The esophageal microbial environment and its metabolites significantly affect the outcome of immunotherapy for ESCC.
Supplementary Figure S4 from Cancer History and Social Support Impact Colorectal Cancer Screening Utilization by Race/Ethnicity
Authors: Tsai Meng-Han , Lee Minjee , Coughlin Steven S. , Eberth Jan M. , Rogers Charles R.
Published: October 2024

Supplementary Figure S4 showed the association between race/ethnicity, cancer history, lack of social support, and CRC screening utilization adjusted for sociodemographic characteristics and health-related factors
Supplementary Figure S5 from Preventive Treatment with a CD73 Small Molecule Inhibitor Enhances Immune Surveillance in K-Ras Mutant Pancreatic Intraepithelial Neoplasia
Authors: Strickland Lincoln N. , Liu Wendao , Hussein Usama , Mardik Nicolette , Chen Xian , Mills Tingting , Vornik Lana A. , Savage Michelle I. , Sei Shizuko , Clifford John , Eltzschig Holger K. , Brown Powel H. , Zhao Zhongming , McAllister Florencia , Bailey-Lundberg Jennifer M.
Published: October 2024

Supplementary Figure S5. Treatment with a CD73 small molecule inhibitor does not change AMP or inosine levels in pancreas tissue or serum.
Supplementary Figure S4 from Preventive Treatment with a CD73 Small Molecule Inhibitor Enhances Immune Surveillance in K-Ras Mutant Pancreatic Intraepithelial Neoplasia
Authors: Strickland Lincoln N. , Liu Wendao , Hussein Usama , Mardik Nicolette , Chen Xian , Mills Tingting , Vornik Lana A. , Savage Michelle I. , Sei Shizuko , Clifford John , Eltzschig Holger K. , Brown Powel H. , Zhao Zhongming , McAllister Florencia , Bailey-Lundberg Jennifer M.
Published: October 2024

Supplementary Figure S4. AB-680 treatments results in distinct changes in gene expression in macrophages, dendritic cells and naïve T cells.
Data from Cancer History and Social Support Impact Colorectal Cancer Screening Utilization by Race/Ethnicity
Authors: Tsai Meng-Han , Lee Minjee , Coughlin Steven S. , Eberth Jan M. , Rogers Charles R.
Published: October 2024

Abstract
This study examined the association among cancer history, social support, and up-to-date colorectal cancer (CRC) screening among four racial/ethnic groups. We conducted a cross-sectional analysis using data on respondents aged 45 to 75 years from the 2022 Behavioral Risk Factor Surveillance System. Our outcome of interest was CRC screening and exposures of interest were race/ethnicity, cancer history, and social support. Weighted multivariable logistic regression was performed. Among 73,869 adults, the CRC screening rate was 66.8% with the highest rate in non-Hispanic (NH), Whites (72.2%), and the lowest in Hispanics (52.6%). Screening rates were higher in adults with a cancer history (81.9%) and those having social support (69%). Hispanic adults with a cancer history had lower screening use (50.9% vs. 77.4% in the no cancer history group; P value < 0.001). Regardless of race/ethnicity, adults without social support had lower screening utilization (P value < 0.05). In effect modification, NH White adults who reported no cancer history and lack of social support were 12% less likely to have CRC screening than those with social support but without cancer history (OR, 0.88; 95% confidence intervals, 0.79–0.98). Similar results were observed among Hispanic adults without a cancer history and social support, with 37% less likely to have CRC screening than those with social support but no cancer history (OR, 0.63; 95% confidence intervals, 0.42–0.93). NH White and Hispanic adults without a cancer history and limited social support were less likely to have CRC screening uptake. By implementing culturally tailored interventions that address social support needs, greater CRC screening compliance may be increased among these populations.

Prevention Relevance: Adherence to CRC screening recommendations reduces cancer incidence and mortality. Effective implementation of culturally tailored interventions that address social support needs and consider cancer history have the potential for improving CRC screening compliance among NH White and Hispanic adults without a cancer history.
Figure S8 from Atypical B Cells Promote Cancer Progression and Poor Response to Bacillus Calmette-Guérin in Non–Muscle Invasive Bladder Cancer
Authors: Yolmo Priyanka , Rahimi Sadaf , Chenard Stephen , Conseil Gwenaëlle , Jenkins Danielle , Sachdeva Kartik , Emon Isaac , Hamilton Jake , Xu Minqi , Rangachari Manu , Michaud Eva , Mansure Jose J. , Kassouf Wassim , Berman David M. , Siemens David R. , Koti Madhuri
Published: October 2024

Immune infiltration in the bladder microenvironment after repeated BCG treatment and B‐cell depletion in BBN exposed mice.
Figure S3 from Atypical B Cells Promote Cancer Progression and Poor Response to Bacillus Calmette-Guérin in Non–Muscle Invasive Bladder Cancer
Authors: Yolmo Priyanka , Rahimi Sadaf , Chenard Stephen , Conseil Gwenaëlle , Jenkins Danielle , Sachdeva Kartik , Emon Isaac , Hamilton Jake , Xu Minqi , Rangachari Manu , Michaud Eva , Mansure Jose J. , Kassouf Wassim , Berman David M. , Siemens David R. , Koti Madhuri
Published: October 2024

Tumor-adjacent TLS characterized using multiplex IF and NanoString GeoMx DSP.
Figure S9 from RNA-encoded Interleukin 2 with Extended Bioavailability Amplifies RNA Vaccine–Induced Antitumor T-cell Immunity
Authors: Peters Daniel , Kranz Lena M. , Eisel David , Diken Mustafa , Kreiter Sebastian , Türeci Özlem , Sahin Ugur , Vormehr Mathias
Published: October 2024

Representative dot plots corresponding to flow cytometry data displayed in Figure 4.
Figure S8 from RNA-encoded Interleukin 2 with Extended Bioavailability Amplifies RNA Vaccine–Induced Antitumor T-cell Immunity
Authors: Peters Daniel , Kranz Lena M. , Eisel David , Diken Mustafa , Kreiter Sebastian , Türeci Özlem , Sahin Ugur , Vormehr Mathias
Published: October 2024

Representative dot plots and histograms corresponding to flow cytometry data displayed in Figure 3.
Supplemental Table S3 from Machine Learning–Directed Conversion of Glioblastoma Cells to Dendritic Cell–Like Antigen-Presenting Cells as Cancer Immunotherapy
Authors: Liu Tianyi , Jin Dan , Le Son B. , Chen Dongjiang , Sebastian Mathew , Riva Alberto , Liu Ruixuan , Tran David D.
Published: October 2024

Real and shuffled networks of 28 Human cancer types in TCGA (Supporting the Materials and Methods Section)
Figure S6 from RNA-encoded Interleukin 2 with Extended Bioavailability Amplifies RNA Vaccine–Induced Antitumor T-cell Immunity
Authors: Peters Daniel , Kranz Lena M. , Eisel David , Diken Mustafa , Kreiter Sebastian , Türeci Özlem , Sahin Ugur , Vormehr Mathias
Published: October 2024

Gating strategy for antigen-specific CD8+ T cells in the spleen.
Figure S2 from RNA-encoded Interleukin 2 with Extended Bioavailability Amplifies RNA Vaccine–Induced Antitumor T-cell Immunity
Authors: Peters Daniel , Kranz Lena M. , Eisel David , Diken Mustafa , Kreiter Sebastian , Türeci Özlem , Sahin Ugur , Vormehr Mathias
Published: October 2024

Expansion of nonvaccine antigen-specific CD8+ T cells in response to RNA-LPX and Alb-IL2 RNA-NP. Number of nonvaccine antigen-specific CD8+ T cells per spleen (gp70 (A), OVA (B)) or per 4 x 106 splenocytes (TRP-1 (C)) 7 days after the last of three weekly i.v. vaccinations with gp70 RNA-LPX (A), OVA RNA-LPX (B) or TRP-1 RNA-LPX (C) combined with Alb-IL2 RNA-NP or Alb RNA-NP (gp70: n=6 mice/group for Alb RNA-NP, n=7 mice/group for Alb-IL2 RNA-NP; OVA, TRP-1: n=5 mice/group). Mean + SEM. Two-tailed Student t-test (A). **P≤0.01.
Supplemental Table S13 from Machine Learning–Directed Conversion of Glioblastoma Cells to Dendritic Cell–Like Antigen-Presenting Cells as Cancer Immunotherapy
Authors: Liu Tianyi , Jin Dan , Le Son B. , Chen Dongjiang , Sebastian Mathew , Riva Alberto , Liu Ruixuan , Tran David D.
Published: October 2024

All public human datasets curated for ML predictions (Supporting Main Figure 7)
Supplemental Figure S3 from Machine Learning–Directed Conversion of Glioblastoma Cells to Dendritic Cell–Like Antigen-Presenting Cells as Cancer Immunotherapy
Authors: Liu Tianyi , Jin Dan , Le Son B. , Chen Dongjiang , Sebastian Mathew , Riva Alberto , Liu Ruixuan , Tran David D.
Published: October 2024

nSCORE (network Systems Calculating Optimal Ranking Engine) (Supporting the Materials and Methods Section)
Supplemental Figure S13 from Machine Learning–Directed Conversion of Glioblastoma Cells to Dendritic Cell–Like Antigen-Presenting Cells as Cancer Immunotherapy
Authors: Liu Tianyi , Jin Dan , Le Son B. , Chen Dongjiang , Sebastian Mathew , Riva Alberto , Liu Ruixuan , Tran David D.
Published: October 2024

Functional confirmation of splenic mouse DCs used in KR158-based mouse DCs vaccine (Supporting Main Figures 3 and 6)
Table S5 from Hypoxia-Induced Long Noncoding RNA HIF1A-AS2 Regulates Stability of MHC Class I Protein in Head and Neck Cancer
Authors: Liao Tsai-Tsen , Chen Yu-Hsien , Li Zih-Yu , Hsiao An-Ching , Huang Ya-Li , Hao Ruo-Xin , Tai Shyh-Kuan , Chu Pen-Yuan , Shih Jing-Wen , Kung Hsing-Jien , Yang Muh-Hwa
Published: October 2024

Characteristics of the HNSCC patients for immunohistochemistry analysis (n = 57).
Table S1 from Hypoxia-Induced Long Noncoding RNA HIF1A-AS2 Regulates Stability of MHC Class I Protein in Head and Neck Cancer
Authors: Liao Tsai-Tsen , Chen Yu-Hsien , Li Zih-Yu , Hsiao An-Ching , Huang Ya-Li , Hao Ruo-Xin , Tai Shyh-Kuan , Chu Pen-Yuan , Shih Jing-Wen , Kung Hsing-Jien , Yang Muh-Hwa
Published: October 2024

Primers for cloning constructs and plasmid information.
Supplementary Figure 3 from Intermittent MEK Inhibition with GITR Costimulation Rescues T-cell Function for Increased Efficacy with CTLA-4 Blockade in Solid Tumor Models
Authors: Dong Lauren , Choi Hyejin , Budhu Sadna , Schulze Isabell , Verma Svena , Mangarin Levi M. , Estrada Nevarro Valeria , Mehanna Nezar , Khan Jonathan F. , Venkatesh Divya , Thach Daniel , Rosen Neal , Wolchok Jedd D. , Merghoub Taha
Published: October 2024

Supplementary Figure 3. MEK inhibition with CKI27 increases HLA and checkpoint ligand expression. (A-B) Human tumor cell lines were treated with DMSO or CKI27 for 72hr and either with or without IFNγ (10ng/mL) for the last 24hr; n=3. FACS analysis of (A) HLA-ABC and HLA-DR and (B) PD-L1, CD80 and CD86 surface expression. MFI values are shown as mean±SEM.
Figure S1 from Hypoxia-Induced Long Noncoding RNA HIF1A-AS2 Regulates Stability of MHC Class I Protein in Head and Neck Cancer
Authors: Liao Tsai-Tsen , Chen Yu-Hsien , Li Zih-Yu , Hsiao An-Ching , Huang Ya-Li , Hao Ruo-Xin , Tai Shyh-Kuan , Chu Pen-Yuan , Shih Jing-Wen , Kung Hsing-Jien , Yang Muh-Hwa
Published: October 2024

Purification and validation of the exosomes from hypoxic HNSCC
Figure 4 from Hypoxia-Induced Long Noncoding RNA HIF1A-AS2 Regulates Stability of MHC Class I Protein in Head and Neck Cancer
Authors: Liao Tsai-Tsen , Chen Yu-Hsien , Li Zih-Yu , Hsiao An-Ching , Huang Ya-Li , Hao Ruo-Xin , Tai Shyh-Kuan , Chu Pen-Yuan , Shih Jing-Wen , Kung Hsing-Jien , Yang Muh-Hwa
Published: October 2024

HIF1A-AS2 downregulates MHC-I through autophagic degradation. A, Western blots showing the expression of HLA-ABC, STAT1 in SAS cells overexpressing HIF1A-AS2 (SAS-HIF1A-AS2) versus SAS-control (SAS-Vec) treated with/without IFNγ. α-Tubulin was used as a loading control. B, A pulse-chase assay for showing the protein degradation of HLA-ABC, HLA-A, and HLA-C in SAS-HIF1A-AS2 versus SAS-Vec treated with cycloheximide to inhibit de novo protein synthesis at different time points. α-Tubulin was used as a loading control. The bottom panel is the quantification of HLA-ABC. C, Western of HLA-ABC, HLA-A, HLA-B, HLA-C, Snail, and LC3B in SAS-HIF1A-AS2 treated with the autophagic inhibitor bafilomycin A1 (Baf.), proteasome inhibitor MG132, and rapamycin (Rap.). Snail is a positive control of proteasome-degraded protein, and LC3B is the control of autophagy-degraded protein. α-Tubulin was used as a loading control. D, Western blot of HLA-ABC and LC3B in SAS-HIF1A-AS2 (left) and HSC3-HIF1A-AS2 (right) treated with/without bafilomycin A1(Baf.) for 12 hours. α-Tubulin was used as a loading control. E, Western blot of HLA-ABC, HLA-C, Snail, and LC3B in SAS overexpression HIF1A-AS2 (SAS-HIF1A-AS2; left) and HSC3 overexpression HIF1A-AS2 (HSC3-HIF1A-AS2; right) treated with/without MG132 for 12 hours. α-Tubulin was used as a loading control.
Supplemental Figure 2 from Augmenting CAR T-cell Functions with LIGHT
Authors: Cai Winson , Tanaka Kento , Mi Xiaoli , Rajasekhar Vinagolu K. , Khan Jonathan F. , Yoo Sarah , de Stanchina Elisa , Rahman Jahan , Mathew Serena , Abrahimi Parwiz , Souness Sydney , Purdon Terence J. , McDowell James R. , Meyerberg Jeremy , Fujino Takeshi , Healey John H. , Abdel-Wahab Omar , Scheinberg David A. , Brentjens Renier J. , Daniyan Anthony F.
Published: October 2024

(A) ELISA quantification of soluble LIGHT in cell culture media after 24 hours of incubation. (B) Supernatant from LIGHT-CAR T cells and second-generation CAR T cells were added to corresponding CAR T cells and in vitro cytolysis was assessed against AsPC1. Data is representative of 2 independent experiments from two different T cell donors. (C) Supernatant from LIGHT-CAR T cells and second-generation CAR T cells were added to corresponding CAR T cells and in vitro cytolysis was assessed against MIAPACA2. Data is representative of 2 independent experiments from two different T cell donors. (D) Cytotoxicity assay with various mesothelin-directed CAR constructs and the addition of recombinant LIGHT to MIAPACA2. Data is representative of 3 independent experiments from two different T cell donors. (E) Mesothelin-directed LIGHT-CAR T cells exhibited similar proliferation in a repetitive antigen stimulation assay with moderately high mesothelin expression PDAC cell line, AsPC1. CAR T cells were cocultured with tumor cells at a 4:1 effector: tumor ratio for 5 days, and then CAR T cells were taken out and put onto new tumor cells at the original E:T ratio. The total fold expansion was quantified from multiplying each round of fold expansion every 5 days. Data is representative of 3 independent experiments of 3 different human donors and data errors were analyzed with mean ± SEM.
Table S1 from MR1 Gene and Protein Expression Are Enhanced by Inhibition of the Extracellular Signal-Regulated Kinase ERK
Authors: Constantin Daniel , Nosi Vladimir , Kehrer Natalie , Vacchini Alessandro , Chancellor Andrew , Contassot Emmanuel , Beshirova Aisha , Prota Gennaro , Navarini Alexander , Mori Lucia , De Libero Gennaro
Published: October 2024

List of genes regulated by BRAF inhibition
Supplementary Figure S5 from The E3 Ubiquitin Ligase FBXO38 Maintains the Antitumor Function of Natural Killer Cells by Sustaining IL15R Signaling
Authors: Shi Yongjing , Zheng Xiaodong , Peng Hui , Xu Chenqi , Sun Rui , Tian Zhigang , Sun Haoyu , Wang Xianwei
Published: October 2024

Supplementary Figure S5. FBXO38 is positively correlated with IL2B and IL2G in human TINK cells
Supplementary Figure S1 from MR1 Gene and Protein Expression Are Enhanced by Inhibition of the Extracellular Signal-Regulated Kinase ERK
Authors: Constantin Daniel , Nosi Vladimir , Kehrer Natalie , Vacchini Alessandro , Chancellor Andrew , Contassot Emmanuel , Beshirova Aisha , Prota Gennaro , Navarini Alexander , Mori Lucia , De Libero Gennaro
Published: October 2024

Supplementary Figure S1
Supplementary Figure S1 from The E3 Ubiquitin Ligase FBXO38 Maintains the Antitumor Function of Natural Killer Cells by Sustaining IL15R Signaling
Authors: Shi Yongjing , Zheng Xiaodong , Peng Hui , Xu Chenqi , Sun Rui , Tian Zhigang , Sun Haoyu , Wang Xianwei
Published: October 2024

Supplementary Figure S1. Down regulation of FBXO38 in IT NK cells
Data from NK Receptor Signaling Lowers TCR Activation Threshold, Enhancing Selective Recognition of Cancer Cells by TAA-Specific CTLs
Authors: Dong Bowen , Obermajer Nataša , Tsuji Takemasa , Matsuzaki Junko , Bonura Cindy M. , Sander Cindy , Withers Henry , Long Mark D. , Chavel Colin , Olejniczak Scott H. , Minderman Hans , Kirkwood John M. , Edwards Robert P. , Storkus Walter J. , Romero Pedro , Kalinski Pawel
Published: October 2024

Abstract
Cytotoxic CD8+ T lymphocyte (CTL) recognition of non-mutated tumor-associated antigens (TAA), present on cancer cells and also in healthy tissues, is an important element of cancer immunity, but the mechanism of its selectivity for cancer cells and opportunities for its enhancement remain elusive. In this study, we found that CTL expression of the NK receptors (NKR) DNAM1 and NKG2D was associated with the effector status of CD8+ tumor-infiltrating lymphocytes and long-term survival of patients with melanoma. Using MART1 and NY-ESO-1 as model TAAs, we demonstrated that DNAM1 and NKG2D regulate T-cell receptor (TCR) functional avidity and set the threshold for TCR activation of human TAA-specific CTLs. Superior co-stimulatory effects of DNAM1 over CD28 involved enhanced TCR signaling, CTL killer function, and polyfunctionality. Double transduction of human CTLs with TAA-specific TCR and NKRs resulted in strongly enhanced antigen sensitivity, without a reduction in antigen specificity and selectivity of killer function. In addition, the elevation of NKR ligand expression on cancer cells due to chemotherapy also increased CTL recognition of cancer cells expressing low levels of TAAs. Our data help explain the ability of self-antigens to mediate tumor rejection in the absence of autoimmunity and support the development of dual-targeting adoptive T-cell therapies that use NKRs to enhance the potency and selectivity of recognition of TAA-expressing cancer cells.
Data from Hypoxia-Induced Long Noncoding RNA HIF1A-AS2 Regulates Stability of MHC Class I Protein in Head and Neck Cancer
Authors: Liao Tsai-Tsen , Chen Yu-Hsien , Li Zih-Yu , Hsiao An-Ching , Huang Ya-Li , Hao Ruo-Xin , Tai Shyh-Kuan , Chu Pen-Yuan , Shih Jing-Wen , Kung Hsing-Jien , Yang Muh-Hwa
Published: October 2024

Abstract
Intratumoral hypoxia not only promotes angiogenesis and invasiveness of cancer cells but also creates an immunosuppressive microenvironment that facilitates tumor progression. However, the mechanisms by which hypoxic tumor cells disseminate immunosuppressive signals remain unclear. In this study, we demonstrate that a hypoxia-induced long noncoding RNA HIF1A Antisense RNA 2 (HIF1A-AS2) is upregulated in hypoxic tumor cells and hypoxic tumor-derived exosomes in head and neck squamous cell carcinoma (HNSCC). Hypoxia-inducible factor 1 alpha (HIF1α) was found to directly bind to the regulatory region of HIF1A-AS2 to enhance its expression. HIF1A-AS2 reduced the protein stability of major histocompatibility complex class I (MHC-I) by promoting the interaction between the autophagy cargo receptor neighbor of BRCA1 gene 1 (NBR1) protein and MHC-I, thereby increasing the autophagic degradation of MHC-I. In HNSCC samples, the expression of HIF1A-AS2 was found to correlate with hypoxic signatures and advanced clinical stages. Patients with high HIF1α and low HLA-ABC expression showed reduced infiltration of CD8+ T cells. These findings define a mechanism of hypoxia-mediated immune evasion in HNSCC through downregulation of antigen-presenting machinery via intracellular or externalized hypoxia-induced long noncoding RNA.
Supplementary Figure S4 from Combined Oxygen-Enhanced MRI and Perfusion Imaging Detect Hypoxia Modification from Banoxantrone and Atovaquone and Track Their Differential Mechanisms of Action
Authors: O’Connor James P.B. , Tessyman Victoria , Little Ross A. , Babur Muhammad , Forster Duncan , Latif Ayşe , Cheung Susan , Lipowska-Bhalla Grazyna , Higgins Geoff S. , Asselin Marie-Claude , Parker Geoff J.M. , Williams Kaye J.
Published: October 2024

Supplementary Figure S4 confirms that there was no drug effect on cell number or viability.
Figure 2 from Combined Oxygen-Enhanced MRI and Perfusion Imaging Detect Hypoxia Modification from Banoxantrone and Atovaquone and Track Their Differential Mechanisms of Action
Authors: O’Connor James P.B. , Tessyman Victoria , Little Ross A. , Babur Muhammad , Forster Duncan , Latif Ayşe , Cheung Susan , Lipowska-Bhalla Grazyna , Higgins Geoff S. , Asselin Marie-Claude , Parker Geoff J.M. , Williams Kaye J.
Published: October 2024

Banoxantrone (BN) induces modification of tumor hypoxia in Calu6 xenografts. A, TMR of [18F] FAZA uptake is increased from baseline at day 1 and 3 in control tumors (Cn; white bars) but was reduced in drug-treated tumors. B, Example, [18F] FAZA PET images with greatest hypoxia represented by orange and red. C, Tumor MRI hypoxic fraction showed similar relative reduction at day 1 and 3, relative to control tumors. D, Example segmented MRI images showing hypoxic (blue), normoxic (yellow), and necrotic (gray) tumor. E, Lower percentage of pimonidazole staining was detected in drug-treated tumors at day 3, compared to controls. F, Example pimonidazole adduct formation images (×40 magnification).
A Patient with Acute Promyelocytic Leukemia Treated with Isotretinoin: A Case Report
Authors: Goldin Ilja , Medinger Michael , Passweg Jakob , Halbeisen Delia
Published: October 2024

Introduction: All-trans retinoic acid (ATRA) in combination with arsenic trioxide (ATO) is standard therapy for low-to-intermediate risk acute promyelocytic leukemia (APL). Isotretinoin, an agent used for acne vulgaris, is similar in its chemical structure and effects to ATRA, and single-case studies report a probable effectiveness in APL. Case Presentation: In this case, a patient with newly diagnosed APL was treated with isotretinoin/ATO instead of ATRA/ATO for nearly 4 weeks due to a prescription error and anyway reached a stable complete remission as if treated with ATRA/ATO. Conclusion: Treatment of APL with isotretinoin instead of ATRA could possibly be effective.
Does Mild and Moderate Hearing Loss Affect Verbal Working Memory and Language Skills in Children?
Authors: Demirtaş Yılmaz Beyza , Yıldırım Gökay Nuriye , Orhan Emre , Özbal Batuk Merve , Çınar Betül Çiçek , Sennaroğlu Gonca
Published: October 2024

Introduction: For a comprehensive approach in children with hearing loss (HL), some cognitive and language skills should also be considered, along with auditory skills. The main aim of this study was to evaluate the working memory and language skills in children with mild to moderate HL. Methods: Forty children with mild to moderate HL between the ages of 4 and 9 years were included in this study. The children with mild and moderate HL were evaluated in two groups. The Meaningless Word Repetition test, Test of Language Development-Primary test, and Meaningful Auditory Integration Scale were administered to assess working memory, language skills, and auditory perception, respectively. Also, the relationship between language and memory skills was evaluated. Results: The study found statistically significant correlations between language skills and working memory test scores. Additionally, statistically significant differences were found between children with mild and moderate HL in terms of language and memory skills (p < 0.001). Conclusion: The children with moderate HL demonstrated poorer performance compared to those with mild HL. Even if it is mild, the degree of HL affects children’s language and memory skills. It is emphasized that the relationship between language and working memory should be taken into consideration in auditory rehabilitation programs for these children.