bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from A Phase II Placebo-Controlled Study of the Effect and Safety of Nanvuranlat in Patients with Advanced Biliary Tract Cancers Previously Treated by Systemic Chemotherapy
Authors: Furuse Junji , Ikeda Masafumi , Ueno Makoto , Furukawa Masayuki , Morizane Chigusa , Takehara Tetsuo , Nishina Tomohiro , Todaka Akiko , Okano Naohiro , Hara Kazuo , Nakai Yousuke , Ohkawa Kazuyoshi , Sasaki Takashi , Sugimori Kazuya , Yokoyama Naoyuki , Yamamoto Kouji
Published: September 2024

AbstractPurpose:
To evaluate the efficacy and safety of nanvuranlat [an L-type amino acid transporter 1 inhibitor] monotherapy as a later-line treatment in advanced, metastatic, and refractory biliary tract cancers.
Patients and Methods:
A multicenter, randomized, double-blind, placebo-controlled phase II study was conducted across fourteen leading Japanese cancer centers and hospitals. Nanvuranlat 25 mg/m2/day or placebo was given intravenously in cycles of 5 consecutive days, followed by 9 days off. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival and disease control rate. Subgroup analysis was performed in patients with high L-type amino acid transporter 1 expression and biliary tract cancer subtypes.
Results:
A total of 211 patients were screened, of which 105 eligible patients were randomized. Among these, 70 received nanvuranlat and 35 received placebo. Nanvuranlat demonstrated an improvement in PFS when compared with placebo (HR, 0.56; 95% confidence interval, 0.34–0.90; P = 0.02). Grade 3 or higher adverse events were reported in 30.0% and 22.9% of those in the nanvuranlat and placebo groups, respectively. The overall survival was not statistically different between nanvuranlat- and placebo-treated patients. An exploratory analysis indicated that nanvuranlat is warranted to evaluate its long-term clinical benefit in patients with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
Conclusions:
Compared with placebo, nanvuranlat improved PFS in patients with advanced and refractory biliary tract cancer with an acceptable safety profile. Further studies of this promising compound are warranted in the population of patients who are exhausted from treatment options.
Data from Spatial Heterogeneity of Immune Regulators Drives Dynamic Changes in Local Immune Responses, Affecting Disease Outcomes in Pancreatic Cancer
Authors: Karamitopoulou Eva , Wenning Anna S. , Acharjee Animesh , Aeschbacher Pauline , Marinoni Ilaria , Zlobec Inti , Gloor Beat , Perren Aurel
Published: September 2024

AbstractPurpose:
Pancreatic ductal adenocarcinoma (PDAC) is considered a low-immunogenic (LI) tumor with a “cold” tumor microenvironment and is mostly unresponsive to immune checkpoint blockade therapies. In this study, we decipher the impact of intratumoral heterogeneity of immune determinants on antitumor responses.
Experimental Design:
We performed spatial proteomic and transcriptomic analyses and multiplex immunofluorescence on multiple tumor regions, including tumor center (TC) and invasive front (IF), from 220 patients with PDAC, classified according to their transcriptomic immune signaling into high-immunogenic PDAC (HI-PDAC, n = 54) and LI PDAC (LI-PDAC, n = 166). Spatial compartments (tumor: pancytokeratin+/CD45− and leukocytes: pancytokeratin−/CD45+) were defined by fluorescence imaging.
Results:
HI-PDAC exhibited higher densities of cytotoxic T lymphocytes with upregulation of T-cell priming–associated immune determinants, including CD40, ITGAM, glucocorticoid-induced TNF–related receptor, CXCL10, granzyme B, IFNG, and HLA-DR, which were significantly more prominent at the IF than at the TC. In contrast, LI-PDAC exhibited immune-evasive tumor microenvironments with downregulation of immune determinants and a negative gradient from TC to IF. Patients with HI-PDAC had significantly better outcomes but showed more frequently exhausted immune phenotypes.
Conclusions:
Our results indicate strategic differences in the regulation of immune determinants, leading to different levels of effectiveness of antitumor responses between HI and LI tumors and dynamic spatial changes, which affect the evolution of immune evasion and patient outcomes. This finding supports the coevolution of tumor and immune cells and may help define therapeutic vulnerabilities to improve antitumor immunity and harness the responsiveness to immune checkpoint inhibitors in patients with PDAC.
Data from Novel ERBB2 Variant Potentially Associated with Resistance against Anti-HER2 Monoclonal Antibody–Based Therapy in ERBB2-Amplified Metastatic Colorectal Cancer
Authors: Iida Naoko , Imai Mitsuho , Okamoto Wataru , Kato Takeshi , Esaki Taito , Kato Ken , Komatsu Yoshito , Yuki Satoshi , Masuishi Toshiki , Nishina Tomohiro , Ebi Hiromichi , Taniguchi Hiroya , Nonomura Norio , Sunakawa Yu , Shiozawa Manabu , Yamazaki Kentaro , Boku Shogen , Bando Hideaki , Shiraishi Yuichi , Kobayashi Maki , Goto Hiroki , Sato Akihiro , Fujii Satoshi , Yoshino Takayuki , Nakamura Yoshiaki
Published: September 2024

AbstractPurpose:
HER2-targeted therapies in ERBB2-amplified metastatic colorectal cancer (mCRC) are effective; however, a notable portion of patients do not respond to treatment, and secondary resistance occurs in most patients receiving these treatments. The purpose of this study was to investigate determinants of treatment efficacy and resistance in patients with ERBB2-amplified mCRC who received HER2-targeted therapy by analyzing multiomics data.
Experimental Design:
We investigated genomic data from a nationwide large cancer genomic screening project, the SCRUM-Japan project. We analyzed paired genome and transcriptome data of tissue and genomic data of ctDNA collected pre- and postprogression in patients enrolled in the related trial, TRIUMPH, in ERBB2-amplified mCRC.
Results:
In 155 patients with ERBB2-amplified solid tumors who received HER2-targeted therapy based on the SCRUM-Japan project, the objective response rate was 50%, 51%, and 35% in ERBB2 wild-type, variant of unknown significance, and pathogenic variant groups, respectively. In the paired genome and transcriptome data analyses in TRIUMPH, we identified the novel splicing-associated variant c.644-66_-2del in one of the 11 patients with paired whole-exome sequencing and whole-transcriptome sequencing data sets, which lacks the binding domain of pertuzumab, in progressed metastatic tumor as a variant with potential pathogenicity. The time-course ctDNA analysis detected c.644-66_-2del as an acquired variant.
Conclusions:
This study highlighted the importance of ERBB2 genomic status when evaluating the efficacy of HER2-targeted therapies in ERBB2-amplified mCRC. The identification of a novel splicing-associated variant may provide insights into potential mechanisms of treatment resistance. Furthermore, we demonstrated the utility of ctDNA to follow the acquired genomic status of mCRC tumors.
Data from Circulating Tumor DNA Assessment for Treatment Monitoring Adds Value to PSA in Metastatic Castration-Resistant Prostate Cancer
Authors: Sweeney Christopher J. , Petry Russell , Xu Chang , Childress Merrida , He Jie , Fabrizio David , Gjoerup Ole , Morley Samantha , Catlett Timothy , Assaf Zoe J. , Yuen Kobe , Wongchenko Matthew , Shah Kalpit , Gupta Pratyush , Hegde Priti , Pasquina Lincoln W. , Mariathasan Sanjeev , Graf Ryon P. , Powles Thomas
Published: September 2024

AbstractPurpose:
Enzalutamide after abiraterone progression is commonly used in metastatic castration-resistant prostate cancer despite a low rate of clinical benefit. Analyzing IMbassador250, a phase III trial assessing enzalutamide with or without atezolizumab after abiraterone, we hypothesized that baseline and early changes in circulating tumor DNA (ctDNA) tumor fraction (TF) may identify patients more likely to exhibit survival benefit from enzalutamide.
Experimental Design:
ctDNA was quantified from plasma samples using a tissue-agnostic assay without buffy coat sequencing. Baseline ctDNA TF, changes in ctDNA TF from baseline to cycle 3 day 1 (C3D1), and detection at C3D1 alone were compared with overall response rate, radiographic progression-free survival (rPFS), median OS (mOS), and 50% reduction in PSA.
Results:
ctDNA TF detection at baseline and/or C3D1 was associated with shorter rPFS and OS in 494 evaluable patients. Detection of ctDNA TF at C3D1, with or without detection at cycle 1 day 1, was associated with worse rPFS and mOS than lack of detection. When ctDNA TF and PSA response at C3D1 were discordant, patients with (ctDNA TF undetected/PSA not reduced) had more favorable outcomes than (ctDNA TF detected/PSA reduced; mOS 22.1 vs. 16 months; P < 0.001).
Conclusions:
In a large cohort of patients with metastatic castration-resistant prostate cancer receiving enzalutamide after abiraterone, we demonstrate the utility of a new tissue-agnostic assay for monitoring molecular response based on ctDNA TF detection and dynamics. ctDNA TF provides a minimally invasive, complementary biomarker to PSA testing and may refine personalized treatment approaches.
Data from Oral and Gut Microbiome Alterations in Oral Chronic GVHD Disease: Results from Close Assessment and Testing for Chronic GVHD (CATCH Study)
Authors: Rashidi Armin , Pidala Joseph , Hamilton Betty K. , Pavletic Steven Z. , Kim Katie , Zevin Alex , Mays Jacqueline W. , Lee Stephanie J.
Published: September 2024

AbstractPurpose:
Whether and how the oral microbiome and its changes in allogeneic hematopoietic cell transplantation (alloHCT) recipients may contribute to oral chronic GVHD (cGVHD) pathogenesis is unknown. In addition, although the oral and colonic microbiota are distinct in healthy adults, whether oral microbes may ectopically colonize the gut in alloHCT patients is unknown.
Experimental Design:
To address these knowledge gaps, longitudinal oral and fecal samples were collected prospectively in the multicenter Close Assessment and Testing for Chronic GVHD study (NCT04188912). Through shotgun metagenomic sequencing of the samples collected at baseline, oral cGVHD onset, first post-cGVHD onset visit, and 1-year post-HCT time points in patients with oral cGVHD (cases; N = 29) or without any cGVHD (controls; N = 51), we examined whether (i) oral and/or gut microbiomes and their longitudinal trajectories differ between cases and controls and (ii) oral and gut microbiomes overlap in alloHCT recipients, especially those developing cGVHD.
Results:
A total of 195 samples were analyzed. The onset of oral cGVHD was characterized by an expansion of Streptococcus salivarius and Veillonella parvula in the oral microbiome. High levels of oral/gut microbiota overlap were observed, particularly in patients with oral cGVHD, suggesting ectopic colonization of the gut by oral bacteria.
Conclusions:
The unusual coalescence of two distant niches in these patients may result in short- or long-term consequences for the host, a novel avenue for future research. In addition, this study suggests a contribution of the oral microbiome to oral cGVHD pathogenesis.
Data from Novel Combinations of Immunotherapies or DNA Damage Repair Inhibitors in Platinum-Refractory Extensive-Stage Small Cell Lung Cancer: The Phase II BALTIC Study
Authors: Reinmuth Niels , Juan-Vidal Oscar , Kowalski Dariusz , Bryl Maciej , Kryzhanivska Anna , Vicente David , Horváth Zsolt , Gálffy Gabriella , Csánky Eszter , Pápai Székely Zsolt , Vynnychenko Ihor , Armstrong Jon , Dalvi Tapashi , Xie Mingchao , Iyer Sonia , Shrestha Yashaswi , Jiang Haiyi , Bondarenko Igor
Published: September 2024

AbstractPurpose:
The phase II, multiarm, signal-searching BALTIC study (NCT02937818) assessed novel treatment combinations for platinum-refractory/resistant extensive-stage small cell lung cancer (ES-SCLC).
Patients and Methods:
Patients with ES-SCLC with progressive disease during or within 90 days of completing first-line platinum-based chemotherapy received one of three regimens: durvalumab plus tremelimumab followed by durvalumab monotherapy (arm A), adavosertib plus carboplatin (arm B), or ceralasertib plus olaparib (arm C). The primary endpoint was the objective response rate. Prespecified exploratory biomarker analyses were conducted in arms A and C.
Results:
In arm A (n = 41), arm B (n = 10), and arm C (n = 21), the confirmed objective response rates were 7.3%, 0%, and 4.8%, respectively. Safety profiles in all arms were consistent with those of the individual drugs. In arm A, patients with PD-L1 expression (tumor cells or immune cells) ≥1% seemed to have a greater likelihood of achieving disease control with durvalumab plus tremelimumab than those with PD-L1 (tumor cells and immune cells) <1%, and lower baseline ctDNA and reduction in the on-treatment ctDNA level were both associated with longer overall survival. Among patients treated with ceralasertib plus olaparib in arm C, specific immune response-relevant circulating chemokines and cytokines were identified as early biomarkers of survival and pharmacodynamic biomarkers.
Conclusions:
In BALTIC, all combination regimens demonstrated tolerable safety profiles, but antitumor activity was limited in refractory/resistant ES-SCLC. Among patients treated with durvalumab plus tremelimumab, an association of on-treatment reduction in ctDNA with longer overall survival suggests the potential use of ctDNA as a surrogate of treatment response, warranting further investigation.
Data from Phase II Trial of HER-Vaxx, a B-cell Peptide-Based Vaccine, in HER2-Overexpressing Advanced Gastric Cancer Patients Under Platinum-Based Chemotherapy (HERIZON)
Authors: Tobias Joshua , Maglakelidze Marina , Andrić Zoran , Ryspayeva Dinara , Bulat Iurie , Nikolić Ivan , Petrović Zoran , Chawla Tanuj , Nagarkar Rajnish , Garner-Spitzer Erika , Zielinski Christoph C. , Chong Leslie Mi Ok , Nixon Bonnie , Ede Nicholas J. , Yavrom Sharon , Kundi Michael , Wiedermann Ursula
Published: September 2024

AbstractPurpose:
A multicenter, randomized, open-label, phase II study (HERIZON; NCT02795988) was conducted to evaluate the clinical and immunologic efficacy of HER-Vaxx (IMU-131), a B-cell, peptide-based vaccine targeting HER2 overexpressed in 6% to 30% of gastroesophageal adenocarcinomas (GEA).
Patients and Methods:
Patients (n = 36) with GEA were treated with standard-of-care chemotherapy (n = 17) or HER-Vaxx plus chemotherapy (n = 19), using the recommended phase 2 dose for the vaccine. Overall survival (OS; primary endpoint), safety, progression-free survival (PFS), clinical response (secondary endpoints), and vaccine-induced HER2-specific antibody levels in serum and correlation with tumor response rates (exploratory endpoints) were investigated.
Results:
A 40% OS benefit [HR, 0.60; median OS, 13.9 months; 80% confidence interval (CI), 7.52–14.32] for patients treated with HER-Vaxx plus chemotherapy compared with OS of 8.31 months (80% CI, 6.01–9.59) in patients that received chemotherapy alone. A 20% PFS difference was obtained for the vaccination arm (HR, 0.80; 80% CI, 0.47, 1.38). No additional toxicity due to HER-Vaxx was observed. The vaccine-induced high levels of HER2-specific total IgG and IgG1 antibodies (P < 0.001 vs. controls) that significantly correlated with tumor reduction (IgG, P = 0.001; IgG1, P = 0.016), had a significant capacity in inhibiting phosphorylation of the intracellular HER2-signaling pathways, mediated antibody-dependent cellular cytotoxicity, and decreased immunosuppressive FOXP3+ regulatory T cells.
Conclusions:
HER-Vaxx plus standard chemotherapy exhibits an excellent safety profile and improves OS. Furthermore, vaccine-induced immune response was significantly associated with reduced tumor size compared with standard-of-care chemotherapy. The presented vaccination approach may substitute for treatment with trastuzumab, upon unavailability or toxicity, based on further evidence of equivalent treatment efficacy.
TREM2-Expressing Multinucleated Giant Macrophages Are a Biomarker of Good Prognosis in Head and Neck Squamous Cell Carcinoma
Authors: Gessain Grégoire , Anzali Ahmed-Amine , Lerousseau Marvin , Mulder Kevin , Bied Mathilde , Auperin Anne , Stockholm Daniel , Signolle Nicolas , Sassi Farah , Marques Da Costa Maria Eugenia , Marchais Antonin , Sayadi Alexandre , Weidner Daniela , Uderhardt Stefan , Blampey Quentin , Nakkireddy Sumanth Reddy , Broutin Sophie , Dutertre Charles-Antoine , Busson Pierre , Walter Thomas , Marhic Alix , Moya-Plana Antoine , Guerlain Johanne , Breuskin Ingrid , Casiraghi Odile , Gorphe Philippe , Classe Marion , Scoazec Jean-Yves , Blériot Camille , Ginhoux Florent
Published: September 2024

Patients with head and neck squamous cell carcinomas (HNSCC) often have poor outcomes due to suboptimal risk management and treatment strategies; yet integrating novel prognostic biomarkers into clinical practice is challenging. Here, we report the presence of multinucleated giant cells (MGC)—a type of macrophages—in tumors from patients with HNSCC, which are associated with a favorable prognosis in treatment-naive and preoperative chemotherapy–treated patients. Importantly, MGC density increased in tumors following preoperative therapy, suggesting a role of these cells in the antitumoral response. To enable clinical translation of MGC density as a prognostic marker, we developed a deep-learning model to automate its quantification on routinely stained pathological whole slide images. Finally, we used spatial transcriptomic and proteomic approaches to describe the MGC-related tumor microenvironment and observed an increase in central memory CD4 T cells. We defined an MGC-specific signature resembling to TREM2-expressing mononuclear tumor-associated macrophages, which colocalized in keratin tumor niches.

Significance:

Novel individual biomarkers are needed to guide therapeutic decisions for patients with head and neck cancer. We report for the first time, granulomas of TREM2-expressing multinucleated giant macrophages in keratin-rich tumor niches, as a biomarker of favorable prognosis and developed a deep-learning model to automate its quantification on routinely stained pathological slides.
CD91 and Its Ligand gp96 Confer Cross-Priming Capabilities to Multiple APCs during Immune Responses to Nascent, Emerging Tumors
Authors: Nayak Devanshi A. , Sedlacek Abigail L. , Cillo Anthony R. , Watkins Simon C. , Binder Robert J.
Published: September 2024

During cancer immunosurveillance, dendritic cells (DC) play a central role in orchestrating T-cell responses against emerging tumors. Capture of miniscule amounts of antigen along with tumor-initiated costimulatory signals can drive maturation of DCs. Expression of CD91 on DCs is essential in cross-priming of T-cell responses in the context of nascent tumors. Multiple DC and macrophage subsets express CD91 and engage tumor-derived gp96 to initiate antitumor immune responses, yet the specific CD91+ antigen-presenting cells (APC) that are required for T-cell cross-priming during cancer immunosurveillance are unknown. In this study, we determined that CD91 expression on type 1 conventional DCs (cDC1) is necessary for cancer immunosurveillance. Specifically, CD91-expressing cDC1 were found to capture the CD91 ligand gp96 from tumors and, upon migration to the lymph nodes, distribute gp96 among lymph node–resident APCs. However, cDC1 that captured tumor-derived gp96 only provided early tumor control, whereas sustained and long-term tumor rejection was bestowed to the host by other gp96+ cross-priming DCs. We further found that the CD91-induced transcriptome in APCs promoted cross-priming of T-cell responses while downregulating immune regulatory pathways. Our results show an elaborate and synchronized division of labor of APCs in the successful elimination of cancer cells via CD91. We predict that the specialized functions of APC subsets can be harnessed for immunotherapy of disease.
Table 3 from ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors
Authors: Chen Christopher T. , Khanna Vishesh , Kummar Shivaani , Abdul-Karim Raghad M. , Sommerhalder David , Tolcher Anthony W. , Ueno Naoto T. , Davis Sarah Lindsey , Orr Douglas W. , Hamilton Erika , Patel Manish R. , Spira Alexander I. , Jauhari Shekeab , Florou Vaia , Duff Maureen , Xu Rongda , Wang Jian , Barkund Shravani R. , Zhou Haiying , Pankov Aleksandr , Kong Wayne , Jahchan Nadine S. , Jackson Erica L. , Sun Jessica D. , Junttila Melissa R. , Multani Pratik S. , Daemen Anneleen , Chow Maneval Edna , Munster Pamela N.
Published: September 2024

Antitumor activity at the RP2D
Supplementary Table 1 from ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors
Authors: Chen Christopher T. , Khanna Vishesh , Kummar Shivaani , Abdul-Karim Raghad M. , Sommerhalder David , Tolcher Anthony W. , Ueno Naoto T. , Davis Sarah Lindsey , Orr Douglas W. , Hamilton Erika , Patel Manish R. , Spira Alexander I. , Jauhari Shekeab , Florou Vaia , Duff Maureen , Xu Rongda , Wang Jian , Barkund Shravani R. , Zhou Haiying , Pankov Aleksandr , Kong Wayne , Jahchan Nadine S. , Jackson Erica L. , Sun Jessica D. , Junttila Melissa R. , Multani Pratik S. , Daemen Anneleen , Chow Maneval Edna , Munster Pamela N.
Published: September 2024

Supplementary Table 1. Statistical Assumption and Sample Size Estimates for MUCE Design
Figure 2 from ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors
Authors: Chen Christopher T. , Khanna Vishesh , Kummar Shivaani , Abdul-Karim Raghad M. , Sommerhalder David , Tolcher Anthony W. , Ueno Naoto T. , Davis Sarah Lindsey , Orr Douglas W. , Hamilton Erika , Patel Manish R. , Spira Alexander I. , Jauhari Shekeab , Florou Vaia , Duff Maureen , Xu Rongda , Wang Jian , Barkund Shravani R. , Zhou Haiying , Pankov Aleksandr , Kong Wayne , Jahchan Nadine S. , Jackson Erica L. , Sun Jessica D. , Junttila Melissa R. , Multani Pratik S. , Daemen Anneleen , Chow Maneval Edna , Munster Pamela N.
Published: September 2024

Study disposition flow diagram of patient disposition. Note: int, intermittent regimen of ORIC-101 administered 5 days on, 2 days off for 21 days out of 28-day cycles; cont, continuous regimen of ORIC-101 administered for 21 days out of 28-day cycles; AE, adverse event; clin, clinical; OST, other solid tumors; PD, progressive disease; radiog, radiographic.
Table S2 from Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon
Authors: Oliero Manon , Cuisiniere Thibault , Ajayi Ayodeji S. , Gerkins Claire , Hajjar Roy , Fragoso Gabriela , Calvé Annie , Vennin Rendos Hervé , Mathieu-Denoncourt Annabelle , Dagbert François , De Broux Éric , Loungnarath Rasmy , Schwenter Frank , Sebajang Herawaty , Ratelle Richard , Wassef Ramses , Richard Carole , Duperthuy Marylise , Gravel Andrée E. , Vincent Antony T. , Santos Manuela M.
Published: September 2024

Table S2 shows primers used
Table S1 from Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon
Authors: Oliero Manon , Cuisiniere Thibault , Ajayi Ayodeji S. , Gerkins Claire , Hajjar Roy , Fragoso Gabriela , Calvé Annie , Vennin Rendos Hervé , Mathieu-Denoncourt Annabelle , Dagbert François , De Broux Éric , Loungnarath Rasmy , Schwenter Frank , Sebajang Herawaty , Ratelle Richard , Wassef Ramses , Richard Carole , Duperthuy Marylise , Gravel Andrée E. , Vincent Antony T. , Santos Manuela M.
Published: September 2024

Table S1 shows cohort characteristics
Supplementary Table 1 from Exploration of Immune-Modulatory Effects of Amivantamab in Combination with Pembrolizumab in Lung and Head and Neck Squamous Cell Carcinoma
Authors: Lim Sun M. , Kang Seong-san , Kim Dong K. , Lee Soo-Hwan , Synn Chun-Bong , Baek Sujeong , Yang Seung M. , Han Yu J. , Kim Mi H. , Han Heekyung , Na Kwangmin , Kim Young T. , Yun Mi R. , Kim Jae H. , Byeon Youngseon , Kim Young S. , Lee Jii B. , Hong Min H. , Curtin Joshua C. , Patel Bharvin , Bergiers Isabelle , Pyo Kyoung-Ho , Cho Byoung C.
Published: September 2024

This table entails staining panels of antibodies used for flow cytometry analysis of PDX tumor samples.
Figure S6 from Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon
Authors: Oliero Manon , Cuisiniere Thibault , Ajayi Ayodeji S. , Gerkins Claire , Hajjar Roy , Fragoso Gabriela , Calvé Annie , Vennin Rendos Hervé , Mathieu-Denoncourt Annabelle , Dagbert François , De Broux Éric , Loungnarath Rasmy , Schwenter Frank , Sebajang Herawaty , Ratelle Richard , Wassef Ramses , Richard Carole , Duperthuy Marylise , Gravel Andrée E. , Vincent Antony T. , Santos Manuela M.
Published: September 2024

Figure S6 shows growth of pks+ E. coli strains isolated from human samples
Supplementary Figure 5 from Exploration of Immune-Modulatory Effects of Amivantamab in Combination with Pembrolizumab in Lung and Head and Neck Squamous Cell Carcinoma
Authors: Lim Sun M. , Kang Seong-san , Kim Dong K. , Lee Soo-Hwan , Synn Chun-Bong , Baek Sujeong , Yang Seung M. , Han Yu J. , Kim Mi H. , Han Heekyung , Na Kwangmin , Kim Young T. , Yun Mi R. , Kim Jae H. , Byeon Youngseon , Kim Young S. , Lee Jii B. , Hong Min H. , Curtin Joshua C. , Patel Bharvin , Bergiers Isabelle , Pyo Kyoung-Ho , Cho Byoung C.
Published: September 2024

This figure shows the selection of cell lines used for in vitro evaluation of the effects of amivantamab on the protein and surface levels EGFR, MET, LDHA and SLC16A3.
Figure S5 from Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon
Authors: Oliero Manon , Cuisiniere Thibault , Ajayi Ayodeji S. , Gerkins Claire , Hajjar Roy , Fragoso Gabriela , Calvé Annie , Vennin Rendos Hervé , Mathieu-Denoncourt Annabelle , Dagbert François , De Broux Éric , Loungnarath Rasmy , Schwenter Frank , Sebajang Herawaty , Ratelle Richard , Wassef Ramses , Richard Carole , Duperthuy Marylise , Gravel Andrée E. , Vincent Antony T. , Santos Manuela M.
Published: September 2024

Figure S5 shows the effect of putrescine on gut microbiota functions
Supplementary Figure 3 from Exploration of Immune-Modulatory Effects of Amivantamab in Combination with Pembrolizumab in Lung and Head and Neck Squamous Cell Carcinoma
Authors: Lim Sun M. , Kang Seong-san , Kim Dong K. , Lee Soo-Hwan , Synn Chun-Bong , Baek Sujeong , Yang Seung M. , Han Yu J. , Kim Mi H. , Han Heekyung , Na Kwangmin , Kim Young T. , Yun Mi R. , Kim Jae H. , Byeon Youngseon , Kim Young S. , Lee Jii B. , Hong Min H. , Curtin Joshua C. , Patel Bharvin , Bergiers Isabelle , Pyo Kyoung-Ho , Cho Byoung C.
Published: September 2024

Figure S3 shows the gating strategy for M panel in immune profiling analysis.
Figure S3 from Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon
Authors: Oliero Manon , Cuisiniere Thibault , Ajayi Ayodeji S. , Gerkins Claire , Hajjar Roy , Fragoso Gabriela , Calvé Annie , Vennin Rendos Hervé , Mathieu-Denoncourt Annabelle , Dagbert François , De Broux Éric , Loungnarath Rasmy , Schwenter Frank , Sebajang Herawaty , Ratelle Richard , Wassef Ramses , Richard Carole , Duperthuy Marylise , Gravel Andrée E. , Vincent Antony T. , Santos Manuela M.
Published: September 2024

Figure S3 shows the effect of putrescine on gut microbiota
Supplementary Figure 2 from Exploration of Immune-Modulatory Effects of Amivantamab in Combination with Pembrolizumab in Lung and Head and Neck Squamous Cell Carcinoma
Authors: Lim Sun M. , Kang Seong-san , Kim Dong K. , Lee Soo-Hwan , Synn Chun-Bong , Baek Sujeong , Yang Seung M. , Han Yu J. , Kim Mi H. , Han Heekyung , Na Kwangmin , Kim Young T. , Yun Mi R. , Kim Jae H. , Byeon Youngseon , Kim Young S. , Lee Jii B. , Hong Min H. , Curtin Joshua C. , Patel Bharvin , Bergiers Isabelle , Pyo Kyoung-Ho , Cho Byoung C.
Published: September 2024

Figure S2 shows the gating strategy for T panel in immune profiling analysis.
Supplementary Figure 1 from Exploration of Immune-Modulatory Effects of Amivantamab in Combination with Pembrolizumab in Lung and Head and Neck Squamous Cell Carcinoma
Authors: Lim Sun M. , Kang Seong-san , Kim Dong K. , Lee Soo-Hwan , Synn Chun-Bong , Baek Sujeong , Yang Seung M. , Han Yu J. , Kim Mi H. , Han Heekyung , Na Kwangmin , Kim Young T. , Yun Mi R. , Kim Jae H. , Byeon Youngseon , Kim Young S. , Lee Jii B. , Hong Min H. , Curtin Joshua C. , Patel Bharvin , Bergiers Isabelle , Pyo Kyoung-Ho , Cho Byoung C.
Published: September 2024

This figure entails the selection of HNSCC and LUSC PDX model based on the H-score of EGFR and MET.
Supplementary Data 1 from Exploration of Immune-Modulatory Effects of Amivantamab in Combination with Pembrolizumab in Lung and Head and Neck Squamous Cell Carcinoma
Authors: Lim Sun M. , Kang Seong-san , Kim Dong K. , Lee Soo-Hwan , Synn Chun-Bong , Baek Sujeong , Yang Seung M. , Han Yu J. , Kim Mi H. , Han Heekyung , Na Kwangmin , Kim Young T. , Yun Mi R. , Kim Jae H. , Byeon Youngseon , Kim Young S. , Lee Jii B. , Hong Min H. , Curtin Joshua C. , Patel Bharvin , Bergiers Isabelle , Pyo Kyoung-Ho , Cho Byoung C.
Published: September 2024

Individual whole slide images of HNSCC PDX tumor used for TME analysis.
Supplementary Table 2 from Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma
Authors: Gonzalez-Kozlova Edgar , Huang Hsin-Hui , Jagede Opeyemi A. , Tuballes Kevin , Del Valle Diane M. , Kelly Geoffrey , Patel Manishkumar , Xie Hui , Harris Jocelyn , Argueta Kimberly , Nie Kai , Barcessat Vanessa , Moravec Radim , Altreuter Jennifer , Duose Dzifa Y. , Kahl Brad S. , Ansell Stephen M. , Yu Joyce , Cerami Ethan , Lindsay James R. , Wistuba Ignacio I. , Kim-Schulze Seunghee , Diefenbach Catherine S. , Gnjatic Sacha
Published: September 2024

Experimental data userd in the article including Olink, CyTOF populational frequencies, Serology and TCRseq beta chain.
Supplementary Table 1 from Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma
Authors: Gonzalez-Kozlova Edgar , Huang Hsin-Hui , Jagede Opeyemi A. , Tuballes Kevin , Del Valle Diane M. , Kelly Geoffrey , Patel Manishkumar , Xie Hui , Harris Jocelyn , Argueta Kimberly , Nie Kai , Barcessat Vanessa , Moravec Radim , Altreuter Jennifer , Duose Dzifa Y. , Kahl Brad S. , Ansell Stephen M. , Yu Joyce , Cerami Ethan , Lindsay James R. , Wistuba Ignacio I. , Kim-Schulze Seunghee , Diefenbach Catherine S. , Gnjatic Sacha
Published: September 2024

CyTOF antibody panel details.
Figure S2 from Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma
Authors: Gonzalez-Kozlova Edgar , Huang Hsin-Hui , Jagede Opeyemi A. , Tuballes Kevin , Del Valle Diane M. , Kelly Geoffrey , Patel Manishkumar , Xie Hui , Harris Jocelyn , Argueta Kimberly , Nie Kai , Barcessat Vanessa , Moravec Radim , Altreuter Jennifer , Duose Dzifa Y. , Kahl Brad S. , Ansell Stephen M. , Yu Joyce , Cerami Ethan , Lindsay James R. , Wistuba Ignacio I. , Kim-Schulze Seunghee , Diefenbach Catherine S. , Gnjatic Sacha
Published: September 2024

Supplemental Figure 2. Cellular marker dynamics in Hodgkin lymphoma during checkpoint blockade treatment. A. Heatmap showing markers and cell types identified through CyTOF (cytometry using time of flight) that significantly change over time. The color indicates the standardized Log2FC in protein expression (Z-Score), and the size of the circles indicate the percent of cells expressing the marker. A dendrogram of the markers sorted hierarchically is shown on the right side. B. Line plots highlight the temporal changes for each of the markers shown in A. The color separates the values per treatment. C. Heatmap showing markers and cell types significantly associated with R (Responder) and NR (Not responder). D. Regression lines for examples of markers and cell types shown in C, separating response (R) and non-response (NR).
Supplementary Table 3 from Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures
Authors: Mahmood Umair , Blake Andrew , Rathee Sanjay , Samuel Leslie , Murray Graeme , Sebag-Montefiore David , Gollins Simon , West Nicholas P. , Begum Rubina , Bach Simon P. , Richman Susan D. , Quirke Phil , Redmond Keara L. , Salto-Tellez Manuel , Koelzer Viktor H. , Leedham Simon J. , Tomlinson Ian , Dunne Philip D. , Buffa Francesca M. , Maughan Tim S. , Domingo Enric
Published: September 2024

Supplementary Table 3
Supplementary Table 2 from Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures
Authors: Mahmood Umair , Blake Andrew , Rathee Sanjay , Samuel Leslie , Murray Graeme , Sebag-Montefiore David , Gollins Simon , West Nicholas P. , Begum Rubina , Bach Simon P. , Richman Susan D. , Quirke Phil , Redmond Keara L. , Salto-Tellez Manuel , Koelzer Viktor H. , Leedham Simon J. , Tomlinson Ian , Dunne Philip D. , Buffa Francesca M. , Maughan Tim S. , Domingo Enric
Published: September 2024

Supplementary Table 2
Supplementary Figure 3 from Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures
Authors: Mahmood Umair , Blake Andrew , Rathee Sanjay , Samuel Leslie , Murray Graeme , Sebag-Montefiore David , Gollins Simon , West Nicholas P. , Begum Rubina , Bach Simon P. , Richman Susan D. , Quirke Phil , Redmond Keara L. , Salto-Tellez Manuel , Koelzer Viktor H. , Leedham Simon J. , Tomlinson Ian , Dunne Philip D. , Buffa Francesca M. , Maughan Tim S. , Domingo Enric
Published: September 2024

Supplementary Figure 3
Supplementary Figure 1 from Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures
Authors: Mahmood Umair , Blake Andrew , Rathee Sanjay , Samuel Leslie , Murray Graeme , Sebag-Montefiore David , Gollins Simon , West Nicholas P. , Begum Rubina , Bach Simon P. , Richman Susan D. , Quirke Phil , Redmond Keara L. , Salto-Tellez Manuel , Koelzer Viktor H. , Leedham Simon J. , Tomlinson Ian , Dunne Philip D. , Buffa Francesca M. , Maughan Tim S. , Domingo Enric
Published: September 2024

Supplementary Figure 1
S:CORT members list from Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures
Authors: Mahmood Umair , Blake Andrew , Rathee Sanjay , Samuel Leslie , Murray Graeme , Sebag-Montefiore David , Gollins Simon , West Nicholas P. , Begum Rubina , Bach Simon P. , Richman Susan D. , Quirke Phil , Redmond Keara L. , Salto-Tellez Manuel , Koelzer Viktor H. , Leedham Simon J. , Tomlinson Ian , Dunne Philip D. , Buffa Francesca M. , Maughan Tim S. , Domingo Enric
Published: September 2024

S:CORT members list
Data from ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors
Authors: Chen Christopher T. , Khanna Vishesh , Kummar Shivaani , Abdul-Karim Raghad M. , Sommerhalder David , Tolcher Anthony W. , Ueno Naoto T. , Davis Sarah Lindsey , Orr Douglas W. , Hamilton Erika , Patel Manish R. , Spira Alexander I. , Jauhari Shekeab , Florou Vaia , Duff Maureen , Xu Rongda , Wang Jian , Barkund Shravani R. , Zhou Haiying , Pankov Aleksandr , Kong Wayne , Jahchan Nadine S. , Jackson Erica L. , Sun Jessica D. , Junttila Melissa R. , Multani Pratik S. , Daemen Anneleen , Chow Maneval Edna , Munster Pamela N.
Published: September 2024

Abstract
Purpose: In preclinical models, glucocorticoid receptor (GR) signaling drives resistance to taxane chemotherapy in multiple solid tumors via upregulation of antiapoptotic pathways. ORIC-101 is a potent and selective GR antagonist that was investigated in combination with taxane chemotherapy as an anticancer regimen preclinically and in a phase 1 clinical trial.

Patients and Methods: The ability of ORIC-101 to reverse taxane resistance was assessed in cell lines and xenograft models, and a phase 1 study (NCT03928314) was conducted in patients with advanced solid tumors to determine the dose, safety, and antitumor activity of ORIC-101 with nab-paclitaxel.

Results: ORIC-101 reversed chemoprotection induced by glucocorticoids in vitro and achieved tumor regressions when combined with paclitaxel in both taxane-naïve and -resistant xenograft models. In the phase 1 study, 21 patients were treated in dose escalation and 62 patients were treated in dose expansion. All patients in dose expansion had previously progressed on a taxane-based regimen. In dose escalation, five objective responses were observed. A preplanned futility analysis in dose expansion showed a 3.2% (95% confidence interval, 0.4–11.2) objective response rate with a median progression-free survival of 2 months (95% confidence interval, 1.8–2.8) across all four cohorts, leading to study termination. Pharmacodynamic analysis of tissue and plasma showed GR pathway downregulation in most patients in cycle 1.

Conclusions: ORIC-101 with nab-paclitaxel showed limited clinical activity in taxane-resistant solid tumors. Despite clear inhibition of GR pathway signaling, the insufficient clinical signal underscores the challenges of targeting a single resistance pathway when multiple mechanisms of resistance may be in play.

Significance: Glucocorticoid receptor (GR) upregulation is a mechanism of resistance to taxane chemotherapy in preclinical cancer models. ORIC-101 is a small molecule GR inhibitor. In this phase 1 study, ORIC-101 plus nab-paclitaxel did not show meaningful clinical benefit in patients who previously progressed on taxanes despite successful GR pathway downregulation.
Feasible Nipple Preservation Techniques for Breast Cancer with Slight Nipple Retraction
Authors: Matsuki Hitomi , Oura Shoji
Published: September 2024

Introduction: Nipple retraction has long been regarded as an absolute contraindication factor for nipple preservation in breast cancer surgery. Case Presentation: A 62-year-old woman was referred to our hospital for the treatment of breast cancer with slight nipple retraction. Imaging findings showed neither direct cancer infiltration to the nipple-areolar complex nor lymphadenopathy. Due to the patient’s strong preference, we attempted to preserve the nipple-areolar complex as follows. First, we made a quasi-complete skin flap except for the nipple-areolar complex area in a thick flap manner. Second, we fully skeletonized the sub-nipple mammary gland. Next, we pinched the skeletonized sub-nipple mammary gland with the scissors and pushed the scissors toward the nipple base as close as possible with the blades kept open. After that, we resected the nipple base using the scissors on pulling the mammary gland toward the opposite direction of the nipple. Frozen section and postoperative pathological study showed clear surgical margins and no lymph node metastasis. The patient developed temporary superficial dermal necrosis of the nipple but healed without leaving any sequelae in the nipple-areolar complex. The patient has been well for 20 months without any recurrences. Conclusion: Our nipple-preserving techniques enable safe nipple preservation even for breast cancer patients with slight nipple retraction.
Possible Association of CD3+CD4−CD8− Phenotype of T-Cell Lymphoma with Peripheral Blood Eosinophilia
Authors: Tabata Rie , Tabata Chiharu
Published: September 2024

Introduction: Because the prognosis of patients with peripheral T-cell lymphoma is poor compared to that of patients with B-cell lymphoma, we want to avoid further organ damage by eosinophilia. Moreover, in patients with some types of lymphoma, blood eosinophilia is implicated in a worse prognosis. To study the risk factors of eosinophilia, the association between lymphoma type, immunophenotypic features, and peripheral blood eosinophil counts were examined in the patients with mature T-cell lymphoma. Methods: We retrospectively examined 28 patients with mature T-cell lymphoma who were admitted to our hospital and whose immunophenotypic features were confirmed using flow cytometric, immunohistochemical analysis, or both between December 2012 and November 2023. Results: We report a possible association between peripheral eosinophilia and peripheral T-cell lymphoma – not otherwise specified and CD3+CD4−D8− (double-negative) phenotypes. Mild eosinophilia was observed in various types, but moderate and severe eosinophilia were observed in patients with peripheral T-cell lymphoma – not otherwise specified. Double-negative phenotype was rarely observed; however, all patients with double-negative phenotype exhibited peripheral blood eosinophilia. In addition, four of the five cases of the double-negative type were peripheral T-cell lymphoma – not otherwise specified. Conclusion: Here, we retrospectively examined patients with peripheral T-cell lymphoma whose immunophenotypic features were confirmed and report a possible association between peripheral eosinophilia and peripheral T-cell lymphoma – not otherwise specified and CD3+CD4−CD8− (double-negative) phenotypes. In addition, clinicians should be aware of the possible risk that patients with lymphocytic hypereosinophilic syndrome of the double-negative phenotype may develop peripheral T-cell lymphoma.
The role of technological pedagogical and content knowledge on career adaptability among teachers in Indonesia and Malaysia
Authors: Kusmaryani Rosita Endang , Widyastuti Tria , Nurhayati Siti Rohmah , Hamzah Hazalizah
Published: September 2024

Since the COVID-19 pandemic, face-to-face learning has been transformed into online learning. This phenomenon was really challenging for teachers because they were not used to it. The adaptability of the teacher becomes an indispensable aspect to face the problem. The ability to integrate materials, pedagogy and technology or technological pedagogical and content knowledge (TPACK) supported the adaptability in implementing online learning. The purpose of this study was to investigate the impact of TPACK on professional adaptability. A sample of 457 junior and senior high school teachers in Indonesia and Malaysia completed the technological pedagogical and content knowledge scale and the career adaptability scale. Based on partial least square analysis, this study found that TPACK played a role in predicting four dimensions of career adaptability: concern, control, curiosity, and confidence. This structural model was also supported with path analysis. Therefore, TPACK becomes an essential aspect in influencing teachers' career adaptability.
Exploring omentin-1 gene expression and insulin-resistance modulation in diabetic and obese male albino rats
Authors: Al-Sowayan Noorah Saleh , Almutawa Aiesha Mohammed
Published: September 2024

Omentin-1, a cytokine secreted by adipose tissue, plays a role in metabolic regulation and insulin sensitivity. However, there is a lack of understanding about the specific effects of high-intensity training (HIT) in diabetic and obese individuals. The present study investigates the effect of a 5-week HIT program on the omentin-1 gene expression and insulin resistance in diabetic and obese male albino rats. Thirty-two rats weighing between 100-120 grams, were procured and divided into groups: the control group (receiving a normal diet), the high-fat diet group (non-diabetic obese rats), the HIT diabetic group (induced diabetes through streptozotocin administration and subjected to HIT), and the diabetic control group (induced diabetes but not subjected to HIT). The HIT diabetic and HIT obese groups underwent a 5-week HIT protocol, involving treadmill running for 60 minutes at 34 m/min speed, five sessions per week. At the end of the experiment, various parameters including glucose, insulin, insulin resistance, LDL, HDL, TC, TG levels, and omentin-1 gene expression assessed using samples obtained from visceral tissue. SPSS version 25 was used to perform statistical analysis, results as mean±SE. One-way ANOVA identified group differences, with significance level (p-value) of less than 0.05. The findings revealed that omentin-1 gene expression significantly increased in the HIT diabetic group following five weeks of training. Both training groups exhibited reductions in insulin, glucose, and insulin resistance levels. It is concluded that a 5-week HIT program can lead to enhanced omentin-1 gene expression and improved insulin resistance in diabetic and obese male albino rats.
Revalidation of the global health questionnaire-12: factor analysis and demographic correlation
Authors: Ratnapuri Adisti , Zubaidah Siti , Mahanal Susriyati , Susanto Hendra , Setiyowati Arbin Janu , Saefi Muhammad
Published: September 2024

Global health questionnaire-12 (GHQ12) is the most common instrument used to measure mental health. However, the factor structure of the GHQ12 has not been fully explored. This study aims to assess the factorial structure of the GHQ12 and explore demographic factors associated with mental wellbeing in a population of prospective biology teachers in Indonesia. This cross-sectional survey was conducted for two weeks in July 2023 by recruiting 1186 students who were predominantly female (85.92%), over 20 years old (68.79%), only studying without working (90.47%), and third year (33.81%). Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to extract and assess the suitability of the resulting models. GHQ12 scores were also reviewed concerning demographic characteristics using comparison tests. Two factors including depression and social dysfunction accounted for 58.78% of the variance. This two-factor model was confirmed to fit the actual data. Additionally, we found differences between men and women on both factors and total scores. In addition, there are differences between students who only study and those who work on depression factors. This study suggests that the factor structure of the GHQ12 is a valid and reliable measurement for evaluating the mental health of prospective biology teachers.
Transcending telemedicine: exploring telemedicine adoption perspectives of physicians
Authors: Naga January Febro , Sison Raymund C.
Published: September 2024

Telemedicine has become indispensable in contemporary healthcare, reshaping patient care worldwide. The utilization of it has significantly risen in the Philippines, particularly during the pandemic, mirroring a global trend. Nevertheless, there is a dearth of studies regarding its pragmatic implementation among Filipino physicians, a crucial aspect for enhancing healthcare delivery. A qualitative analysis utilized in-depth interviews with experienced physicians in the Philippines. The researchers employed an inductive methodology to investigate how 13 physicians integrate telemedicine into their private medical practices. The selection of participants was purposeful, specifically targeting physicians with more than two years of experience in telemedicine. The qualitative data collected was subjected to a rigorous thematic analysis, comprehensively examining the current telemedicine integration situations. The examination of the data indicated a central theme: ‘Transcending Telemedicine’, emphasizing its influence that goes beyond being a mere technological tool. It overcomes time, space, and geography constraints, enhancing physicians’ ability to serve patients. There are four subcategories connected that contribute to or hinder the achievement of this goal: factors influencing adoption and factors influencing implementation and responses and reactions to telemedicine adoption. This paper contributes to the general understanding of telemedicine’s function in healthcare, specifically in the setting of a developing country. It emphasizes the necessity for continuous support and adjustment to maximize its benefits.