tbuckley/cabot-search huggingface dataset:
353O Efficacy and safety of ENZ-124 versus innovator cetuximab in combination with platinum-based chemotherapy in patients with recurrent locoregional or metastatic squamous cell carcinoma of the head and neck (SCCHN)
Authors: N. Dhamne, M. Jain, R. Nagarkar, S.K.K. Das Majumdar, C.D. Deshmukh, R. Dana, P. Ganesan, K. Chatterjee, S. Chatterjee, K. Prabhash, A. Sharma, V.K. Mahobia, R. Kumar, P. S.s., M. A, P.K. Chaitnya, V.G. Choudhary, H. Malhotra, S.V. Aagre, V. Maniar
Journal: Annals of Oncology (2023)
198P Effectiveness of lenvatinib in patients with unresectable hepatocellular carcinoma: A multicenter observational study in Japan
Authors: N. Izumi, M. Kudo, K. Motomura, Y. Inaba, Y. Katamura, Y. Kondo, K. Yabushita, K. Motoyoshi, J. Furuse
Journal: Annals of Oncology (2023)
339P A comparison of survival of patients with relapsed or refractory diffuse large B cell lymphoma undergoing allogeneic stem cell transplantation or receiving CAR-T therapy
Authors: K. Hayashino, H. Nishimori, K. Fujiwara, K. Kondo, C. Matsubara, T. Terao, W. Kitamura, C. Kamoi, K. Seike, H. Fujiwara, N. Asada, D. Ennishi, K. Fujii, N. Fujii, K-I. Matsuoka, Y. Maeda
Journal: Annals of Oncology (2023)
284TiP CYCLONE 3: A phase III, randomized, double-blind, placebo-controlled study of abemaciclib in combination with abiraterone plus prednisone in men with high-risk metastatic hormone-sensitive prostate cancer
Authors: N. Matsubara, N. Agarwal, M.R. Smith, R.R. McKay, T. Todenhöfer, J.M. Piulats Rodriguez, K.L. Chung, D. Heirich, S. Sherwood, C. Schaverien, N. Fasnacht, A. Lithio, K. Nacerddine, T. Zhang
Journal: Annals of Oncology (2023)
334MO A multicenter retrospective study to understand the clinical characteristics, treatment patterns, and outcomes of CLL patients in the Middle East: A subgroup analysis of the CREEK study
Authors: R.M. Abdelfattah Soliman, A. Alhuraiji, Y. Buyukasik, M. Siddiqui, S. Alamoudi, H. Alshehri, A. Aboutaleb, F.J. Gonzalez Hernandez, V. Rajadhyaksha, A. Absi
Journal: Annals of Oncology (2023)
375P Survival and prognostic factors of head and neck squamous cell carcinoma patients treated with either definitive CCRT or post operative CCRT with platinum-based chemotherapy in Rajavithi hospital, Thailand
Authors: W. Samadee, K. Maneenil, S. Payapwattanawong, P. Tienchaiananda, S. Sanguausai
Journal: Annals of Oncology (2023)
437P A randomized single blinded phase II trial comparing efficacy and quality of life of topical aloe vera gel plus urea cream versus urea cream alone for prevention of hand-foot syndrome in cancer patients receiving capecitabine
Authors: L. Wanichtanom, M. Boonsiri, G. Vrakornvoravuti, A. Sutepvarnon
Journal: Annals of Oncology (2023)
418P Decoding the intricate cellular makeup of immune-related adverse events using single-cell and spatial analysis
Authors: D. Shek, J. Lai, B. Gloss, H. Mahajan, A. Nagrial, T. Moujaber, M.S. Carlino, B. Gao, S.A. Read, G. Ahlenstiel
Journal: Annals of Oncology (2023)
329MO HLX208, a novel BRAF V600E inhibitor, in adult patients with Langerhans cell histiocytosis and/or Erdheim-Chester disease harbouring BRAF V600E mutation
Authors: X-X. Cao, Y. Wu, P. Liu, T. Ding, H. Ye, Z. Cai, Y. Zhang, J. Ma, Y. Xu, G. Fu, C. Hu, X. Hou, Q. Wang, J. Zhu, J. Li
Journal: Annals of Oncology (2023)
434MO Increased eosinophil is a universal biomarker for immune-related adverse events induced by immune checkpoint inhibitors in various cancer patients: A retrospective multidisciplinary study
Authors: Y. Tasaki, Y. Sugiyama, I. Nanami, M. Yoshihisa, M. Iida, K. Odagiri, Y. Kimura, Y. Hotta, T. Naiki, S. Hamamoto, T. Yasui, Y. Hibi
Journal: Annals of Oncology (2023)
368P Distinct gene expression profiling explored using nanostring tumor signalling 360 panel with validations in different clinical stages of oral submucous fibrosis patients: A first Indian study
Authors: Y. Madhavan, A. Lochan G, V. Shyamsundar, M. Kuppuloganathan, A. Krishnamurthy, V. Ramshankar, D. Catakapatri Venugopal
Journal: Annals of Oncology (2023)
372P Effectiveness of HAN-MI-RADS (head and neck molecular imaging-reporting and data system) criterion in head and neck squamous cell carcinoma post concurrent chemoradiotherapy
Authors: M. Gupta, A. Jajodia, P. Alhawat, M. Gairola, M. Agarwal, P.S. Choudhury
Journal: Annals of Oncology (2023)
421P Comprehensive genomic profiling (CGP) unravels somatic BRCA (sBRCA) and homologous recombinant repair (HRR) gene alterations across multi-cancer spectrum
Authors: R. Kodandapani, S.M. Lingaraju, K. Raghavendrachar, G. Balaram, V. Erappareddy, V. Keriyappa, S.N. Ghorpade, S. Patil, S. Chiradoni Thungappa, S. Papaiah Sheela, S. Belagutti Jayappa, S. Bhattacharjee, R. Dasgupta, M. Naseer R, D. Hattangdi, A. Ravichandran, U. Bahadur, B.S. Ajaikumar, M. Ghosh
Journal: Annals of Oncology (2023)
361MO Characterizing the role of NSD family of histone methyltransferases in the head and neck squamous cell carcinoma tumor immune microenvironment
Authors: Y. Boumber, S.K. Deshmukh, S. Wu, J. Xiu, A. Farrell, A. Desai, C. Kim, F. Abdulla, A. Vanderwalde, T. Wise-Draper, J.M. Johnson
Journal: Annals of Oncology (2023)
Biguanide chitosan microneedles with cell-free DNA scavenging ability for psoriasis therapy
Authors: Zihao Liu, Yu Wang, Yuhan Zhang, Liufu Hu, Bozhi Chen, Yang Li, Xindong Guo, Bingran Yu, Fu-Jian Xu
Journal: Bioactive Materials (2023)

High levels of cell-free DNA (cfDNA) induce psoriasis. Currently, the treatment of psoriasis has the disadvantages of penetration difficulty, suppression of normal immunity, and skin irritation. In this study, biguanide chitosan microneedles (BGC-MNs) were prepared to treat psoriasis by removing cfDNA from the dermis through the skin barrier. The effects of chitosan with different bisguanidine contents on DNA-binding capacity, biocompatibility, and inflammation inhibition were compared, revealing that chitosan containing 20% bisguanidine (BGC2) was found to have the best overall performance. In vitro, BGC2 effectively cleared cfDNA and inhibited the production of inflammatory factors. BGC-MN made from BGC2 had good mechanical and solubility properties. In vivo, BGC-MNs cleared cfDNA, reduced the level of inflammatory factors in the dermis, and exerted a good therapeutic effect on mice with psoriasis. These results suggested that BGC-MNs provided a new approach to treating psoriasis in terms of scavenging cfDNA and exerting anti-inflammatory effects.
Ca &amp; Mn dual-ion hybrid nanostimulator boosting anti-tumor immunity via ferroptosis and innate immunity awakening
Authors: Xi Deng, Tianzhi Liu, Yutong Zhu, Jufeng Chen, Ze Song, Zhangpeng Shi, Hangrong Chen
Journal: Bioactive Materials (2023)

Limited by low tumor immunogenicity and the immunosuppressive tumor microenvironment (TME), triple-negative breast cancer (TNBC) has been poorly responsive to immunotherapy so far. Herein, a Ca & Mn dual-ion hybrid nanostimulator (CMS) is constructed to enhance anti-tumor immunity through ferroptosis inducing and innate immunity awakening, which can serve as a ferroptosis inducer and immunoadjuvant for TNBC concurrently. On one hand, glutathione (GSH) depletion and reactive oxygen species (ROS) generation can be achieved due to the mixed valence state of Mn in CMS. On the other hand, as an exotic Ca2+ supplier, CMS causes mitochondrial Ca2+ overload, which further amplifies the oxidative stress. Significantly, tumor cells undergo ferroptosis because of the inactivation of glutathione peroxidase 4 (GPX4) and accumulation of lipid peroxidation (LPO). More impressively, CMS can act as an immunoadjuvant to awaken innate immunity by alleviating intra-tumor hypoxia and Mn2+-induced activation of the STING signaling pathway, which promotes polarization of tumor-associated macrophages (TAMs) and activation of dendritic cells (DCs) for antigen presentation and subsequent infiltration of tumor-specific cytotoxic T lymphocytes (CTLs) into tumor tissues. Taken together, this work demonstrates a novel strategy of simultaneously inducing ferroptosis and awakening innate immunity, offering a new perspective for effective tumor immunotherapy of TNBC.
Co-delivery of oxaliplatin prodrug liposomes with Bacillus Calmette-Guérin for chemo-immunotherapy of orthotopic bladder cancer
Authors: Cheng Ma, Xiaofang Zhong, Rong Liu, Xiaojia Yang, Zhiqiang Xie, Yongshun Zhang, Yanhua Xu, Hairui Wang, Chunting He, Guangsheng Du, Tao Gong, Xun Sun
Journal: Journal of Controlled Release (2023)
hsa_circ_0007919 induces LIG1 transcription by binding to FOXA1/TET1 to enhance the DNA damage response and promote gemcitabine resistance in pancreatic ductal adenocarcinoma
Authors: Lei Xu, Xiao Ma, Xiuzhong Zhang, Chong Zhang, Yi Zhang, Shuai Gong, Nai Wu, Peng Zhang, Xinyu Feng, Jiaxuan Guo, Mengmeng Zhao, Zeqiang Ren, Pengbo Zhang
Journal: Molecular Cancer (2023)

Abstract Background Circular RNAs (circRNAs) play important roles in the occurrence and development of cancer and chemoresistance. DNA damage repair contributes to the proliferation of cancer cells and resistance to chemotherapy-induced apoptosis. However, the role of circRNAs in the regulation of DNA damage repair needs clarification. Methods RNA sequencing analysis was applied to identify the differentially expressed circRNAs. qRT-PCR was conducted to confirm the expression of hsa_circ_0007919, and CCK-8, FCM, single-cell gel electrophoresis and IF assays were used to analyze the proliferation, apoptosis and gemcitabine (GEM) resistance of pancreatic ductal adenocarcinoma (PDAC) cells. Xenograft model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor growth and DNA damage in vivo. RNA sequencing and GSEA were applied to confirm the downstream genes and pathways of hsa_circ_0007919. FISH and nuclear-cytoplasmic RNA fractionation experiments were conducted to identify the cellular localization of hsa_circ_0007919. ChIRP, RIP, Co-IP, ChIP, MS-PCR and luciferase reporter assays were conducted to confirm the interaction among hsa_circ_0007919, FOXA1, TET1 and the LIG1 promoter. Results We identified a highly expressed circRNA, hsa_circ_0007919, in GEM-resistant PDAC tissues and cells. High expression of hsa_circ_0007919 correlates with poor overall survival (OS) and disease-free survival (DFS) of PDAC patients. Hsa_circ_0007919 inhibits the DNA damage, accumulation of DNA breaks and apoptosis induced by GEM in a LIG1-dependent manner to maintain cell survival. Mechanistically, hsa_circ_0007919 recruits FOXA1 and TET1 to decrease the methylation of the LIG1 promoter and increase its transcription, further promoting base excision repair, mismatch repair and nucleotide excision repair. At last, we found that GEM enhanced the binding of QKI to the introns of hsa_circ_0007919 pre-mRNA and the splicing and circularization of this pre-mRNA to generate hsa_circ_0007919. Conclusions Hsa_circ_0007919 promotes GEM resistance by enhancing DNA damage repair in a LIG1-dependent manner to maintain cell survival. Targeting hsa_circ_0007919 and DNA damage repair pathways could be a therapeutic strategy for PDAC.
Targeting the epigenome to reinvigorate T cells for cancer immunotherapy
Authors: Dian Xiong, Lu Zhang, Zhi-Jun Sun
Journal: Military Medical Research (2023)

Abstract Cancer immunotherapy using immune-checkpoint inhibitors (ICIs) has revolutionized the field of cancer treatment; however, ICI efficacy is constrained by progressive dysfunction of CD8 + tumor-infiltrating lymphocytes (TILs), which is termed T cell exhaustion. This process is driven by diverse extrinsic factors across heterogeneous tumor immune microenvironment (TIME). Simultaneously, tumorigenesis entails robust reshaping of the epigenetic landscape, potentially instigating T cell exhaustion. In this review, we summarize the epigenetic mechanisms governing tumor microenvironmental cues leading to T cell exhaustion, and discuss therapeutic potential of targeting epigenetic regulators for immunotherapies. Finally, we outline conceptual and technical advances in developing potential treatment paradigms involving immunostimulatory agents and epigenetic therapies.
Metabolic control of puberty: 60 years in the footsteps of Kennedy and Mitra’s seminal work
Authors: Greg M. Anderson, Jennifer W. Hill, Ursula B. Kaiser, Victor M. Navarro, Ken K. Ong, John R. B. Perry, Vincent Prevot, Manuel Tena-Sempere, Carol F. Elias
Journal: Nature Reviews Endocrinology (2023)
First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial
Authors: Karim Fizazi, Arun A. Azad, Nobuaki Matsubara, Joan Carles, Andre P. Fay, Ugo De Giorgi, Jae Young Joung, Peter C. C. Fong, Eric Voog, Robert J. Jones, Neal D. Shore, Curtis Dunshee, Stefanie Zschäbitz, Jan Oldenburg, Dingwei Ye, Xun Lin, Cynthia G. Healy, Nicola Di Santo, A. Douglas Laird, Fabian Zohren, Neeraj Agarwal
Journal: Nature Medicine (2023)

Abstract Preclinical evidence has suggested an interplay between the androgen receptor, which largely drives the growth of prostate cancer cells, and poly(ADP-ribose) polymerase. This association provides a rationale for their co-inhibition for the treatment of metastatic castration-resistant prostate cancer (mCRPC), an area of unmet medical need. The phase 3 TALAPRO-2 study investigated combining the poly(ADP-ribose) polymerase inhibitor talazoparib with enzalutamide versus enzalutamide alone as first-line treatment of mCRPC. Patients were prospectively assessed for tumor alterations in DNA damage response genes involved in homologous recombination repair (HRR). Two cohorts were enrolled sequentially: an all-comers cohort that was enrolled first (cohort 1; N = 805 (169 were HRR-deficient)), followed by an HRR-deficient-only cohort (cohort 2; N = 230). We present results from the alpha-controlled primary analysis for the combined HRR-deficient population ( N = 399). Patients were randomized in a 1:1 ratio to talazoparib or placebo, plus enzalutamide. The primary endpoint, radiographic progression-free survival, was met (median not reached at the time of the analysis for the talazoparib group versus 13.8 months for the placebo group; hazard ratio, 0.45; 95% confidence interval, 0.33 to 0.61; P &lt; 0.0001). Data for overall survival, a key secondary endpoint, are immature but favor talazoparib (hazard ratio, 0.69; 95% confidence interval, 0.46 to 1.03; P = 0.07). Common adverse events in the talazoparib group were anemia, fatigue and neutropenia. Combining talazoparib with enzalutamide significantly improved radiographic progression-free survival in patients with mCRPC harboring HRR gene alterations, supporting talazoparib plus enzalutamide as a potential first-line treatment for these patients. ClinicalTrials.gov Identifier: NCT03395197 .
Plasma Biomarker Strategy for Selecting Patients With Alzheimer Disease for Antiamyloid Immunotherapies
Authors: Niklas Mattsson-Carlgren, Lyduine E. Collij, Erik Stomrud, Alexa Pichet Binette, Rik Ossenkoppele, Ruben Smith, Linda Karlsson, Juan Lantero-Rodriguez, Anniina Snellman, Olof Strandberg, Sebastian Palmqvist, Nicholas J. Ashton, Kaj Blennow, Shorena Janelidze, Oskar Hansson
Journal: JAMA Neurology (2023)

Antiamyloid immunotherapies against Alzheimer disease (AD) are emerging. Scalable, cost-effective tools will be needed to identify amyloid β (Aβ)-positive patients without an advanced stage of tau pathology who are most likely to benefit from these therapies. Blood-based biomarkers might reduce the need to use cerebrospinal fluid (CSF) or positron emission tomography (PET) for this.
Blood Pressure at Different Life Stages Over the Early Life Course and Intima-Media Thickness
Authors: Yaxing Meng, James E. Sharman, Juhani S. Koskinen, Markus Juonala, Jorma S. A. Viikari, Marie-Jeanne Buscot, Feitong Wu, Brooklyn J. Fraser, Suvi P. Rovio, Mika Kähönen, Tapani Rönnemaa, Antti Jula, Harri Niinikoski, Olli T. Raitakari, Katja Pahkala, Costan G. Magnussen
Journal: JAMA Pediatrics (2023)

Although cardiovascular disease (CVD) begins in early life, the extent to which blood pressure (BP) at different life stages contributes to CVD is unclear.
Electrocardiogram Recording in the Prone Position
Authors: Miguel Angel Cobos Gil, Jesús Diz-Díaz, Fabian Islas
Journal: JAMA Internal Medicine (2023)

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A 52-Year-Old With Painful Fingertips
Authors: Hideki Oka, Shuji Sumitomo, Koichiro Ohmura
Journal: JAMA (2023)

A patient had cold, cyanotic fingertips with small ulcerations. Laboratory testing showed leukocytosis, eosinophilia, and elevated D-dimer level; results of tests for antinuclear antibodies, antiphospholipid antibodies, antineutrophil cytoplasmic antibodies against proteinase 3 and myeloperoxidase, and HIV were negative. What is the diagnosis and what would you do next?
Linking Prenatal Environmental Exposures to Lifetime Health with Epigenome-Wide Association Studies: State-of-the-Science Review and Future Recommendations
Authors: Kelly M. Bakulski, Freida Blostein, Stephanie J. London
Journal: Environmental Health Perspectives (2023)

The prenatal environment influences lifetime health; epigenetic mechanisms likely predominate. In 2016, the first international consortium paper on cigarette smoking during pregnancy and offspring DNA methylation identified extensive, reproducible exposure signals. This finding raised expectations for epigenome-wide association studies (EWAS) of other exposures.
Aneuploidy Landscape in Precursors of Ovarian Cancer
Authors: Yeh Wang, Christopher Douville, Yen-Wei Chien, Brant G. Wang, Chi-Long Chen, Andre Pinto, Saron Ann Smith, Ronny Drapkin, M. Herman Chui, Tricia Numan, Russell Vang, Nickolas Papadopoulos, Tian-Li Wang, Ie-Ming Shih
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Serous tubal intraepithelial carcinoma (STIC) is now recognized as the main precursor of ovarian high-grade serous carcinoma (HGSC). Other potential tubal lesions include p53 signatures and tubal intraepithelial lesions. We aimed to investigate the extent and pattern of aneuploidy in these epithelial lesions and HGSC to define the features that characterize stages of tumor initiation and progression. Experimental Design: We applied RealSeqS to compare genome-wide aneuploidy patterns among the precursors, HGSC (cases, n = 85), and histologically unremarkable fallopian tube epithelium (HU-FTE; control, n = 65). On the basis of a discovery set (n = 67), we developed an aneuploidy-based algorithm, REAL-FAST (Repetitive Element AneupLoidy Sequencing Fallopian Tube Aneuploidy in STIC), to correlate the molecular data with pathology diagnoses. We validated the result in an independent validation set (n = 83) to determine its performance. We correlated the molecularly defined precursor subgroups with proliferative activity and histology. Results: We found that nearly all p53 signatures lost the entire Chr17, offering a “two-hit” mechanism involving both TP53 and BRCA1 in BRCA1 germline mutation carriers. Proliferatively active STICs harbor gains of 19q12 (CCNE1), 19q13.2, 8q24 (MYC), or 8q arm, whereas proliferatively dormant STICs show 22q loss. REAL-FAST classified HU-FTE and STICs into 5 clusters and identified a STIC subgroup harboring unique aneuploidy that is associated with increased proliferation and discohesive growth. On the basis of a validation set, REAL-FAST showed 95.8% sensitivity and 97.1% specificity in detecting STIC/HGSC. Conclusions: Morphologically similar STICs are molecularly distinct. The REAL-FAST assay identifies a potentially “aggressive” STIC subgroup harboring unique DNA aneuploidy that is associated with increased cellular proliferation and discohesive growth. REAL-FAST offers a highly reproducible adjunct technique to assist the diagnosis of STIC lesions.
Evaluation of the SSTR2-targeted Radiopharmaceutical 177Lu-DOTATATE and SSTR2-specific 68Ga-DOTATATE PET as Imaging Biomarker in Patients with Intracranial Meningioma
Authors: Sylvia C. Kurz, Elcin Zan, Christine Cordova, Andrea B. Troxel, Marissa Barbaro, Joshua S. Silverman, Matija Snuderl, David Zagzag, Douglas Kondziolka, John G. Golfinos, Andrew S. Chi, Erik P. Sulman
Journal: Clinical Cancer Research (2023)

Abstract Purpose: There are no effective medical therapies for patients with meningioma who progress beyond surgical and radiotherapeutic interventions. Somatostatin receptor type 2 (SSTR2) represents a promising treatment target in meningiomas. In this multicenter, single-arm phase II clinical study (NCT03971461), the SSTR2-targeting radiopharmaceutical 177Lu-DOTATATE is evaluated for its feasibility, safety, and therapeutic efficacy in these patients. Patients and Methods: Adult patients with progressive intracranial meningiomas received 177Lu-DOTATATE at a dose of 7.4 GBq (200 mCi) every eight weeks for four cycles. 68Ga-DOTATATE PET-MRI was performed before and six months after the start of the treatment. The primary endpoint was progression-free survival (PFS) at 6 months (PFS-6). Secondary endpoints were safety and tolerability, overall survival (OS) at 12 months (OS-12), median PFS, and median OS. Results: Fourteen patients (female = 11, male = 3) with progressive meningiomas (WHO 1 = 3, 2 = 10, 3 = 1) were enrolled. Median age was 63.1 (range 49.7–78) years. All patients previously underwent tumor resection and at least one course of radiation. Treatment with 177Lu-DOTATATE was well tolerated. Seven patients (50%) achieved PFS-6. Best radiographic response by modified Macdonald criteria was stable disease (SD) in all seven patients. A &amp;gt;25% reduction in 68Ga-DOTATATE uptake (PET) was observed in five meningiomas and two patients. In one lesion, this corresponded to &amp;gt;50% reduction in bidirectional tumor measurements (MRI). Conclusions: Treatment with 177Lu-DOTATATE was well tolerated. The predefined PFS-6 threshold was met in this interim analysis, thereby allowing this multicenter clinical trial to continue enrollment. 68Ga-DOTATATE PET may be a useful imaging biomarker to assess therapeutic outcome in patients with meningioma.
Staphylococcus aureus lysate induces an IgE response via memory B cells in nasal polyps
Authors: Kun Du, Yan Zhao, Xin Zhang, Chenduo Li, Yun Hao, Xiaonan Du, Yiran Yang, Xiaofeng Qin, Yue Hu, Ying Li, Yue Wang, Yan Chen, Yan Li, Wei Wang, Xiangdong Wang, Sun Ying, Luo Zhang
Journal: Journal of Allergy and Clinical Immunology (2023)