tbuckley/cabot-search huggingface dataset:
Medication for Opioid Use Disorder and Treatment Retention Among Pregnant Individuals
Authors: Valerie S. Ganetsky, Noa Krawczyk, Alene Kennedy-Hendricks
Journal: JAMA Network Open (2025)

Importance Treatment retention for pregnant individuals with opioid use disorder (OUD) is critical, especially during the high-potency synthetic opioid (HPSO) era. Current data on the relationship between medication for opioid use disorder (MOUD) receipt in specialty substance use treatment facilities and retention are needed for this population. Objective To examine the association between MOUD inclusion in treatment and 6-month treatment retention among pregnant individuals with OUD in publicly funded specialty treatment facilities during the HPSO era. Design, Setting, and Participants This cross-sectional study pooled data from January 1, 2015, to December 31, 2021, from the Treatment Episode Data Set-Discharges, a national dataset managed by the Substance Abuse and Mental Health Services Administration that tracks annual discharges from state-licensed, publicly funded substance use treatment facilities. Individuals who were pregnant at the time of admission, reported an opioid (heroin, nonprescription methadone, or other opiates and synthetics) as their primary substance, and were discharged from ambulatory, nonintensive outpatient facilities were included. Data were analyzed November 2023 to April 2024. Exposure MOUD inclusion in a treatment episode. Main Outcomes and Measures The main outcome was treatment retention (length of stay &amp;amp;gt;6 months vs ≤6 months). To account for the nonrandom assignment to MOUD, inverse probability of treatment–weighted logistic regression models were estimated adjusting for sociodemographics; substance use, mental health, and treatment history; treatment admission–related variables; census division; state policy characteristics; and year fixed effects. Results Of 29 981 treatment episodes, most involved individuals aged 25 to 34 years (19 106 [63.7%]). Approximately two-thirds of 29 071 episodes in the final analysis (19 884 [68.4%]) included MOUD across all study years. From 2015 to 2021, MOUD inclusion in treatment episodes increased by 9.1 percentage points, from 65.0% to 74.1%. Treatment episodes with MOUD were associated with greater odds of 6-month treatment retention compared with those without MOUD (adjusted odds ratio, 1.86 [95% CI, 1.72-2.01]). This finding translated to an estimated 14.2 percentage point greater adjusted probability of 6-month retention among treatment episodes with MOUD (43.1%) vs those without it (28.9%). Conclusions and Relevance In this cross-sectional study of treatment episodes from ambulatory, nonintensive facilities, MOUD inclusion among pregnant individuals was associated with significant improvements in treatment retention. However, retention remained low during the HPSO era. These findings underscore the importance of MOUD in improving OUD-related outcomes in this high-risk population.
Abstract 3226: Intratumoral manipulation of melanoma using novel hyperthermic treatment to enhance anti-PD-L1 therapy
Authors: Nicole DeSouza, Danielle Quaranto, Kaci Kopec, Jan Geliebter, Raj K. Tiwari, Mark D. Hurwitz
Journal: Cancer Research (2025)

Abstract Despite tremendous advancement in the understanding and manipulation of immune checkpoint molecules in immunotherapeutic design, there are still vast limitations in treatment efficacy. Immunotherapy manipulates the immune checkpoint blockade (ICB), blocking negative regulators of the immune system-preventing tumor immune evasion. Combination therapy enhances the mechanistic actions of each individual component, enhancing tumoricidal behavior. Thermal ablation to induce cancer cell death as a therapeutic adjuvant is an understudied area. B16-F10 melanoma cells were grown at 37°C or 41°C. B16-F10 cells grown at 41°C decreased cell migration by 70% in 24 hours. B16-F10 cell proliferation was decreased at 41°C by 62% at 48 hours and 94% at 72 hours. Protein expression profiles were evaluated under hyperthermic conditions in vitro. Expression of pERK and ERK decreased by 86% and 50% and Caspase-3 increased by 31% at 41°C. Cell stress can induce death pathways and the heat shock protein response simultaneously, therefore we investigated inducible Hsp70 expression. Hsp70 expression was undetectable at 37°C and 188% at 41°C. Cytokine analysis of conditioned media showed that at 41°C, TNF-α expression was increased and IL-4 expression was decreased, suggesting a proinflammatory shift in cytokine profiles at higher temperatures. In support of our data, hyperthermia-induced TNF-α apoptotic responses have been reported. Programmed cell death ligand (PD-L1) is expressed by tumors to suppress immune cells and induce tolerogenic phenotypes within the tumor microenvironment. We observed that hyperthermic potentiation decreased the expression of this checkpoint molecule in B16-F10 by 35%. Therefore, we hypothesize that hyperthermia modulates the tumor microenvironment to enhance their responsiveness to checkpoint immunotherapies. Based on these promising in vitro results, we plan to further explore the clinical aspect of our findings through a translation in vivo. B16-F10 cells will be implanted onto C57BL/6 mice and treated with infrared radiation in combination with either anti-PD-L1, anti-PD-1, or IL-15. Citation Format: Nicole DeSouza, Danielle Quaranto, Kaci Kopec, Jan Geliebter, Raj K. Tiwari, Mark D. Hurwitz. Intratumoral manipulation of melanoma using novel hyperthermic treatment to enhance anti-PD-L1 therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3226.
Abstract 1663: Discovery of novel, potent and orally bioavailable SMARCA2 PROTACs with synergistic anti-tumor activity in combination with KRAS G12C inhibitors
Authors: Yonathan Lissanu, Sasi Kotagiri, Nicholas Blazanin, Yawen Wang, Yanyan Han, Xiaobing Liang
Journal: Cancer Research (2025)

Abstract Cancer genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex including SMARCA4 in non-small cell lung cancer with a frequency of up to 33% in advanced stage disease, making it the most frequently mutated complex in lung cancer. We and others have identified SMARCA2 to be synthetic lethal to SMARCA4, indicating SMARCA2 is a high value therapeutic target. Here, we disclose the discovery and characterization of potent, selective and orally bioavailable Cereblon-based SMARCA2 PROTACs. Biochemically, YDR1 and YD54 are potent SMARCA2 degraders with an average DC50 of 7.7nM and 3.5nM respectively in SMARCA4 mutant lung cancer cells. Phenotypically, both YDR1 and YD54 selectively inhibited growth of SMARCA4 mutant cancer cells. Further, we showed anti-tumor growth inhibitory activity of YDR1 and YD54 in SMARCA4 mutant xenograft models of lung cancer. Finally, we show that YDR1 and YD54 synergize with the KRAS G12C inhibitor sotorasib to inhibit growth of SMARCA4 and KRAS G12C co-mutant lung cancer cells. These findings provide additional evidence for the utility of single agent or combination regimens containing SMARCA2 PROTACs as synthetic lethal therapeutics against SMARCA4 mutant cancers. Citation Format: Yonathan Lissanu, Sasi Kotagiri, Nicholas Blazanin, Yawen Wang, Yanyan Han, Xiaobing Liang. Discovery of novel, potent and orally bioavailable SMARCA2 PROTACs with synergistic anti-tumor activity in combination with KRAS G12C inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1663.
Abstract 3243: Fragmentomic features of plasma cell-free DNA in patients with osteosarcoma
Authors: Anastasia E. Mackeracher, Joanna Przybyl
Journal: Cancer Research (2025)

The rapid advancement of liquid biopsy technologies represents a major breakthrough in cancer management, allowing for sensitive detection of tumor-derived molecules and providing real-time insights into disease progression. Osteosarcoma (OS), the most common primary bone malignancy, currently lacks robust biomarkers for therapy response. We hypothesize that a multi-omic and multi-modal approach to identifying OS-specific markers in circulating tumor DNA (ctDNA) will facilitate precise patient stratification and improve treatment outcomes. It has been demonstrated by others that plasma ctDNA in OS patients carry specific genomic markers, such as point mutations and copy number alterations. However, the fragmentomic features of cell-free DNA (e.g., fragment length and nucleotide composition) remain poorly characterized in OS patients. To provide the rationale for studying fragmentomic features of plasma DNA in OS, we sought to demonstrate the feasibility of detecting distinct fragmentomic patterns in the publicly available whole genome sequencing data from cfDNA of 3 OS patients (NCBI SRA accession number PRJNA917431) together with our previously published shallow whole genome sequencing data from cell-free DNA of 7 patients with leiomyosarcoma, 12 patients with leiomyoma, 3 patients with dedifferentiated liposarcoma and 3 patients with well-differentiated liposarcoma (PMIDs: 29463554, 32232185, 34986184). We determined the first 4 nucleotide sequence (i.e., a 4-mer motif) on each 5′ fragment end of plasma DNA molecules. We calculated the frequency of each of the 256 possible motifs and normalized it to the total number of reads in each specimen. We applied multiclass differential analysis of the frequency of these motifs in 5 different types of tumors, and identified 64 motifs significantly enriched in OS (mean frequency difference between groups &amp;gt; 2.5-fold, false discovery rate &amp;lt; 0.05). In OS cell-free DNA, we observed decrease of motifs associated with DNASE1L3 nuclease (e.g., CCCA, CCAG, CCTG) and increase of motifs such as TAAA, AAAA, and TTTT. In the next steps, we will examine the expression of different DNA nucleases in patient tissue specimens by immunohistochemistry and will analyze plasma DNA from a new cohort of 50 OS patients to validate our preliminary findings. We will investigate whether these fragmentomic patterns of cell-free DNA have the predictive and prognostic value in OS patients. Our preliminary results warrant further studies of the frequency and diversity of the 4-mer motifs and expression of different DNA nucleases in OS. Citation Format: Anastasia E. Mackeracher, Joanna Przybyl. Fragmentomic features of plasma cell-free DNA in patients with osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3243.
Acute Blood Pressure Lowering and Risk of Ischemic Lesions on MRI After Intracerebral Hemorrhage
Authors: Ken S. Butcher, Brian Buck, Dar Dowlatshahi, Laura C. Gioia, Mahesh Kate, Ana C. Klahr, Ashwin Sivasubramaniam, Ashfaq Shuaib, Alan Wilman, Vijay K. Sharma, Georgios Tsivgoulis, Christos Krogias, Ashkan Shoamanesh
Journal: JAMA Neurology (2025)

Importance Diffusion-weighted imaging (DWI) lesions have been demonstrated in patients with subacute intracerebral hemorrhage (ICH), suggesting ischemic injury, which may be related to blood pressure (BP) reduction. Objective To test the hypothesis that acute intensive BP lowering is associated with DWI lesions after ICH. Design, Setting, and Participants The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial 2 (ICHADAPT-2) was a multicenter, randomized, open-label, blinded–end point trial. Between November 2012 and August 2022, patients with ICH presenting within 6 hours of onset were randomized to a systolic BP (SBP) target of less than 140 mm Hg or less than 180 mm Hg. The trial was conducted at 3 comprehensive stroke centers in Canada and Australia, including 1 telestroke referral hub and 1 community stroke hospital. A total of 162 patients with acute ICH were randomized. The primary analysis population was restricted to those undergoing DWI at 48 hours. Intervention Patients were randomly assigned to an acute SBP target of less than 140 mm Hg or less than 180 mm Hg. Main Outcome and Measure The primary end point was the incidence of acute DWI lesions on brain magnetic resonance imaging obtained 48 ± 12 hours after randomization. Results DWI was obtained in 79 (48% female) patients with a mean (SD) age of 71 (13) years and median baseline ICH volume of 11.2 (range, 0.5-122.2) mL. The median times from onset to randomization and DWI were 3.17 (range, 0.7-14.6) hours and 51.6 (range, 17.0-121.4) hours, respectively. Mean (SD) baseline SBP was 183 (22) mm Hg in the less than 140 mm Hg target group and 181 (28) mm Hg in the less than 180 mm Hg target group. Mean SBP was lower over the 48-hour period after randomization in the less than 140 mm Hg group (mean difference, 18.9 mm Hg [95% CI, 17.6-20.2]; P &amp;amp;lt; .001). DWI lesions were detected in 13 of 42 patients (31%) in the less than 140 mm Hg group and 14 of 37 patients (38%) in the less than 180 mm Hg group (odds ratio, 0.74 [95% CI, 0.12-4.64]; P = .32). The median number of DWI lesions (1 [95% CI, 1-10] vs 1.5 [95% CI, 1-10]; P = .26) and total DWI lesion volume (0.1 [95% CI, 0.01-41.3] mL vs 0.3 [95% CI, 0.02-2.03] mL; P = .17) were not different in the less than 140 mm Hg and less than 180 mm Hg groups. Conclusions and Relevance DWI lesion frequency and volume were unaffected by intensive antihypertensive therapy. These results support the safety of early BP reduction in acute ICH.
Abstract 2020: Fibroblast derived type III collagen pro-peptides (PRO-C3) in plasma is associated with outcome for patients with NSCLC treated with anti-PD1 plus chemotherapy
Authors: Nicholas Willumsen, Lola Lecru, Thibaut Brugat, John Stagg, Bertrand Routy, Morten A. Karsdal
Journal: Cancer Research (2025)

Abstract Background: Tumor fibrosis is essential for defining outcome of patients with various solid tumors including lung cancer. The associated cancer associated fibroblasts (CAFs) activation and increased deposition of type III collagen leads to immune exclusion and high interstitial pressure in the tumor microenvironment. Recently, the USA FDA issued a Letter of Support to encourage use of the non-invasive fibrosis biomarker PRO-C3 (type III collagen pro-peptides) in patients with solid tumors (https://www.fda.gov/media/169332/download). Here we investigate PRO-C3 as a prognostic biomarker in patients with non-small cell lung cancer (NSCLC). Methods: First, we investigated the PRO-C3 production (measured by ELISA) and total collagen deposition (Sirius red staining) in primary lung CAFs activated with TGF-beta, by use of the validated scar-in-a-jar in vitro model. Second, we measured PRO-C3 in pre-treatment plasma samples from 40 patients with stage IIIa to IVb NSCLC. Patients were treated with Pembrolizumab (anti-PD1) plus platinum-doublet chemotherapy (carboplatin, cisplatin, pemetrexed, or paclitaxel). PRO-C3 was correlated to overall survival outcome (OS) by Kaplan Meier analysis and Cox regression analysis after allocating patients into PRO-C3 subgroups (below/above the median of 51.5 ng/mL). Results: PRO-C3 was produced by lung CAFs after activation with TGF-beta in vitro and PRO-C3 correlated to increased net-collagen deposition. Among the 40 patients with NSCLC, the median follow-up was 13.2 months. Patients with high PRO-C3 had a median OS of 9.0 months compared to 31.5 months in patients with low PRO-C3 (log-rank p-value=0.0023). In support, patients with high PRO-C3 had a Hazard Ratio (HR) for OS of 3.8 (95%CI: 1.5-9.7, p=0.004). Conclusions: Type III collagen pro-peptides (PRO-C3) was produced by activated lung CAFs and is a surrogate of fibrogenesis. High PRO-C3 levels in pre-treatment plasma was associated with poor outcome for patients with NSCLC treated with anti-PD1 plus chemotherapy. These data suggest that quantifying tumor fibrosis is important for prognostication of patients with lung cancer. Citation Format: Nicholas Willumsen, Lola Lecru, Thibaut Brugat, John Stagg, Bertrand Routy, Morten A. Karsdal. Fibroblast derived type III collagen pro-peptides (PRO-C3) in plasma is associated with outcome for patients with NSCLC treated with anti-PD1 plus chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2020.
Abstract 4746: PLB-001, a novel anti-dll3 ADC with topoisomerase 1 inhibitor-based linker-payload for treatment of SCLC
Authors: Yingdong Lu, None xin li, Ganyuan Xiao, Kia J. Puan, None Ling xu, Mao Yin
Journal: Cancer Research (2025)

Abstract Delta-like ligand 3 (DLL3) is a promising target for antibody-drug conjugates (ADCs) in the treatment of small cell lung cancer (SCLC) due to its high expression on the cell surface of SCLC cells and minimal expression in normal tissues. With highly specific, fast internalized mAbs from antibody screening, various types of payloads including tubulin and TOPI inhibitors were conjugated with different platforms, linkers, conjugation methods available from our linker-payload arsenal to obtain the optimal ADC. Here, we present a novel DLL3 targeted ADC, PLB-001, which using a highly potent topoisomerase I inhibitor exatecan, conjugated to a humanized IgG1 antibody, through a highly hydrophilic, enzyme-cleavable linker with a DAR of 8. PLB-001 demonstrated strong in vitro efficacy in several different SCLC cell lines correlating with DLL3 expression levels. This ADC also exhibited potent and durable antitumor effects in cell line-derived and patient-derived xenograft models, and exhibited favorable pharmacokinetic profiles. These preclinical result support PLB-001 as a potential candidate for the treatment of DLL3-positive SCLC Citation Format: Yingdong Lu, xin li, Ganyuan Xiao, Kia J. Puan, Ling xu, Mao Yin. PLB-001, a novel anti-dll3 ADC with topoisomerase 1 inhibitor-based linker-payload for treatment of SCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4746.
Abstract 3912: Transcriptional heterogeneity between hemangiosarcoma and nodular hyperplasia using patient-derived cell lines and orthotopic xenograft model revealed new therapeutic targets
Authors: Yishan Liu, Haru Yamamoto, Mohamed Elbadawy, Amira Abugomaa, Tatsuya Usui, Kazuaki Sasaki
Journal: Cancer Research (2025)

Abstract Human angiosarcoma (AS) is a rare and aggressive subtype of soft tissue sarcoma of endothelial cell origin with a propensity for local recurrence and metastasis. The optimal treatment of metastatic AS is unclear and is associated with a generally poor prognosis unless diagnosed early. The lack of insight into the pathogenesis always causes treatment failure in the clinic. To discover new treatment strategies for AS, it is necessary to develop new and relevant preclinical models for AS. Dogs commonly suffer from a similar neoplasm, called hemangiosarcoma (HA), with breeds like the golden retriever carrying heritable genetic factors that put them at high risk. Angiosarcomas and HA were reported to share pathology, immunohistochemical characteristics, and molecular signatures. Therefore, HA is considered a closer preclinical model for advancing AS research than rodent models. In veterinary clinic, malignant HA always occurs with nodular hyperplasia (NH), a kind of benign tumor. However, the AS orthotopic xenograft mouse still needs standard guidelines for validation. In this study, we successfully generated 5 canine HA cell lines from fresh patient tumor tissues. We compared the RNA sequencing data between HA and NH patient-derived cell strains (5:5). Data revealed that pathways related to autophagy and lysosomal membrane were found upregulated in HA compared to NH. Additionally, PIK3IP1, HIP1, PLAAT3, and MARVELD3 can be considered potential pharmacological targets and biomarkers for HA. Furthermore, we established an orthotopic xenograft model on mouse spleen using canine patient-derived HA cell lines by splenic injection. The results of xenograft spleen mass and drug screening test of toceranib, carboplatin, doxorubicin and cyclophosphamide using xenograft mouse HA cells showed corresponded sensitivity, supported that our model could maintain the original features of the patient tumor. In conclusion, the transcriptional difference between HA and NH might provide a better understanding of the progress of blood vessel sarcoma, and new pharmacological targets and biomarkers for diagnosis. Also, the xenograft model study may provide a reference for both AS and HA therapeutic predictions in basic medical science. Citation Format: Yishan Liu, Haru Yamamoto, Mohamed Elbadawy, Amira Abugomaa, Tatsuya Usui, Kazuaki Sasaki. Transcriptional heterogeneity between hemangiosarcoma and nodular hyperplasia using patient-derived cell lines and orthotopic xenograft model revealed new therapeutic targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3912.
Non–Risk-Based Lung Cancer Screening With Low-Dose Computed Tomography
Authors: Caichen Li, Bo Cheng, Jianfu Li, Shan Xiong, Wenhai Fu, Yu Jiang, Chujing Zhou, Ran Zhong, Feng Li, Qing Zhang, Hengrui Liang, Wei Wang, Chi-Fu Jeffrey Yang, Alexandra L. Potter, Xiaoqin Du, Qiuxia Qiu, Chunyu Yang, Baoqing Sun, Ying Chen, Junzhe Liu, Bin Xu, Nanshan Zhong, Wenhua Liang, Jianxing He
Journal: JAMA (2025)

This study assesses non–risk-based low-dose computed tomographic screening to assess lung cancer detection in the general population and evaluate outcomes by risk stratification.