tbuckley/cabot-search huggingface dataset:
Defeating lethal cancer: Interrupting the ecologic and evolutionary basis of death from malignancy
Authors: Kenneth J. Pienta, Patrick L. Goodin, Sarah R. Amend
Journal: CA A Cancer Journal for Clinicians (2025)

Despite the advances in cancer prevention, early detection, and treatments, all of which have led to improved cancer survival, globally, there is an increased incidence in cancer-related deaths. Although each patient and each tumor is wholly unique, the tipping point to incurable disease is common across all patients: the dual capacity for cancers to metastasize and resist systemic treatment. The discovery of genetic mutations and epigenetic variation that emerges during cancer progression highlights that evolutionary and ecology principles can be used to understand how cancer evolves to a lethal phenotype. By applying such an eco-evolutionary framework, the authors reinterpret our understanding of the metastatic process as one of an ecologic invasion and define the eco-evolutionary paths of evolving therapy resistance. With this understanding, the authors draw from successful strategies optimized in evolutionary ecology to define strategic interventions with the goal of altering the evolutionary trajectory of lethal cancer. Ultimately, studying, understanding, and treating cancer using evolutionary ecology principles provides an opportunity to improve the lives of patients with cancer.
Colorectal Cancer: Pathogenesis and Targeted Therapy
Authors: Jingyuan Li, Jiashu Pan, Lisheng Wang, Guang Ji, Yanqi Dang
Journal: MedComm (2025)

Colorectal cancer (CRC) ranks among the most prevalent malignant neoplasms globally. A growing body of evidence underscores the pivotal roles of genetic alterations and dysregulated epigenetic modifications in the pathogenesis of CRC. In recent years, the reprogramming of tumor cell metabolism has been increasingly acknowledged as a hallmark of cancer. Substantial evidence suggests a crosstalk between tumor cell metabolic reprogramming and epigenetic modifications, highlighting a complex interplay between metabolism and the epigenetic genome that warrants further investigation. Biomarkers associated with the pathogenesis and metabolic characteristics of CRC hold significant clinical implications. Nevertheless, elucidating the genetic, epigenetic, and metabolic landscapes of CRC continues to pose considerable challenges. Here, we attempt to summarize the key genes driving the onset and progression of CRC and the related epigenetic regulators, clarify the roles of gene expression and signaling pathways in tumor metabolism regulation, and explore the potential crosstalk between epigenetic events and tumor metabolic reprogramming, providing a comprehensive mechanistic explanation for the malignant progression of CRC. Finally, by integrating reliable targets from genetics, epigenetics, and metabolic processes that hold promise for translation into clinical practice, we aim to offer more strategies to overcome the bottlenecks in CRC treatment.
Emerging Pathogenetic Mechanisms and New Drugs for Anemia in Myelofibrosis and Myelodysplastic Syndromes
Authors: Naseema Gangat, Ayalew Tefferi
Journal: American Journal of Hematology (2025)

Anemia in myeloid neoplasms is multifaceted, with heterogeneous pathogenetic mechanisms that include ineffective erythropoiesis, hepcidin-induced iron-restricted erythropoiesis, and abnormal inflammatory cytokine production. Current management of anemia is challenged by limited approved drugs that specifically treat anemia in myelofibrosis (MF) and myelodysplastic syndrome (MDS). Newer therapies target the transforming growth factor beta (TGF-β)-bone morphogenic protein/sons of mothers against decapentaplegic (BMP-SMAD) signaling pathway, which plays a significant role in ineffective erythropoiesis (SMAD 2/3) and abnormal hepcidin production (SMAD 1/5/8). These include TGF-β ligand traps (luspatercept, elritercept), activin A receptor type 1 (ACVR1)/activin receptor-like kinase 2 (ALK2) inhibitors (momelotinib, zilurgisertib), and anti-hemojuvelin antibody-based therapies (DISC-0974). Luspatercept and momelotinib are approved for anemia related to lower-risk MDS and MF, respectively, and represent an important addition to the treatment armamentarium, along with imetelstat, a telomerase inhibitor, recently ratified for anemia in lower-risk MDS. A promising strategy to overcome the limitations of existing anemia-directed therapies includes the use of drug combinations with complementary mechanisms (luspatercept + erythropoiesis stimulating agents, luspatercept + momelotinib, DISC-0974 + momelotinib), and harnessing the erythropoietic potential of sodium-glucose co-transporter-2 inhibitors (SGLT-2I). Future research should address the complex pathophysiology of anemia, standardize definitions for anemia with gender-specified cutoffs, implement uniform erythroid response criteria, and consider early therapeutic intervention in clinical trials for anemia-directed therapies.
Depth of Response From Fixed‐Duration Treatment Is Associated With Superior Survival in Waldenstrom Macroglobulinemia
Authors: Jonas Paludo, Jithma P. Abeykoon, Nirosha D. Perera, Shayna Sarosiek, Joshua Gustine, Andres Ramirez‐Gamero, Marzia Varettoni, Alessandra Tedeschi, Chiara Cavalloni, Anna Maria Frustaci, Levi D. Pederson, Saurabh S. Zanwar, Prashant Kapoor, Thomas M. Habermann, Thomas E. Witzig, Robert A. Kyle, Morie A. Gertz, Susan M. Geyer, Steven P. Treon, Jorge J. Castillo, Stephen M. Ansell
Journal: American Journal of Hematology (2025)

As the treatment paradigm for Waldenström macroglobulinemia (WM) continues to evolve, the debate surrounding the prioritization of depth of response versus disease control as therapeutic goals gains significant relevance. However, the impact of depth of response from fixed-duration therapy on overall survival (OS) was unclear. This multicenter study evaluated the prognostic impact of depth of response using a landmark survival analysis. A total of 440 patients with WM treated with frontline fixed-duration regimens were included. Attaining a major response (MaR) was associated with superior outcomes, including significantly longer OS. The estimated 5-year PFS rates for patients with MaR at 6 months versus not were 50% versus 32%, respectively, p < 0.001, and the estimated 5-year OS rates for patients with MaR at 6 months versus not were 89% versus 70%, respectively, p < 0.001. In a multivariable analysis, MaR at 6 months was independently associated with superior PFS (HR 0.66, p = 0.007) and OS (HR 0.28, p < 0.001). Similar results were seen when considering deeper responses (CR + VGPR vs. PR). Depth of response at 6 months is an important prognostic marker in WM and an independent predictor of PFS and OS. These results support its utilization as a suitable endpoint in clinical studies in WM.
The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions
Authors: Huimin Yuan, Ruochen Xu, Senlin Li, Mengzhu Zheng, Qingyi Tong, Ming Xiang, Yonghui Zhang
Journal: MedComm (2025)

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, predominantly associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These infections drive persistent liver inflammation, culminating in cellular dysregulation, fibrosis, and cancer. Despite advancements in targeted therapies, drug resistance and the lack of reliable biomarkers for patient stratification still terribly hinder the treatment of viral HCC. To this end, the review delves into the intricate mechanisms underlying the malignant transformation of viral hepatitis to HCC, including viral integration, genomic instability, epigenetic modifications, oxidative stress, gut microbiota dysbiosis, chronic inflammation, immune escape, and abnormal signaling pathways, highlighting their complex interactions and synergies. Cutting-edge preclinical and clinical advancements in HCC management, including lifestyle modifications, drug therapies, immunotherapies, gene-based approaches, and innovative treatments, are further investigated, with particular priority given to their therapeutic potential and future applications in overcoming current limitations. By synthesizing recent scientific and clinical insights, this review aims to deepen the understanding of HCC pathogenesis in the context of chronic viral hepatitis, paving the way for novel therapeutic targets and personalized treatment strategies, ultimately improving patient outcomes.
Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia With Myelodysplasia‐Related Genetic Features: Relevance of the Genetic Underlying Category. A Retrospective Analysis on Behalf of the Acute Leukemia Working Party of the <scp>EBMT</scp>
Authors: Jordi Esteve, Arnon Nagler, Myriam Labopin, Jurjen Versluis, Jaime Sanz, Tobias Gedde‐Dahl, David Burns, Mieke Roeven, Hélène Labussière‐Wallet, Peter Von Dem Borne, Gwendolyn Van Gorkom, Nathalie Contentin, Andreas Neubauer, Eva Maria Wagner‐Drouet, Nicolaus Kröger, Mohamad Mohty, Fabio Ciceri
Journal: American Journal of Hematology (2025)

Patients (pts) with myelodysplasia-related AML (MR-AML) are now genetically recategorized, with three different groups in the International Consensus Classification: AML with mutated TP53 (TP53-AML), with myelodysplasia-related gene mutations (MR-GM AML), and with myelodysplasia-related cytogenetic abnormalities (MR-CG AML). Moreover, TP53-AML is determined by the presence of an additional complex karyotype (TP53-mut CK and non-CK AML, respectively). Nonetheless, the relevance of this classification to transplantation outcomes is largely unknown. We analyzed the outcomes of pts. with MR-AML undergoing allogeneic hematopoietic cell transplantation in first complete remission between 2010 and 2022 according to these genetic categories. Overall, 1152 patients were identified: 379 (33%), 328 (28%), 246 (21%), and 199 (17%) with MR-GM, TP53-mut CK, MR-CG, and TP53-mut non-CK AML, respectively. Median age was 60 years; median year of transplant was 2020. Unrelated donors and reduced-intensity conditioning were used in 65% and 61% of cases, respectively. Outcomes differed markedly among genetic categories, with an increasing relapse incidence (20.2%, 29.2%, 44.6%, and 57.6% at 2 years), and decreasing LFS (60%, 55.3%, 40.6%, and 20.2% at 2 years), overall survival (65.7%, 60.1%, 47.1%, and 24.5% at 2 years), and graft-versus-host disease-free, relapse-free survival (46.9%, 39.5%, 31.9%, and 13.2% at 2 years) in MR-GM, MR-CG, TP53-mut non-CK, and TP53-mut CK AML, respectively. These differences were confirmed in the multivariate analysis (hazard ratio for LFS: 0.21, 0.33 and 0.61 in MR-GM, MR-CG, and TP53-mut non-CK, with respect to reference TP53-mut CK AML group). This study confirms the strong impact of genetic grouping of MR-AML on transplant outcomes.
Donor Age Matters for Haploidentical <scp>HCT</scp> Patients Even After Adjusting for <scp>HLA</scp> Factors: A Machine Learning Approach
Authors: Rohtesh S. Mehta, Rodney Sparapani, Tao Wang, Stephen Spellman, Stephanie J. Lee, Effie W. Petersdorf
Journal: American Journal of Hematology (2025)
Gasotransmitters in Modern Medicine: Promises and Challenges in the Use of Porous Crystalline Carriers
Authors: Rosana V. Pinto, Moisés L. Pinto, Christian Serre
Journal: Advanced Healthcare Materials (2025)

Gas therapy using gasotransmitters is of exponential interest due to the growing recognition of gas signaling molecules that can be involved in multiple therapeutic actions. Finding suitable methods for delivering these molecules is crucial, and porous materials, notably metal-organic frameworks (MOFs), have shown exceptional potential as gas carriers, enabling safe and controlled local delivery. The challenges to translate these MOF therapies to clinical use require not only to validate the mechanisms of action and signaling pathways for the released gas molecules but also get a deep understanding into the MOF rational design, as it requires a combination of features to maximize the therapeutic outcomes. In this perspective, we outline the key criteria for designing suitable MOFs for gas delivery applications and highlight the expanding range of therapeutic opportunities these materials may offer. Readers can use these insights of MOF design and features to develop gasotransmitter therapies with realistic clinic interest.
GLP-1 receptor agonists in kidney transplant recipients with pre-existing diabetes: a retrospective cohort study
Authors: Babak J Orandi, Yusi Chen, Yiting Li, Garyn T Metoyer, Krista L Lentine, Michael Weintraub, Sunjae Bae, Nicole M Ali, Bonnie E Lonze, Christine J Ren-Fielding, Holly Lofton, Akash Gujral, Dorry L Segev, Mara McAdams-DeMarco
Journal: The Lancet Diabetes & Endocrinology (2025)
Adverse Impact of Pre‐Transplant Liver Dysfunction in Allogeneic Hematopoietic Cell Transplantation
Authors: Yukiko Misaki, Masaharu Tamaki, Ryu Yanagisawa, Noriko Doki, Naoyuki Uchida, Masatsugu Tanaka, Tetsuya Nishida, Masashi Sawa, Yuta Hasegawa, Shuichi Ota, Makoto Onizuka, Sakata‐Yanagimoto Mamiko, Yuta Katayama, Noboru Asada, Junya Kanda, Takahiro Fukuda, Yoshiko Atsuta, Yoshinobu Kanda, Kimikazu Yakushijin, Hideki Nakasone
Journal: American Journal of Hematology (2025)

Although the hematopoietic cell transplantation (HCT)-comorbidity index (HCT-CI) score is associated with an increased risk of mortality after allogeneic HCT, it remains unclear how pre-HCT liver dysfunction affects clinical outcomes. We retrospectively compared clinical HCT outcomes among four groups stratified according to the presence of HCT-CI liver and other organ scores, using a Japan transplant registry database between 2010 and 2020. Of the 14235 recipients, 1527 tested positive for an HCT-CI liver score including HBV or HCV hepatitis (n = 503). The 5-year overall survival (OS) was significantly lower in the HCT-CI liver(+) other(+) and HCT-CI liver(-) other(+) groups compared to the HCT-CI liver(+) other(-) and HCT-CI liver(-) other(-) groups [49.9% vs. 59% vs. 66.5% vs. 68.3%, p < 0.001]. A multivariate analysis showed that both the HCT-CI liver(+) other(+) [HR 1.62, p < 0.001] and HCT-CI liver(-) other(+) groups [HR 1.21, p < 0.001] were significantly associated with inferior OS. Similarly, both the HCT-CI liver(+) other(+) [HR 1.89, p < 0.001] and liver(-) other(+) groups [HR 1.26, p < 0.001] were significantly associated with an increased risk of NRM. On the other hand, the HCT-CI liver(+) other(-) group was not associated with either OS or NRM. Separately analyzing the subcohorts with or without HCT-CI other scores, the presence of an HCT-CI liver score alone did not affect survival, while the co-presence of pretransplant liver dysfunction seemed to synergistically increase the adverse impact on OS and NRM among recipients with other organ comorbidities. Further studies will be needed to identify optimal strategies for recipients with pretransplant liver dysfunction.
Non‐Covalent Interaction Induced Supramolecular Precipitate with Hetero‐Motif Polyionic Junction for Durable Antimicrobial Activity and Infected Wound Healing
Authors: Xuejiao Wang, Lianbo He, Huanling He, Qiyang Cai, Zhi Su, Hao Sun, Hu Zhu
Journal: Advanced Healthcare Materials (2025)

The advent of the COVID-19 pandemic has underscored the pressing demand for antimicrobial materials that offer both durability and efficacy. Herein, the successful design and fabrication of a "water-insoluble" supramolecular precipitate is reported through the "bottom-up" assembly of polyanion sodium alginate (SA) with the antimicrobial motifs A2G and Cu2+. This innovative hetero-motif polyionic junction leverages a network of hydrogen bonds aligning with electrostatic interactions, and hydrophobic effects to mitigate the rapid release of active components, providing exceptional long-term antimicrobial efficacy against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Candida albicans (C. albicans). Specifically, it retains an impressive 99.9% efficacy against S. aureus even after enduring 10 successive wash cycles. The hydroxyl groups in A2G-Cu-SA confer exceptional adhesion to a wide array of substrates. This robust adherence is complemented by its enduring antibacterial properties, with the material maintaining a 99.9% efficacy rate after being submerged in water for an extended period of 100 days. In vivo and in vitro studies substantiate the biocompatibility of A2G-Cu-SA, while its clinical potential is evidenced by the enhanced healing of S. aureus-infected wounds upon titanium sheet coating. This innovation meets the current need for effective antimicrobials and contributes to sustainable medical advancements.
Loss of Socs2 improves molecular responses to IFNα in a mouse model of myeloproliferative neoplasms driven by JAK2-V617F
Authors: Marc Usart, Quentin Kimmerlin, Jan Stetka, Cédric Stoll, Shivam Rai, Tiago Almeida Fonseca, Riikka Karjalainen, Hui Hao-Shen, Julien Roux, Athimed El Taher, Dylan Lynch, Nikolai Makukhin, Alessio Ciulli, Radek C. Skoda
Journal: Leukemia (2025)
A prospective ultrasound study of whole blood metals and incidence of uterine leiomyomata
Authors: Ruth Geller, Amelia K. Wesselink, Birgit Claus Henn, Kristen Upson, Marco Vinceti, Quaker E. Harmon, Donna D. Baird, Ganesa Wegienka, Lauren A. Wise
Journal: Environmental Health Perspectives (2025)

Uterine leiomyomata (UL), hormone-dependent neoplasms, are a major source of gynecologic morbidity. Metals are hypothesized to influence UL risk through endocrine disruption, and their effects may vary by vitamin D status.
The IL-6 axis in vascular inflammation: effects of IL-6 receptor blockade on vascular lesions from patients with giant-cell arteritis
Authors: Marc Corbera-Bellalta, Farah Kamberovic, Roser Alba-Rovira, Ester Planas-Rigol, Sergio Prieto-González, Núria Farran-Centelles, Ester Tobías, Anna Jordán, Marco A Alba, Eduard Quintana, Georgina Espígol-Frigolé, Maria C Cid
Journal: Annals of the Rheumatic Diseases (2025)

Blocking interleukin (IL)-6-receptor with tocilizumab has been a major advance in the treatment of giant-cell arteritis (GCA), supporting a crucial role of IL-6 receptor signalling. However, nearly half of the patients are not able to maintain glucocorticoid- free remission with tocilizumab. The impact of tocilizumab on vascular lesions of GCA is largely unknown since conflicting results have been obtained by imaging. The expression and functional role of IL-6-receptor in GCA immunopathology has not been previously investigated. This study aimed to investigate expression of IL-6 receptor in GCA and control arteries and to assess the impact of tocilizumab on ex vivo-cultured temporal arteries and aortic tissue from patients with GCA. This study used a hypothesis-driven, candidate molecule transcriptomic approach using ex vivo temporal artery and aortic tissue culture, quantitative real-time polymerase chain reaction, immunofluorescence, Western Blot, immunoassay, adhesion, and chemotaxis assays. IL-6 receptor protein expressed intensively in GCA compared with that in control arteries. Tocilizumab decreased expression/phosphorylation of STAT3 and reduced expression of STAT3-dependent molecules including suppressor of cytokine signalling 3, CCL-2, and ICAM-1 in cultured GCA-involved arteries and patients' peripheral blood mononuclear cells (PBMCs). A similar trend was observed in aortic tissue. Consistently, tocilizumab reduced PBMC adhesiveness to vascular smooth muscle cells and human umbilical vein endothelial cells and chemotaxis towards supernatants of tocilizumab-treated GCA arteries. In some specimens, tocilizumab increased STAT1 phosphorylation and expression of STAT1-dependent chemokines including CXCL9 and CXCL10. Tocilizumab has a significant impact on vascular lesions by reducing, but not abrogating, key molecules involved in PBMC recruitment. About half of the patients may activate alternative inflammatory pathways in their lesions as a potential escape mechanism to tocilizumab that deserves further investigation.
Addendum: Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease
Authors: Erik Schäffner, Mar Bosch-Queralt, Julia M. Edgar, Maria Lehning, Judith Strauß, Niko Fleischer, Theresa Kungl, Peter Wieghofer, Stefan A. Berghoff, Tilo Reinert, Martin Krueger, Markus Morawski, Wiebke Möbius, Alonso Barrantes-Freer, Jens Stieler, Ting Sun, Gesine Saher, Markus H. Schwab, Christoph Wrede, Maximilian Frosch, Marco Prinz, Daniel S. Reich, Alexander Flügel, Christine Stadelmann, Robert Fledrich, Klaus-Armin Nave, Ruth M. Stassart
Journal: Nature Neuroscience (2025)
A phase II trial of Naxitamab plus stepped-up dosing of GM-CSF for patients with high-risk neuroblastoma in first complete remission
Authors: Brian H. Kushner, Shakeel Modak, Audrey Mauguen, Ellen M. Basu, Kim Kramer, Stephen S. Roberts, Irene Y. Cheung, Nai-Kong V. Cheung
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Naxitamab is a humanized form of the murine anti-GD2 monoclonal antibody (mAb) 3F8. In an international trial, naxitamab+GM-CSF was effective against chemo-resistant high-risk neuroblastoma (HR-NB), leading to approval by the Food and Drug Administration. We now report results with patients in 1st complete remission (CR). Patients and Methods: The primary objective of this phase II protocol 16-1643 (Clinicaltrials.gov NCT03033303) was to assess event-free survival (EFS) of HR-NB patients in 1st CR treated with naxitamab+GM-CSF plus isotretinoin. HR-NB was defined as MYCN-amplified disease (any age) or metastatic disease at age &amp;gt;18 months. Cycles of immunotherapy were administered monthly up to 5 cycles and comprised: 1) subcutaneously-administered priming doses of GM-CSF 250µg/m2/day on days -4-to-0 (Wednesday-Sunday), followed by a step-up to 500µg/m2/day on days +1-to-+5 (Monday-Friday), and 2) naxitamab infused intravenously (30-90”) on days +1, +3, and +5 (Monday-Wednesday-Friday, i.e., 3 doses/cycle). Naxitamab was 3mg/kg/infusion (9mg/kg/cycle, i.e., ~270mg/m2/cycle). Isotretinoin 160mg/m2/day started post-cycle 2, x14 days/course, x6 courses. Results: Fifty-nine HR-NB patients (53 stage 4, 6 stage 3) were enrolled 2/2017-7/2020. At 36 months, EFS/OS were 73%/93%, but 50/59 patients received post-protocol treatment (vaccine and/or DFMO). 6/18 relapses were isolated in the central nervous system (CNS). Longer time from diagnosis to enrollment was a significantly adverse prognostic factor (p=0.04). 21/59 patients took no isotretinoin. Treatment was tolerable allowing outpatient administration. Conclusions: Naxitamab+GM-CSF is a good option to consolidate 1st CR of HR-NB patients, including those who did not undergo ASCT. Efforts to prevent CNS relapse are warranted.