tbuckley/cabot-search huggingface dataset:
NCCN Guidelines® Insights: Palliative Care, Version 2.2021
Authors: Maria Dans, Jean S. Kutner, Rajiv Agarwal, Justin N. Baker, Jessica R. Bauman, Anna C. Beck, Toby C. Campbell, Elise C. Carey, Amy A. Case, Shalini Dalal, Danielle J. Doberman, Andrew S. Epstein, Leslie Fecher, Joshua Jones, Jennifer Kapo, Richard T. Lee, Elizabeth T. Loggers, Susan McCammon, William Mitchell, Adeboye B. Ogunseitan, Diane G. Portman, Kavitha Ramchandran, Linda Sutton, Jennifer Temel, Melissa L. Teply, Stephanie Y. Terauchi, Jane Thomas, Anne M. Walling, Finly Zachariah, Mary Anne Bergman, Ndiya Ogba, Mallory Campbell
Journal: Journal of the National Comprehensive Cancer Network (2021)

Palliative care has evolved to be an integral part of comprehensive cancer care with the goal of early intervention to improve quality of life and patient outcomes. The NCCN Guidelines for Palliative Care provide recommendations to help the primary oncology team promote the best quality of life possible throughout the illness trajectory for each patient with cancer. The NCCN Palliative Care Panel meets annually to evaluate and update recommendations based on panel members' clinical expertise and emerging scientific data. These NCCN Guidelines Insights summarize the panel's recent discussions and highlights updates on the importance of fostering adaptive coping strategies for patients and families, and on the role of pharmacologic and nonpharmacologic interventions to optimize symptom management.
Alternatively Spliced Tissue Factor Promotes Atherosclerosis by Increasing Foam Cell Formation via LOX-1 and SR-A1 up-regulation
Authors: Daniel Alicea, Saboor Hekmaty, David T. Rodriguez, Peter Bhandari, Dong Kwong Yang, Dongtak Jeong, Jason C. Kovacic, Johan L. Bjorkegren, Juan J. Badimon, Thomas Weber, Roger J. Najjar, Valentin Fuster, Chiara Giannarelli
Journal: Circulation (2015)
Continuous versus intermittent extended adjuvant letrozole for breast cancer: final results of randomized phase III SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy
Authors: G. Jerusalem, S. Farah, A. Courtois, J. Chirgwin, S. Aebi, P. Karlsson, P. Neven, E. Hitre, M.P. Graas, E. Simoncini, E. Abdi, C. Kamby, A. Thompson, S. Loibl, J. Gavilá, K. Kuroi, C. Marth, B. Müller, S. O’Reilly, A. Gombos, T. Ruhstaller, H.J. Burstein, M. Rabaglio, B. Ruepp, K. Ribi, G. Viale, R.D. Gelber, A.S. Coates, S. Loi, A. Goldhirsch, M.M. Regan, M. Colleoni
Journal: Annals of Oncology (2021)
Thematic Analysis of Challenges of Care Coordination for Underinsured and Uninsured Cancer Survivors With Chronic Conditions
Authors: Bijal A. Balasubramanian, Robin T. Higashi, Serena A. Rodriguez, Navid Sadeghi, Noel O. Santini, Simon Craddock Lee
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Although a majority of underinsured and uninsured patients with cancer have multiple comorbidities, many lack consistent connections with a primary care team to manage chronic conditions during and after cancer treatment. This presents a major challenge to delivering high-quality comprehensive and coordinated care. <h3>Objective</h3> To describe challenges and opportunities for coordinating care in an integrated safety-net system for patients with both cancer and other chronic conditions. <h3>Design, Setting, and Participants</h3> This multimodal qualitative study was conducted from May 2016 to July 2019 at a county-funded, vertically integrated safety-net health system including ambulatory oncology, urgent care, primary care, and specialty care. Participants were 93 health system stakeholders (clinicians, leaders, clinical, and administrative staff) strategically and snowball sampled for semistructured interviews and observation during meetings and daily processes of care. Data collection and analysis were conducted iteratively using a grounded theory approach, followed by systematic thematic analysis to organize data, review, and interpret comprehensive findings. Data were analyzed from March 2019 to March 2020. <h3>Main Outcomes and Measures</h3> Multilevel factors associated with experiences of coordinating care for patients with cancer and chronic conditions among oncology and primary care stakeholders. <h3>Results</h3> Among interviews and observation of 93 health system stakeholders, system-level factors identified as being associated with care coordination included challenges to accessing primary care, lack of communication between oncology and primary care clinicians, and leadership awareness of care coordination challenges. Clinician-level factors included unclear role delineation and lack of clinician knowledge and preparedness to manage the effects of cancer and chronic conditions. <h3>Conclusions and Relevance</h3> Primary care may play a critical role in delivering coordinated care for patients with cancer and chronic diseases. This study's findings suggest a need for care delivery strategies that bridge oncology and primary care by enhancing communication, better delineating roles and responsibilities across care teams, and improving clinician knowledge and preparedness to care for patients with cancer and chronic conditions. Expanding timely access to primary care is also key, albeit challenging in resource-limited safety-net settings.
Simple Intervention Motivates Expectant Fathers to Quit Smoking
Authors: Anita Slomski
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
DNA-PK inhibition by M3814 enhances chemosensitivity in non-small cell lung cancer
Authors: Manni Wang, Siyuan Chen, Yuquan Wei, Xiawei Wei
Journal: Acta Pharmaceutica Sinica B (2021)

A significant proportion of non-small cell lung cancer (NSCLC) patients experience accumulating chemotherapy-related adverse events, motivating the design of chemosensitizating strategies. The main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks (DSB). It is thus conceivable that DNA-dependent protein kinase (DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy. The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC. We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis. M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549, H460 and H1703 NSCLC cell lines. In the four combinations based on two NSCLC xenograft models and two chemotherapy, we also observed tumor regression at tolerated doses in vivo. Moreover, we identified a P53-dependent accelerated senescence response by M3814 following treatment with paclitaxel/etoposide. The present study provides a theoretical basis for the use of M3814 in combination with paclitaxel and etoposide in clinical practice, with hope to aid the optimization of NSCLC treatment.
A prevalent neglect of environmental control in mammalian cell culture calls for best practices
Authors: Shannon G. Klein, Samhan M. Alsolami, Alexandra Steckbauer, Silvia Arossa, Anieka J. Parry, Gerardo Ramos Mandujano, Khaled Alsayegh, Juan Carlos Izpisua Belmonte, Mo Li, Carlos M. Duarte
Journal: Nature Biomedical Engineering (2021)
Abstract #190: Identification and characterization of tumor-initiating cells with stem-like properties from a recurrent hepatocellular carcinoma
Authors: Zhiqian Zhang, Xiaolan Xu, Baocai Xing, Yu Wang, Haibo Han, Wei Zhao
Journal: Cancer Research (2009)

The high rate of recurrence has been the major thread for hepatocellular carcinoma (HCC) treatment. However, little is known about the biological characteristics of recurrent HCC cells. Two cell lines, Hep-11 and Hep-12, were established from a single HCC patient\#8217;s primary and recurrent tumor tissues respectively, and were proved to have the same clone origin. The Hep-12 cells, originated from the recurrent HCC,possessed strong clonogenic potential in soft agar, as few as 100 Hep-12 cells could initiate tumor growth in serial transplantation assay, and all single Hep-12 clones obtained by limit dilution were tumorigenic, while the primary HCC-derived Hep-11 cells were non-tumorigenic even with 10,000 cells injected. Compared with Hep-11, Hep-12 were more sensitive to paclitaxel, but more resistant to doxorubicin (ADM), cisplatin (DPP) and hydroxycamptothecin (HCPT) which had been previously administrated to the patient. Furthermore, Hep-12 expressed higher level of Poly (ADP-ribose) polymerase-1 (PARP-1) than Hep-11, and PARP-1 inhibition potentiated the sensitivity to HCPT in Hep-12 but not in Hep-11. These results demonstrated that most of the recurrent HCC-derived cells, Hep-12, were tumor-initiating cells with stem-like properties and selective drug resistance profile, and the elevated expression of PARP-1 was responsible for their resistance to HCPT. These would provide important information for designing therapeutic strategies against recurrent HCC.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 190.
Sub 5 nm Gd<sup>3+</sup>–Hemoporfin Framework Nanodots for Augmented Sonodynamic Theranostics and Fast Renal Clearance
Authors: Peng Geng, Nuo Yu, Xiaohan Liu, Qin Zhu, Mei Wen, Qian Ren, Pu Qiu, Haijun Zhang, Maoquan Li, Zhigang Chen
Journal: Advanced Healthcare Materials (2021)

Abstract Metal–organic nanomaterials have emerged as promising therapeutic agents to produce reactive oxygen species (ROS) under ultrasound (US) or light irradiation for tumor treatments. However, their relatively large sizes (ranging from tens to hundreds of nanometers) usually lead to low ROS utilization and body metabolism, thus enlarging their long‐term toxicity and low therapeutic effect. To solve these shortcomings, herein the ultrasmall Gd 3+ –hemoporfin framework nanodots (GdHF‐NDs， ≈5 nm) is reported as efficient nano‐sonosensitizers. Compared with GdHF aggregation (GdHF‐A, ≈400 nm), the ultrasmall GdHF‐NDs generate 2.3‐fold toxic ROS amount under similar conditions, due to shorter diffusion path and larger relative specific surface area. When the GdHF‐NDs dispersion is introvenously injected into tumor‐bearing mouse, they are accumulated within tumors to provide high magnetic resonance imaging (MRI) contrast. Under US irradiation, the GdHF‐NDs achieve a better sonodynamic therapeutic efficacy for tumors, compared with that from GdHF‐A. More importantly, owing to ultrasmall size, most of GdHF‐NDs can be rapidly cleared through the renal pathway. Therefore, GdHF‐NDs can be used as a biosafety and high‐performance sonodynamic agent for cancer theranostics.
Larotrectinib in a Patient With Advanced Pleomorphic Liposarcoma of the Uterus
Authors: Anisley Valenciaga, O. Hans Iwenofu, Gabriel Tinoco
Journal: Journal of the National Comprehensive Cancer Network (2021)

Pleomorphic liposarcoma of the uterus (PLU) is an extremely rare disease with poor prognosis. Limited treatment options exist for these patients, and disease recurrence usually occurs rapidly within months of initial diagnosis. Few case reports of metastatic PLU are available in the literature. We describe a 70-year-old woman who presented with a large uterus and ovarian mass on imaging and negative serum tumor markers and endometrial biopsy. Staging revealed localized disease. Surgical resection revealed PLU on pathology. Immunohistochemistry was negative for smooth muscle actin (SMA), S100, and MDM2, and positive for CD10 and cyclin-D1. She was treated with adjuvant therapy and experienced disease recurrence in the liver at 15 months from surgery. Genetic testing of the metastasis showed IQGAP - NTRK3 gene fusion. She was given entrectinib but continued to show progression in the liver. Right partial hepatectomy was performed, showing positivity for CD10, BCL-1, MDM2, and SMA on tumor staining. Treatment was switched to pazopanib with disease progression in the neck. She was treated with larotrectinib last, showing no disease progression and adequate tolerance of therapy after 18 months of this treatment. This is the first case in the literature of metastatic PLU with NRTK3 fusion treated with sequential first-generation NRTK inhibitors. More case reports are needed to identify commonalities and therapeutic options. Genetic testing in all PLU cases is needed for targeted therapy approaches.
生成3次元血管柄付き骨のための工学的光橋かけ二成分ヒドロゲル構築物【Powered by NICT】
Authors: Kazemzadeh-Narbat Mehdi, Rouwkema Jeroen, Annabi Nasim, Cheng Hao, Ghaderi Masoumeh, Cha Byung-Hyun, Aparnathi Mansi, Khalilpour Akbar, Byambaa Batzaya, Jabbari Esmaiel, Tamayol Ali, Khademhosseini Ali
Journal: Advanced Healthcare Materials (2017)
Lung-Resident Memory CD8<sup>+</sup> T Cells in Human Influenza: How Innate Are They?
Authors: Thi H. O. Nguyen, Katherine Kedzierska
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

cancer risk existed across GRS categories, and there was additive interaction between these two parameters.Hence, compared with those with low GRS and low air pollution, the high GRS and high pollution group had the highest risk of lung cancer.This occurred using multiple measures of pollution.Of note, exposures below the current regulated threshold levels were significantly linearly associated with lung cancer risk.The study is not without limitations.The exposure measures were based on a single sampling at baseline.Therefore, there is a potential for exposure misclassification during follow up.Moreover, this cohort design may be prone to left truncation, whereby subjects at risk before baseline do not remain observable until the start of follow up, leading to potential bias in the presence, direction, or magnitude of an association.Some other sources of lung carcinogen exposure were not characterized, such as occupational exposures.Finally, the smoking variables were simple, with 15% missing and imputed, although sensitivity analysis found robust results.The generalizability to other world populations, with different population admixture, requires further study.Nevertheless, the results are impressive and highlight the importance of improving air quality, even below current thresholds values.Although additional gene-environment interaction studies such as this one are needed to identify specific interactions, the highest priority should remain enforceable societal-level actions to reduce exposure to air pollution globally.Susceptibility to diseases such as lung cancer is conferred not only by heritable factors but also acquired ones, such as comorbidities, age, and socioeconomic disparities.The most effective public health policy is to protect those among us who are more vulnerable, thus affording a wider umbrella of protection for the entire population.
A calmodulin-binding transcription factor links calcium signaling to antiviral RNAi defense in plants
Authors: Yunjing Wang, Qian Gong, Yuyao Wu, Fan Huang, Asigul Ismayil, Danfeng Zhang, Huangai Li, Hanqing Gu, Márta Ludman, Károly Fátyol, Yijun Qi, Keiko Yoshioka, Linda Hanley-Bowdoin, Yiguo Hong, Yule Liu
Journal: Cell Host & Microbe (2021)
Novel oncolytic adenovirus expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitor activates multiple immune effector populations leading to enhanced tumor killing in vitro, in vivo and with patient-derived tumor organoids
Authors: Firas Hamdan, Erkko Ylösmäki, Jacopo Chiaro, Yvonne Giannoula, Maeve Long, Manlio Fusciello, Sara Feola, Beatriz Martins, Michaela Feodoroff, Gabriella Antignani, Salvatore Russo, Otto Kari, Moon Hee Lee, Petrus Järvinen, Harry Nisen, Anna Kreutzman, Jeanette Leusen, Satu Mustjoki, Thomas G McWilliams, Mikaela Grönholm, Vincenzo Cerullo
Journal: Journal for ImmunoTherapy of Cancer (2021)

Despite the success of immune checkpoint inhibitors against PD-L1 in the clinic, only a fraction of patients benefit from such therapy. A theoretical strategy to increase efficacy would be to arm such antibodies with Fc-mediated effector mechanisms. However, these effector mechanisms are inhibited or reduced due to toxicity issues since PD-L1 is not confined to the tumor and also expressed on healthy cells. To increase efficacy while minimizing toxicity, we designed an oncolytic adenovirus that secretes a cross-hybrid Fc-fusion peptide against PD-L1 able to elicit effector mechanisms of an IgG1 and also IgA1 consequently activating neutrophils, a population neglected by IgG1, in order to combine multiple effector mechanisms.The cross-hybrid Fc-fusion peptide comprises of an Fc with the constant domains of an IgA1 and IgG1 which is connected to a PD-1 ectodomain via a GGGS linker and was cloned into an oncolytic adenovirus. We demonstrated that the oncolytic adenovirus was able to secrete the cross-hybrid Fc-fusion peptide able to bind to PD-L1 and activate multiple immune components enhancing tumor cytotoxicity in various cancer cell lines, in vivo and ex vivo renal-cell carcinoma patient-derived organoids.Using various techniques to measure cytotoxicity, the cross-hybrid Fc-fusion peptide expressed by the oncolytic adenovirus was shown to activate Fc-effector mechanisms of an IgA1 (neutrophil activation) as well as of an IgG1 (natural killer and complement activation). The activation of multiple effector mechanism simultaneously led to significantly increased tumor killing compared with FDA-approved PD-L1 checkpoint inhibitor (Atezolizumab), IgG1-PDL1 and IgA-PDL1 in various in vitro cell lines, in vivo models and ex vivo renal cell carcinoma organoids. Moreover, in vivo data demonstrated that Ad-Cab did not require CD8+ T cells, unlike conventional checkpoint inhibitors, since it was able to activate other effector populations.Arming PD-L1 checkpoint inhibitors with Fc-effector mechanisms of both an IgA1 and an IgG1 can increase efficacy while maintaining safety by limiting expression to the tumor using oncolytic adenovirus. The increase in tumor killing is mostly attributed to the activation of multiple effector populations rather than activating a single effector population leading to significantly higher tumor killing.
MICA/B antibody induces macrophage-mediated immunity against acute myeloid leukemia
Authors: Pedro Henrique Alves da Silva, Samantha Xing, Andriana G. Kotini, Eirini P. Papapetrou, Xiaoyu Song, Kai W. Wucherpfennig, John Mascarenhas, Lucas Ferrari de Andrade
Journal: Blood (2021)
Neonatal Fc receptor-targeted lignin-encapsulated porous silicon nanoparticles for enhanced cellular interactions and insulin permeation across the intestinal epithelium
Authors: João P. Martins, Patrícia Figueiredo, Shiqi Wang, Erika Espo, Elena Celi, Beatriz Martins, Marianna Kemell, Karina Moslova, Ermei Mäkilä, Jarno Salonen, Mauri A. Kostiainen, Christian Celia, Vincenzo Cerullo, Tapani Viitala, Bruno Sarmento, Jouni Hirvonen, Hélder A. Santos
Journal: Bioactive Materials (2021)

Oral insulin delivery could change the life of millions of diabetic patients as an effective, safe, easy-to-use, and affordable alternative to insulin injections, known by an inherently thwarted patient compliance. Here, we designed a multistage nanoparticle (NP) system capable of circumventing the biological barriers that lead to poor drug absorption and bioavailability after oral administration. The nanosystem consists of an insulin-loaded porous silicon NP encapsulated into a pH-responsive lignin matrix, and surface-functionalized with the Fc fragment of immunoglobulin G, which acts as a targeting ligand for the neonatal Fc receptor (FcRn). The developed NPs presented small size (211 ± 1 nm) and narrow size distribution. The NPs remained intact in stomach and intestinal pH conditions, releasing the drug exclusively at pH 7.4, which mimics blood circulation. This formulation showed to be highly cytocompatible, and surface plasmon resonance studies demonstrated that FcRn-targeted NPs present higher capacity to interact and being internalized by the Caco-2 cells, which express FcRn, as demonstrated by Western blot. Ultimately, in vitro permeability studies showed that Fc-functionalized NPs induced an increase in the amount of insulin that permeated across a Caco-2/HT29-MTX co-culture model, showing apparent permeability coefficients (Papp ) of 2.37 × 10-6 cm/s, over the 1.66 × 10-6 cm/s observed for their non-functionalized counterparts. Overall, these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.
CXCR4 hyperactivation cooperates with TCL1 in CLL development and aggressiveness
Authors: Richard Lewis, H. Carlo Maurer, Nikita Singh, Irene Gonzalez-Menendez, Matthias Wirth, Markus Schick, Le Zhang, Konstandina Isaakidis, Anna Katharina Scherger, Veronika Schulze, Junyan Lu, Thorsten Zenz, Katja Steiger, Roland Rad, Leticia Quintanilla-Martinez, Marion Espeli, Karl Balabanian, Ulrich Keller, Stefan Habringer
Journal: Leukemia (2021)

Abstract Aberrant CXCR4 activity has been implicated in lymphoma pathogenesis, disease progression, and resistance to therapies. Using a mouse model with a gain-of-function CXCR4 mutation ( CXCR4 C1013G ) that hyperactivates CXCR4 signaling, we identified CXCR4 as a crucial activator of multiple key oncogenic pathways. CXCR4 hyperactivation resulted in an expansion of transitional B1 lymphocytes, which represent the precursors of chronic lymphocytic leukemia (CLL). Indeed, CXCR4 hyperactivation led to a significant acceleration of disease onset and a more aggressive phenotype in the murine Eµ-TCL1 CLL model. Hyperactivated CXCR4 signaling cooperated with TCL1 to cause a distinct oncogenic transcriptional program in B cells, characterized by PLK1/FOXM1-associated pathways. In accordance, Eµ-TCL1;CXCR4 C1013G B cells enriched a transcriptional signature from patients with Richter’s syndrome, an aggressive transformation of CLL. Notably, MYC activation in aggressive lymphoma was associated with increased CXCR4 expression. In line with this finding, additional hyperactive CXCR4 signaling in the Eµ-Myc mouse, a model of aggressive B-cell cancer, did not impact survival. In summary, we here identify CXCR4 hyperactivation as a co-driver of an aggressive lymphoma phenotype.
Seven years later: do we still have an EDGE?
Authors: Prashant Kedia
Journal: Endoscopy (2021)

I read with pleasure the systemic review of Prakash et al. on the outcomes, adverse events, and knowledge gaps of endoscopic ultrasound (EUS)-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) [1]. EDGE was the first example of an EUS-directed entero-enteral anastomosis performed in a human using a lumen-apposing metal stent (LAMS) [2]. While initially met with criticism, EDGE has become accepted as a viable technique to manage pancreaticobiliary disease in patients with Roux-en-Y gastric bypass (RYGB) anatomy. Since its use in EDGE, EUS-guided entero-enteral anastomoses have been expanded to the management of other disease processes, including gastric outlet obstruction and afferent loop syndrome. Despite the increasing popularity of EDGE, a lack of procedural standardization and large-scale generalizable data on its short- and long-term outcomes have hindered its widespread adoption.