tbuckley/cabot-search huggingface dataset:
Abstract IA018: Linking obesity-associated inflammation with cancer metastasis
Authors: Sheri A. McDowell, Robin Luo, Jonathan D. Spicer, Andrew J. Dannenberg, Logan A. Walsh, Daniela F. Quail
Journal: Cancer Research (2021)

Abstract Obesity is associated with increased incidence and mortality of multiple tumor types, and competes with smoking tobacco as the leading preventable risk factor for all cancer-related deaths. In breast cancer, epidemiological studies have shown that obesity is linked to enhanced metastasis to lung and liver. However, it is not known how to improve cancer outcomes in the obese patient population as the mechanistic link between obesity and cancer progression is currently lacking. Using genetic and diet-induced obesity mouse models, it was previously shown that obesity promotes pulmonary metastasis of breast cancer by inducing lung neutrophilia via a IL5–GM-CSF signaling axis. We have now determined that neutrophils are reprogrammed by obesity within the lung to produce elevated levels of reactive oxygen species (ROS) and release neutrophil extracellular traps (NETs). This in turn weakens endothelial barrier integrity, leading to enhanced microvascular permeability and tumor cell extravasation into the lung parenchyma. This effect can be reversed by targeting ROS via pharmacological or genetic approaches, or by preventing NETosis using PAD4 inhibitors. To confirm the translational relevance of our findings, we performed imaging mass cytometry on lung metastasis samples from cancer patients, and observed a significant correlation between body mass index and NETosis, neutrophil oxidative burst, and ROS status. Given the high prevalence of obesity on an international scale, our data provide insight into mechanisms of cancer progression for a significant proportion of the adult population, including (potentially) those who are metabolically obese but normal weight. Citation Format: Sheri A. McDowell, Robin Luo, Jonathan D. Spicer, Andrew J. Dannenberg, Logan A. Walsh, Daniela F. Quail. Linking obesity-associated inflammation with cancer metastasis [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA018.
Abstract 12248: The Beneficial Effects of Cardiac Stem Cell Therapy on Left Ventricular Function and Structure Persists for at Least One Year in Rats With Acute Myocardial Infarction
Authors: Xian-liang Tang, Qianhong Li, Gregg Rokosh, Ning Chen, Santosh K Sanganalmath, Heather Stowers, Greg Hunt, Roberto Bolli
Journal: Circulation (2012)

Administration of cardiac stem cells (CSCs) after acute or chronic myocardial infarction (MI) results in functional and structural LV improvement. However, no study has used a follow-up longer than...
Predictions of mortality related to four major cancers in China, 2020 to 2030
Authors: Ning Li, Peng Wu, Yubing Shen, Cuihong Yang, Luwen Zhang, Yali Chen, Zixing Wang, Jingmei Jiang
Journal: Cancer Communications (2021)

Abstract Background Cancer has become a global health problem, and assessments of cancer mortality are important for effective public health policy‐making and adequate resource allocation. In this study, we aimed to predict the mortality rates and numbers of deaths related to four common cancers (lung, liver, stomach, and esophagus) in China from 2020 to 2030 and to estimate the corresponding cancer burden caused by population aging and tobacco smoking. Methods Cancer mortality data (2004–2017) were extracted from China's death surveillance datasets, and China's population figures (2020–2030) were obtained from the United Nations population projections. Smoking prevalence data were retrieved from a World Health Organization global report, and relative risks of smoking and cancers were derived from large‐scale Asian studies. We predicted the deaths related to the four major cancers and age‐standardized mortality rates using joinpoint regression and linear regression models. The tobacco smoking‐related burden of these four major cancers was estimated using the population attributable fraction. Results Unlike lung cancer mortality which was predicted to continue to increase, the age‐standardized mortality rates for digestive cancers (liver, stomach, and esophageal cancers) are predicted to decline over the next decade. The number of deaths caused by the four major cancers is predicted to increase from 1,490,304 in 2020 to 1,823,960 in 2030. The age‐specific mortality rates of the four major cancers are predicted to increase with age after 40–45 years, peaking in the age groups of 80–84 and ≥85 years. In 2030, the combined number of deaths from the four examined cancers among adults aged ≥65 years is predicted to be 1,167,153, accounting for 64% of all deaths from these cancers. Tobacco smoking is predicted to contribute to nearly 29% of deaths from these cancers, corresponding to 527,577 deaths. Conclusions The overall trend in the combined total mortality from four major cancers is predicted to decline over the next decade; however, the corresponding death toll is expected to surge, in the context of China's population aging and high smoking prevalence. These estimates provide data‐driven evidence for China to implement effective cancer control measures in the future.
Fabricated illness: guidance is updated as survey shows nearly all paediatricians see potential cases
Authors: Elisabeth Mahase
Journal: BMJ (2021)

The Royal College of Paediatrics and Child Health (RCPCH) has provided new guidance on how to spot and investigate potential cases of fabricated or induced illness (FII) and discuss the findings with parents or care givers.1

The guidance, an update from 2009, provides procedures for safeguarding children who present with perplexing presentations (PP) or FII and advice on how to minimise harm to children.

It comes after a 2018 survey of RCPCH members showed the scale at which paediatricians are faced with PP. Nearly all (92%) respondents (216) recalled seeing at least one PP within the previous 12 months and 30% had seen more than five. Respondents reported 69 different condition presentations, …
CXCR6 deficiency impairs cancer vaccine efficacy and CD8<sup>+</sup>resident memory T-cell recruitment in head and neck and lung tumors
Authors: Soumaya Karaki, Charlotte Blanc, Thi Tran, Isabelle Galy-Fauroux, Alice Mougel, Estelle Dransart, Marie Anson, Corinne Tanchot, Lea Paolini, Nadege Gruel, Laure Gibault, Francoise Lepimpec-Barhes, Elizabeth Fabre, Nadine Benhamouda, Cecile Badoual, Diane Damotte, Emmanuel Donnadieu, Sebastian Kobold, Fathia Mami-Chouaib, Rachel Golub, Ludger Johannes, Eric Tartour
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Resident memory T lymphocytes (T RM ) are located in tissues and play an important role in immunosurveillance against tumors. The presence of T RM prior to treatment or their induction is associated to the response to anti-Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1) immunotherapy and the efficacy of cancer vaccines. Previous work by our group and others has shown that the intranasal route of vaccination allows more efficient induction of these cells in head and neck and lung mucosa, resulting in better tumor protection. The mechanisms of in vivo migration of these cells remains largely unknown, apart from the fact that they express the chemokine receptor CXCR6. Methods We used CXCR6 -deficient mice and an intranasal tumor vaccination model targeting the Human Papillomavirus (HPV) E7 protein expressed by the TC-1 lung cancer epithelial cell line. The role of CXCR6 and its ligand, CXCL16, was analyzed using multiparametric cytometric techniques and Luminex assays. Human biopsies obtained from patients with lung cancer were also included in this study. Results We showed that CXCR6 was preferentially expressed by CD8 + T RM after vaccination in mice and also on intratumoral CD8 + T RM derived from human lung cancer. We also demonstrate that vaccination of Cxcr6-deficient mice induces a defect in the lung recruitment of antigen-specific CD8 + T cells, preferentially in the T RM subsets. In addition, we found that intranasal vaccination with a cancer vaccine is less effective in these Cxcr6 -deficient mice compared with wild-type mice, and this loss of efficacy is associated with decreased recruitment of local antitumor CD8 + T RM . Interestingly, intranasal, but not intramuscular vaccination induced higher and more sustained concentrations of CXCL16, compared with other chemokines, in the bronchoalveolar lavage fluid and pulmonary parenchyma. Conclusions This work demonstrates the in vivo role of CXCR6-CXCL16 axis in the migration of CD8 + resident memory T cells in lung mucosa after vaccination, resulting in the control of tumor growth. This work reinforces and explains why the intranasal route of vaccination is the most appropriate strategy for inducing these cells in the head and neck and pulmonary mucosa, which remains a major objective to overcome resistance to anti-PD-1/PD-L1, especially in cold tumors.
Tailored immunotherapy approach with nivolumab in advanced transitional cell carcinoma (TITAN-TCC).
Authors: Marc-Oliver Grimm, Bernd Schmitz-Dräger, Uwe Zimmermann, Barbara Grün, Gustavo Bruno Baretton, Marc Schmitz, Susan Foller, Martin Schostak, Friedemann Zengerling, Ulrike Schumacher, Wolfgang C. Loidl, Johannes Meran
Journal: Journal of Clinical Oncology (2021)

446 Background: Several PD-1 immune-checkpoint inhibitors including Nivolumab (Nivo) are approved in urothelial cancer. Recently, in the front line setting, improved activity of combined PD-L1 and CTLA4 immune-checkpoint inhibition has been reported and a phase III trial with Nivolumab + Ipilimumab (Nivo+Ipi) is ongoing. Here we report a response-based tailored approach starting treatment with Nivo monotherapy using Nivo+Ipi as immunotherapeutic “boost”. Methods: Between July 2017 and April 2019 86 patients were enrolled and treated according to protocol version 3 (cohort 1). Patients started with Nivo 240 mg Q2W induction. After 4 dosings and tumor assessment at week 8 (i) responders (PR/CR) to Nivo monotherapy continued with maintenance while (ii) patients with stable (SD) or progressive disease (PD) received 2 cycles Nivo3+Ipi1 followed by another 2 cycles Nivo1+Ipi3 if not responding. Median follow-up is 8.7 months. The primary endpoint is confirmed investigator-assessed objective response rate (ORR) per RECIST1.1. Secondary endpoints include activity of Nivo monotherapy at week 8, remission rate with Nivo+Ipi “boosts”, safety, overall survival and quality of life. Results: Of the patients 42, 39 and 5 were first, second and third line, respectively. Median age was 67 years (range 45-84), 61 patients (71 %) were male and 25 female. ORR with Nivo monotherapy at first assessment (week 8) was 29 % and 23 % in first and second/third line, respectively. Of the patients 41 received Nivo+Ipi “boosts” after week 8 while 12 received later “boosts”. Best overall response (BOR) rate with Nivo induction ± Nivo+Ipi “boosts” was 48 % and 27 % in first and second/third line, respectively. In first line 7/17 (41 %) patients receiving Nivo+Ipi after week 8 had an improved response compared to 2/24 (8.3 %) in second/third line. Of the patients who continued with Nivo maintenance after week 8 and received later “boosts” 2/12 (17 %) had a PR and 2/12 (17 %) improved to SD. Treatment-related AEs will be presented. Conclusions: TITAN–TCC explores a response-driven use of Nivo+Ipi as an immunotherapeutic “boost”. In first line, this significantly improved ORR compared to the expected response rate of Nivo monotherapy, providing further evidence to the added value of Ipi in combination with Nivo. Further follow-up is ongoing to characterize duration and depth of response. Clinical trial information: NCT03219775 . Research Sponsor: Bristol-Myers Squibb[Table: see text]
Use of bone modifying agents in patients with metastatic castrate-sensitive prostate cancer.
Authors: Aaron Philip Mitchell, Akriti A. Mishra, Peter B Bach, Michael J. Morris
Journal: Journal of Clinical Oncology (2021)

68 Background: Bone modifying agents (BMAs) do not prevent skeletal related events (SREs) among patients with metastatic, castration-sensitive prostate cancer (mCSPC). Within this population, BMAs are recommended for prevention of osteoporotic fractures but not for SRE prevention. Utilization patterns of BMAs among patients with mCSPC have not been described, and it is unknown whether these patients may receive BMAs intended for SRE prevention unnecessarily. We conducted this study to measure BMA use among mCSPC patients who are unlikely to have an indication for osteoporotic fracture prevention. Methods: We used linked SEER-Medicare data. Our cohort included men newly diagnosed with de-novo stage IV prostate adenocarcinoma during 2007-2015. We included those age &gt; = 66 at diagnosis, who lived at least 60 days after diagnosis, had continuous enrollment in Medicare Parts A and B from 180 days prior to diagnosis through the outcome period and Part D from diagnosis through outcome period, and who received androgen deprivation or antiandrogen therapy after diagnosis. We excluded patients who had previously received BMAs, or who had existing osteoporosis, osteopenia, hypercalcemia, or prior bone fracture. Our primary outcome was receipt of a BMA (zoledronic acid or denosumab) within 180 days of prostate cancer diagnosis, during which time the development of castrate-resistant disease is unlikely to arise. We also assessed receipt of BMAs within 90 days of diagnosis as a secondary outcome. We used multivariable logistic regression to assess patient factors associated with BMA use. Results: Our sample included 2,998 patients. Median age at diagnosis was 77. 77% of patients were white, 12% were Black, and 11% were of other race/ethnicity. 77% of patients were treated in the physician office setting and 23% the hospital outpatient setting. Overall, 24% received a BMA within 180 days of diagnosis; 18% did within 90 days. BMA therapy was more common among patients treated in the hospital outpatient vs. physician office setting (OR 1.25, 95%CI 1.03-1.52). Age, race/ethnicity, comorbidity, and renal disease were not associated with likelihood of BMA therapy. There was substantial variation across the study period: 19% of patients received BMAs from 2007-2009 (19% zoledronic acid, 0% denosumab), and 29% from 2012-2015 (9% zoledronic acid, 21% denosumab). Conclusions: Use of BMAs among patients with mCSPC is common. In this cohort of mCSPC patients, who were unlikely to have a BMA indication for osteoporotic fracture prevention based on the absence of history of osteoporosis, osteopenia, or fracture, nearly one-quarter received BMAs. The increase in BMA use which occurred during the 2007-2015 study period appears to have been driven by increased utilization of denosumab following its approval in 2010. Use of BMAs in patients with mCSPC without a need for osteoporotic fracture prevention may constitute overuse.
Chinese Glioma Genome Atlas (CGGA): A Comprehensive Resource with Functional Genomic Data from Chinese Glioma Patients
Authors: Zheng Zhao, Ke-Nan Zhang, Qiangwei Wang, Guanzhang Li, Fan Zeng, Ying Zhang, Fan Wu, Ruichao Chai, Zheng Wang, Chuanbao Zhang, Wei Zhang, Zhaoshi Bao, Tao Jiang
Journal: Genomics Proteomics & Bioinformatics (2021)

Gliomas are the most common and malignant intracranial tumors in adults. Recent studies have revealed the significance of functional genomics for glioma pathophysiological studies and treatments. However, access to comprehensive genomic data and analytical platforms is often limited. Here, we developed the Chinese Glioma Genome Atlas (CGGA), a user-friendly data portal for the storage and interactive exploration of cross-omics data, including nearly 2000 primary and recurrent glioma samples from Chinese cohort. Currently, open access is provided to whole-exome sequencing data (286 samples), mRNA sequencing (1018 samples) and microarray data (301 samples), DNA methylation microarray data (159 samples), and microRNA microarray data (198 samples), and to detailed clinical information (age, gender, chemoradiotherapy status, WHO grade, histological type, critical molecular pathological information, and survival data). In addition, we have developed several tools for users to analyze the mutation profiles, mRNA/microRNA expression, and DNA methylation profiles, and to perform survival and gene correlation analyses of specific glioma subtypes. This database removes the barriers for researchers, providing rapid and convenient access to high-quality functional genomic data resources for biological studies and clinical applications. CGGA is available at http://www.cgga.org.cn.
Baseline and post-treatment circulating tumor cell (CTC) counts with prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Michael Sun, Justin M Lebenthal, Jones T. Nauseef, Muhammad Junaid Niaz, Sabrina Guervil, Escarleth Fernandez, Amie Patel, Angela Tan, Panagiotis J. Vlachostergios, Joseph Osborne, Ana M. Molina, Cora N. Sternberg, David M. Nanus, Neil Harrison Bander, Scott T. Tagawa
Journal: Journal of Clinical Oncology (2021)

158 Background: CTC counts are an independent prognostic factor in men with mCRPC; certain changes following treatment (conversion from detectable to undetectable or unfavorable to favorable) are associated with improved overall survival. Most PSMA-TRT efficacy data have focused on PSA or imaging changes. Here, we describe baseline and post-treatment CTC counts from subjects receiving PSMA-TRT. Methods: Men with mCRPC treated on prospective clinical trials of PSMA-TRT and with available CTC counts (CellSearch) were included in our analysis. Depending upon the era of the trial, post-treatment counts were performed at 4-6 (initial era) or 12 weeks (recent era) after a single cycle of PSMA-TRT (individual trial data reported elsewhere). We describe CTC counts at baseline and compare pre-treatment counts to those after PSMA-TRT. Results: 116 men treated with PSMA-TRT had baseline CTC count (90 with both pre- and post-treatment CTC). Forty-four patients (37.9%) received 177Lu-J951, 46 (39.7%) received 177Lu-PSMA-617, and 26 (22.4%) received 225Ac-J591. Median age was 71.5. Fifty-eight patients (50%) had previously received taxane chemotherapy, median PSA was 82.98 ng/mL, and 66 (56.9%) were in the high-risk Halabi (CALGB) prognostic group. Eighty-nine out of one hundred sixteen (76.7%) had detectable baseline CTC and 58/116 (50%) had unfavorable baseline CTC count. Forty-nine out of seventy (70%) had post-treatment CTC count decline, 23/70 (32.9%) converted from detectable to undetectable, and 17/47 (36.2%) converted from unfavorable to favorable. CTC changes stratified by type of PSMA-TRT are reported in the table. Conclusions: This is the largest analysis of CTC changes in patients who have received PSMA-TRT. In addition to PSA changes and other previously reported outcomes, even when low doses of radionuclide therapy as part of dose-escalation studies are included, the majority with detectable CTC counts have post-treatment CTC count decline. A significant portion of patients experience favorable CTC changes. [Table: see text]
Exploration and insights into the cellular internalization and intracellular fate of amphiphilic polymeric nanocarriers
Authors: Samrat Mazumdar, Deepak Chitkara, Anupama Mittal
Journal: Acta Pharmaceutica Sinica B (2021)

The beneficial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate. Moreover, the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the cell towards different organelles thereby not only influencing their pharmacokinetic and pharmacodynamic properties but also bioavailability, therapeutic efficacy and toxicity. Therefore, an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential. In order to direct nanoparticles towards specific sub-cellular organelles the physicochemical attributes of nanocarriers can be manipulated. These include particle size, shape and surface charge/chemistry. Restricting the particle size of nanocarriers below 200 nm contributes to internalization via clathrin and caveolae mediated pathways. Similarly, a moderate negative surface potential confers endolysosomal escape and targeting towards mitochondria, endoplasmic reticulum (ER) and Golgi. This review aims to provide an insight into these physicochemical attributes of nanocarriers fabricated using amphiphilic graft copolymers affecting cellular internalization. Fundamental principles understood from experimental studies have been extrapolated to draw a general conclusion for the designing of optimized nanoparticulate drug delivery systems and enhanced intracellular uptake via specific endocytic pathway.
Covid-19 trials: allow recruitment by everyone in healthcare, including those not previously involved in research
Authors: Mark A Rickenbach
Journal: BMJ (2021)

Darzi and colleagues are right to highlight research recruitment, because, before the pandemic, research activity had fallen in almost all specialties in England. 1 The Principle study, mentioned, is a step change with full online consent and follow-up.It has allowed recruitment by everyone in healthcare, including those not previously involved in research.Primary care covers every medical condition and almost every patient in the UK.A trusted GP often knows the patient over many years, and they hold a comprehensive healthcare record.This leads to higher rates of recruitment from direct GP contact.However, it is who undertakes the research, rather than who recruits, which determines funding.Both should be considered by the national Clinical Research Network (CRN) to allow appropriate resource allocation.More support from research staff firmly embedded in primary care is needed, but the financial risk to individual GPs is significant.The independent contractor model pays GP partners from what is left over when all services have been paid for.Add the risks of taking on staff to a falling income, with widespread closures of GP surgeries, and this can literally lead to loss of a GP's house.Improved models to fund research staff include additional funds to offset on costs and risk, employment by local CRNs, employment by larger local research hubs, local direct enhanced services arrangements, and primary care network (PCN) based researchers.PCN additional roles have worked well for other staff provided there is full funding, including overheads.
The Pangenomic Classification of Pituitary Neuroendocrine Tumors: Quality Histopathology is Required for Accurate Translational Research
Authors: Ozgur Mete, Shereen Ezzat, Arie Perry, Shozo Yamada, Silvia Uccella, Ashley B. Grossman, Sylvia L. Asa
Journal: Endocrine Pathology (2021)