tbuckley/cabot-search huggingface dataset:
A Conserved Mito-Cytosolic Translational Balance Links Two Longevity Pathways
Authors: Marte Molenaars, Georges E. Janssens, Evan G. Williams, Aldo Jongejan, Jiayi Lan, Sylvie Rabot, Fatima Joly, Perry D. Moerland, Bauke V. Schomakers, Marco Lezzerini, Yasmine J. Liu, Mark A. McCormick, Brian K. Kennedy, Michel van Weeghel, Antoine H.C. van Kampen, Ruedi Aebersold, Alyson W. MacInnes, Riekelt H. Houtkooper
Journal: Cell Metabolism (2020)

Slowing down translation in either the cytosol or the mitochondria is a conserved longevity mechanism. Here, we found a non-interventional natural correlation of mitochondrial and cytosolic ribosomal proteins (RPs) in mouse population genetics, suggesting a translational balance. Inhibiting mitochondrial translation in C. elegans through mrps-5 RNAi repressed cytosolic translation. Transcriptomics integrated with proteomics revealed that this inhibition specifically reduced translational efficiency of mRNAs required in growth pathways while increasing stress response mRNAs. The repression of cytosolic translation and extension of lifespan from mrps-5 RNAi were dependent on atf-5/ATF4 and independent from metabolic phenotypes. We found the translational balance to be conserved in mammalian cells upon inhibiting mitochondrial translation pharmacologically with doxycycline. Lastly, extending this in vivo, doxycycline repressed cytosolic translation in the livers of germ-free mice. These data demonstrate that inhibiting mitochondrial translation initiates an atf-5/ATF4-dependent cascade leading to coordinated repression of cytosolic translation, which could be targeted to promote longevity.
Immunoscintigraphy in axial spondyloarthritis: a new imaging modality for sacroiliac inflammation
Authors: Philippe Carron, Thomas Renson, Manouk de Hooge, Bieke Lambert, Kathia De Man, Lennart Jans, Dirk Elewaut, Filip E Van den Bosch
Journal: Annals of the Rheumatic Diseases (2020)

Imaging of sacroiliac joints (SIJ) is one of the cornerstones in early recognition of axial spondyloarthritis (axSpA).1 Currently, MRI is the preferred technique to visualise bone marrow oedema (BME), which can be defined as sacroiliitis when certain criteria are met.2 However, the definition of sacroiliitis as being ‘highly suggestive for axSpA’ has limitations in situations when BME is subtle or when SpA-like BME lesions are present due to other conditions such as mechanical stress.3 4 This underscores the need for additional and more specific imaging modalities. Given the marked efficacy of tumour necrosis factor (TNF) inhibitors in axSpA, with approximately 50% of patients achieving a clinically important response,5 we reasoned that molecular imaging studies aiming at selectively visualising TNFα in vivo at the site of clinical inflammation could be an attractive approach. Therefore, we set up a proof-of-concept study in axSpA patients by performing scintigraphy with Tc99m-labelled certolizumab pegol (CZP) as tracer. We investigated the agreement between tracer uptake on immunoscintigrapy and BME on MRI at the same localisation of the SIJ. CZP was conjugated with succinimidyl-6-hydrazino-nicotinamide (S-HYNIC), a bifunctional crosslinker. Subsequently, solutions of 1.25 mg conjugated S-HYNIC CZP were used to radiolabel with Tc99m. Seven axSpA patients (71.4% male; mean age 36±5.7 …
Abstract 16972: Introducing Advance Care Planning Into the Transition Process: The ACHD Patient Perspective
Authors: Lindsay A Edwards, Katherine Hansen, Christy Sillman, Emily Dong, Caroline Scribner, Anitra Romfh, George K Lui, Susan M Fernandes
Journal: Circulation (2018)

Introduction: The goal of the transition process from pediatric to adult care for congenital heart disease (CHD) patients, in additional to uninterrupted care, is to educate adolescents and young adults (AYAs) about their health and encourage them to develop strong self-care, decision-making, and communication skills. Adults are expected to voice their own values, opinions, and healthcare goals, especially when it comes to end-of-life (EOL) care, and, thus, it has been suggested to introduce advance care planning (ACP) into the transition process. To help inform timing of first ACP, we asked ACHD patients to share their opinions. Methods: Patients seen in the outpatient ACHD clinic from April-May 2018 completed a survey assessing their ACP preferences. Disease severity was recorded as simple, moderate, or complex. Health literacy was assessed with The Newest Vital Sign tool. Mann-Whitney U and Fisher’s exact tests were used to evaluate associations between demographics, health literacy, disease complexity, perceived health status and ACP preferences. Results: Forty-five patients (median age 37.6y, range 19.8-71.9y; 58% female; 67% Caucasian) were included. Disease complexity was moderate in 51% and severe in 39%, and 82% enrollees considered themselves in good health. Most (76%) thought ACP was moderately or extremely important. Regarding timing of ACP, 76% thought ACP should be discussed before getting sick, while healthy or when first diagnosed with a life-threatening illness . Participants reported that in late adolescence (16+) or early adulthood, AYAs with CHD are capable of knowing their EOL care wishes (68%), and ACP discussions should be introduced (76%). While higher income was associated with ACP importance, no demographic or disease complexity associations were found for ACP preferences. Conclusions: Adults with ACHD report that ACP is of high importance and should be discussed early in the disease course; however, they believe that it is not until late adolescence or early adulthood that AYAs are truly capable of knowing what kind of EOL care they want, and that ACP discussions should be initiated at this age. This valuable insight informs provider understanding of when ACP conversations can appropriately be initiated.
Response to salvage chemotherapy after progression on immune checkpoint inhibitors in patients with advanced urothelial carcinoma.
Authors: Seung-Hoon Beom, Sun Young Rha, Joong Bae Ahn, Sang Joon Shin
Journal: Journal of Clinical Oncology (2020)

519 Background: Immune checkpoint inhibitors (ICI) are active in patients with advanced urothelial carcinoma which progressed to platinum-based chemotherapy. Recent data suggest that exposure to ICI improves response to salvage chemotherapy (SCT) in several cancer types. Here we evaluated whether PD-1/PD-L1 inhibitors affect the antitumor effects of SCT after ICI in patients with urothelial carcinoma. Methods: A retrospective study was conducted at Yonsei Cancer Center. Eligibility criteria were patients who received at least one SCT as 3rd-line or beyond, following progression after platinum-based chemotherapy and ICI and for whom efficacy data were available between January 2017 and September 2019. We evaluated efficacy outcomes to each therapy, including ORR by RECIST version 1.1, progression-free survival (PFS), and overall survival (OS). Results: In total, 35 patients met the inclusion criteria and were included in the analyses. ICIs were given as monotherapy and they were administrated as second-line in 48% and as later line in 52%. Twenty-six patients (74%) received a anti-PD-L1 inhibitor and 9 (26%) did a anti-PD-1 inhibitor. SCT included single paclitaxel (60%), MVAC (26%), gemcitabine/platinum combination (9%), and pemetrexed (6%). The ORR to SCT was 26%. Among 9 patients who received MVAC, 5 (55.5%) achieved a partial response. Median progression-free survival was 2.5 months and median overall survival was 7.8 months. A number of prior chemotherapy regimens was associated with response to SCT on univariate analysis. Conclusions: In urothelial cancer patients, the confirmed ORR (26%) to SCT after ICI exposure was higher as compared to historical data from the pre-ICI era. These data indicate that anti–PD-1/PD-L1 inhibitors could make tumors more vulnerable to subsequent chemotherapy.
A prospective study of the relationship between clinical outcomes of enzalutamide and serum androgen levels measured by LC-MS/MS in patients with CRPC.
Authors: Yoshiyuki Miyazawa, Takeshi Miyao, Toshiyuki Nakamura, Yutaka Takezawa, Nobuaki Shimizu, Yasushige Matsuo, Haruyuki Ogura, Tomoyuki Takei, Daisuke Oka, Seiji Arai, Yoshitaka Sekine, Hidekazu Koike, Hiroshi Matsui, Yasuhiro Shibata, Kazuhiro Suzuki
Journal: Journal of Clinical Oncology (2020)

146 Background: Enzalutamide (ENZ) is commonly used to treat patients with castration resistant prostate cancer (CRPC). However, the kinetics of serum androgen levels before and after ENZ treatment are unknown. We elucidated the kinetics of serum androgens and explored the possibility of identifying a useful marker for predicting the effects of ENZ. Methods: We conducted a prospective study from 2014 to 2018 at Gunma University Hospital and related facilities. 104 CRPC patients treated with ENZ were analyzed. We investigated the PSA reduction rate (50%, 90%), PSA-progression-free survival (PFS), and overall survival (OS) after administration. To measure levels of androgens accurately we measured serum androgen levels using LC-MS/MS. OS and PSA-PFS were assessed according to the PCWG 2 criteria. This study was approved by the Institutional Review Board of Gunma University Hospital (No. 1177). Results: The 50% and 90% PSA decline rates were 62.5% and 25.0%, respectively. Median serum testosterone (T), dihydrotestosterone (DHT), androstenedione (A-dione), and dehydroepiandrosterone-sulfate levels were 49.0, 5.8, 222.2, and 326.3 pg/ml, respectively. Mean serum levels of T, DHT, and A-dione increased significantly 12 and 24 weeks after compared to before treatment (p &lt; 0.05). We performed a multivariate analysis using a Cox regression to predict OS and PSA-PFS. ECOG PS (0 vs. 1–2), hemoglobin (Hb ≥ 12.5 vs. &lt; 12.5 g/dL), albumin (≥ 3.9 vs. &lt; 3.9 g/dL), visceral metastasis (no vs. yes), EOD (0–2 vs. 3–4), docetaxel treatment (no vs. yes), and DHT level (≥11.25 vs. &lt; 11.25 pg/mL, 11.25 was third quartile) were significant predictors of OS (p &lt; 0.05). Hb (≥12.5 vs. &lt; 12.5 g/dL), docetaxel treatment (no vs. yes), and level of DHT (≥ 5.9 vs. &lt; 5.9 pg/mL) were significant predictors of PSA-PFS (p &lt; 0.05). As a result of the binomial logistic analysis of the predictors of fatigue and decreased appetite, the presence of visceral metastasis (yes) and low DHT (&lt;5.9 pg/mL) were significant predictors of expression. Conclusions: These results suggest that serum androgen levels before ENZ treatment may be useful for predicting efficacy, prognosis, and the incidence of adverse events.
Plasma DNA End-Motif Profiling as a Fragmentomic Marker in Cancer, Pregnancy, and Transplantation
Authors: Peiyong Jiang, Kun Sun, Wenlei Peng, Suk Hang Cheng, Meng Ni, Philip C. Yeung, Macy M.S. Heung, Tingting Xie, Huimin Shang, Ze Zhou, Rebecca W.Y. Chan, John Wong, Vincent W.S. Wong, Liona C. Poon, Tak Yeung Leung, W.K. Jacky Lam, Jason Y.K. Chan, Henry L.Y. Chan, K.C. Allen Chan, Rossa W.K. Chiu, Y.M. Dennis Lo
Journal: Cancer Discovery (2020)

Abstract Plasma DNA fragmentomics is an emerging area of research covering plasma DNA sizes, end points, and nucleosome footprints. In the present study, we found a significant increase in the diversity of plasma DNA end motifs in patients with hepatocellular carcinoma (HCC). Compared with patients without HCC, patients with HCC showed a preferential pattern of 4-mer end motifs. In particular, the abundance of plasma DNA motif CCCA was much lower in patients with HCC than in subjects without HCC. The aberrant end motifs were also observed in patients with other cancer types, including colorectal cancer, lung cancer, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma. We further observed that the profile of plasma DNA end motifs originating from the same organ, such as the liver, placenta, and hematopoietic cells, generally clustered together. The profile of end motifs may therefore serve as a class of biomarkers for liquid biopsy in oncology, noninvasive prenatal testing, and transplantation monitoring. Significance: Plasma DNA molecules originating from the liver, HCC and other cancers, placenta, and hematopoietic cells each harbor a set of characteristic plasma DNA end motifs. Such markers carry tissue-of-origin information and represent a new class of biomarkers in the nascent field of fragmentomics. This article is highlighted in the In This Issue feature, p. 627
FDG-PET in mTOR inhibitor therapy (mTOR Rx): A study of the relationship between Akt/mTOR and glycolytic pathways
Authors: Wen Ma, Dongweon Song, Heather Jacene, Felip Vilardell, Xiang Feng Zhang, Wells Messersmith, Chris Endres, Antonio Jimeno, Martin Pomper, Manuel Hidalgo
Journal: Cancer Research (2008)

4966  Background: The Akt/mTOR pathway is a target for anti-cancer therapy but there is a lack of predictive biomarkers for response to guide the clinical development of mTOR inhibitors. [18F]-fluorodeoxyglucose - positron emission tomography (FDG-PET) is a non-invasive means to evaluate glycolysis in neoplasm. We investigated the role of FDG-PET in predicting response to mTOR Rx in preclinical and clinical models and correlated the findings with changes in Akt/mTOR and glycolytic pathways. Methods: Six sets of human derived tumor xenograft (xeno)-bearing nude mice models were developed and treated with daily temsirolimus (mTOR inhibitor, TEM) and vehicle (control) for 2 weeks. Each set had 6 tumors in control and TEM-treated groups respectively (n=12 in each set). Tumor growths were measured and harvested at the end of experiment. Preclinical FDG-PETs were obtained at baseline and after 1 week, and quantified as SUVmax. Δ%SUVmax was calculated as {[(SUVmax at 1 week - SUVmax at baseline)/(SUVmax at baseline)] x 100}, and TEM xenos were compared to controls within each set. Tumor expression of pAkt, pp70 and GLUT1 were investigated by Western Blot (WB) and immunochemistry (IHC) and compared to control. Serial clinical FDG-PET scans of cancer patients (pts) treated with mTOR Rx on clinical trial were correlated with clinical response to validate preclinical findings. Results:Preclinical models identified 4 sets of xenos that were TEM-resistant (TR) and 2 -sensitive (TS). The SUVmax of controls in all xeno sets increased after 1 week of vehicle treatment (Δ%SUVmax > 0%). Among the 4 TR xenos, 2 had stable/increased SUVmax after 1 week of treatment (Δ%SUVmax >= -10%)(PET resistant, PET-R) and 2 had decreased SUVmax (Δ%SUVmax
Salvage ipilimumab associated with a significant response in sarcomatoid renal cell carcinoma
Authors: Gemlyn George, Laura Schmidt, Parag Tolat, Mathew Riese, Deepak Kilari
Journal: Journal for ImmunoTherapy of Cancer (2020)

Metastatic sarcomatoid renal cell carcinoma (sRCC) is an aggressive variant of RCC with generally poor prognosis. Treatment with vascular endothelial growth factor inhibitors or chemotherapy generates only short-lived responses. Recent research has suggested a role for combination checkpoint inhibition as first line treatment for metastatic sRCC. This therapy consists of induction with cytotoxic T-lymphocyte-associated protein 4 inhibitor, ipilimumab, administered with programmed cell death protein 1 (PD-1) inhibitor, nivolumab. After completion of four cycles of combination therapy, single-agent maintenance nivolumab is recommended until progression. Patients who progress on maintenance nivolumab are switched to alternate therapy. Herein, we present a case of a patient with RCC who progressed on maintenance nivolumab who, on retreatment with ipilimumab, demonstrated a significant response In addition, we summarize important findings to support the role of salvage ipilimumab in patients with sRCC.
Biomarkers of prolonged time to treatment failure in metastatic castration-resistant prostate cancer patients treated with abiraterone or enzalutamide: A real life patients-based nomogram and web app.
Authors: Maysa Tamara Silveira Vilbert, Natasha Carvalho Pandolfi, Marcelle Goldner Cesca, Vinicius Fernando Calsavara, Marcelo Corassa, José Augusto Rinck, Aldo A. Dettino, Ricardo Lima Coelho, Mariana Xerfan, Thiago Bueno Oliveira
Journal: Journal of Clinical Oncology (2020)

202 Background: Survival outcomes for metastatic castration resistant prostate cancer (mCRPC) patients (pts) have greatly improved following the approval of Docetaxel and abiraterone(Abi)/enzalutamide(Ez). However, it is not clear who is likely to benefit more from these therapies in real life clinical practice. Methods: A retrospective cohort study was performed with mCRPC pts treated with Abi/Ez in pre-Docetaxel setting. Primary endpoint: to identify predictive biomarkers of long time to treatment failure (TTF), develop a nomogram and convert it into a web app. Secondary endpoint: to correlate biomarkers with overall survival (OS). Kaplan Meier survival estimates and Cox Regression models were used for time-to-event analyses. Statistical analysis was made with R software. All statistical tests were two-sided and statistical significance was fixed at 0.05. Results: From May2012 to October2017, 117 pts were assessed, 81 received Abi and 36 Ez. Median follow-up of 21 months (mo), estimated median TTF was 12.8mo (95%CI 9.98-15.7) for the total population. Predictive biomarkers for TTF included in the first nomogram model were time from start of androgen deprivation therapy (tADT) to start of Abi/Ez, pain at baseline, Gleason score, baseline testosterone and lower PSA nadir in castration sensitive prostate cancer (CSPC). The second nomogram model included pain and Gleason plus neutrophil counts, tADT to CRPC and baseline PSA at CRPC. C-index: 0.726 and 0.731 respectively, providing a reliable prediction of long-term benefit with Abi/Ez in this setting. All these characteristics were significantly associated with OS. Conclusions: The two nomogram achieved a good internal validation and can work as a tool to the decision-making process of the best strategy to first-line therapy in mCRPC pts.[Table: see text]
Fracture rates in radium223 (Ra223) treated mCRPC patients (pts): A real-world analysis in 177 pts treated at a single community center 2010-2018.
Authors: Yen Thi Kim Hong Cao, Michael Elias, Janson Trieu, Vanessa Rojas, Michael J. Anderson, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2020)

41 Background: Ra223 was FDA approved 5/15/13 as a life extending therapy in conjunction with Standard of Care (SOC) agents for mCRPC in the ALSYMPCA trial. However, agents such as abiraterone (abi) and enzalutamide (enza) were not part of the SOC regimens allowed during conduct of ALSYMPCA. Phase 2 and expanded access programs (EAPs) suggested enhanced activity when abi or enza were given with Ra223. A phase 3 trial (ERA223 Smith et al. Lancet Oncology 2019) comparing Ra223 +/-abi showed an increased fracture (Fx) rate (29% vs 11%) and no survival advantage for the combo, leading to regulatory restrictions on abi and Ra223 combination therapy. However, only 41% of pts in ERA223 received bone health agents (BHAs). This center participated in ALSYMPCA and in the US EAP and based on those data, BHAs were consistently administered monthly during Ra223. The Fx rate in ERA223 did not mirror our clinical experience and thus our institutional Ra223 database was reviewed. Methods: Cohort analysis of pts who received Ra223 for mCRPC under the supervision of NJV. Follow-up was until date of death or last data entry. Results: 177 pts received Ra223 between 11/2010 and 8/2018. Median age 73 at 1st Ra223 (range 40-93); Median PSA (15.8- at 1st Ra223 (range 0.1-1952); Demographics-AA-10, C-130, Asian-9, unspecified- 28; Median Gleason score 8, Median Alk Phos 95 at 1st Ra233 (range 25-1515). Median mos of prior ADT 23 (range 0-247mos). Pts on concurrent abi + pred + Ra223 69 (39%); abi + Ra223 7 (4%); abi + pred prior to Ra223 54 (31%); abi prior to Ra223 4 (2.3%). Enza + Ra223 51 (29%); enza prior to Ra223 39 (22%). 164 pts (93%) were on BHAs before or during Ra223 (denosumab 86 concurrent vs zoledronic acid 64 concurrent). 10 pts (5.6%) had Fxs reported after the start of Ra223 (4 with concurrent abi, 3 with concurrent enza, 3 on Ra 223 w/o concurrent abi or enza; 8/10 Fxs occurred while on BHA’s). Conclusions: In contrast to the ERA223 study where 11-29% of pts experienced Fxs, this real-world experience with Ra223 in which 164/177 pts (93%) received BHAs before or during Ra223 saw a 5.6% Fx rate. When Ra223 was given concurrently with abi or enza and BHAs, the Fx rate was 6/177 (3.4%).
Antibiotic Treatment and Immune Checkpoint Inhibitor Therapy in Patients With Cancer
Authors: Zhenyu Yang, Shiyou Wei, Lunxu Liu
Journal: JAMA Oncology (2020)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
Over-the-scope clip closure of an iatrogenic gastro-colic fistula following maldeployment of a lumen-apposing metal stent
Authors: Edward J. Despott, Nikolaos Lazaridis, Gavin Johnson, Tomonori Yano, Alberto Murino
Journal: Endoscopy (2020)

A 44-year-old man with a 3-month history of necrotizing pancreatitis was referred for endoscopic ultrasound (EUS)-guided drainage of infected 12 × 5 cm symptomatic walled-off necrosis (WON) [1] ([Fig. 1 a]). At EUS, a large partially cystic/solid lesion, interpreted as the WON, was identified. A 20-mm lumen-apposing metal stent (LAMS; Hot AXIOS, Boston Scientific, Marlborough, Massachusetts, USA) and plastic pigtail stent were deployed through the posterior gastric wall. The patient was well following the procedure. However, computed tomography (CT) revealed that the LAMS had been incorrectly deployed into the colon ([Fig. 2]), and the WON had spontaneously improved (3 × 2 cm) ([Fig. 1 b]).