tbuckley/cabot-search huggingface dataset:
Exosomal TUBB3 mRNA expression level to predict prognosis for abiraterone treatment in metastatic prostate patients.
Authors: Sha Zhu, Guangxi Sun, Jindong Dai, Xingming Zhang, Junru Chen, Xudong Zhu, Jinge Zhao, Haoran Zhang, Yuchao Ni, Zhipeng Wang, Pengfei Shen, Hao Zeng
Journal: Journal of Clinical Oncology (2020)

244 Background: TUBB3 (Class III β-tubulin), a dynamic component of microtubules, is considered a prognostic biomarker of tumor aggressiveness and poor survival. Previous studies have researched into its indication of resistance to chemotherapeutic drugs. However, its association with abiraterone, a next-generation androgen-axis targeting drug in prostate cancer has not been studied yet. In this study, we aimed to find out if exosomal TUBB3 expression could predict the efficacy of abiraterone in metastatic prostate cancer patients. Methods: Blood samples of metastatic prostate cancer patients during different disease stages were collected. We isolated the exosomes and extracted the RNA for analysis of TUBB3 by ddPCR. Absolute target mRNA concentration was measured by ddPCR as copies per milliliter (copies/20ul). Clinical data were collected for all patients. Primary study endpoint was progression-free survival (PFS). Statistical analyses were performed with SPSS 25.0. Results: A total of 54 metastatic prostate cancer patients who have received abiraterone treatment were enrolled. Baseline characteristics are comparable between high (≥10 copies/20ul) and low (&lt;10 copies/20ul) TUBB3 expression groups. Univariate analyses revealed that baseline hemoglobin≤120g/L, baseline sodium concentration &gt;140 mmol/L, baseline potassium concentration &gt;4.39 mmol/L and high exosomal TUBB3 expression were associated with shorter PFS, while only baseline sodium concentration and exosomal TUBB3 expression were independent prognosticators in multivariate analyses. In subsequently subgroup analyses, high exosomal TUBB3 expression demonstrates particularly high hazard ratio in multiple subgroups (patients younger than 70 years old, without neuroendocrine differentiation and immunohistochemical androgen-receptor splice variant 7 expression, with baseline PSA &gt;100 ng/mL, and patients receiving abiraterone as first-line therapy). Conclusions: Exosomal TUBB3 expression has potential in making treatment plan and predict prognosis in metastatic prostate cancer patients. High exosomal TUBB3 expression indicates poor response to abiraterone, especially as first line therapy.
Secondary analysis of PURE-01: Role of FDG-PET/CT in evaluating lymph node involvement of patients with muscle invasive bladder cancer (MIBC) receiving neoadjuvant pembrolizumab and radical cystectomy (RC).
Authors: Laura Marandino, Antonella Capozza, Alberto Briganti, Daniele Raggi, Elena Farè, Filippo Pederzoli, Andrea Gallina, Marco Bandini, Umberto Capitanio, Marco Bianchi, Giorgio Gandaglia, Nicola Fossati, Patrizia Giannatempo, Ettore Seregni, Andrea Salonia, Francesco Montorsi, Alessandra Alessi, Andrea Necchi
Journal: Journal of Clinical Oncology (2020)

445 Background: FDG-PET/CT has limited utility in clinical N0 (cN0) patients (pts) with MIBC who receive neoadjuvant chemotherapy and RC or RC alone (Dason, AUA19). Methods: In PURE-01 (NCT02736266), 3 courses of 200 mg pembrolizumab, q3 weeks, were administered prior to RC. Pts were assessed with thorax-abdomen CT scan and with PET/CT scan during screening and before RC. Imaging review and analysis was internally performed. For each pt with lymph node (LN) increased uptake in abdomino-pelvic area, the SUVmax and the short-axis size of the most intense LN were recorded. All pts underwent extended pelvic LN dissection (LND) with packeted node submission. Results: From 02/17 to 06/2019, 103 total evaluable pts (206 PET/TC scans) were enrolled ad treated. Six pts (5.8%) had LN uptake at baseline PET/CT: mean SUVmax=2.75; mean short axis: 6.2 mm. Eight pts (7.8%) had LN uptake at PET/CT post-pembrolizumab: mean SUVmax=4.21; mean short axis: 7.2mm. The rate of pathologic LN positive (pN+) disease was 15.5% (16 pts). The performance of post-pembrolizumab PET/CT in predicting pN+ disease is indicated in the Table. In total, 4/6 pts (66.7%) with baseline FDG uptake revealed as pN+ vs 12/97 (12.4%) with no baseline FDG uptakes (p=0.005). A total of 39 pts (37.9%) developed inflammatory FDG-uptakes post-pembrolizumab in several target organs/regions: top 5 sites were thyroid (N=21, 61.8%), stomach and mediastinum (13 pts each, 12.6%), lung (N=10, 9.7%), other lymph nodes (N=4, 3.9%). These changes were clinically evident (signs/symptoms or laboratory changes) in 15 pts (38.5%). Conclusions: Criteria for eligibility of cN0 pts to single-agent neoadjuvant pembrolizumab trials may be enhanced with PET/CT use. Three cycles of pembrolizumab determined profound inflammatory changes, whose long-term impact on safety is still to be determined. Clinical trial information: NCT02736266 . [Table: see text]
Case 6-2020: A 34-Year-Old Woman with Hyperglycemia
Authors: Miriam S. Udler, Camille E. Powe, Christina A. Austin-Tse
Journal: New England Journal of Medicine (2020)

A 34-year-old woman was evaluated for hyperglycemia. Nine years earlier, she had had an elevated glucose level, and subsequently, diabetes was diagnosed during her four pregnancies. Both of her parents had type 2 diabetes. Currently, the body-mass index was 25.4 and the glycated hemoglobin level 6.2%. A diagnostic test was performed.
Circulating Immune Cell Composition and Cancer Risk: A Prospective Study Using Epigenetic Cell Count Measures
Authors: Charlotte Le Cornet, Konstantin Schildknecht, Araceli Rossello Chornet, Renée T. Fortner, Sandra González Maldonado, Verena A. Katzke, Tilman Kühn, Theron Johnson, Sven Olek, Rudolf Kaaks
Journal: Cancer Research (2020)

Abstract Although ample evidence indicates that immune cell homeostasis is an important prognostic outcome determinant in patients with cancer, few studies have examined whether it also determines cancer risk among initially healthy individuals. We performed a case–cohort study including incident cases of breast (n = 207), colorectal (n = 111), lung (n = 70), and prostate (n = 201) cancer as well as a subcohort (n = 465) within the European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort. Relative counts of neutrophils, monocytes, and lymphocyte sublineages were measured by qRT-PCR. HRs and 95% confidence intervals were used to measure the associations between relative counts of immune cell and cancer risks. When relative counts of immune cell types were taken individually, a significant positive association was observed between relative counts of FOXP3+ regulatory T cells (Tregs) and lung cancer risk, and significant inverse associations were observed between relative CD8+ counts and risks of lung and breast cancer (overall and ER+ subtype). Multivariable models with mutual adjustments across immune markers showed further significant positive associations between higher relative FOXP3+ T-cell counts and increased risks of colorectal and breast cancer (overall and ER− subtype). No associations were found between immune cell composition and prostate cancer risk. These results affirm the relevance of elevated FOXP3+ Tregs and lower levels of cytotoxic (CD8+) T cells as risk factors for tumor development. Significance: This epidemiologic study supports a role for both regulatory and cytotoxic T cells in determining cancer risk among healthy individuals. See related commentary by Song and Tworoger, p. 1801
Remote Ischemic Preconditioning Modifies the Plasma Proteome in Children Undergoing Repair of Tetralogy of Fallot: a Randomized Controlled Trial
Authors: Joanne M Hepponstall, Vera Ignjatovic, Steve Binos, Chantal Attard, Vasiliki Kariaftis, Yves d'Udekem, Paul Monagle, Igor Konstantinov
Journal: Circulation (2013)
Abstract 14130: GPR40/GPR84 Modulator PBI-4050 Improves Left Heart Disease-Induced Pulmonary Hypertension by Reducing Lung Fibrosis, and Suppresses Myofibroblastic Differentiation of Human Lung Fibroblasts
Authors: Mohamed Jalloul Nsaibia, Quang T Nguyen, Brigitte Grouix, Lyne Gagnon, Jocelyn Dupuis
Journal: Circulation (2018)

Introduction: Heart failure with reduced ejection fraction (HFrEF) causes lung remodeling characterized by myofibroblasts proliferation and fibrosis leading to a restrictive lung syndrome with pulm...
Corrigendum to Difference of PDT induced apoptotic gene expression in 2D and 3D nasopharyngeal carcinoma cell Models
Authors: R.W.K. Wu, E.S.M. Chu, J.W.M. Yuen, Z. Huang
Journal: Annals of Oncology (2020)

The authors regret that the original funding acknowledgement of this publication was incomplete. The correct acknowledgement should read as follows: Funding: The work described in this paper was fully supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (project no.: UGC/FDS17/M02/15). The authors would like to apologise for any inconvenience caused. Difference of PDT induced apoptotic gene expression in 2D and 3D nasopharyngeal carcinoma cell modelsAnnals of OncologyVol. 30PreviewNasopharyngeal Carcinoma (NPC) is one of the top 10 cancers in Hong Kong. Photodynamic Therapy (PDT) is an alternative treatment approach to NPC. We previously reported that PDT induced both apoptosis and necrosis in 2D and 3D NPC models but in different manners, yet the underline biological mechanism is still unknown. In this pilot study we measured 3 apoptotic related gene expression, including c-Myc, p53 and Notch-1 genes using 2D and 3D EBV+ c666-1 cell models at pre- and post- FosPeg (FP) PDT treatment. Full-Text PDF Open Archive
Effectiveness and Safety of a Glutaraldehyde-Modified Microcrystalline Tyrosine (MCT)-Associated Extract of Mites in Children and Adult Patients With Allergic Rhinitis With Or Without Asthma
Authors: Carla Toran, Jose Luis Perez Formoso, Valentina Gutierrez Vall De Ca, Zulay Almeida Sanchez, José Antonio Álvarez, Ignacio Garcia-Nunez, Juan Linana Santafe, Juan Antonio Martinez Tadeo, José Luis Justicia, Anna Sala Cunill
Journal: Journal of Allergy and Clinical Immunology (2020)
Screening and identification of novel promoter signatures in clear cell renal cell carcinoma metastasis.
Authors: Yuan-Yuan Qu, Xi Tian, Wenhao Xu, Aihemutaijiang Anwaier, Dingwei Ye, Hailiang Zhang
Journal: Journal of Clinical Oncology (2020)

737 Background: Clear cell renal cell carcinoma (ccRCC) patient usually face aggressive progression when metastasis occurs. Therefore, in-depth investigation is needed to elucidate underlying mechanisms behind the metastasis of ccRCC to promote therapeutic benefits.This study aims to explore and investigate prognostic gene expression profiles based on multi-cohorts. Methods: Three microarray datasets were obtained from the Gene Expression Omnibus (GEO) database to screen and identify differentially expressed genes (DEGs) according to normalization annotation information. A total of 112 DEGs with functional enrichment were identified as candidate prognostic biomarkers. A protein–protein interaction network (PPI) of DEGs was developed, and the modules were analyzed using STRING and Cytoscape. Results: LASSO Cox regression suggested 31 significant involved genes, and 10 hub genes were identified as independent oncogenes in ccRCC patients. Distinct integrated scores of the hub genes mRNA expression showed statistical significance in predicting disease-free survival (DFS; p&lt;0.001) and overall survival (OS; p&lt;0.001) in TCGA and real-world cohorts. Meanwhile, ROC curves were constructed to validate specificity and sensitivity of the Cox regression penal to predict prognosis. The AUC index for the integrated genes scores was 0.758 for OS and 0.772 for DFS. Conclusions: In conclusion,the present study identifies DEGs and hub genes that may be involved in earlier recurrence and poor prognosis of ccRCC. The expression levels of ADAMTS9, C1S, DPYSL3, H2AFX, MINA, PLOD2, RUNX1, SLC19A1, TPX2 and TRIB3 are of high prognostic value, and may help us understand better the underlying carcinogenesis or progression of ccRCC.
亜急性ステント血栓症(SAT)の診断に苦慮した狭心症症例 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: 櫻川浩一郎, 草野栄郷, 入田昭子, 米倉剛, 瀬戸信二
Journal: Circulation (2008)
Cost-effectiveness of pembrolizumab in combination with axitinib as first-line treatment for advanced renal cell carcinoma.
Authors: Arielle G. Bensimon, Yichen Zhong, Umang Swami, Allison Briggs, Joshua Young, Yuan Feng, Yan Song, James Signorovitch, Oluwakayode Adejoro, Abhiroop Chakravarty, Mei Chen, Rodolfo F. Perini, Daniel M. Geynisman
Journal: Journal of Clinical Oncology (2020)

716 Background: Pembrolizumab/axitinib significantly prolonged progression-free survival (PFS) and overall survival (OS) vs. sunitinib in a phase 3 trial KEYNOTE-426 among previously untreated patients with advanced renal cell carcinoma (RCC). This study assessed the cost-effectiveness of pembrolizumab/axitinib vs. other first-line treatments of advanced RCC from a US payer perspective. Methods: A partitioned survival model with 3 states (progression-free, progressed, death) evaluated costs and quality-adjusted life years (QALYs) for pembrolizumab/axitinib and other first-line regimens: sunitinib and pazopanib in the overall population; sunitinib, cabozantinib, and nivolumab/ipilimumab in the subgroup with poor/intermediate IMDC risk. Time on treatment, PFS, and OS were extrapolated using parametric models fitted to KEYNOTE-426 data (24 Aug 2018 cutoff) for pembrolizumab/axitinib and sunitinib, and hazard ratios from network meta-analyses for other comparators. Costs of first-line and subsequent treatment, adverse events, medical resources, and terminal care were estimated based on trial results, drug labels, and published sources. Utilities were derived through mixed-effects regressions of KEYNOTE-426 EQ-5D data. Results: Over a lifetime, the incremental cost-effectiveness ratios (ICERs) for pembrolizumab/axitinib were below willingness-to-pay thresholds of $150,000/QALY or $180,000/QALY (approx. 3 × gross domestic product per capita) vs. all comparators in the overall and intermediate/poor risk populations (table). Results were robust in deterministic and probabilistic sensitivity analyses. Conclusions: Pembrolizumab/axitinib is associated with higher QALYs and considered cost-effective vs. other first-line treatments of advanced RCC in the US.[Table: see text]
A phase II study assessing the safety and efficacy of ASP1650 in male patients with incurable platinum refractory germ cell tumors.
Authors: Nabil Adra, David J. Vaughn, Lawrence Einhorn, Nasser H. Hanna, Matt Rosales, Ahsan Arozullah, Darren R. Feldman
Journal: Journal of Clinical Oncology (2020)

TPS424 Background: Testicular cancer (TC) is the most common solid malignancy in men aged 15-35 yrs; germ cell tumors (GCTs) account for 95% of TC. Claudin 6 (CLDN6) is a tight junction membrane protein whose expression in normal tissue is confined to embryonic cells but is frequently aberrantly expressed in GCTs. ASP1650 (also known as IMAB027) is a monoclonal antibody targeted against CLDN6 that can induce antibody-dependent cell-mediated and complement-dependent cytotoxicity in CLDN6-expressing cells and has demonstrated potent antitumor effects in preclinical models of TC. Methods: This phase 2 study with a safety run-in (NCT03760081) will enroll ≤46 male patients (pts) with advanced GCTs who have had prior cisplatin-based combination chemotherapy and ≥1 salvage regimen. In the safety run-in, an initial ASP1650 dose level will be evaluated in 3 pts. If tolerated, a new cohort of 3 pts will begin at the next dose level per the Bayesian Optimal Interval Design. A Dose Evaluation Committee will assess tolerability and determine maximum tolerated dose. Once the recommended phase 2 dose (RP2D) has been established, ≤34 pts will be enrolled in phase 2 and will receive ASP1650 in 2-week cycles for up to 12 cycles or until study discontinuation criteria is met. Phase 2 of the study will utilize a Simon’s 2-stage design to allow for early termination. In stage I, 13 pts, including pts from the RP2D cohort of the safety run-in, will be evaluated for response. If there is ≤1 response among these 13 pts, the study will be stopped, otherwise an additional 21 pts will be enrolled in stage II. Primary endpoints of the study include establishment of the RP2D and confirmation of overall response rate, as assessed by modified RECIST v1.1 response criteria (RECIST v1.1 + serum tumor markers [βhCG and AFP]). Secondary endpoints include the determination of safety/tolerability and pharmacokinetic profiles as well as other efficacy measures (eg, clinical benefit rate; progression-free survival; change in serum tumor biomarkers). Enrollment is currently ongoing; as of Sept 12, 2019, 6 pts have enrolled and 2 are still on active treatment. Clinical trial information: NCT03760081.
Next-generation sequencing (NGS) of tumor tissue from &gt;4000 men with metastatic castration-resistant prostate cancer (mCRPC): The PROfound phase III study experience.
Authors: Maha H. A. Hussain, Joaquin Mateo, Shahneen Kaur Sandhu, Karim Fizazi, Fred Saad, Neal D. Shore, David Olmos, Claire Corcoran, Caroline Sibilla, Alexander Kohlmann, Carrie A. Adelman, Julia Andrea Elvin, Carsten Dietrich Goessl, Joseph Burgents, Johann S. De Bono
Journal: Journal of Clinical Oncology (2020)

195 Background: The PROfound study (NCT02987543) showed that olaparib provides a statistically significant improvement in radiographic progression-free survival versus physician’s choice of enzalutamide or abiraterone in mCRPC patients (pts) with alterations in genes with a direct or indirect role in the homologous recombination repair (HRR) pathway. This is the largest study to date with central, prospective tumor tissue testing in pts with mCRPC. Here, we report learnings during testing in the PROfound study. Methods: An investigational clinical trial assay, based on the FoundationOne CDx NGS test developed in partnership with Foundation Medicine, Inc (FMI), was used to prospectively identify pts with qualifying alterations in ≥1 of 15 prespecified genes, including BRCA1, BRCA2 or ATM. Tumor testing was conducted centrally using archival or recent biopsy from primary or metastatic tissue. Results: Of 4047 pts who submitted tumor samples, 2792 (69%) were successfully sequenced and yielded a biomarker status. Categories for test failure (n=1255; 31%) were pathology review failure in 277 (6.8%) pts (eg estimated tumor fraction &lt;20% or tumor volume &lt;0.2 mm 2 ), DNA extraction failure in 533 (13.2%) pts, and failure after DNA extraction in 280 (6.9%) pts, with 165 (4.1%) pts in &gt;1 category. Regarding the sample disposition, approximately two-thirds of samples were from core needle biopsies, although higher success rates were observed with larger samples (ie prostatectomy). Samples were mainly from the prostate gland, with &lt;5% from bone. Most samples were from archived tissue of primary tumors; only ~10% were from newly collected tissue. Test turnaround time, as well as representation of sample characteristics and country of origin relative to success rate, will be presented. Conclusions: The PROfound study has demonstrated that tissue testing to identify HRR alterations in men with mCRPC is feasible. Careful selection of high-quality tumor tissue samples is key to ensure success both at pathology review and during downstream steps of the NGS tissue testing process. Clinical trial information: NCT02987543.
Targeting proinsulin to local immune cells using an intradermal microneedle delivery system; a potential antigen-specific immunotherapy for type 1 diabetes
Authors: Farah Arikat, Stephanie J. Hanna, Ravinder K. Singh, Luciano Vilela, F. Susan Wong, Colin M. Dayan, Sion A. Coulman, James C. Birchall
Journal: Journal of Controlled Release (2020)
The Management of Chronic Insomnia Disorder and Obstructive Sleep Apnea: Synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines
Authors: Vincent Mysliwiec, Jennifer L. Martin, Christi S. Ulmer, Susmita Chowdhuri, Matthew S. Brock, Christopher Spevak, James Sall
Journal: Annals of Internal Medicine (2020)

Description: In September 2019, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) approved a new joint clinical practice guideline for assessing and managing patients with chronic insomnia disorder and obstructive sleep apnea (OSA). This guideline is intended to give health care teams a framework by which to screen, evaluate, treat, and manage the individual needs and preferences of VA and DoD patients with either of these conditions. Methods: In October 2017, the VA/DoD Evidence-Based Practice Work Group initiated a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature, created three 1-page algorithms, and advanced 41 recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Recommendations: This synopsis summarizes the key recommendations of the guideline in 3 areas: diagnosis and assessment of OSA and chronic insomnia disorder, treatment and management of OSA, and treatment and management of chronic insomnia disorder. Three clinical practice algorithms are also included.
The spinal distribution of metastatic renal cell carcinoma: Support for locoregional rather than arterial hematogenous mode of early bony dissemination.
Authors: Kyrollis Attalla, Cihan Duzgol, Lily McLaughlin, Jessica Flynn, Irina Ostrovnaya, Renzo G. DiNatale, Andrew W. Silagy, Jonathan Coleman, Chung-Han Lee, Maria Isabel Carlo, Martin H Voss, Paul Russo, Mark Bilsky, A. Ari Hakimi, Nelson Moss
Journal: Journal of Clinical Oncology (2020)

742 Background: To investigate the distribution of spinal metastasis in metastatic renal cell carcinoma (mRCC) and to explore relationships between biological and clinical factors and patterns of spinal spread. Methods: An institutional database was queried to identify patients with mRCC and spinal metastatic involvement from June 2005 – November 2018. A blinded radiologist examined all cross-sectional imaging involving the spine and scored each level for absence or presence of disease. Clinical and biologic features including primary tumor size and degree of spinal and non-bony metastatic involvement (including regional lymph node and distant deposits) were collected. Spinal distributions were evaluated by the Kolmogorov Smirnov test and compared across radiographic and clinical parameters. Results: One-hundred patients with 685 spinal levels involved by mRCC were evaluated. A nonuniform spatial distribution was observed across the cohort; a preponderance of thoracolumbar involvement was noted with the mode at L3 (p&lt;0.001). No difference in metastatic distribution was observed in right versus left-sided tumors. Tumors &lt;4cm compared to &gt;7cm, patients who had distant spread versus bone-only disease, and patients with increasing number of spine levels involved (1 versus &gt;5 levels) had a significantly different distribution (p&lt;0.001 for all comparisons). Smaller tumor size, distant spread, and greater number of involved levels appeared to have a more uniform distribution of spinal metastasis. Conclusions: These data support a dominant locoregional as opposed to arterial hematogenous mechanism for the early dissemination of mRCC to the spine. This is concordant with the theory of the valveless Batson plexus acting as a conduit for such spread, as the kidneys are compartmentally distinct from, but reside just anterior to the spine at L1-L3. Characterizations of the biologic molecular features contributing to osseous tropism and aggressive tumor biology (as seen in the subset of patients with uniform spread, such as outlier patients with small tumors), have implications for surveillance and are an area of active investigation.