tbuckley/cabot-search huggingface dataset:
<i>TERT</i> Promoter Mutation Detection in Cell-Free Tumor-Derived DNA in Patients with <i>IDH</i> Wild-Type Glioblastomas: A Pilot Prospective Study
Authors: Tareq A. Juratli, Sebastian Stasik, Amir Zolal, Caroline Schuster, Sven Richter, Dirk Daubner, Mazen A. Juratli, Rachel Thowe, Silke Hennig, Meriem Makina, Matthias Meinhardt, Tim Lautenschlaeger, Gabriele Schackert, Dietmar Krex, Christian Thiede
Journal: Clinical Cancer Research (2018)

Abstract Purpose: We conducted a pilot study to assess the feasibility and the potential implications of detecting TERT promoter (TERTp)–mutant cell-free tumor-derived DNA (tDNA) in the cerebrospinal fluid (CSF) and plasma of glioblastoma patients. Experimental Design: Matched CSF and plasma samples were collected in 60 patients with glial tumors. The CSF collection was obtained during surgery, before any surgical manipulation of the tumor. The extracted tDNA and corresponding tumor DNA samples were analyzed for TERTp and isocitrate dehydrogenase (IDH) hotspot mutations. In addition, the variant allele frequency (VAF) of TERTp mutation in the CSF-tDNA was correlated with tumor features and patients’ outcome. Results: Thirty-eight patients had TERTp-mutant/IDH wild-type glioblastomas. The matched TERTp mutation in the CSF-tDNA was successfully detected with 100% specificity (95% CI, 87.6–100%) and 92.1% sensitivity (95% CI, 78.6–98.3%) (n = 35/38). In contrast, the sensitivity in the plasma-tDNA was far lower [n = 3/38, 7.9% (95% CI, 1.6–21.4%)]. We concordantly observed a longer overall survival of patients with low VAF in the CSF-tDNA when compared with patients with high VAF, irrespective of using the lower quartile VAF [11.45%; 14.0 mo. (95% confidence interval, CI, 10.3–17.6) vs. 8.6 mo. (95% CI, 4.1–13.2), P = 0.035], the lower third VAF [13%; 15.4 mo. (95% CI, 11.6–19.2) vs. 8.3 mo. (95% CI, 2.3–14.4), P = 0.008], or the median VAF [20.3%; 14.0 mo. (95% CI, 9.2–18.7) vs. 8.6 mo. (95% CI, 7.5–9.8), P = 0.062] to dichotomize the patients. Conclusions: This pilot study highlights the value of CSF-tDNA for an accurate and reliable detection of TERTp mutations. Furthermore, our findings suggest that high TERTp mutation VAF levels in the CSF-tDNA may represent a suitable predictor of poor survival in glioblastoma patients. Further studies are needed to complement the findings of our exploratory analysis. Clin Cancer Res; 24(21); 5282–91. ©2018 AACR.
Prospective, randomized, double‐blind assessment of topical bakuchiol and retinol for facial photoageing
Authors: S. Dhaliwal, I. Rybak, S.R. Ellis, M. Notay, M. Trivedi, W. Burney, A.R. Vaughn, M. Nguyen, P. Reiter, S. Bosanac, H. Yan, N. Foolad, R.K. Sivamani
Journal: British Journal of Dermatology (2018)

Bakuchiol is a phytochemical that has demonstrated cutaneous antiageing effects when applied topically. Early studies have suggested that bakuchiol is a functional analogue of topical retinoids, as both compounds have been shown to induce similar gene expression in the skin and lead to improvement of cutaneous photodamage. No in vivo studies have compared the two compounds for efficacy and side-effects.To compare the clinical efficacy and side-effect profiles of bakuchiol and retinol in improving common signs of cutaneous facial ageing.This was a randomized, double-blind, 12-week study in which 44 patients were asked to apply either bakuchiol 0·5% cream twice daily or retinol 0·5% cream daily. A facial photograph and analytical system was used to obtain and analyse high-resolution photographs of patients at 0, 4, 8 and 12 weeks. Patients also completed tolerability assessment questions to review side-effects. During study visits, a board-certified dermatologist, blinded to study group assignments, graded pigmentation and redness.Bakuchiol and retinol both significantly decreased wrinkle surface area and hyperpigmentation, with no statistical difference between the compounds. The retinol users reported more facial skin scaling and stinging.Our study demonstrates that bakuchiol is comparable with retinol in its ability to improve photoageing and is better tolerated than retinol. Bakuchiol is promising as a more tolerable alternative to retinol.
Characterization and evaluation of liver fibrosis grade in patients with chronic hepatitis B virus infection and normal transaminases
Authors: San Juan López Cristina, Casado Martín Marta, González Sánchez Mercedes, Porcel Martín Almudena, Hernández Martínez Álvaro, Vega Sáenz Jose Luis, Parrón Carreño Tesifón
Journal: Clinical and Molecular Hepatology (2018)

The objective of our study was to determine the epidemiological, laboratory, and serological characteristics of patients with chronic hepatitis B virus (HBV) infection and normal transaminases. The study also aimed to evaluate liver damage by measuring the liver fibrosis (LF) grade and to identify possible factors associated with the presence of fibrosis.A retrospective observational study was conducted in patients with chronic HBV infection and classified as inactive carriers or immune-tolerant. Epidemiological variables of age, sex, immigrant, alcohol consumption, and body mass index (BMI), as well as virological variables (HBV DNA) and transaminase level were collected throughout the follow-up. The LF grade was evaluated by transient elastography. The cutoff value for significant fibrosis (SF) was liver stiffness ≥7.9 kPa.A total of 214 patients were included in the analysis, and 62% of them had a BMI ≥25 kg/m2 . During follow-up, 4% of patients showed transaminase elevation (<1.5 times normal). Most patients had a viral DNA level <2,000 IU/mL (83%). Data on LF were available in 160 patients; of these, 14% had SF, 9% F3, and 6% F4. The variables associated with the presence of SF were transaminase alteration during follow-up, as 23% of patients with SF had elevated transaminases versus 3% of patients without SF (P<0.005), and BMI, as the vast majority of patients with SF (88%) had a BMI ≥25 kg/m2 versus 56% of patients without SF (P<0.05).In patients with chronic HBV infection and normal transaminases, liver damage does not seem to be related to DNA levels, alcohol consumption, or immigrant status. SF seems to be associated with transaminase alteration during follow-up and elevated BMI. It is therefore recommended to measure LF grade with validated non-invasive methods in such patients.
Long non-coding RNA-SNHG7 acts as a target of miR-34a to increase GALNT7 level and regulate PI3K/Akt/mTOR pathway in colorectal cancer progression
Authors: Yang Li, Changqian Zeng, Jialei Hu, Yue Pan, Yujia Shan, Bing Liu, Li Jia
Journal: Journal of Hematology & Oncology (2018)

Colorectal cancer (CRC) arises in a multistep molecular network process, which is from either discrete genetic perturbation or epigenetic dysregulation. The long non-coding RNAs (lncRNAs), emerging as key molecules in human malignancy, has become one of the hot topics in RNA biology. Aberrant O-glycosylation is a well-described hallmark of many cancers. GALNT7 acts as a glycosyltransferase in protein O-glycosylation, involving in the occurrence and development of CRC. The microarrays were used to survey the lncRNA and mRNA expression profiles of primary CRC cell line SW480 and metastatic CRC cell line SW620. Cell proliferation, migration, invasion, and apoptosis were assayed. Xenograft mouse models were used to determine the role of lncRNA-SNHG7 in CRC in vivo. In addition, CNC analysis and competing endogenous analysis were used to detect differential SNHG7 and relational miRNAs expression in CRC cell lines. SNHG7 expression showed a high fold (SW620/SW480) in CRC microarrays. The CRC patients with high expression of SNHG7 had a significantly poor prognosis. Furthermore, SNHG7 promoted CRC cell proliferation, metastasis, mediated cell cycle, and inhibited apoptosis. SNHG7 and GALNT7 were observed for co-expression by CNC analysis, and a negative correlation of SNHG7 and miR-34a were found by competing endogenous RNA (ceRNA) analysis. Further results indicated that SNHG7 facilitated the proliferation and metastasis as a competing endogenous RNA to regulate GALNT7 expression by sponging miR-34a in CRC cell lines. SNHG7 also played the oncogenic role in regulating PI3K/Akt/mTOR pathway by competing endogenous miR-34a and GALNT7. The CRC-related SNHG7 and miR-34a might be implicated in CRC progression via GALNT7, suggesting the potential usage of SNHG7/miR-34a/GALNT7 axis in CRC treatment.
<i>Notes from the Field:</i> Domestically Acquired Verona Integron-Mediated Metallo-β-Lactamase-Producing Enterobacteriaceae — Indiana, 2016–2017
Authors: D.J. Shannon, Sara Blosser, Maroya Walters, Alex Kallen, Christine Feaster
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), Verona integron-mediated metallo-ß
Abstract 3619: The role of CXCR4 in progression of malignant glioma
Authors: Mingli Liu
Journal: Cancer Research (2018)

Abstract High grade malignant gliomas are devastating, uniformly fatal cancers for which no effective therapies exist. Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Recent studies have shown that cytokines/chemokines can regulate many malignant features of tumor cells. CXCL12/CXCR4 axis activates various signaling pathways that promote chemotaxis, adhesion and migration, cell proliferation and survival. PI3 kinase, Ras, stress-activated protein kinase (SAPK)/c-Jun Nterminal kinase (JNK), phospholipase C (PLC)/mitogen-activated protein kinase (MAPK), p38 MAPK and AKT are all downstream effectors of CXCL12/CXCR4 axis, through which tumor cell growth, dissemination and migration are facilitated. To enhance our understanding of the development and progression of glioma which may lead to novel and useful biomarkers and/or therapeutic targets in the context of GBM, we analyzed the role of CXCR4 in glioma using the published data and literature. (1).To determine the prognostic role of CXCR4 in malignant glioma, we analyzed the microarray data from Rembrandt Databases by Affymetrix HG U133 v2.0 Plus on 523 glioma patients. Kaplan-Meier analysis of overall survival showed that glioma patients with high CXCR4 expression (n=329) have short overall survival compared to those with low CXCR4 expression (n=54), logrank test: P=2.2e-8 9. Among GBM, high CXCR4 expression (n=178) have short overall survival compared to those with low CXCR4 expression (n=9), logrank test: P=0.044. Among Astrocytoma, high CXCR4 expression (n=102) have short overall survival compared to those with low CXCR4 expression (n=33), logrank test: P=0.0247 (http://www.betastasis.com/glioma/rembrandt/kaplan-meier_survival_curve/). (2).To determine the relationship between glioma progression and chemokine receptor CXCR4, we made a meta-analysis based on 14 published articles. All 14 eligible studies having 805 patients from China and USA were included. These studies showed that CXCR4 expression in glioma was correlated to high WHO grade glioma (OR=8.26, 95% CI=3.42-19.93, P&amp;lt;0.00001). Our results indicate that CXCR4 is a predictive marker for malignant glioma progression and survival. Suppression of CXCR4 inhibited proliferation, migration, and invasion of malignant human gliomas indicating that CXCR4 may represent a novel and promising target for therapeutic intervention of malignant glioma. Citation Format: Mingli Liu. The role of CXCR4 in progression of malignant glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3619.
Extracellular vesicles in DLBCL provide abundant clues to aberrant transcriptional programming and genomic alterations
Authors: Sarah C. Rutherford, Angela A. Fachel, Sheng Li, Seema Sawh, Ashlesha Muley, Jennifer Ishii, Ashish Saxena, Pilar M. Dominguez, Eloisi Caldas Lopes, Xabier Agirre, Nyasha Chambwe, Fabian Correa, Yanwen Jiang, Kristy L. Richards, Doron Betel, Rita Shaknovich
Journal: Blood (2018)
Abstract 2334: Sialylation of the TNFR1 death receptor promotes cancer cell survival
Authors: Andrew T. Holdbrooks, Matthew J. Schultz, Zhongyu Liu, Daniel C. Bullard, Susan L. Bellis
Journal: Cancer Research (2018)

Abstract Studies have well-established that activation of TNFR1, a ubiquitously expressed cell surface receptor, by TNF can induce either cell survival or cell death signaling cascades, however, the mechanisms regulating TNFR1 to initiate these disparate outcomes are poorly understood. TNF-induced apoptosis is initiated by clustering of activated TNFR1 at the cell surface, followed by internalization of the receptor complexes and subsequent caspase activation. Conversely, surface retention of activated TNFR1 promotes cell survival signaling mediated by NFκB and MAPKs pathways. Our group has identified a glycosylation-dependent mechanism that controls this TNFR1 signaling switch (i.e. apoptosis vs. survival). Specifically, we have found that TNFR1 activity is modified by the addition of a distinct sugar, an α2-6 linked sialic acid, by the Golgi sialyltransferase, ST6Gal-I. Importantly, ST6Gal-I is highly upregulated in numerous cancer types, and through its sialylation of a select cohort of cell surface receptors, various studies have indicated ST6Gal-I as a potent tumor cell survival factor. The effect of sialylation on TNFR1 was examined in multiple cancer cell models, including leukemia and epithelial cancer cell lines with forced overexpression or knockdown of ST6Gal-I. These models show that TNFR1 sialylation blocks TNF-induced apoptosis (indicated by the inhibition of caspase activation), and data from our group suggests that the underlying mechanism of this inhibition of apoptosis involves the sialylation-driven interference of TNFR1 oligomerization and internalization. Considering sialylated TNFR1 is retained on the cell surface following activation, we hypothesize that cells with abundant ST6Gal-I not only block TNFR1-mediated apoptosis but also divert signaling towards survival, indicated by increased activity and expression of many pro-survival factors (NFkB, AKT, etc.). Based on these collective findings, we conclude that the ST6Gal-I-mediated sialylation of TNFR1 controls the cellular response to TNF by blocking TNFR1 internalization, resulting in apoptosis inhibition and the promotion of survival signaling. Considering the tumor microenvironment is rich in immune cell-derived TNF, we posit that ST6Gal-I protects tumor cells within this inflammatory milieu by providing a mechanism by which tumor cells can evade immune cell killing. Citation Format: Andrew T. Holdbrooks, Matthew J. Schultz, Zhongyu Liu, Daniel C. Bullard, Susan L. Bellis. Sialylation of the TNFR1 death receptor promotes cancer cell survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2334.
Sustained complete response of advanced hepatocellular carcinoma with metronomic capecitabine: a report of three cases
Authors: Giovanni Brandi, Michela Venturi, Stefania De Lorenzo, Francesca Garuti, Giorgio Frega, Andrea Palloni, Ingrid Garajovà, Francesca Abbati, Gioconda Saccoccio, Rita Golfieri, Maria Abbondanza Pantaleo, Maria Aurelia Barbera
Journal: Cancer Communications (2018)

Abstract Background Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer‐related death. Sorafenib, a multitarget angiogenesis inhibitor, is an approved frontline treatment for advanced HCC in Western countries, although a complete response (CR) to treatment is infrequently reported. Capecitabine, an oral fluoropyrimidine, has been shown to be effect in both treatment‐naïve patients and those previously treated with sorafenib. To date, however, only one case of sustained CR to metronomic capecitabine has been reported. Case presentation We describe three cases of advanced HCC treated with metronomic capecitabine where a CR was obtained. In the first case, capecitabine was administered as first line therapy; in the second case, capecitabine was used after intolerance to sorafenib; while in the third case, capecitabine was administered after sorafenib failure. Conclusion Capecitabine is a potentially important treatment option for patients with advanced HCC and may even represent a cure in certain cases.
Relapse of Wilms' tumour and detection methods: a retrospective analysis of the 2001 Renal Tumour Study Group–International Society of Paediatric Oncology Wilms' tumour protocol database
Authors: Jesper Brok, Marta Lopez-Yurda, Harm V Tinteren, Taryn D Treger, Rhoikos Furtwängler, Norbert Graf, Christophe Bergeron, Marry M van den Heuvel-Eibrink, Kathy Pritchard-Jones, Øystein E Olsen, Beatriz de Camargo, Arnauld Verschuur, Filippo Spreafico
Journal: The Lancet Oncology (2018)
Multiple HBV transfusion transmissions from undetected occult infections: revising the minimal infectious dose
Authors: Daniel Candotti, Sonny Michael Assennato, Syria Laperche, Jean-Pierre Allain, Snezna Levicnik-Stezinar
Journal: Gut (2018)

HBV infection by blood components is currently prevented in most developed countries by combining sensitive HBV surface antigen (HBsAg) assays, nucleic acid testing (NAT) and in a few of them antibodies against the HBV core antigen (anti-HBc) screening. HBV transmissions by blood components from three repeat donors tested negative for HBsAg and HBV DNA with a highly sensitive screening test (limit of detection (LOD): 3.4 IU/mL) were investigated.30 of the 47 recipients of components produced from these three donors were examined. Transfusion transmission was confirmed by phylogenetic analysis of viral sequences obtained from recipients and donors following viral particle concentration.9 of 31 (29%) recipients were infected: 7 infections were related to 200 mL of fresh frozen plasma and 2 infections to red blood cells containing 20 mL plasma. Transfusion transmission was confirmed by >99% identity of donor/recipient sequences in five cases, probable in three and possible in one. HBV active infection remained unsuspected for 24-57 months in three recipients. Five non-infected recipients carried anti-HBs when transfused. Six patients transfused with platelet concentrates treated with a pathogen reduction method were not infected. These data enabled to revise previous estimate of the minimal infectious dose from approximately 100 to 16 copies (or 3 IU) of HBV DNA.HBV transfusion transmission from occult HBV infection carrying extremely low viral loads is related to plasma volume transfused and possibly prevented by anti-HBs. HBV blood safety could be further improved by either anti-HBc screening, HBV DNA NAT with a LOD of 0.8 copies/mL (0.15 IU/mL) or pathogen reduction of blood components.
Evaluation of food allergy candidate loci in the Genetics of Food Allergy study
Authors: Ingo Marenholz, Sarah Grosche, Franz Rüschendorf, Birgit Kalb, Katharina Blumchen, Rupert Schlags, Neda Harandi, Mareike Price, Gesine Hansen, Jürgen Seidenberg, Songül Yürek, Georg Homuth, Carsten O. Schmidt, Markus M. Nöthen, Norbert Hubner, Bodo Niggemann, Kirsten Beyer, Young-Ae Lee
Journal: Journal of Allergy and Clinical Immunology (2018)
The Integration of Radiotherapy with Immunotherapy for the Treatment of Non–Small Cell Lung Cancer
Authors: Eric C. Ko, David Raben, Silvia C. Formenti
Journal: Clinical Cancer Research (2018)

Five-year survival rates for non-small cell lung cancer (NSCLC) range from 14% to 49% for stage I to stage IIIA disease, and are <5% for stage IIIB/IV disease. Improvements have been made in the outcomes of patients with NSCLC due to advancements in radiotherapy (RT) techniques, the use of concurrent chemotherapy with RT, and the emergence of immunotherapy as first- and second-line treatment in the metastatic setting. RT remains the mainstay treatment in patients with inoperable early-stage NSCLC and is given concurrently or sequentially with chemotherapy in patients with locally advanced unresectable disease. There is emerging evidence that RT not only provides local tumor control but also may influence systemic control. Multiple preclinical studies have demonstrated that RT induces immunomodulatory effects in the local tumor microenvironment, supporting a synergistic combination approach with immunotherapy to improve systemic control. Immunotherapy options that could be combined with RT include programmed cell death-1/programmed cell death ligand-1 blockers, as well as investigational agents such as OX-40 agonists, toll-like receptor agonists, indoleamine 2,3-dioxygenase-1 inhibitors, and cytokines. Here, we describe the rationale for the integration of RT and immunotherapy in patients with NSCLC, present safety and efficacy data that support this combination strategy, review planned and ongoing studies, and highlight unanswered questions and future research needs.
Phase II Studies with Refametinib or Refametinib plus Sorafenib in Patients with <i>RAS</i>-Mutated Hepatocellular Carcinoma
Authors: Ho Yeong Lim, Philippe Merle, Karl Heinz Weiss, Thomas Yau, Paul Ross, Vincenzo Mazzaferro, Jean-Frédéric Blanc, Yuk Ting Ma, Chia Jui Yen, Judit Kocsis, Su Pin Choo, Wattana Sukeepaisarnjaroen, René Gérolami, Jean-François Dufour, Edward J. Gane, Baek-Yeol Ryoo, Markus Peck-Radosavljevic, Thong Dao, Winnie Yeo, Wisut Lamlertthon, Satawat Thongsawat, Michael Teufel, Katrin Roth, Diego Reis, Barrett H. Childs, Heiko Krissel, Josep M. Llovet
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Refametinib, an oral MEK inhibitor, has demonstrated antitumor activity in combination with sorafenib in patients with RAS-mutated hepatocellular carcinoma (HCC). Two phase II studies evaluated the efficacy of refametinib monotherapy and refametinib plus sorafenib in patients with RAS-mutant unresectable or metastatic HCC. Patients and Methods: Eligible patients with RAS mutations of cell-free circulating tumor DNA (ctDNA) determined by beads, emulsion, amplification, and magnetics technology received twice-daily refametinib 50 mg ± sorafenib 400 mg. Potential biomarkers were assessed in ctDNA via next-generation sequencing (NGS). Results: Of 1,318 patients screened, 59 (4.4%) had a RAS mutation, of whom 16 received refametinib and 16 received refametinib plus sorafenib. With refametinib monotherapy, the objective response rate (ORR) was 0%, the disease control rate (DCR) was 56.3%, overall survival (OS) was 5.8 months, and progression-free survival (PFS) was 1.9 months. With refametinib plus sorafenib, the ORR was 6.3%, the DCR was 43.8%, OS was 12.7 months, and PFS was 1.5 months. In both studies, time to progression was 2.8 months. Treatment-emergent toxicities included fatigue, hypertension, and acneiform rash. Twenty-seven patients had ctDNA samples available for NGS. The most frequently detected mutations were in TERT (63.0%), TP53 (48.1%), and β-catenin (CTNNB1; 37.0%). Conclusions: Prospective testing for RAS family mutations using ctDNA was a feasible, noninvasive approach for large-scale mutational testing in patients with HCC. A median OS of 12.7 months with refametinib plus sorafenib in this small population of RAS-mutant patients may indicate a synergistic effect between sorafenib and refametinib—this preliminary finding should be further explored. Clin Cancer Res; 24(19); 4650–61. ©2018 AACR.