tbuckley/cabot-search huggingface dataset:
Gene profiling of genistein’s effect in men with prostate cancer.
Authors: Yongzeng Ding, Li Xu, Shan Chen, William Catalona, David L. Kelly, Borko Jovanovic, Irene B. Helenowski, Ximing Yang, Michael Pins, Raymond Bergan
Journal: Cancer Research (2006)

5265  Genistein is a putative prostate cancer (PCa) chemopreventative agent. Both epidemiological studies conducted by others, as well as preclinical molecular pharmacology studies performed by us, indicate that genistein has the potential to inhibit metastasis. Prospective studies aimed at evaluating the effects of genistein upon prostate cells in man are lacking. As genistein may be an effective chemopre ventive agent but may be operating through other mechanisms, it is also notable that effective methods to broadly screen for molecular effects in target tissue in man are also lacking. After completing a phase I trial, we have implemented a phase 2 trial in men about to undergo radical prostatectomy, thus providing tissue from those treated with genistein and controls. We have recently developed a robust and accurate method which allows high density gene array profiles to be performed on specific prostate cell populations recovered from intact tissue by laser capture microdissection. In the current study we examine normal prostate epithelial cells, and compare gene expression profiles between control subjects (N = 11) and genistein treated (N = 8). From over 12,000 genes analyzed, 10 were identified as significantly differentially expressed. Importantly, 3 genes have a clear mechanistic relationship to genistein. HCF2 is an anticoagulant factor involved in cell migration. BASP1 is a neural tissue-enriched protein and motility-associated factor. HSP90 is in the same family as HSP27, which we have recently shown regulates PCa cell matrix metalloproteinase type 2 (MMP-2) induction and invasion. In summary, robust in vivo molecular profiling at the level of individual cell types is now possible, and provides key mechanistic information about therapeutic intervention.
PTH-047 Microscopic colitis in patients undergoing two week wait colonoscopy for chronic diarrhoea
Authors: Jeremy Nayagam, Sarah Fleming, Vishal Mehta, Alistair McNair, Aathavan Loganayagam
Journal: Endoscopy (2018)

<h3>Introduction</h3> Chronic diarrhoea is an indication for referral on the Colorectal two week wait (TWW) pathway for suspected malignancy. Microscopic colitis (MC) characteristically presents with chronic watery diarrhoea. The frequency of MC diagnosed in TWW patients has not been systematically evaluated, but from available literature is diagnosed in 0.1%–2.8% of patients. We sought to define the incidence of MC in our cohort of patients who underwent colonoscopy for chronic diarrhoea on TWW pathway. <h3>Methods</h3> All colonoscopies performed in a single NHS District General Hospital over a 4 year period (1/1/12 – 31/12/15) under the TWW pathway with one of the indications for investigation listed as chronic diarrhoea were identified from the electronic endoscopy database. Information on patient demographics, endoscopy reports and histological diagnoses were collected. For patients with histology definitive or suspicious for MC, the slides were re-reviewed by a single Histopathology Consultant with an interest in gastrointestinal disease. Further clinical information from case notes was obtained for definitive cases of MC. <h3>Results</h3> Colonoscopy was performed in 533 patients in this time period, with a median age of 62 years, 55.2% were female. Out of these, 91.2% had colonic biopsies taken, and 84.2% had colonic biopsies from macroscopically normal mucosa, to exclude the diagnosis of MC. 21 patients (3.9% of all patients) were diagnosed with MC (6 with collagenous colitis, 15 with lymphocytic colitis). This subgroup had a median age of 76 years, 76.2% were female. 48% were on proton pump inhibitors, 19% had a diagnosis of hypothyroidism, 10% had a known malignancy (non colorectal). <h3>Conclusions</h3> In our experience, random colonic biopsies were taken in the majority of patients referred on the TWW pathway with chronic diarrhoea in order to assess for MC. MC is a relatively common diagnosis and from our cohort of patients it was mainly seen in elderly females. MC should be considered in patients with chronic diarrhoea undergoing colonoscopy for suspected malignancy.
Biodegradable<i>β</i>‐Cyclodextrin Conjugated Gelatin Methacryloyl Microneedle for Delivery of Water‐Insoluble Drug
Authors: Xingwu Zhou, Zhimin Luo, Avijit Baidya, Han‐jun Kim, Canran Wang, Xing Jiang, Moyuan Qu, Jixiang Zhu, Li Ren, Fereshteh Vajhadin, Peyton Tebon, Niyuan Zhang, Yumeng Xue, Yudi Feng, Chengbin Xue, Yi Chen, KangJu Lee, Junmin Lee, Shiming Zhang, Chun Xu, Nureddin Ashammakhi, Samad Ahadian, Mehmet Remzi Dokmeci, Zhen Gu, Wujin Sun, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2020)

Transdermal delivery of water-insoluble drugs via hydrogel-based microneedle (MN) arrays is crucial for improving their therapeutic efficacies. However, direct loading of water-insoluble drug into hydrophilic matrices remains challenging. Here, a biodegradable MN array patch that is fabricated from naturally derived polymer conjugates of gelatin methacryloyl and β-cyclodextrin (GelMA-β-CD) is reported. When curcumin, an unstable and water-insoluble anticancer drug, is loaded as a model drug, its stability and solubility are improved due to the formation of an inclusion complex. The polymer-drug complex GelMA-β-CD/CUR can be formulated into MN arrays with sufficient mechanical strength for skin penetration and tunable drug release profile. Anticancer efficacy of released curcumin is observed in three-dimensional B16F10 melanoma models. The GelMA-β-CD/CUR MN exhibits relatively higher therapeutic efficacy through more localized and deeper penetrated manner compared with a control nontransdermal patch. In vivo studies also verify biocompatibility and degradability of the GelMA-β-CD MN arrays patch.
Targeting mitochondrial fission as a potential therapeutic for abdominal aortic aneurysm
Authors: Hannah A Cooper, Stephanie Cicalese, Kyle J Preston, Tatsuo Kawai, Keisuke Okuno, Eric T Choi, Shingo Kasahara, Haruhito A Uchida, Nozomu Otaka, Rosario Scalia, Victor Rizzo, Satoru Eguchi
Journal: Cardiovascular Research (2020)

Abstract Aims Angiotensin II (AngII) is a potential contributor to the development of abdominal aortic aneurysm (AAA). In aortic vascular smooth muscle cells (VSMCs), exposure to AngII induces mitochondrial fission via dynamin-related protein 1 (Drp1). However, pathophysiological relevance of mitochondrial morphology in AngII-associated AAA remains unexplored. Here, we tested the hypothesis that mitochondrial fission is involved in the development of AAA. Methods and results Immunohistochemistry was performed on human AAA samples and revealed enhanced expression of Drp1. In C57BL6 mice treated with AngII plus β-aminopropionitrile, AAA tissue also showed an increase in Drp1 expression. A mitochondrial fission inhibitor, mdivi1, attenuated AAA size, associated aortic pathology, Drp1 protein induction, and mitochondrial fission but not hypertension in these mice. Moreover, western-blot analysis showed that induction of matrix metalloproteinase-2, which precedes the development of AAA, was blocked by mdivi1. Mdivi1 also reduced the development of AAA in apolipoprotein E-deficient mice infused with AngII. As with mdivi1, Drp1+/− mice treated with AngII plus β-aminopropionitrile showed a decrease in AAA compared to control Drp1+/+ mice. In abdominal aortic VSMCs, AngII induced phosphorylation of Drp1 and mitochondrial fission, the latter of which was attenuated with Drp1 silencing as well as mdivi1. AngII also induced vascular cell adhesion molecule-1 expression and enhanced leucocyte adhesion and mitochondrial oxygen consumption in smooth muscle cells, which were attenuated with mdivi1. Conclusion These data indicate that Drp1 and mitochondrial fission play salient roles in AAA development, which likely involves mitochondrial dysfunction and inflammatory activation of VSMCs.
HSCT provides effective treatment for lymphoproliferative disorders in children with primary immunodeficiency
Authors: Giulia Prunotto, Ugonna T. Offor, Sujith Samarasinghe, Robert Wynn, Ajay Vora, Ben Carpenter, Claire Gowdy, Kieran McHugh, Kevin P. Windebank, Attilio Maria Rovelli, Mary A. Slatter, Andrew R. Gennery, Paul Veys, Chris M. Bacon, Simon Bomken, Giovanna Lucchini
Journal: Journal of Allergy and Clinical Immunology (2020)
Corrigendum to “From perinuclear to intranuclear localization: A cell-penetrating peptide modification strategy to modulate cancer cell migration under mild laser irradiation and improve photothermal therapeutic performance” [Biomaterials 223 (2019) 119443]
Authors: Ge Gao, Yao-Wen Jiang, Hao-Ran Jia, Wei Sun, Yuxin Guo, Xin-Wang Yu, Xiaoyang Liu, Fu-Gen Wu
Journal: Biomaterials (2020)
Sphingolipids as prognostic biomarkers of neurodegeneration, neuroinflammation, and psychiatric diseases and their emerging role in lipidomic investigation methods
Authors: Daan van Kruining, Qian Luo, Gerhild van Echten-Deckert, Michelle M. Mielke, Andrew Bowman, Shane Ellis, Tiago Gil Oliveira, Pilar Martinez-Martinez
Journal: Advanced Drug Delivery Reviews (2020)

Lipids play an important role in neurodegeneration, neuroinflammation, and psychiatric disorders and an imbalance in sphingolipid levels is associated with disease. Although early diagnosis and intervention of these disorders would clearly have favorable long-term outcomes, no diagnostic tests currently exist that can accurately identify people at risk. Reliable prognostic biomarkers that are easily accessible would be beneficial to determine therapy and treatment response in clinical trials. Recent advances in lipidomic investigation methods have greatly progressed the knowledge of sphingolipids in neurodegenerative and psychiatric disorders over the past decades although more longitudinal studies are needed to understand its exact role in these disorders to be used as potential tools in the clinic. In this review, we give an overview of the current knowledge of sphingolipids in neurodegenerative and psychiatric disorders and explore recent advances in investigation methods. Finally, the potential of sphingolipid metabolism products and signaling molecules as potential biomarkers for diagnosis, prognostic, or surrogate markers of treatment response is discussed.
Second-Trimester Miscarriage in a Pregnant Woman With SARS-CoV-2 Infection
Authors: David Baud, Gilbert Greub, Guillaume Favre, Carole Gengler, Katia Jaton, Estelle Dubruc, Léo Pomar
Journal: JAMA (2020)

Lan Dong, MD; Jinhua Tian, MD; Songming He, MD; Chuchao Zhu, MD; Jian Wang, MD; Chen Liu, MD; Jing Yang, MD
PTH-011 Role of the new-generation cholangioscopy in the diagnosis of indeterminate biliary lesions: a multi-centre study
Authors: Noor Bekkali, Nick Church, Alison Winstanley, George Goodchild, Sham Direkze, Kofi Oppong, George Webster
Journal: Endoscopy (2018)

<h3>Background</h3> Accurate diagnosis in patients with indeterminate biliary strictures remains challenging. Advances in cholangioscope design might facilitate improved visual and pathological diagnosis. <h3>Objective</h3> To compare the diagnostic yield between brushings, cholangioscopy-directed Spybite biopsies (SB) and visual impression at cholangioscopy in patients presenting with indeterminate strictures referred for cholangioscopy. <h3>Methods</h3> Prospective audit data was collected from 3 tertiary centres between June 2015-August 2017. Continuous data was expressed in mean values with 95% confidence intervals (CI) and categorical data was analysed using chi-square test. <h3>Results</h3> 76 (41 M) patients, mean age 57 years (95% CI 53–62), had cholangioscopy for indeterminate strictures. Six patients were excluded from analysis as they were lost to follow-up (n=3) or were awaiting further investigations (n=3). Seven patients (10%) had strictures in association with stones. Of 69 (90%) with indeterminate strictures 40 (53%) had had previous negative brush cytology, 9 (11.8%) had had non-diagnostic FNA, and one had negative intraductal biopsies. Brushings were repeated at cholangioscopy in 31 patients, with sensitivity and specificity of 33% (95%CI 12%–62%) and 100% (95%CI 79%–100%) for malignancy, respectively. Cholangioscopy guided SBs were taken in 58 patients and SB were not taken in 12 patients due to: stones mimicking strictures n=7, normal mucosa n=3, Mirrizi n=1, scope impassable due to stricture n=1. The SB had sensitivity and specificity of 44% (95%CI 23%–66%) and 100% (95%CI 90%–100%), respectively. Overall, a mean number of 4.6 (95% CI 3.7–5.5) SB samples were taken per patient with median size 2.2 mm (range 0.9–7). There was no difference in size between reported sufficient 1.5 (0.5–2.4) mm or insufficient 1.9 mm (1.5–2.3) biopsies. Pathologist reported insufficient (PANC-1) SB biopsies in 6 patients (10%) and these correlated with more false negative (FN) findings compared to sufficient biopsies (p=0.001). Cholangioscopic views were excellent in all patients and had sensitivity and specificity of 73% (95%CI 50%–89%) and 67% (95%CI 51–80), respectively. Sensitivity and specificity for SB were significantly different between those for visual impression (p=0.0004). <h3>Conclusion</h3> The new generation cholangioscope has acceptable diagnostic yield, where visual impression exceeds the conventional SB confirmation Despite excellent visualisation of indeterminate strictures a definitive visual diagnosis remains challenging. It is hoped that further improvements in tissue acquisition technologies might advance pathological diagnosis.
PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice
Authors: Iñaki Eguren-Santamaria, Miguel F. Sanmamed, Sarah B. Goldberg, Harriet M. Kluger, Miguel A. Idoate, Benjamin Y. Lu, Jesús Corral, Kurt A. Schalper, Roy S. Herbst, Ignacio Gil-Bazo
Journal: Clinical Cancer Research (2020)

Abstract Immune checkpoint inhibitors (ICI) have revolutionized the management of advanced non–small cell lung cancer (NSCLC). However, most pivotal phase III trials systematically excluded patients with active brain metastases, precluding the generalization of the results. Although theoretically restricted from crossing the blood–brain barrier, the novel pharmacokinetic/pharmacodynamic profiles of anti-PD-1/PD-L1 drugs have prompted studies to evaluate their activity in patients with NSCLC with active central nervous system (CNS) involvement. Encouraging results have suggested that ICI could be active in the CNS in selected patients with driver-negative advanced NSCLC with high PD-L1 expression and low CNS disease burden. Single-agent CNS response rates around 30% have been reported. Beyond this particular setting, anti-PD-1/PD-L1 antibodies have been evaluated in patients receiving local therapy for brain metastases (BM), addressing concerns about potential neurologic toxicity risks associated with radiotherapy, more specifically, radionecrosis (RN). Accordingly, a variety of clinical and imaging strategies are being appropriately developed to evaluate tumor response and to rule out pseudoprogression or radionecrosis. Our purpose is to critically summarize the advances regarding the role of systemic anti-PD-1/PD-L1 antibodies for the treatment of NSCLC BM. Data were collected from the PubMed database, reference lists, and abstracts from the latest scientific meetings. Recent reports suggest anti-PD-1/PD-L1 agents are active in a subset of patients with NSCLC with BM showing acceptable toxicity. These advances are expected to change soon the management of these patients but additional research is required to address concerns regarding radionecrosis and the appropriate sequencing of local and systemic therapy combinations.
Abstract P5-15-03: Cost-effectiveness of ‘radioguided occult lesion localization’ (ROLL) versus ‘wire-guided localization’ (WGL) in breast conserving surgery for non-palpable breast cancer: results from a randomized controlled multicentre trial
Authors: EL Postma, E Koffijberg, HM Verkooijen, AJ Witkamp, MA van den Bosch, R van Hillegersberg
Journal: Cancer Research (2012)

Abstract Background: Accurate pre-operative localization of non-palpable breast cancer is essential to achieve complete resection. Radio-guided occult lesion localization (ROLL) has been introduced as an alternative for wire-guided localization (WGL). Although efficacy of ROLL has been established in a RCT, cost-effectiveness of ROLL compared with WGL is not yet known. Objective. To determine whether ROLL has acceptable cost-effectiveness compared with WGL. Methods. An economic evaluation was performed alongside a randomized controlled trial (ClinicalTrials.gov, number NCT00539474). Women (&amp;gt;18 years) with histologically proven non-palpable breast cancer and eligible for breast conserving treatment with sentinel node procedure were randomized to ROLL(n = 162) or WGL (n = 152). Empirical data on direct medical costs was collected, and changes in quality of life were measured over a 6 months period. Bootstrapping was used to assess uncertainty in cost-effectiveness estimates, and sensitivity of the results to the missing data approach was investigated. Results. In total, 314 patients with 316 invasive breast cancers were enrolled. On average ROLL required the same time as WGL for the initial procedure (119 vs. 118 min.), resulted in a 7% higher re-interventions risk (27% vs. 20%, p = 0.163), a 13% higher complication risk (30% vs. 17%, p = 0.006) but showed similar health effects (difference 0.00 QALYs 95%CI (−0.04 to 0.05). Total costs were also similar for ROLL and WGL (+ €26 per patient 95% CI-250 to 311). Conclusion. ROLL is comparable to WGL with respect to both costs and quality of life, and will therefore not lead to more cost-effective medical care. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-15-03.
Эффективность использования Bifidobacterium infantis 35624 у больных неалкогольной жировой болезнью печени
Authors: Ye.S. Sirchak, V.I. Griga, O.I. Petrichko, Y.I. Рichkar
Journal: GASTROENTEROLOGY (2020)

Актуальность. Неалкогольная жировая болезнь печени (НАЖБП) охватывает спектр заболеваний, тесно связанных с метаболическими факторами риска. Цель: изучить эффективность терапии с использованием препарата Bifidobacterium infantis (B.infantis) 35624 на динамику проявлений депрессии у больных НАЖБП и сахарным диабетом (СД) 2-го типа. Материалы и методы. Обследовано 56 больных НАЖБП. Больные разделены на 2 группы: больные I группы (n = 26) для коррекции дисбиоза толстой кишки (ДТК) получали комбинированный пробиотик; II группы (n = 30) — препарат B.іnfantis. Нарушение функций центральной нервной системы определяли с помощью таких нейропсихометрических тестов, как шкала самооценки Спилбергера — Ханина, шкала депрессии Бека (BDI), шкала Zung, Торонтская алекситимическая шкала. Результаты. Анализ микробиологического исследования фекалий у обследованных больных обеих групп до лечения указывает на выраженные изменениями в количественном и качественном составе микрофлоры толстой кишки. У больных НАЖБП и СД 2-го типа соматическая патология сопровождается выраженными проявлениями депрессии, тревожности, неуверенности в себе. Продемонстрировано значительное уменьшение выраженности депрессии, тревожности на фоне нормализации микробного состава толстой кишки при длительном приеме B.infantis 35624 у больных НАЖБП и СД 2-го типа. Выводы. У больных НАЖБП и СД 2-го типа установлено ДТК преимущественно II (у 53,3–53,8 % обследованных) и I степеней (у 30,0–30,8 % обследованных). У больных НАЖБП и СД 2-го типа определяются тревожные расстройства, умеренно выраженные проявления депрессии по шкале Спилбергера — Ханина, BDI, шкале Zung и Торонтской шкале, что требует соответствующей коррекции. Курсовой прием B.infantis 35624 у больных НАЖБП и СД 2-го типа является эффективным средством не только для коррекции дисбиоза толстой кишки, но и коррекции проявлений депрессии и тревожных состояний у данных пациентов.
Sentinel lymph node biopsy after neoadjuvant chemotherapy is accurate in breast cancer patients with a clinically negative axillary nodal status at presentation.
Authors: P Gimbergues, C Abrial, G Le Bouedec, F Cachin, F Penault-Llorca, M Mouret-Reynier, F Kwiatkowski, J Maublant, A Tchirkov, J Dauplat, P Chollet, X Durando
Journal: Cancer Research (2009)

Abstract Abstract #1020 Background: In breast cancer, neoadjuvant chemotherapy (NAC) is widely used in order to enable a conservative surgery. In patients treated with NAC, the use of sentinel lymph node (SLN) biopsy, which is a good predictor of the axillary nodal status in previously untreated patients, is still discussed. The aim of our study was to determine clinicopathological factors that may influence the accuracy of SLN biopsy after NAC.&amp;#x2028; Patients and methods : Between March 2001 and December 2006, 129 patients with infiltrating breast carcinoma were studied prospectively. Preoperatively, all of them underwent NAC. At surgery, SLN biopsy followed by axillary lymph node (ALN) dissection was performed. Lymphatic mapping was done using the isotope method.&amp;#x2028; Results : The SLN identification rate was 93.8% (121/129). Fifty-six out of the 121 sucessfully mapped patients had positive ALN. Eight out of these 56 patients had tumor-free SLN (false-negative rate of 14.3%). The false-negative rate was correlated with larger tumor size (T1-T2 versus T3; p=0.045) and positive clinical nodal status (N0 versus N1-N2; p=0.003) before NAC. In particular, the false-negative rate was 0% (0/29) in N0 patients and 29.6% (8/27) in N1-N2 patients. Clinical and pathological responses to NAC did not influence the accuracy of SLN biopsy.&amp;#x2028; Conclusion : Our results show that clinical nodal status is the main clinicopathological factor influencing the false-negative rate of SLN biopsy after NAC for breast cancer. SLN biopsy after NAC can predict the ALN status with a high accuracy in patients who are clinically lymph node negative at presentation. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1020.