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Treatment implications of posterior fossa ependymoma subgroups

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Chinese Journal of Cancer 2016年第11期35卷 563-566页

作者： Vijay Ramaswamy michael d.Taylor division of Haematology/Oncology Hospital for Sick Children division of Neurosurgery Hospital for Sick Children

Posterior fossa ependymoma comprises two distinct molecular entities,ependymoma_posterior fossa A(EPN_PFA)and ependymoma_posterior fossa B(EPN_PFB),with differentiable gene expression *** yet,the response of the two entities to treatment is *** determine the relationship between the two molecular subgroups of posterior fossa ependymoma and treatment,we studied a cohort of 820 patients with molecularly profiled,clinically annotated posterior fossa *** found that the strongest predictor of poor outcome in patients with posterior fossa ependymoma across the entire age spectrum was molecular subgroup EPN_PFA,which was recently reported in the paper entitled "Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era:a retrospective multicohort analysis" in the Journal ofClinical *** with incompletely resected EPN_PFA tumors had a very poor outcome despite receiving adjuvant radiation therapy,whereas a substantial proportion of patients with EPN_PFB tumors can be cured with surgery alone.

关键词： Posterior fossa ependymoma Genomics Radiation PFA

Semi-linear Wave Equations with Effective damping

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Chinese Annals of Mathematics,Series B 2013年第3期34卷 345-380页

作者： Marcello d'ABBICCO Sandra LUCENTE michael REISSIG department of Mathematics University of BariVia E. Orabona 4 70125 Bari Italy Faculty for Mathematics and Computer Science Technical University Bergakademie FreibergPrferstr. 909596 Freiberg Germany

The authors study the Cauchy problem for the semi-linear damped wave equation utt-△u＋b（t）ut=f（u）,u（0,χ）=u0（χ）,ut（0,χ）=u1（χ） in any space dimension n ≥ 1. It is assumed that the time-dependent damping term b（t）〉 0 is effective, and in particular tb（t） →∞ as t →∞. The global existence of small energy data solutions for｜f（u）｜≈｜u｜^p in the supercritical case of p 〉 1＋ 2/n and p ≤n/n-2 for n ≥ 3 is proved.

关键词： Semi-linear equations damped wave equations Critical exponent Global existence

Key Factors to Consider When Introducing a New Vaccine in Low-Income Settings: Lessons from Malawi Expanded Program on Immunization

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World Journal of Vaccines 2024年第1期14卷 1-23页

作者： Samuel Mpinganjira Kimberly Konono Joseph Mwaka Adidja Amani Habtamu Anteneh michael Ngigi Boston Zimba Atupele Kapito Institute for Global Health Santa Chiara Lab Universita degli Studi di Siena Siena Italy School of Public and Global Health Kamuzu University of Health Sciences Blantyre Malawi Faculty of Medicine and Biomedical Sciences of the University of Yaound 1 Yaound Cameroon department of Public Health University of Glasgow Glasgow UK

Introduction: As new vaccines become available, countries must assess the relevance to introduce them into their vaccination schedules. Malawi has recently introduced several new vaccines and plans to introduce more. This study was conducted to identify key factors that need to be considered when deciding to introduce a new vaccine and current challenges faced by low and middle income countries using Malawi as an example. Methodology: The study employed a desk review approach, examining published literature from various sources such as PubMed, Medline, and Google Scholar. Policy documents from organizations like the World Health Organization, GAVI the Alliance, and the Ministry of Health for Malawi were also included. A total of 99 articles and documents on new vaccine introduction, challenges of immunization, policy documents in immunization and health systems strengthening were included. The review focused on addressing five key areas critical to new vaccine introduction namely: the need for a vaccine, availability of the vaccine, safety and effectiveness of the vaccine, demand for the vaccine, and the prudent use of public or private funds. Results: Malawi considered the burden of cervical cancer and the significance of malaria in the country when introducing the HPV and malaria vaccines. The country opted for vaccines that can be handled by the cold chain capacity and available human resources. despite that malaria vaccine and Typhoid Conjugate Vaccine trials were done in country, there are limited vaccine safety and efficacy trials conducted in Malawi, leading to a reliance on WHO-prequalified vaccines. demand for newly introduced vaccines varied, with high demand for Oral Cholera Vaccine during a cholera outbreak, while demand for COVId-19 vaccines decreased over time. Although cost-effectiveness studies were limited in the country, 2 studies indicated that Typhoid Conjugate Vaccine and malaria vaccine would be cost effective. All these have been implemented d

关键词： Vaccine Introduction Implementation Expanded Program on Immunization Low-Income Stakeholders

Importance of gastrin in the pathogenesis and treatment of gastric tumors

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World Journal of Gastroenterology 2009年第1期15卷 1-16页

作者： michael d Burkitt Andrea Varro d Mark Pritchard Gastroenterology Unit School of Clinical Sciences University of LiverpoolAshton Street Liverpool L69 3GE United Kingdom The Physiological Laboratory School of Biomedical Sciences University of LiverpoolCrown Street Liverpool L69 3BX United Kingdom

In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffi n cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia,such as immunization with G17dT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.

关键词： Helicobacter py/ori Hypergastrinemia Neuroendocrine Gastric carcinoma Proton pumpinhibitor

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窥探宇宙空洞

环球科学 2024年第3期 24-31页

作者：迈克尔·d.勒莫尼克姚瑶(译) 蔡一夫(审校) 不详

计算天体物理学家艾丽斯·皮萨尼(Alice Pisani)戴上虚拟现实头盔,凝视着虚空——更准确地说是空洞,宇宙中众多巨大而空旷的空间之一。皮萨尼回忆道:“这真是太神奇了。”起初,她面前的空中盘旋着一团闪亮的光点,每个光点都代表一个星系。

关键词：天体物理学家萨尼空洞艾丽斯虚拟现实头盔宇宙光点

CdC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3519-3532页

作者： Alvaro Quintanal-Villalonga Kenta Kawasaki Esther Redin Fathema Uddin Swanand Rakhade Vidushi durani Amin Sabet Moniquetta Shafer Wouter R.Karthaus Samir Zaidi Yingqian A.Zhan Parvathy Manoj Harsha Sridhar dennis Kinyua Hong Zhong Barbara P.Mello Metamia Ciampricotti Umesh K.Bhanot Irina Linkov Juan Qiu Radhika A.Patel Colm Morrsey Sanjoy Mehta Jesse Barnes michael C.Haffner Nichlas d.Socci Richard P.Koche Elisa de Stanchina Sonia Molina-Pinelo Sohrab Salehi Helena A.Yu Joseph M.Chan Charles M.Rudin department of Medicine Thoracic Oncology ServiceMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Cancer Biology and Genetics Program Sloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Vagelos College of Physicians and Surgeons Columbia UniversityNew YorkNYUSA Weill Cornell Graduate School of Medical Sciences Weill Cornell MedicineNew YorkNYUA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Center for Epigenetics Research Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Pathology Core Facilty Department of Pathology and Laboratory MedicineMSKCCNew YorkNYUSA Antitumor Assessment Core Memorial Sloan Kettering Cancer CenterNew YorkNYUSA divisionsof Human Biology and Clinical Research Fred Hutchinon Cancer CenterSeattleWAUSA deparmentof Urology University of WashingtonSeattleWAUSA Gene Editing&Screening Core Facility Memorial Sloan Kettering Cancer Center New YorkNYUSA department of Laboratory Medicine and Pathology University of WashingtonSeattleWAUSA Bioinfomatics CoreFacility Memorial Soan Kettering Cancer CenterNew YorkNYUSA Institute of Biomedicine of Seille(Bis) HURCSCUniversidad de SevillaSevilleSpain Computational Oncology Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Well Cornell Medical College New York NYUSA Present address:Swiss Institute for Experimental Cancer Research(ISREC) School of Life SciencesEPFLLausanneSwitzerland

Neuroendocrine(NE)transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor *** to date,even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53(TP53)and Retinoblastoma Transcriptional Corepressor 1(RB1)mutations in their tumors,no therapeutic strategies are available to prevent or delay histological *** of the cell cycle kinase Cell division Cycle 7(CdC7)occurred in tumors during the initial steps of NE transformation,already after TP53/RB1 co-inactivation,leading to induced sensitivity to the CdC7 inhibitor ***7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYC Proto-Oncogen(MYC),implicated in stemness and histological *** overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy,even in the presence of ***7 inhibition also markedly extended response to standard cytotoxics(cisplatin,irinotecan)in lung and prostate small cell carcinoma *** results nominate CdC7 inhibition as a therapeutic strategy to constrain lineage plasticity,as well as to effectively treat NE tumors de novo or after *** simurosertib clinical efficacy trials are ongoing,this concept could be readily translated for patients at risk oftransformation.

关键词： tumors markedly transformation

Enhanced electrogastrography: A realistic way to salvage a promise that was never kept?

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World Journal of Gastroenterology 2017年第25期23卷 4517-4528页

作者： michael d Poscente Martin P Mintchev department of Electrical and Computer Engineering University of Calgary

To enhance the clinical utility of electrogastrography (EGG), which has been recorded since 1922, but is clinically unutilized. METHOdSAn innovative method to salvage the promise of EGG is proposed by introducing a preliminary procedure, while maintaining the electrodes, standardized equipment, and signal processing utilized in the well-established EGG testing of today. The proposed enhanced EGG (EEGG) protocol involves swallowing an ingestible capsule containing miniature electronic oscillator embedded in an expandable, self-disintegratable, biocompatible pseudobesoar residing in the stomach for the duration of the test. The benefits of the proposed approach are outlined, tested and discussed in details. RESULTSExperiments were performed on eight mongrel dogs (6F, 4M, 23.8 ± 3.3 kg). Four were administered an active EEGG capsule, while the rest were given a deactivated (battery removed) capsule. Pharmacologically facilitated gastric motility revealed a significant (P dices obtained by force transducers implanted directly on the stomach, and the motility indices obtained by EEGG. A particular emphasis was made on preserving standard EGG-related hardware and software in order to facilitate the introduction of the proposed EEGG in environments which already utilize standard EGG testing. The expanded intragastric pseudobezoar containing the miniature electronic oscillator was retained during the tests, and could be disintegrated on demand. CONCLUSIONEnhancing standard EGG by an ingestible, self-expanding and self-disintegrating pseudobesoar containing a miniature electronic oscillator can be an important avenue for clinical applicability of this test.

关键词： Electrogastrography Functional dyspepsia Gastroparesis Ingestible oscillator Pseudobesoar

Epigenetic Repression of Male Gametophyte- Specific Genes in the Arabidopsis Sporophyte

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Molecular Plant 2013年第4期6卷 1176-1186页

作者： Robert d. Hoffmann michael G. Palmgren Centre for Membrane Pumps in Cells and disease--PUMPKIN Danish National Research Foundation Department of Plant and Environmental SciencesUniversity of Copenhagen Thorvaldsensvej 40 DK-1871 Frederiksberg Denmark

Tissue formation, the identity of cells, and the functions they fulfill, are results of gene regulation. The male gametophyte of plants, pollen, is outstanding in this respect as several hundred genes expressed in pollen are not expressed in the sporophyte. How pollen-specific genes are down-regulated in the sporophyte has yet to be established. In this study, we have performed a bioinformatics analysis of publicly available genome-wide epigenetics data of sev- eral sporophytic tissues. By combining this analysis with dNase ! footprinting data, we assessed means by which the repression of pollen-specific genes in the Arabidopsis sporophyte is conferred. Our findings show that, in seedlings, the majority of pollen-specific genes are associated with histone-3 marked by mono- or trimethylation of Lys-27 （H3K27me1/ H3K27me3）, both of which are repressive markers for gene expression in the sporophyte. Analysis of dNase footprint profiles of pollen-specific genes in the sporophyte displayed closed chromatin proximal to the start codon. We describe a model of two-staged gene regulation in which a lack of nucleosome-free regions in promoters and histone modifications in open reading frames repress pollen-specific genes in the sporophyte.

关键词： male gametophyte epigenetics gene repression dNase I footprinting transcription factors bioinformatics.

diversity of Gene Expression in Hepatocellular Carcinoma Cells

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Genomics, Proteomics & Bioinformatics 2015年第6期13卷 377-382页

作者： Fan Zhang Li Cui michael d.Kuo department of Molecular and Medical Genetics University of North Texas Health Science Center department of Neurosciences School of Medicine University of California department of Radiological Sciences University of California Los Angeles David Geffen School of Medicine

Understanding tumor diversity has been a long-lasting and challenging question for researchers in the field of cancer heterogeneity or tumor evolution. Studies have reported that com- pared to normal cells, there is a higher genetic diversity in tumor cells, while higher genetic diversity is associated with higher progression risks of tumor. We thus hypothesized that tumor diversity also holds true at the gene expression level. To test this hypothesis, we used t-test to compare the means of Simpson＇s diversity index for gene expression （SdIG） between tumor and non-tumor samples. We found that the mean SdIG in tumor tissues is significantly higher than that in the non-tumor or normal tissues （P 〈 0.05） for most datasets. We also combined microarrays and next-generation sequencing data for validation. This cross-platform and cross-experimental validation greatly increased the reliability of our results.

关键词： Gene expression Hepatocellular carcinomacell diversity Mieroarray Next-generation sequencing