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Artemisinin, GABA signaling and cell reprogramming： when an old drug meets modern medicine

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Science Bulletin 2017年第6期62卷 386-387页

作者： Hai-Kun Liu division of molecular Neurogenetics German Cancer Research Center (DI(FZ) DKFZ-ZMBH Alliance Heidelberg 69120 Germany

The hormone-secreting endocrine cells(α,β,δ,ε and PP cells)form pancreatic islets,which are strongly involved in regulation of *** of insulin-producingβcells is the major cause of type 1 *** progress in cell reprogramming demonstrates the feasibility of generating functionalβcells to treat type 1 diabetes[1].However,a non-invasive in vivo approach forβcell reprogramming is still ***,two reports in

关键词： GABA cell Artemisinin,GABA signaling and cell reprogramming:when an old drug meets modern medicine

Gastric leptomeningeal carcinomatosis: Multi-center retrospective analysis of 54 cases

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World Journal of Gastroenterology 2009年第40期15卷 5086-5090页

作者： Sung Yong Oh Su-Jin Lee Jeeyun Lee Suee Lee Sung-Hyun Kim Hyuk-Chan Kwon Gyeong-Won Lee Jung Hun Kang In Gyu Hwang Joung-Soon Jang Ho Yeong Lim Young Suk Park Won Ki Kang Hyo-Jin Kim Department of Internal Medicine and Medical Research Center for Cancer molecular therapy Dong-A University College of Medicine division of Hematology/Oncology Department of MedicineSamsung Medical Center Department of InternalMedicine Gyeongsang National University School of Medicine Department of Internal Medicine College of MedicineChung-Ang University

AIM： To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis （LMC） of gastric ***： We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to ***： The male-to-female ratio was 32：22, and the patients ranged in age from 28 to 78 years （median,48.5 years）. The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clini-cal or pathologic tumor, node and metastasis stage ofthe primary gastric cancer wasin 38 patients （70%）.The median interval from diagnosis of the primarymalignancy to the diagnosis of LMC was 6.3 mo, rang-ing between 0 and 73.1 mo. Of the initial endoscopic f indings for the 45 available patients, 23 （51%） of the patients were Bormann typeand 15 （33%） patientswere Bormann type. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache （85%） and nausea/vomiting （58%） were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases （82%）. Intrathecal （IT） chemotherapy was administered to 36 patients-primarily methotrexate alone （61%）, but also in combi-nation with hydrocortisone/± Ara-C （39%）. The median number of IT treatments was 7 （range, 1-18）. Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Sev-enteen patients （46%） achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk （95% CI： 4.3-9.1 wk）. In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration （P = 0.038, P = 0.010, and P = 0.002, respectively）. However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer sur

关键词： Carcinomatosis Gastric cancer Intrathecal chemotherapy Leptomeningeal

Potential of kynurenine metabolites in drug development against neurodegenerative diseases

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Neural Regeneration Research 2021年第2期16卷 308-309页

作者： Lenka Kubicova Vladimir Chobot division of molecular Systems Biology Department of Ecogenomics and Systems BiologyFaculty of Life SciencesUniversity of ViennaViennaAustria

Reactive oxygen species(ROS)and kynurenines:Kynurenines represent a relatively heterogenous group of tryptophan metabolites(Figure 1 A).The amino acid tryptophan is metabolized in the humans by the kynurenine or serotonin *** a long time,the kynurenine pathway was assumed primarily to constitute the source for nicotinamide-adenine dinucleotide phosphate,one of the most utilized redox active enzyme cofactors.

关键词： Figure assumed utilized

Pancreatic acinar cell carcinoma: A review on molecular profiling of patient tumors

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World Journal of Gastroenterology 2017年第45期23卷 7945-7951页

作者： Ahmad Al-Hader Rami N Al-Rohil Haiyong Han Daniel Von Hoff division of Hematology/Oncology Indiana University School of Medicine Department of Pathology Vanderbilt University School of Medicine molecular Medicine division Translational Genomics Research Institute (TGen)

Pancreatic carcinomas with acinar differentiation are rare,accounting for 1%-2% of adult pancreatic tumors; they include pancreatic acinar cell carcinoma(PACC),pancreatoblastoma,and carcinomas of mixed differentiation. Patients with PACC have a prognosis better than pancreatic ductal adenocarcinomas but worse than pancreatic neuroendocrine tumors. Reports of overall survival range from 18 to 47 mo. A literature review on PACCs included comprehensive genomic profiling and whole exome sequencing on a series of more than 70 patients as well as other diagnostic studies including immunohistochemistry. Surgical resection of PACC is the preferred treatment for localized and resectable tumors. The efficacy of adjuvant treatment is unclear. Metastatic PACCs are generally not curable and treated with systemic chemotherapy. They are moderately responsive to chemotherapy with different regimens showing various degrees of response in case reports/series. Most of these regimens were developed to treat patients with pancreatic ductal adenocarcinomas or colorectal adenocarcinomas. Review of PACC's molecular profiling showed a number of gene alterations such as: SMAD4,BRAF,BRCA2,TP53,RB1,MEN1,JAK-1,BRCA-1,BRCA-2,and DNA mismatch repair abnormalities. PACCs had multiple somatic mutations with some targetable with available drugs. Therefore,molecular profiling of PACC should be an option for patients with refractory PACC.

关键词： Pancreatic acinar cell carcinoma molecular profiling Targeted therapy

Size does not determine the grade of malignancy of early invasive colorectal cancer

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World Journal of Gastroenterology 2009年第22期15卷 2708-2713页

作者： Takahisa Matsuda Yutaka Saito Takahiro Fujii Toshio Uraoka Takeshi Nakajima Nozomu Kobayashi Fabian Emura Akiko Ono Tadakazu Shimoda Hiroaki Ikematsu Kuang-I Fu Yasushi Sano Takahiro Fujimori Endoscopy division National Cancer Center Hospital Clinical Laboratory division National Cancer Center Hospital division of Digestive Endoscopy and Gastrointestinal Oncology National Cancer Center Hospital East Department of Surgical and molecular Pathology Dokkyo University School of Medicine

AIM： To clarify the clinicopathological characteristics of small and large early invasive colorectal cancers （EI-CRCs）, and to determine whether malignancy grade depends on size. METHODS： A total of 583 consecutive EI-CRCs treated by endoscopic mucosal resection or surgery at the National Cancer Center Hospital between 1980 and 2004 were enrolled in this study. Lesions were classified into two groups based on size： small （≤10 ram） and large （〉10 ram）. Clinicopathological features, incidence of lymph node metastasis （LNM） and risk factors for LNM, such as depth of invasion, lymphovascular invasion （LVI） and poorly differentiated adenocarcinoma （PDA） were analyzed in all resected specimens. RESULTS： There were 120 （21%） small and 463 （79%） large lesions. Histopathological analysis of the small lesion group revealed submucosal deep cancer （sin： 1〉1000 μm） in 90 （75%） cases, LVI in 26 （22%） cases, and PDA in 12 （10%） cases. Similarly, the large lesion group exhibited submucosal deep cancer in 380 （82%） cases, LVI in 125 （27%） cases, and PDA in 79 （17%） cases. The rate of LNM was 11.2% and 12.1% in the small and large lesion groups, ***： Small EI-CRC demonstrated the same aggressiveness and malignant potential as large cancer.

关键词： Colorectal cancer Submucosal invasion Lymph node metastasis Endoscopic mucosal resection

Taking advantage of drug resistance, a new approach in the war on cancer

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Frontiers of Medicine 2018年第4期12卷 490-495页

作者： Liqin Wang Rene Bernards division of molecular Carcinogenesis Oncode Institute The Netherlands Cancer Institute Plesmanlaan 121 1066 CX Amsterdam The Netherlands

Identification of the driver mutations in cancer has resulted in the development of a new category of molecularly targeted anti-cancer drugs. However, as was the case with conventional chemotherapies, the effectiveness of these drugs is limited by the emergence of drug-resistant variants. While most cancer therapies are given in combinations that are designed to avoid drug resistance, we discuss here therapeutic approaches that take advantage of the changes in cancer cells that arise upon development of drug resistance. This approach is based on notion that drug resistance comes at a fitness cost to the cancer cell that can be exploited for therapeutic benefit. We discuss the development of sequential drug therapies in which the first therapy is not given with curative intent, but to induce a major new sensitivity that can be targeted with a second drug that selectively targets the acquired vulnerability. This concept of collateral sensitivity has hitherto not been used on a large scale in the clinic and holds great promise for future cancer therapy.

关键词： cancer drug resistance genetic screens senescence targeted therapy

Tumor-infiltrating B cells come into vogue

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World Journal of Gastroenterology 2013年第1期19卷 8-11页

作者： Michael Linnebacher division of molecular Oncology and Immunotherapy Department of General SurgeryUniversity of RostockD-18057 RostockGermany

Lymphocyte infiltration into solid tumors has been recognized as a main determinator of positive *** the most part this is attributed to cytotoxic T cells capable of directly destroying malignant ***,when considering the complex composition of the human immune system,recent findings of Nielsenet al on a potentially central role of tumor-infiltrating B cells is not really *** this commentary article,I want to highlight the enormous potential impact of this observation for basic and translational research,prognostic procedures and ultimately for the development of future therapeutic concepts.

关键词： CD20 + tumor-infiltrating lymphocytes Tumorinfiltrating B cells Prognosis Immunotherapy Functional immunology

Iron-Mediated Oxidative DNA Damage Detected by Fluorometric Analysis of DNA Unwinding in Isolated Rat Liver Nuclei

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Biomedical and Environmental Sciences 1991年第3期4卷 232-241页

作者： SAURA C.SAHU MELISSA C.WASHINGTON molecular Toxicolgy Laboratory Division of Toxicologlcal StudiesFood and Drug AdministrationWashingtonD.C.20204Molecular Toxicolgy LaboratoryDivision of Toxicologlcal StudiesFood and Drug AdministrationWashingtonD.C.20204

Studies were performed to determine the extent of nuclear DNA degradation induced by iron, iron-ascorbate, or iron-bleomycin under aerobic conditions in a model system using isolated rat liver nuclei. The effects of five antioxidants (catalase, superoxide dismutase, dimethyl sulfoxide, glutathione and diallyl sulfide) on this oxidative nuclear damage were also investigated. At the 0.05 level for statistical significance, iron induced concentration-dependent DNA degradation, and this effect was enhanced by ascorbate and bleomycin. The antioxidants catalase, dimethyl sulfoxide, and diallyl sulfide significantly reduced the iron-ascorbate-induced DNA damage, whereas superoxide dismutase and dimethyl sulfoxide significantly reduced iron-bleomycin-induced damage. Glutathione significantly increased the iron-bleomycin-induced DNA damage. These results suggest that the reactive oxygen species generated by iron, iron-ascorbate, and iron-bleomycin are responsible for the DNA strand breaks in isolated rat liver nuclei.

关键词： Iron-Mediated Oxidative DNA Damage Detected by Fluorometric Analysis of DNA Unwinding in Isolated Rat Liver Nuclei DNA

Review of deep learning and artificial intelligence models in fetal brain magnetic resonance imaging

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World Journal of Clinical Cases 2023年第16期11卷 3725-3735页

作者： Farzan Vahedifard Jubril O Adepoju Mark Supanich Hua Asher Ai Xuchu Liu Mehmet Kocak Kranthi K Marathu Sharon E Byrd Department of diagnostic Radiology and Nuclear Medicine Rush Medical CollegeChicagoIL 606012United States division for diagnostic Medical Physics Department of Radiology and Nuclear MedicineRush University Medical CenterChicagoIL 606012United States

Central nervous system abnormalities in fetuses are fairly common,happening in 0.1%to 0.2%of live births and in 3%to 6%of *** initial detection and categorization of fetal Brain abnormalities are *** detecting and segmenting fetal brain magnetic resonance imaging(MRI)could be timeconsuming,and susceptible to interpreter *** intelligence(AI)algorithms and machine learning approaches have a high potential for assisting in the early detection of these problems,improving the diagnosis process and follow-up *** use of AI and machine learning techniques in fetal brain MRI was the subject of this narrative review *** AI,anatomic fetal brain MRI processing has investigated models to predict specific landmarks and segmentation *** gestation age weeks(17-38 wk)and different AI models(mainly Convolutional Neural Network and U-Net)have been *** models'accuracy achieved 95%and *** could help preprocess and postprocess fetal images and reconstruct ***,AI can be used for gestational age prediction(with one-week accuracy),fetal brain extraction,fetal brain segmentation,and placenta *** fetal brain linear measurements,such as Cerebral and Bone Biparietal Diameter,have been *** of brain pathology was studied using diagonal quadratic discriminates analysis,Knearest neighbor,random forest,naive Bayes,and radial basis function neural network *** learning methods will become more powerful as more large-scale,labeled datasets become *** shared fetal brain MRI datasets is crucial because there aren not many fetal brain pictures ***,physicians should be aware of AI's function in fetal brain MRI,particularly neuroradiologists,general radiologists,and perinatologists.

关键词： Artificial intelligence Fetal brain Magnetic resonance imaging Neuroimaging