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https://www.readbyqxmd.com/read/28531881/first-in-man-dose-escalation-and-pharmacokinetic-study-of-cap7-1-a-novel-prodrug-of-etoposide-in-adults-with-refractory-solid-tumours
#1
U Keilholz, L Rohde, P Mehlitz, M Knoedler, A Schmittel, V Kümmerlen, K Klinghammer, P Treasure, M Lassus, G Steventon, M Machacek, N Utku
AIM: An open-label, phase I dose-escalation trial was performed in adult patients with various solid cancers to identify the maximum tolerated dose (MTD), to assess the safety, pharmacokinetic profile and anti-tumour activity of the new prodrug CAP7.1. The prodrug is converted to its active moiety etoposide via carboxylesterases in selective cells leading to a better tolerability and higher efficacy in therapeutic resistance cells and children with refractory neuroblastoma. PATIENTS AND METHODS: Eligible adult patients with advanced, refractory, solid malignancies received CAP7...
May 19, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28529742/intraductal-tubulopapillary-neoplasm-accompanied-by-invasive-carcinoma-of-the-pancreas-a-case-report-and-review-of-the-literature
#2
Li Niu, Zhigao Xu, Huan Liu, Hong Cao, Guifang Yang
Intraductal tubulopapillary neoplasms (ITPNs) are rare pancreatic neoplasms accounting for ~0.4% of pancreatic tumors. However, their clinicopathological characteristics have not been clearly determined and the number of available clinical studies on this type of tumor is limited at present. Due to the rare incidence of ITPN, diagnosis is often delayed. We herein present a unique case of a 38-year-old man who was diagnosed with ITPN accompanied with invasive carcinoma of the pancreas and underwent total pancreatectomy...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28528185/simvastatin-ameliorate-memory-deficits-and-inflammation-in-clinical-and-mouse-model-of-alzheimer-s-disease-via-modulating-the-expression-of-mir-106b
#3
Wenzhong Huang, Zhenyu Li, Liandong Zhao, Wei Zhao
BACKGROUND: Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, and several studies have shown that AD is closely related to the inflammation, so anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of simvastatin on inflammation was investigated and the underlying mechanisms were explored. METHODS: First, we tested the effect of simvastatin on AD in clinical research...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28527894/hfe-genotype-affects-exosome-phenotype-in-cancer
#4
Oliver D Mrowczynski, A B Madhankumar, Becky Slagle-Webb, Sang Y Lee, Brad E Zacharia, James R Connor
Neuroblastoma is the third most common childhood cancer, and timely diagnosis and sensitive therapeutic monitoring remain major challenges. Tumor progression and recurrence is common with little understanding of mechanisms. A major recent focus in cancer biology is the impact of exosomes on metastatic behavior and the tumor microenvironment. Exosomes have been demonstrated to contribute to the oncogenic effect on the surrounding tumor environment and also mediate resistance to therapy. The effect of genotype on exosomal phenotype has not yet been explored...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28526904/neuroblastoma-invading-the-kidney-through-the-renal-hilum
#5
Ryu Yanagisawa, Yoshifumi Ogiso, Tomoko Furukawa
No abstract text is available yet for this article.
May 19, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28526132/old-and-novel-functions-of-caspase-2
#6
M A Miles, T Kitevska-Ilioski, C J Hawkins
Although caspase-2 is a highly conserved protease that has received a lot of research attention, consensus about its roles and the molecular mechanisms that underpin them has been elusive. Recent improvements to our understanding of the activities of caspase-2 have been facilitated by the development and refinement of techniques allowing identification of cellular processes instigated by this caspase. Following DNA damage, caspase-2 can be activated in a molecular complex called the "PIDDosome"; however, other stimuli provoke caspase-2-dependent activities that do not appear to involve this complex...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28525978/notch-ligand-delta-like-1-as-a-novel-molecular-target-in-childhood-neuroblastoma
#7
P Bettinsoli, G Ferrari-Toninelli, S A Bonini, C Prandelli, M Memo
BACKGROUND: Neuroblastoma is the most common extracranial solid malignancy in childhood, responsible for 15% of all pediatric cancer deaths. It is an heterogeneous disease that does not always respond to classical therapy; so the identification of new and specific molecular targets to improve existing therapy is needed. We have previously demonstrated the involvement of the Notch pathway in the onset and progression of neuroblastoma. In this study we further investigated the role of Notch signaling and identified Delta-like 1 (DLL1) as a novel molecular target in neuroblastoma cells with a high degree of MYCN amplification, which is a major oncogenic driver in neuroblastoma...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28525458/unusual-presentation-of-relapse-in-neuroblastoma-pancreatic-metastases-detected-by-123i-mibg-scintigraphy
#8
Maria Felicia Villani, Maria Luisa D'Andrea, Aurora Castellano, Milena Pizzoferro, Maria Carmen Garganese
Neuroblastoma is the most common extracranial solid tumor in children and accounts for 8% to 10% of all childhood cancers. The spread of metastases is both lymphatic and hematogenous. Hematogenous route occurs most commonly in bone marrow and cortical bone; pancreatic metastases are very rare, and there are few reports about this topic in medical literature. We report the case of a 14-year-old boy who suffers a third relapse of neuroblastoma: in this patient I-MIBG confirms that lesions detected by CT were due to a relapse in pancreatic tissue and influenced subsequent therapeutic management...
May 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28525450/neuroblastoma-presenting-as-non-mibg-avid-widespread-soft-tissue-metastases-without-bone-involvement-revealed-by-fdg-pet-ct-imaging
#9
Nelleke Tolboom, Sabah E Servaes, Hongming Zhuang
Soft tissue metastases from neuroblastoma very rarely occur without concurrent osseous metastases. We report 1 case of non-MIBG-avid, high-risk neuroblastoma in a pediatric patient who had widespread soft tissue metastases without concurrent osseous lesion on FDG PET/CT imaging.
May 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28525366/mesenchymal-stem-cell-carriers-enhance-antitumor-efficacy-of-oncolytic-adenoviruses-in-an-immunocompetent-mouse-model
#10
Esther Rincón, Teresa Cejalvo, Deepak Kanojia, Arantzazu Alfranca, Miguel Ángel Rodríguez-Milla, Raul Andrés Gil Hoyos, Yu Han, Lingjiao Zhang, Ramón Alemany, Maciej S Lesniak, Javier García-Castro
Oncolytic virotherapy represents a promising alternative for cancer treatment; however, viral delivery to the tumor represents a major challenge. Mesenchymal stem cells (MSCs) chemotax to tumors, and can serve as a viral delivery tool. Previously, we demonstrated antitumor therapeutic efficacy for mesenchymal stem cells (MSCs) infected with the oncolytic human adenovirus ICOVIR5 (Celyvir) for treatment of neuroblastoma patients. Given the lack of suitable immunocompetent preclinical models, the mechanism underlying Celyvir antitumor activity remains unknown...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524166/homology-mediated-end-joining-based-targeted-integration-using-crispr-cas9
#11
Xuan Yao, Xing Wang, Xinde Hu, Zhen Liu, Junlai Liu, Haibo Zhou, Xiaowen Shen, Yu Wei, Zijian Huang, Wenqin Ying, Yan Wang, Yan-Hong Nie, Chen-Chen Zhang, Sanlan Li, Leping Cheng, Qifang Wang, Yan Wu, Pengyu Huang, Qiang Sun, Linyu Shi, Hui Yang
Targeted integration of transgenes can be achieved by strategies based on homologous recombination (HR), microhomology-mediated end joining (MMEJ) or non-homologous end joining (NHEJ). The more generally used HR is inefficient for achieving gene integration in animal embryos and tissues, because it occurs only during cell division, although MMEJ and NHEJ can elevate the efficiency in some systems. Here we devise a homology-mediated end joining (HMEJ)-based strategy, using CRISPR/Cas9-mediated cleavage of both transgene donor vector that contains guide RNA target sites and ∼800 bp of homology arms, and the targeted genome...
May 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28523530/bag-1l-protects-sh-sy5y-neuroblastoma-cells-against-hypoxia-re-oxygenation-through-up-regulating-hsp70-and-activating-pi3k-akt-signaling-pathway
#12
Yun Wang, Chao Jia, Qing-Shu Li, Chun-Yu Xie, Nan Zhang, Yan Qu
BCL-2-associated athanogene-1(BAG-1) is a multifunctional and anti-apoptotic protein that was first identified as a binding partner of BCL-2. But the effects and mechanisms for BAG-1 against hypoxic damage is unclear up to now. Whether BAG-1 could protect the human brain against hypoxic damage through up-regulating 70 kDa heat shock proteins (HSP70) and PI3K/AKT pathway activation? In present study, we examined the changes of HSP70 and AKT and p-AKT protein level in SH-SY5Y cells with BAG-1L gene over-expression subjected to hypoxia/re-oxygenation injury...
May 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28522589/identification-of-cancer-targeted-tropomyosin-inhibitors-and-their-synergy-with-microtubule-drugs
#13
Mark A Currier, Justine R Stehn, Ashleigh Swain, Duo Chen, Jeff Hook, Eleanor Eiffe, Andrew Heaton, David Brown, Brooke Nartker, David W Eaves, Nina Kloss, Herbert Treutlein, Jun Zeng, Irina B Alieva, Vera B Dugina, Edna C Hardeman, Peter W Gunning, Timothy P Cripe
Actin filaments, with their associated tropomyosin polymers, and microtubules are dynamic cytoskeletal systems regulating numerous cell functions. While anti-microtubule drugs are well-established, anti-actin drugs have been more elusive. We previously targeted actin in cancer cells by inhibiting the function of a tropomyosin isoform enriched in cancer cells, Tpm3.1, using a first-in-class compound, TR100. Here, we screened over 200 other anti-tropomyosin analogues for anti-cancer and on-target activity using a series of in vitro cell-based and biochemical assays...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522149/measuring-absolute-blood-perfusion-in-mice-using-dynamic-contrast-enhanced-ultrasound
#14
Abbas Shirinifard, Suresh Thiagarajan, Melissa D Johnson, Christopher Calabrese, András Sablauer
We investigated the feasibility of estimating absolute tissue blood perfusion using dynamic contrast-enhanced ultrasound (CEUS) imaging in mice. We developed a novel method of microbubble administration and a model-free approach to estimate absolute kidney perfusion, and explored the kidney as a reference organ to estimate absolute perfusion of a neuroblastoma tumor. We performed CEUS on the kidneys of CD1 nude mice using the VisualSonics VEVO 2100 imaging system. We estimated individual kidney blood perfusion using the burst-replenishment (BR) technique...
May 15, 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/28521633/cd30-expression-in-pediatric-neoplasms-study-of-585-cases
#15
Jinjun Cheng, Haiqing Zhu, John Kim Choi
CD30 is a member of the tumor necrosis factor receptor superfamily, member 8 (TNFRSF8), and its normal expression is restricted to activated T and B cells. In tumor cells, CD30 expression is most commonly associated with lymphoid malignancies (Hodgkin and non-Hodgkin lymphomas) and is a therapeutic target using anti-CD30 antibody. CD30 expression has been reported also in mostly adult non-lymphoid malignancies, raising the possibility of CD30-targeted therapy for additional tumors. In this study, we examined the incidence of CD30 expression in 251 hematopoietic and 334 non-hematopoietic cases of pediatric tumors...
June 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28521631/immunohistochemical-profile-of-myc-protein-in-pediatric-small-round-blue-cell-tumors
#16
Karen M Chisholm, Chandra Krishnan, Amy Heerema-McKenney, Yasodha Natkunam
Deregulation of MYC oncoprotein in cancers can result from multiple oncogenic mechanisms. Although MYC translocations define Burkitt lymphoma and MYC protein expression is a poor prognostic factor in undifferentiated neuroblastomas, the distribution of MYC protein (c-MYC) across other pediatric small round blue cell tumors (SRBCT) has not been well characterized. We undertook this study to assess MYC protein expression in a large cohort of pediatric lymphomas, sarcomas, and other SRBCT. Tissue microarrays containing 302 SRBCT were successfully evaluated by immunohistochemistry using anti-MYC clone Y69, with nuclear positivity scored as 0%, 1%-25%, 26%-50%, 51%-75%, or 76%-100%...
June 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28521627/disseminated-bacillus-calmette-gu%C3%A3-rin-osteomyelitis-in-twin-sisters-related-to-stat1-gene-deficiency
#17
Sabah Boudjemaa, Linda Dainese, Sébastien Héritier, Caroline Masserot, Samia Hachemane, Jean-Laurent Casanova, Aurore Coulomb, Jacinta Bustamante
Mendelian susceptibility to mycobacterial disease is a rare syndrome characterized by severe clinical infections usually caused by weakly virulent mycobacterial species such as Bacillus Calmette-Guérin vaccines and environmental nontuberculous mycobacteria or more virulent mycobacteria as mycobacterium tuberculosis. Since 1996, 9 genes including 7 autosomal ( STAT1, IFNGR1, IFNGR2, IL12B, IL12RB1, ISG15, and IRF8) and 2 X-linked genes ( NEMO and CYBB) have been identified. Allelic heterogeneity leaded to recognize about 18 genetic diseases with variable clinical phenotypes, but sharing a same physiological mechanism represented by a defect in human IL-12-dependant-INF-γ-mediated immunity...
June 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28521413/chromosome-t-7-11-p15-p15-translocation-in-acute-myeloid-leukemia-coexisting-with-multilineage-dyspoiesis-and-mutations-in-nras-and-wt1-a-case-report-and-literature-review
#18
Jingke Yang, Xiaodong Lyu, Xinghu Zhu, Xiangguang Meng, Wenli Zuo, Hao Ai, Mei Deng
The chromosomal translocation t(7;11)(p15;p15) and the resulting nucleoporin 98-homeobox A9 (NUP98-HOXA9) gene fusion is rare but recurrent genetic abnormity in acute myeloid leukemia (AML). The present study describes a case of AML plus maturation (-M2) with multilineage dyspoiesis in a 30-year-old male in whom a 46,XY,t(7;11)(p15;p15) karyotype was detected through chromosome analysis. Subsequent molecular and sequencing analysis demonstrated a NUP98-HOXA9 fusion gene with a type I fusion between NUP98 exon 12 and HOXA9 exon 1b, and mutations in neuroblastoma V-Ras oncogene homolog and Wilms tumor 1...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521285/arid1b-alterations-identify-aggressive-tumors-in-neuroblastoma
#19
Soo Hyun Lee, Jung-Sun Kim, Siyuan Zheng, Jason T Huse, Joon Seol Bae, Ji Won Lee, Keon Hee Yoo, Hong Hoe Koo, Sungkyu Kyung, Woong-Yang Park, Ki Woong Sung
Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521076/phase-i-study-of-perifosine-monotherapy-in-patients-with-recurrent-or-refractory-neuroblastoma
#20
Kimikazu Matsumoto, Hiroyuki Shichino, Hiroshi Kawamoto, Yoshiyuki Kosaka, Motoaki Chin, Koji Kato, Hideo Mugishima
PURPOSE: Perifosine is an alkylphospholipid analog that inhibits or modulates signaling through signal transduction pathways such as Akt, which is enhanced in neuroblastoma (NB) by activation of tyrosine kinase receptors. We conducted a phase I study of perifosine in Japanese patients with recurrent or refractory NB. EXPERIMENTAL DESIGN: All patients enrolled were over 2 years of age; all had refractory or relapsed NB and a performance status of greater than 50%...
May 18, 2017: Pediatric Blood & Cancer
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