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https://www.readbyqxmd.com/read/29322496/wt1-peptide-based-immunotherapy-for-advanced-thymic-epithelial-malignancies
#1
Yusuke Oji, Masayoshi Inoue, Yoshito Takeda, Naoki Hosen, Yasushi Shintani, Manabu Kawakami, Takuya Harada, Yui Murakami, Miki Iwai, Mari Fukuda, Sumiyuki Nishida, Jun Nakata, Yoshiki Nakae, Satoshi Takashima, Toshiaki Shirakata, Hiroko Nakajima, Kana Hasegawa, Hiroshi Kida, Takashi Kijima, Soyoko Morimoto, Fumihiro Fujiki, Akihiro Tsuboi, Eiichi Morii, Satoshi Morita, Junichi Sakamoto, Atsushi Kumanogoh, Yoshihiro Oka, Meinoshin Okumura, Haruo Sugiyama
Thymic epithelial tumors are rare malignancies, and no optimal therapeutic regimen has been defined for patients with advanced disease. Patients with advanced thymic epithelial tumors, which were resistant or intolerable to prior therapies, were eligible for this study. Patients received 9 mer-WT1-derived peptide emulsified with Montanide ISA51 adjuvant via intradermal administration once a week as a monotherapy. After the 3 month-protocol treatment, the treatment was continued mostly at intervals of 2 to 4 weeks until disease progression or intolerable adverse events occurred...
January 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29320783/wt1-gene-mutation-p-r462w-in-a-46-xy-dsd-patient-from-egypt-with-gonadoblastoma-and-review-of-the-literature
#2
Inas Mazen, Heba Hassan, Alaa Kamel, Mona Mekkawy, Ken McElreavey, Mona Essawi
WT1 gene mutations have been described in 46,XY patients with ambiguous genitalia or complete gonadal dysgenesis with or without Wilms' tumor, nephropathy, gonadoblastoma, and other defects, e.g., cryptorchidism or hypospadias. p.R462W is a hot spot mutation in exon 9 and is the most common mutation in patients with Denys-Drash syndrome. However, in this study we report an Egyptian patient with a novel phenotype carrying the p.R462W mutation. We also review the heterogeneity of phenotypes of previously reported patients with the p...
January 11, 2018: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/29317712/muc4-immunohistochemistry-is-useful-in-distinguishing-epithelioid-mesothelioma-from-adenocarcinoma-and-squamous-cell-carcinoma-of-the-lung
#3
Amany Sayed Mawas, Vishwa Jeet Amatya, Kei Kushitani, Yuichiro Kai, Yoshihiro Miyata, Morihito Okada, Yukio Takeshima
The differential diagnosis of epithelioid mesothelioma from lung adenocarcinoma and squamous cell carcinoma requires the positive and negative immunohistochemical markers of mesothelioma. The IMIG guideline has suggested the use of Calretinin, D2-40, WT1, and CK5/6 as mesothelial markers, TTF-1, Napsin-A, Claudin 4, CEA as lung adenocarcinoma markers p40, p63, CK5/6, MOC-31 as squamous cell markers. However, use of other immunohistochemical markers is still necessary. We evaluated 65 epithelioid mesotheliomas, 60 adenocarcinomas, and 57 squamous cell carcinomas of the lung for MUC4 expression by immunohistochemistry and compared with the previously known immunohistochemical markers...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29306105/distinct-gene-alterations-with-a-high-percentage-of-myeloperoxidase-positive-leukemic-blasts-in-de-novo-acute-myeloid-leukemia
#4
Rena Kamijo, Hidehiro Itonaga, Rika Kihara, Yasunobu Nagata, Tomoko Hata, Norio Asou, Shigeki Ohtake, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Tomoki Naoe, Hitoshi Kiyoi, Yasushi Miyazaki
The myeloperoxidase (MPO)-positivity of blasts in bone marrow smears is an important marker for not only the diagnosis, but also the prognosis of acute myeloid leukemia (AML). To investigate the relationship between genetic alterations and MPO-positivity, we performed targeted sequencing for 51 genes and 10 chimeric gene transcripts in 164 newly diagnosed de novo AML patients; 107 and 57 patients were classified as AML with >50% MPO-positive blasts (MPO-high group) and ≤50% MPO-positive blasts, (MPO-low group), respectively...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29304833/a-phase-i-study-of-selinexor-in-combination-with-high-dose-cytarabine-and-mitoxantrone-for-remission-induction-in-patients-with-acute-myeloid-leukemia
#5
Amy Y Wang, Howard Weiner, Margaret Green, Hua Chang, Noreen Fulton, Richard A Larson, Olatoyosi Odenike, Andrew S Artz, Michael R Bishop, Lucy A Godley, Michael J Thirman, Satyajit Kosuri, Jane E Churpek, Emily Curran, Kristen Pettit, Wendy Stock, Hongtao Liu
BACKGROUND: Novel therapies for patients with acute myeloid leukemia (AML) are imperative, particularly for those with high-risk features. Selinexor, an exportin 1 (XPO1/CRM1) inhibitor, has demonstrated anti-leukemia activity as a single agent, as well as in combination with anthracyclines and/or DNA-damaging agents. METHODS: We report the findings of a phase I dose escalation trial with cohort expansion in 20 patients with newly diagnosed or relapsed/refractory AML that combined selinexor with age-adjusted high-dose cytarabine and mitoxantrone (HiDAC/Mito)...
January 5, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29288199/comparison-of-t-cell-activities-mediated-by-human-tcrs-and-cars-that-use-the-same-recognition-domains
#6
Daniel T Harris, Marlies V Hager, Sheena N Smith, Qi Cai, Jennifer D Stone, Philipp Kruger, Melissa Lever, Omer Dushek, Thomas M Schmitt, Philip D Greenberg, David M Kranz
Adoptive T cell therapies have achieved significant clinical responses, especially in hematopoietic cancers. Two types of receptor systems have been used to redirect the activity of T cells, normal heterodimeric TCRs or synthetic chimeric Ag receptors (CARs). TCRs recognize peptide-HLA complexes whereas CARs typically use an Ab-derived single-chain fragments variable that recognizes cancer-associated cell-surface Ags. Although both receptors mediate diverse effector functions, a quantitative comparison of the sensitivity and signaling capacity of TCRs and CARs has been limited due to their differences in affinities and ligands...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29286103/gene-expression-profiling-of-acute-myeloid-leukemia-samples-from-adult-patients-with-aml-m1-and-m2-through-boutique-microarrays-real-time-pcr-and-droplet-digital-pcr
#7
Luiza Handschuh, Maciej Kaźmierczak, Marek C Milewski, Michał Góralski, Magdalena Łuczak, Marzena Wojtaszewska, Barbara Uszczyńska-Ratajczak, Krzysztof Lewandowski, Mieczysław Komarnicki, Marek Figlerowicz
Acute myeloid leukemia (AML) is the most common and severe form of acute leukemia diagnosed in adults. Owing to its heterogeneity, AML is divided into classes associated with different treatment outcomes and specific gene expression profiles. Based on previous studies on AML, in this study, we designed and generated an AML-array containing 900 oligonucleotide probes complementary to human genes implicated in hematopoietic cell differentiation and maturation, proliferation, apoptosis and leukemic transformation...
December 28, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29285297/identification-of-wt1-as-determinant-of-heptatocellular-carcinoma-and-its-inhibition-by-chinese-herbal-medicine-salvia-chinensis-benth-and-its-active-ingredient-protocatechualdehyde
#8
Ning Wang, Hor-Yue Tan, Yau-Tuen Chan, Wei Guo, Sha Li, Yibin Feng
Candidates from Chinese herbal Medicine might be preferable in drug discovery as the abundant experiences of traditional use usually hint the clinical efficacy. In this study, we screened the anti-tumour effect of several commonly used Chinese herbal Medicines on human hepatocellular carcinoma cells (HCC). We identified that Salvia chinensia Benth. (Shijianchuan in Chinese, SJC) exhibited prominent in vitro inhibition of HCC cells and suppressed the orthotopic growth of HCC in the liver of mice and repressed the lung metastasis of tumour cells...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29274817/cytotoxicity-and-inhibition-of-leukemic-cell-proliferation-by-sesquiterpenes-from-rhizomes-of-mah-lueang-curcuma-cf-viridiflora-roxb
#9
Songyot Anuchapreeda, Nattakanwadee Khumpirapang, Kawinnat Rupitiwiriya, Leelawat Tho-Iam, Aroonchai Saiai, Siriporn Okonogi, Toyonobu Usuki
Curcuma cf. viridiflora Roxb., also known as Mah-Lueang in Thai, belongs to the Zingiberaceae family and is grown from rhizomes. The rhizome of the plant has been used for medicinal purposes, in particular, to treat paralysis in Thai traditional medicine. However, no biologically active compounds have been reported from Mah-Lueang yet. In this study, natural compounds were isolated from Mah-Lueang and structurally determined by spectroscopic methods, including electrospray ionization mass spectrometry and nuclear magnetic resonance...
December 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29251621/-donor-chimerism-and-minimal-residual-disease-monitoring-in-leukemia-patients-after-allo-hsct
#10
K V Bogdanov, D V Motorin, T S Nikulina, O S Pisotskaya, D V Babenetskaya, Y V Mirolyubova, O Y Volkova, A Y Zaritskiy
In present research the comparative analysis of donor chimerism (DC) using different tests was performed to improve the diagnostic tool in patients with malignant hematological disorders after allo-HSCT. The RBC antigen typing, identification of ABO blood type and quantitative analysis of InDel-, STR-, Y-polymorphisms were carried out for detection of DC. In addition, the expression of well-known oncogenes and CD-markers for monitoring MRD was evaluated to predict relapse and clinical outcome. According to our research, the analysis of InDel polymorphism using AlleleSEQR-PCR is more sensitive test for estimation of DC as compared with other assays...
November 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/29247494/podocyte-and-endothelial-cell-injury-develop-nephrotic-syndrome-in-proliferative-lupus-nephritis
#11
Aya Nawata, Satoshi Hisano, Shohei Shimajiri, Ke-Yong Wang, Yoshiya Tanaka, Toshiyuki Nakayama
AIMS: Nephrotic syndrome (NS) is a major manifestation of lupus nephritis (LN). The dysregulation of podocyte, glomerular basement membrane (GBM) and endothelial cell (EC) develops proteinuria in glomerular diseases. The aim of our study is to clarify whether the dysregulation of these barriers is associated with NS in proliferative LN and membranous LN. METHODS AND RESULTS: Fifty six patients with NS including minimal change NS in 15, primary membranous nephropathy (PMN) in 13, Class III/IV LN in 15 and Class V LN in 13 were enrolled in this study...
December 15, 2017: Histopathology
https://www.readbyqxmd.com/read/29246788/alteration-of-connexin43-expression-in-a-rat-model-of-obesity-related-glomerulopathy
#12
Yongli Zhao, Guohua Li, Yuchuan Wang, Zhengjuan Liu
It is accepted that alteration of connexin43 (Cx43) expression in glomeruli is a common pathological response in several forms of kidney diseases. To date, however the change of the Cx43 expression in obesity-related glomerulopathy (ORG) has not been reported. In this study, the alteration of Cx43 expression in the glomeruli of rat with ORG was defined. Five-week-old rats were fed with high-fat diet for 18weeks to establish the ORG model, then the histological change of glomeruli, the foot process effacement of podocyte, the markers for podocyte injury (nephrin,podocin and WT1) and Cx43 expression in glomeruli were examined respectively...
December 12, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29240258/dna-and-rna-binding-by-the-wilms-tumour-gene-1-wt1-protein-kts-and-kts-isoforms-from-initial-observations-to-recent-global-genomic-analyses
#13
REVIEW
Tove Ullmark, Giorgia Montano, Urban Gullberg
The Wilms' tumour gene 1 protein (WT1) is a zinc finger transcription factor found indispensable for foetal development. WT1 has also been implicated in the development of tumours in several organ systems, including acute myeloid leukaemia (AML). Four main WT1 isoforms come from two alternative splice events. One alternative splice results in the inclusion or exclusion of three amino acids, KTS, between zinc fingers three and four in the WT1 protein. The KTS insert has been extensively investigated due to the functional implications for DNA and RNA binding...
December 14, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29227476/the-molecular-landscape-of-pediatric-acute-myeloid-leukemia-reveals-recurrent-structural-alterations-and-age-specific-mutational-interactions
#14
Hamid Bolouri, Jason E Farrar, Timothy Triche, Rhonda E Ries, Emilia L Lim, Todd A Alonzo, Yussanne Ma, Richard Moore, Andrew J Mungall, Marco A Marra, Jinghui Zhang, Xiaotu Ma, Yu Liu, Yanling Liu, Jaime M Guidry Auvil, Tanja M Davidsen, Patee Gesuwan, Leandro C Hermida, Bodour Salhia, Stephen Capone, Giridharan Ramsingh, Christian Michel Zwaan, Sanne Noort, Stephen R Piccolo, E Anders Kolb, Alan S Gamis, Malcolm A Smith, Daniela S Gerhard, Soheil Meshinchi
We present the molecular landscape of pediatric acute myeloid leukemia (AML) and characterize nearly 1,000 participants in Children's Oncology Group (COG) AML trials. The COG-National Cancer Institute (NCI) TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA and microRNA sequencing and CpG methylation profiling. Validated DNA variants corresponded to diverse, infrequent mutations, with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including new gene fusions and focal deletions of MBNL1, ZEB2 and ELF1, were disproportionately prevalent in young individuals as compared to adults...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29225486/desmoplastic-small-round-blue-cell-tumor-a-review-of-treatment-and-potential-therapeutic-genomic-alterations
#15
REVIEW
Ajaz Bulbul, Bridget Noel Fahy, Joanne Xiu, Sadaf Rashad, Asrar Mustafa, Hatim Husain, Andrea Hayes-Jordan
Desmoplastic small round blue cell tumors (DSRCTs) originate from a cell with multilineage potential. A molecular hallmark of DSRCT is the EWS-WT1 reciprocal translocation. Ewing sarcoma and DSRCT are treated similarly due to similar oncogene activation pathways, and DSRCT has been represented in very limited numbers in sarcoma studies. Despite aggressive therapy, median survival ranges from 17 to 25 months, and 5-year survival rates remain around 15%, with higher survival reported among those undergoing removal of at least 90% of tumor in the absence of extraperitoneal metastasis...
2017: Sarcoma
https://www.readbyqxmd.com/read/29218546/establishing-cut-off-points-with-clinical-relevance-for-bcl-2-cyclin-d1-p16-p21-p27-p53-sox11-and-wt1-expression-in-glioblastoma-a-short-report
#16
Emma Camacho-Urkaray, Jorge Santos-Juanes, Francisco Borja Gutiérrez-Corres, Beatriz García, Luis M Quirós, Isabel Guerra-Merino, José Javier Aguirre, Iván Fernández-Vega
PURPOSE: Glioblastoma (GBM) ranks among the most challenging cancers to treat and there is an urgent need for clinically relevant prognostic and diagnostic biomarkers. Here, we set out to investigate the expression of eight proteins (bcl-2, cyclin D1, p16, p21, p27, p53, Sox11 and WT1) in GBM with the specific aim to establish immunohistochemistry cut-off points with clinical relevance. METHODS: Immunohistochemistry (IHC) was used to examine protein expression in 55 surgical GBM specimens using H-scores, and IHC cut-off points were established using the Cutoff Finder web platform...
December 7, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29207642/crosstalk-in-competing-endogenous-rna-network-reveals-the-complex-molecular-mechanism-underlying-lung-cancer
#17
Xiang Jin, Yinghui Guan, Hui Sheng, Yang Liu
We investigated the transcriptional mechanism underlying lung cancer development. RNA sequencing analysis was performed on blood samples from lung cancer cases and healthy controls. Differentially expressed microRNAs (miRNAs), circular RNAs (circRNAs), mRNAs (genes), and long non-coding RNAs (lncRNA) were identified, followed by pathway enrichment analysis. Based on miRNA target interactions, a competing endogenous network was established and significant nodes were screened. Differentially expressed transcriptional factors were retrieved from the TRRUST database and the transcriptional factor regulatory network was constructed...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29199245/primary-renal-mixed-tumor-characterized-by-marked-proliferation-of-osteoblast-like-cells-with-osteoid-formation-in-a-swine
#18
Yuki Oshima, Yuri Nakagawa, Tsutae Kashima, Masako Matsunaga, Shohei Kushima, Yukichi Tanaka
Renal mixed tumor characterized by the absence of nephrogenic blastema and the presence of predominant osteoid-producing osteoblast-like cells occurred in the kidney of a 6-month-old, hybrid, female pig. At the post-mortem examination, the tumor was found as a calcified grayish-white mass at the cranial end of the left kidney. Histologically the tumor consisted of 3 growth areas of poorly differentiated spindle cells, osteoid-producing osteoblast-like cells, and luminal epithelial cells. Transition from the spindle cells to the osteoblast-like cells or the luminal epithelial cells was observed...
December 1, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29187024/ossifying-renal-tumor-of-infancy-report-of-a-case-with-positive-wt-1-immunohistochemistry-and-high-mitotic-index-and-review-of-the-literature
#19
Benoit Vaillancourt, Luc Oligny, Julie Déry, Julie Franc-Guimond, Dorothée Bouron-Dal Soglio
Ossifying renal tumor of infancy (ORTI) is a rare, benign pediatric tumor of the kidney. Since first reported by Chatten in 1980, 23 cases have been published. Previous authors have argued that ORTI might originate from nephrogenic rests, thereby sharing a pathogenic relationship with Wilms' tumor (WT). ORTI is characterized histologically by a population of polygonal osteoblast-like cells around an osteoid core and densely cellular component of blastemal-like or spindle cells. While the immunohistochemical profile of the cellular components has been reported, to the best of our knowledge, the status of WT1 expression has only been reported once, where it showed negative marking...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/29170757/human-pluripotent-stem-cell-derived-epicardial-progenitors-can-differentiate-to-endocardial-like-endothelial-cells
#20
Xiaoping Bao, Vijesh J Bhute, Tianxiao Han, Tongcheng Qian, Xiaojun Lian, Sean P Palecek
During heart development, epicardial progenitors contribute various cardiac lineages including smooth muscle cells, cardiac fibroblasts, and endothelial cells. However, their specific contribution to the human endothelium has not yet been resolved, at least in part due to the inability to expand and maintain human primary or pluripotent stem cell (hPSC)-derived epicardial cells. Here we first generated CDH5-2A-eGFP knock-in hPSC lines and differentiated them into self-renewing WT1+ epicardial cells, which gave rise to endothelial cells upon VEGF treatment in vitro...
June 2017: Bioengineering & Translational Medicine
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