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Matthew J Atherton, Kyle B Stephenson, Jonathan Pol, Fuan Wang, Charles Lefebvre, David F Stojdl, Jake K Nikota, Anna Dvorkin-Gheva, Andrew Nguyen, Lan Chen, Stephanie Johnson-Obaseki, Patrick J Villeneuve, Jean-Simon Diallo, Jim Dimitroulakos, Yonghong Wan, Brian D Lichty
The viral transforming proteins E6 and E7 make human papilloma virus positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multi-functional CD8+ T-cell responses...
September 14, 2017: Cancer Immunology Research
Peter P Ruvolo, Huaxian Ma, Vivian R Ruvolo, Xiaorui Zhang, Hong Mu, Wendy Schober, Ivonne Hernandez, Miguel Gallardo, Joseph Khoury, Jorge Cortes, Michael Andreeff, Sean M Post
Nearly one-third of patients with acute myeloid leukemia have FMS-Like Tyrosine Kinase 3 mutations and thus have poor survival prospects. Receptor tyrosine kinase Anexelekto is critical for FMS-Like Tyrosine Kinase 3 signaling and participates in FMS-Like Tyrosine Kinase 3 inhibitor resistance mechanisms. Thus, strategies targeting Anexelekto could prove useful for acute myeloid leukemia therapy. ONO-7475 is an inhibitor with high specificity for Anexelekto and MER Tyrosine Kinase. Here we report that ONO-7475 potently arrested growth and induced apoptosis in acute myeloid leukemia with internal tandem duplication mutation of FMS-Like Tyrosine Kinase 3...
September 14, 2017: Haematologica
Cheryl Fischer, Mary Petriccione, Stephanie Vitolano, Edith Guarini, Mary Elizabeth Davis, Ira J Dunkel
BACKGROUND: Ophthalmic artery chemosurgery (OAC) is associated with grade 3 and 4 neutropenia, however the effect on T-cell number and function is unknown. The purpose of this retrospective review was to confirm that patients treated with OAC do not develop immunosuppression warranting Pneumocystis pneumonia prophylaxis. PROCEDURE: IRB approval was obtained for a single center retrospective review of immune function tests in retinoblastoma patients who received OAC...
September 12, 2017: Journal of Pediatric Hematology/oncology
Kummamuri V Sreelakshmi, Anita Chandra, Subramanian Krishnakumar, Viswanathan Natarajan, Vikas Khetan
Purpose: In retinoblastoma, adjuvant chemotherapy after enucleation is given in eyes with histopathological high-risk features (HRFs) to reduced mortality. Anterior chamber seeds (AC seeds) on histopathological evaluation are a contentious finding. This study attempts to determine the effect of AC seeds on the survival rate. Methods: This is a retrospective case record review. Eyes were divided into four groups: those with neither AC seeds nor HRFs, those with only HRFs, those with only AC seeds, and those with both HRFs and AC seeds...
September 1, 2017: Investigative Ophthalmology & Visual Science
Katy C Liu, Scott D Walter, Avni P Finn, Miguel A Materin
A 14-day-old girl presented with bilateral hereditary retinoblastoma. At 3 months, a slight bend in the superotemporal arcade was observed to have developed into a venous loop. With concern for an occult lesion along the arcade, handheld optical coherence tomography (hhOCT) confirmed a small tumor and helped to guide prompt laser treatment while sparing the venous arcade. A venous loop is a previously unrecognized clinical finding that preceded the clinical detection and hhOCT confirmation of the tumor. The authors hypothesize that the venous loop was induced by pro-angiogenic factors secreted by the tumor...
September 1, 2017: Ophthalmic Surgery, Lasers & Imaging Retina
Jian-Hua Wang, Lin-Jing Yuan, Rong-Xin Liang, Zi-Gang Liu, Bo-Hai Li, Zhe-Sheng Wen, Shu-Ting Huang, Min Zheng
The authors' previous study demonstrated that Golgi phosphoprotein 3 (GOLPH3) was significantly overexpressed in esophageal squamous cell carcinoma (ESCC), correlating with poor patient survival. In the present study, GOLPH3 stable overexpression and knockdown KYSE‑140 cell lines were constructed. Cell proliferation, colony formation, cell cycle progression and tumorigenesis assays were performed. The results revealed that GOLPH3 promoted ESCC cell growth and proliferation. The effects of GOLPH3 on the mechanistic target of rapamycin (mTOR) and Wnt/β‑catenin signaling pathways were investigated using western blot analyis and dual‑luciferase reporter assays, and were observed to be activated in cells with GOLPH3 overexpression...
September 13, 2017: Molecular Medicine Reports
Ge Yang, Yang Fu, Luxi Zhang, Xiaoyan Lu, Qiuming Li
MicroRNAs are increasingly recognized as important regulators of cancer. The aim of the present study was to investigate the role of miR-106b in the regulation of Y79 retinoblastoma. Y79 cells were transfected with antisense oligonucleotides (ASO) against miR-106b (ASO-miR-106b) or ASO-control. After transfection, the levels of miR-106b were monitored with real-time PCR (RT-PCR). The effects of ASO-miR-106b transfection on cell viability was evaluated by Cell Counting Kit-8 (CCK-8) analysis at 24, 48 and 72 h after transfection...
August 30, 2017: Oncology Reports
Dan Song, Jiandong Diao, Yongjing Yang, Yahong Chen
It has previously been demonstrated that multiple microRNAs (miRNAs or miRs) are aberrantly expressed in retinoblastoma (RB) and contribute to RB initiation and progression. miR‑382 has been revealed to be aberrantly expressed and therefore exhibits a key role in the progression of various types of cancer. However, the expression pattern, functional roles and underlying molecular mechanism of miR‑382 in RB remain unknown. The present study investigated the expression levels of miR‑382 and its effects on RB cells and the underlying regulatory mechanism of its action...
August 29, 2017: Molecular Medicine Reports
Cristina Stefan, Freddie Bray, Jacques Ferlay, Biying Liu, D Maxwell Parkin
Measurement of incidence rates of childhood cancer in Africa is difficult. The study 'Cancer of Childhood in sub Saharan Africa' brings together results from 16 population-based registries which, as members of the African Cancer Registry Network (AFCRN), have been evaluated as achieving adequate coverage of their target population. The cancers are classified according to the third revision of the International Classification of Childhood Cancer (ICCC-3) and recorded rates in Africa are compared with those in childhood populations in the UK, France, and the USA...
2017: Ecancermedicalscience
Chungoo Park, Sunkyung Choi, Yong-Eun Kim, Siyeo Lee, Su-Hyung Park, Robert S Adelstein, Sachiyo Kawamoto, Kee K Kim
Rbfox RNA-binding proteins play important roles in the regulation of alternative pre-mRNA splicing, but their role in other gene regulatory mechanisms is not well understood. Here, we show that Rbfox2 is a novel constituent of cytoplasmic stress granules, the translational silencing machinery assembled in response to cellular stress. We also show that the RNA binding activity of the Rbfox family protein is crucial for its localization into stress granules. To investigate the role of Rbfox2 in stress granules we used RNA-immunoprecipitation sequencing to identify cytoplasmic transcriptome-wide targets of Rbfox2...
September 11, 2017: Scientific Reports
J-P Diagne, A S Sow, A M Ka, A M Wane, P A Ndoye Roth, E A Ba, M E De Medeiros, J M Ndiaye, H M Diallo, H Kane, S Sow, M Nguer, E M Sy, P A Ndiaye
PURPOSE: The purpose was to record the causes of leukocoria among children under 10years of age and to determine the proportion of rare causes of leukocoria. PATIENTS AND METHODS: This retrospective study was conducted over a period of ten years, from January 1, 2004 to December 31, 2013, in patients under 10years of age who were referred for leukocoria. RESULTS: Leukocoria represented one of the ten reasons for consultation among children under 10years of age...
September 8, 2017: Journal Français D'ophtalmologie
Q Tu, J Hao, X Zhou, L Yan, H Dai, B Sun, D Yang, S An, L Lv, B Jiao, C Chen, R Lai, P Shi, X Zhao
Pancreatic cancer is among the deadliest malignancies; however, the genetic events that lead to pancreatic carcinogenesis in adults remain unclear. In vivo models in which these genetic alterations occur in adult animals may more accurately reflect the features of human cancer. In this study, we demonstrate that inactivation of Cdkn2b (p15ink4b) is necessary for induction of pancreatic cancer by oncogenic KRAS(G12D) expression and inactivation of Tp53 and Cdkn2a in adult mouse pancreatic ductal cells (P60 or older)...
September 11, 2017: Oncogene
Ryusuke Murakami, Noriomi Matsumura, J B Brown, Koichiro Higasa, Takanobu Tsutsumi, Mayumi Kamada, Hisham Abou-Taleb, Yuko Hosoe, Sachiko Kitamura, Ken Yamaguchi, Kaoru Abiko, Junzo Hamanishi, Tsukasa Baba, Masafumi Koshiyama, Yasushi Okuno, Ryo Yamada, Fumihiko Matsuda, Ikuo Konishi, Masaki Mandai
Previous studies have reported genome-wide mutation profile analyses in ovarian clear cell carcinomas (OCCCs). This study aims to identify specific novel molecular alterations by combined analyses of somatic mutation and copy number variation. We performed whole exome sequencing of 39 OCCC samples with 16 matching blood tissue samples. Four hundred twenty-six genes had recurrent somatic mutations. Among the 39 samples, ARID1A (62%) and PIK3CA (51%) were frequently mutated, as were genes such as KRAS (10%), PPP2R1A (10%), and PTEN (5%), that have been reported in previous OCCC studies...
September 5, 2017: American Journal of Pathology
Nicholas Villarino, Lia Signaevskaia, Jaco van Niekerk, Rachel Medal, Heejung Kim, Reyhaneh Lahmy, Kathleen Scully, Anthony Pinkerton, Sangwun Kim, Andrew Lowy, Pamela Itkin-Ansari
The average survival for patients with Pancreatic Ductal Adenocarcinoma (PDA) is merely 6 months, underscoring the need for new therapeutic approaches. During PDA progression, pancreatic acinar cells lose activity of the ClassI/II bHLH factors that regulate quiescence. We previously found that promoting transcriptional activity of the Class I bHLH factor E47 in highly aggressive PDA cells induced stable growth arrest in vitro and in vivo. To translate these findings for clinical utility, we developed a high throughput screening platform to identify small molecule inducers of Class I/II bHLH activity...
August 8, 2017: Oncotarget
Luís Cardoso, Mark Stevenson, Rajesh V Thakker
Parathyroid carcinoma (PC) may occur as part of a complex hereditary syndrome or an isolated (i.e. non-syndromic) non-hereditary (i.e. sporadic) endocrinopathy. Studies of hereditary, and syndromic forms of PC, which include the hyperparathyroidism-jaw tumour syndrome (HPT-JT), multiple endocrine neoplasia types 1 and 2 (MEN1 and MEN2), and familial isolated primary hyperparathyroidism (FIHP), have revealed some genetic mechanisms underlying PC. Thus, cell division cycle 73 (CDC73) germline mutations cause HPT-JT, and CDC73 mutations occur in 70% of sporadic PC, but in only ∼2% of parathyroid adenomas...
September 7, 2017: Human Mutation
Lynn A Sheldon
The regulation of cell cycle progression by steroid hormones and growth factors is important for maintaining normal cellular processes including development and cell proliferation. Deregulated progression through the G1/S and G2/M cell cycle transitions can lead to uncontrolled cell proliferation and cancer. The transcription factor E2F1, a key cell cycle regulator, targets genes encoding proteins that regulate cell cycle progression through the G1/S transition as well as proteins important in DNA repair and apoptosis...
September 7, 2017: Cell Cycle
Anindya Kundu, Maitrayee DasGupta
Rhizobia-legume interaction activates SYM-pathway that recruits cytokinin signaling for induction of nodule primordia in the cortex. In Arachis hypogaea, bradyrhizobia invade through natural cracks developed in the lateral root base and are directly endocytosed in the cortical cells to generate the nodule primordia. To unravel the role of cytokinin signaling in Arachis hypogaea, RNA-interference (RNAi) of cytokinin receptor Histidine-Kinase1 (AhHK1) was done. AhHK1-RNAi downregulated the expression of Type-A Response Regulators like AhRR5 and AhRR3 along with several symbiotic genes indicating both cytokinin signaling and SYM-Pathway was affected...
September 6, 2017: Molecular Plant-microbe Interactions: MPMI
Hee Won Yang, Mingyu Chung, Takamasa Kudo, Tobias Meyer
Regulation of cell proliferation is necessary for immune responses, tissue repair, and upkeep of organ function to maintain human health. When proliferating cells complete mitosis, a fraction of newly born daughter cells immediately enter the next cell cycle, while the remaining cells in the same population exit to a transient or persistent quiescent state. Whether this choice between two cell-cycle pathways is due to natural variability in mitogen signalling or other underlying causes is unknown. Here we show that human cells make this fundamental cell-cycle entry or exit decision based on competing memories of variable mitogen and stress signals...
September 6, 2017: Nature
Francis L Munier, Marie-Claire Gaillard, Sarah Decembrini, Massimo Bongiovanni, Maja Beck-Popovic
BACKGROUND: The anterior chamber has been shown by pharmacokinetic studies to represent a sanctuary never achieving a tumoricidal dose with the present administration routes, such as systemic, intra-arterial, or intravitreal injections. METHOD: A novel intracameral chemotherapy technique is described to control aqueous seeding in a pilot unilateral group E retinoblastoma case with primary aqueous seeding. Anterior segment toxicity was carefully monitored. RESULTS: Control of the retinal tumor and vitreous seeding was achieved by intra-arterial and intravitreal chemotherapies...
July 2017: Ocular Oncology and Pathology
Nathalie Cassoux, Isabelle Aerts, Livia Lumbroso-Le Rouic, Paul Freneaux, Laurence Desjardins
AIMS: Herein we report successful eye salvage following combined intravitreal and intracameral administration of melphalan for anterior chamber recurrence of retinoblastoma. METHODS: A 12-month-old boy was referred with a sporadic bilateral retinoblastoma staged as group D and V in the right eye and group E and V in the left eye. Treatment initially involved 6 cycles of 3 drugs followed by focal treatments. The left eye was enucleated. Three months after the end of systemic chemotherapy, multiple recurrent lesions were noted in the ciliary body and the anterior chamber...
July 2017: Ocular Oncology and Pathology
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