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Pancreatic Cancer Progression Relies upon Mutant p53-Induced Oncogenic Signaling Mediated by NOP14

15.05.2017 | Yongxing Du; Ziwen Liu; Lei You; Pengjiao Hou; Xiaoxia Ren; Tao Jiao; Wenjing Zhao; Zongze Li; Hong Shu; Changzheng ..., Cancer Research, 2017

Mutant p53 (mutp53) proteins promote tumor invasion and metastasis in pancreatic ductal adenocarcinoma (PDAC). However, the mechanism underlying sustained activation of mutp53 oncogenic signaling is currently unclear. In this study, we report that NOP14 nucleolar protein (NOP14) expression is ...


Cell-Cycle Regulation Accounts for Variability in Ki-67 Expression Levels

15.05.2017 | Michal Sobecki; Karim Mrouj; Jacques Colinge; François Gerbe; Philippe Jay; Liliana Krasinska; Vjekoslav Dulic; Dani ..., Cancer Research, 2017

The cell proliferation antigen Ki-67 is widely used in cancer histopathology, but estimations of Ki-67 expression levels are inconsistent and understanding of its regulation is limited. Here we show that cell-cycle regulation underlies variable Ki-67 expression in all situations analyzed, ...


Differential Expression of VEGFA Isoforms Regulates Metastasis and Response to Anti-VEGFA Therapy in Sarcoma

15.05.2017 | William R. English; Sarah Jane Lunt; Matthew Fisher; Diane V. Lefley; Mohit Dhingra; Yu-Chin Lee; Karina Bingham; Ja ..., Cancer Research, 2017

Elevated plasma concentrations of soluble VEGFA isoforms are associated with poor prognosis in parallel with improved response to treatment with the anti-VEGFA antibody bevacizumab. To uncover the underlying mechanism to these observations, we administered anti-VEGFA therapy to mice bearing ...


Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors

15.05.2017 | Takayuki Kosaka; Junko Tanizaki; Raymond M. Paranal; Hideki Endoh; Christine Lydon; Marzia Capelletti; Claire E. Rep ..., Cancer Research, 2017

Insertion mutations in EGFR and HER2 both occur at analogous positions in exon 20. Non–small cell lung cancer (NSCLC) patients with tumors harboring these mutations seldom achieve clinical responses to dacomitinib and afatinib, two covalent quinazoline–based inhibitors of EGFR or HER2, ...


Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment

15.05.2017 | Sobeyda B. Gomez-Chou; Agnieszka Katarzyna Swidnicka-Siergiejko; Niharika Badi; Myrriah Chavez-Tomar; Gregory B. Les ..., Cancer Research, 2017

Lipocalin-2 (LCN2) promotes malignant development in many cancer types. LCN2 is upregulated in patients with pancreatic ductal adenocarcinoma (PDAC) and in obese individuals, but whether it contributes to PDAC development is unclear. In this study, we investigated the effects of Lcn2 depletion on ...


Morphoproteomic Characterization of Lung Squamous Cell Carcinoma Fragmentation, a Histological Marker of Increased Tumor Invasiveness

15.05.2017 | Ruben Casanova; Daniel Xia; Undine Rulle; Paolo Nanni; Jonas Grossmann; Bart Vrugt; Reto Wettstein; Rafael Ballester ..., Cancer Research, 2017

Accurate stratification of tumors is imperative for adequate cancer management. In addition to staging, morphologic subtyping allows stratification of patients into additional prognostic groups. In this study, we used an image-based computational method on pan-cytokeratin IHC stainings to ...


SSRP1 Cooperates with PARP and XRCC1 to Facilitate Single-Strand DNA Break Repair by Chromatin Priming

15.05.2017 | Ying Gao; Changling Li; Leizhen Wei; Yaqun Teng; Satoshi Nakajima; Xiukai Chen; Jianquan Xu; Brittany Legar; Hongqia ..., Cancer Research, 2017

DNA single-strand breaks (SSB) are the most common form of DNA damage, requiring repair processes that to initiate must overcome chromatin barriers. The FACT complex comprised of the SSRP1 and SPT16 proteins is important for maintaining chromatin integrity, with SSRP1 acting as an histone H2A/H2B ...


Individualized Breast Cancer Characterization through Single-Cell Analysis of Tumor and Adjacent Normal Cells

15.05.2017 | Manjushree Anjanappa; Angelo Cardoso; Lijun Cheng; Safa Mohamad; Andrea Gunawan; Susan Rice; Yan Dong; Lang Li; Geor ..., Cancer Research, 2017

There is a need to individualize assays for tumor molecular phenotyping, given variations in the differentiation status of tumor and normal tissues in different patients. To address this, we performed single-cell genomics of breast tumors and adjacent normal cells propagated for a short duration ...


Tumor Dormancy and Relapse: From a Natural Byproduct of Evolution to a Disease State

15.05.2017 | Masoud H. Manjili, Cancer Research, 2017

Species evolve by mutations and epigenetic changes acting on individuals in a population; tumors evolve by similar mechanisms at a cellular level in a tissue. This article reviews growing evidence about tumor dormancy and suggests that (i) cellular malignancy is a natural byproduct of ...


miR-34a and miR-34b/c Suppress Intestinal Tumorigenesis

15.05.2017 | Longchang Jiang; Heiko Hermeking, Cancer Research, 2017

The p53-inducible miR-34a and miR-34b/c genes are frequently silenced in colorectal cancer. To address the in vivo relevance of miR-34a/b/c function for suppression of intestinal tumor formation, we generated Apc Min/+ mice with deletions of the miR-34a and/or miR-34b/c genes separately or in ...


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