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https://www.readbyqxmd.com/read/28650466/ror2-mediated-alternative-wnt-signaling-regulates-cell-fate-and-adhesion-during-mammary-tumor-progression
#1
K Roarty, A D Pfefferle, C J Creighton, C M Perou, J M Rosen
Cellular heterogeneity is a common feature in breast cancer, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53-null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt β-catenin-dependent signaling activity and non-canonical β-catenin-independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28649985/attenuation-of-rna-polymerase-ii-pausing-mitigates-brca1-associated-r-loop-accumulation-and-tumorigenesis
#2
Xiaowen Zhang, Huai-Chin Chiang, Yao Wang, Chi Zhang, Sabrina Smith, Xiayan Zhao, Sreejith J Nair, Joel Michalek, Ismail Jatoi, Meeghan Lautner, Boyce Oliver, Howard Wang, Anna Petit, Teresa Soler, Joan Brunet, Francesca Mateo, Miguel Angel Pujana, Elizabeth Poggi, Krysta Chaldekas, Claudine Isaacs, Beth N Peshkin, Oscar Ochoa, Frederic Chedin, Constantine Theoharis, Lu-Zhe Sun, Tyler J Curiel, Richard Elledge, Victor X Jin, Yanfen Hu, Rong Li
Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers...
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28649649/patterns-of-cell-cycle-checkpoint-deregulation-associated-with-intrinsic-molecular-subtypes-of-human-breast-cancer-cells
#3
Jacquelyn J Bower, Leah D Vance, Matthew Psioda, Stephanie L Smith-Roe, Dennis A Simpson, Joseph G Ibrahim, Katherine A Hoadley, Charles M Perou, William K Kaufmann
Genomic instability is a hallmark of breast cancer, contributes to tumor heterogeneity, and influences chemotherapy resistance. Although Gap 2 and mitotic checkpoints are thought to prevent genomic instability, the role of these checkpoints in breast cancer is poorly understood. Here, we assess the Gap 2 and mitotic checkpoint functions of 24 breast cancer and immortalized mammary epithelial cell lines representing four of the six intrinsic molecular subtypes of breast cancer. We found that patterns of cell cycle checkpoint deregulation were associated with the intrinsic molecular subtype of breast cancer cell lines...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28647611/autophagy-suppresses-isoprenaline-induced-m2-macrophage-polarization-via-the-ros-erk-and-mtor-signaling-pathway
#4
Meihua Shan, Junfang Qin, Fengjiao Jin, Xiao Han, Haitao Guan, Xiaoge Li, Jiahui Zhang, Hongyao Zhang, Yue Wang
The objective of this study was to examine the effect of autophagy on stress-induced M2 macrophage polarization in the tumor microenvironment of breast cancer and to determine whether the underlying mechanism was related to the reactive oxygen species (ROS)/ERK and mTOR pathway. In vitro, we found that the basal autophagy level in mouse RAW 264.7 macrophages decreased with the incubation of tumor cell culture supernatant. Similarly, the polarization of RAW 264.7 to M2 macrophages was inhibited by the autophagy inducer rapamycin and increased by the autophagy inhibitor 3-MA or by siBeclin1...
June 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28644140/a-pathways-based-prediction-model-for-classifying-breast-cancer-subtypes
#5
Tong Wu, Yunfeng Wang, Ronghui Jiang, Xinliang Lu, Jiawei Tian
Breast cancer is highly heterogeneous and is classified into four subtypes characterized by specific biological traits, treatment responses, and clinical prognoses. We performed a systemic analysis of 698 breast cancer patient samples from The Cancer Genome Atlas project database. We identified 136 breast cancer genes differentially expressed among the four subtypes. Based on unsupervised clustering analysis, these 136 core genes efficiently categorized breast cancer patients into the appropriate subtypes. Functional enrichment based on Kyoto Encyclopedia of Genes and Genomes analysis identified six functional pathways regulated by these genes: JAK-STAT signaling, basal cell carcinoma, inflammatory mediator regulation of TRP channels, non-small cell lung cancer, glutamatergic synapse, and amyotrophic lateral sclerosis...
June 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28642964/metastasis-of-breast-cancer-cells-to-the-bone-lung-and-lymph-nodes-promotes-resistance-to-ionizing-radiation
#6
Takamitsu Hara, Manabu Iwadate, Kazunoshin Tachibana, Satoshi Waguri, Seiichi Takenoshita, Nobuyuki Hamada
BACKGROUND: Metastasis represents the leading cause of breast cancer deaths, necessitating strategies for its treatment. Although radiotherapy is employed for both primary and metastatic breast cancers, the difference in their ionizing radiation response remains incompletely understood. This study is the first to compare the radioresponse of a breast cancer cell line with its metastatic variants and report that such metastatic variants are more radioresistant. MATERIALS AND METHODS: A luciferase expressing cell line was established from human basal-like breast adenocarcinoma MDA-MB-231 and underwent in vivo selections, whereby a cycle of inoculations into the left cardiac ventricle or the mammary fat pad of athymic nude mice, isolation of metastases to the bone, lung and lymph nodes visualized with bioluminescence imaging, and expansion of obtained cells was repeated twice or three times...
June 22, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28641234/improved-boundary-segmentation-of-skin-lesions-in-high-frequency-3d-ultrasound
#7
B Sciolla, P Delachartre, L Cowell, T Dambry, B Guibert
In this article, we propose a segmentation algorithm for skin lesions in 3D high-frequency ultrasound images. The segmentation is done on melanoma and Basal-cell carcinoma tumors, the most common skin cancer types, and could be used for diagnosis and surgical excision planning in a clinical context. Compared with previously proposed algorithms, which tend to underestimate the size of the lesion, we propose two new boundary terms which provide significant improvements of the accuracy. The first is a probabilistic boundary expansion (PBE) term designed to broaden the segmented area at the boundaries, which uses the feature asymmetry criterion...
June 15, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/28638810/common-malignant-cutaneous-conditions-among-albinos-in-kenya
#8
Seyed Emad Emadi, Andrew Juma Suleh, Farhang Babamahmoodi, Fatemeh Ahangarkani, Vanessa Betty Chelimo, Beatrice Mutai, Seyyed Reza Raeeskarami, Alireza Ghanadan, Seyed Naser Emadi
Background: Albinos in Africa are at constant risk of developing skin cancer due to the damage caused by ultra-violet exposure. This study identifies the common skin conditions among albinos in Kenya as a country located along the equator. Methods: In this descriptive study on albino patients who were admitted to Mbagathi District Hospital in Nairobi, Kenya the census method was used for sampling and a total of 151 albinos were registered. All necessary data including age, gender, type, site and the number of skin lesions were recorded...
2017: Medical Journal of the Islamic Republic of Iran
https://www.readbyqxmd.com/read/28638726/downregulation-of-antigen-presentation-associated-pathway-proteins-is-linked-to-poor-outcome-in-triple-negative-breast-cancer-patient-tumors
#9
Martin H Pedersen, Brian L Hood, Hans Christian Beck, Thomas P Conrads, Henrik J Ditzel, Rikke Leth-Larsen
Triple-negative breast cancer (TNBC) is a heterogeneous subtype with varying disease outcomes. Tumor-infiltrating lymphocytes (TILs) are frequent in TNBC and have been shown to correlate with outcome, suggesting an immunogenic component in this subtype. However, other factors intrinsic to the cancer cells may also influence outcome. To identify proteins and molecular pathways associated with recurrence in TNBC, 34 formalin-fixed paraffin-embedded (FFPE) primary TNBC tumors were investigated by global proteomic profiling using mass spectrometry...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28633434/psip1-p75-promotes-tumorigenicity-in-breast-cancer-cells-by-promoting-the-transcription-of-cell-cycle-genes
#10
Deepak K Singh, Omid Gholamalamdari, Mahdieh Jadaliha, Xiao Ling Li, Yo-Chuen Lin, Yang Zhang, Shuomeng Guang, Seyedsasan Hashemikhabir, Saumya Tiwari, Yuelin J Zhu, Abid Khan, Anu Thomas, Arindam Chakraborty, Virgilia Macias, Andre K Balla, Rohit Bhargava, Sarath Chandra Janga, Jian Ma, Supriya G Prasanth, Ashish Lal, Kannanganattu V Prasanth
Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in breast cancer initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in breast cancer progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma...
June 17, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28633362/human-papillomavirus-related-oropharyngeal-cancer
#11
M Taberna, M Mena, M A Pavón, L Alemany, M L Gillison, R Mesía
High-risk (HR) human papillomavirus (HPV) is now recognised as the principal cause of the increasing incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) in some parts of the world.The primary risk factor for developing HPV-related OPSCC is oral HPV-infection and the majority of oral HPV-infections are acquired by oral sex. Progression into a OPSCC includes persistent infection with evasion of immune response in the microenvironment, the activation of viral early genes (E6, E7) in basal epithelial cells, the deregulation of cell cycle and the accumulation of chromosomal instability...
June 15, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28632797/approach-to-management-of-giant-basal-cell-carcinomas
#12
Sarah E Mott, William J Hunter, Edibaldo Silva, Christopher J Huerter
Basal cell carcinoma (BCC) is a common nonmelanoma skin cancer with increasing incidence in the United States and worldwide. It is strongly linked to UV radiation exposure and typically is slow growing. Malignancy in BCCs is due to local growth and invasion rather than metastasis, and the prognosis is generally favorable. We report the case of a 60-year-old man with a large, locally destructive giant BCC on the right side of the upper back that was successfully treated via complete surgical excision (SE) and did not recur in the subsequent 36 months...
May 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28632148/claw-foot-a-case-report
#13
Alessandro Innocenti, Francesco Ciancio, Cecilia Taverna, Sara Tanini, Aurelio Portincasa, Domenico Parisi, Marco Innocenti, Vincenzo De Giorgi
A cutaneous horn could be defined as a conical projection on the surface of skin made of cornified material and resembling an animal horn. These lesions most commonly affect light-skinned men aged between 50 to 89 years and usually appear in sun exposed areas. Radiation, chronic irritation and even human papilloma virus-2 infection may be precipitating factors. More than half of the cases originate from either malignant or premalignant lesions, therefore the base of the lesion must be carefully examined histologically...
June 8, 2017: Annali Italiani di Chirurgia
https://www.readbyqxmd.com/read/28631369/inoperable-infiltrative-basal-cell-carcinoma-successfully-treated-with-vismodegib
#14
Omid Zargari, Seyyede Zeinab Azimi, Siamak Geranmayeh
Basal cell carcinoma (BCC) is the most common skin cancer but usually has a good prognosis. However, there is a subset of BCC cases with a less favorable prognosis. For patients with locally advanced, recurrent or metastatic BCCs who are not suitable for surgery or radiotherapy, small-molecule drug inhibitors of hedgehog pathway are a new therapeutic opportunity. Here, we present a case of infiltrative BCC with multiple recurrences. Wide excision with reconstructive plastic surgery was performed initially with adjuvant radiotherapy...
June 19, 2017: Dermatologic Therapy
https://www.readbyqxmd.com/read/28629521/erythropoietin-promotes-glioblastoma-via-mir-451-suppression
#15
Begum Alural, Zeynep O Ayyildiz, Kemal U Tufekci, Sermin Genc, Kursad Genc
Erythropoietin (EPO) is an erythropoiesis stimulating growth factor and hormone. EPO has been widely used in the treatment of chronic renal failure, cancer, and chemotherapy-related anemia for three decades. However, many clinical trials showed that EPO treatment may be associated with tumorigenesis and cancer progression. EPO is able to cross blood-brain barriers, and this may lead to an increased possibility of central nervous system tumors such as glioblastoma. Indeed, EPO promotes glioblastoma growth and invasion in animal studies...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28629477/identification-of-egf-nf-%C3%AE%C2%BAb-foxc1-signaling-axis-in-basal-like-breast-cancer
#16
Stacey Chung, Yanli Jin, Bingchen Han, Ying Qu, Bowen Gao, Armando E Giuliano, Xiaojiang Cui
BACKGROUND: The pathogenesis of human basal-like breast cancer (BLBC) is not well understood and patients with BLBC have a poor prognosis. Expression of the epidermal growth factor receptor (EGFR) and nuclear factor-κB (NF-κB) is well-known to be upregulated in BLBC. The forkhead box C1 (FOXC1) transcription factor, an important prognostic biomarker specific for BLBC, has been shown to be induced by EGF and is critical for EGF effects in breast cancer cells. How FOXC1 is transcriptionally activated in BLBC is not clear...
June 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28625978/the-alkylating-chemotherapeutic-temozolomide-induces-metabolic-stress-in-idh1-mutant-cancers-and-potentiates-nad-depletion-mediated-cytotoxicity
#17
Kensuke Tateishi, Fumi Higuchi, Julie Miller, Mara V A Koerner, Nina Lelic, Ganesh M Shankar, Shota Tanaka, David E Fisher, Tracy Batchelor, A John Iafrate, Hiroaki Wakimoto, Andrew S Chi, Daniel P Cahill
IDH1-mutant gliomas are dependent upon the canonical coenzyme nicotinamide adenine dinucleotide (NAD+) for survival. It is known that Poly(ADP-ribose) polymerase (PARP) activation consumes NAD+ during base excision repair (BER) of chemotherapy-induced DNA damage. We therefore hypothesized that a strategy combining NAD+ biosynthesis inhibitors with the alkylating chemotherapeutic agent temozolomide (TMZ) could potentiate NAD+ depletion-mediated cytotoxicity in mutant IDH1 cancer cells. To investigate the impact of TMZ on NAD+ metabolism, patient-derived xenografts and engineered mutant IDH1-expressing cell lines were exposed to TMZ, in vitro and in vivo, both alone and in combination with nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, which block NAD+ biosynthesis...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28624814/pd-l1-and-intratumoral-immune-response-in-breast-cancer
#18
Zhi-Qiang Wang, Katy Milne, Heather Derocher, John R Webb, Brad H Nelson, Peter H Watson
PURPOSE: PD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic significance. METHODS: Immunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized by molecular subtype. RESULTS: Across the entire cohort, PD-L1 tumor cell expression was observed in 73/443 (16...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621756/p53-expression-as-a-diagnostic-biomarker-in-ulcerative-colitis-associated-cancer
#19
REVIEW
Kazuhiro Kobayashi, Hiroyuki Tomita, Masahito Shimizu, Takuji Tanaka, Natsuko Suzui, Tatsuhiko Miyazaki, Akira Hara
Ulcerative colitis (UC) is defined as an idiopathic inflammatory disorder primarily involving the mucosa and submucosa of the colon. UC-associated colon cancers (also known as colitic cancers) develop through the inflammation-dysplasia sequence, which is a major problem affecting the prognosis of patients with UC. It is therefore very important to detect malignancy from UC at an early stage. As precancerous lesions arising in UC, there are pathological adenomatous changes, basal cell changes, in situ anaplasia, clear cell changes, and pan-cellular change...
June 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28621677/genome-wide-methylome-and-chromatin-interactome-identify-abnormal-enhancer-to-be-risk-factor-of-breast-cancer
#20
Yuan Wang, Da-Peng Hao, Jing-Jing Li, Li Wang, Li-Jun Di
Enhancer is critical cis regulatory elements in gene expression. To understand whether and how the aberrant enhancer activation may contribute to cancer risk, the differentially methylated enhancers (eDMRs) in normal and malignant breast tissues were identified and analyzed. By incorporating genome-wide chromatin interaction, integrated analysis of eDMRs and target gene expression identified 1,272 enhancer-promoter pairs. Surprisingly, two functionally distinct groups of genes were identified in these pairs, one showing better correlation to enhancer methylation (eRGs) and the other showing better correlation to promoter methylation (pRGs), and the former group is functionally enriched with cancer related genes...
June 2, 2017: Oncotarget
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