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https://www.readbyqxmd.com/read/28533435/enzymatic-inactivation-of-endogenous-igg-by-ides-enhances%C3%A2-therapeutic-antibody-efficacy
#1
Sofia Järnum, Anna Runström, Robert Bockermann, Lena Winstedt, Max Crispin, Christian Kjellman
Endogenous plasma IgG sets an immunological threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP). Here we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcγ-receptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28532671/ochratoxin-a-transport-by-the-human-breast-cancer-resistance-protein-bcrp-multidrug-resistance-protein-2-mrp2-and-organic-anion-transporting-polypeptides-1a2-1b1-and-2b1
#2
Xiaozhe Qi, Els Wagenaar, Wentao Xu, Kunlun Huang, Alfred H Schinkel
Ochratoxin A (OTA) is a fungal secondary metabolite that can contaminate various foods. OTA has several toxic effects like nephrotoxicity, hepatotoxicity, and neurotoxicity in different animal species, but its mechanisms of toxicity are still unclear. How OTA accumulates in kidney, liver, and brain is as yet unknown, but transmembrane transport proteins are likely involved. We studied transport of OTA in vitro, using polarized MDCKII cells transduced with cDNAs of the efflux transporters mouse (m)Bcrp, human (h)BCRP, mMrp2, or hMRP2, and HEK293 cells overexpressing cDNAs of the human uptake transporters OATP1A2, OATP1B1, OATP1B3, or OATP2B1 at pH7...
May 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28529560/ruanjian-sanjie-decoction-exhibits-antitumor-activity-by-inducing-cell-apoptosis-in-breast-cancer
#3
Xiumei Zhao, Jing Zhao, Renjie Hu, Qiang Yao, Guixian Zhang, Hongsheng Shen, Ernesto Yagüe, Yunhui Hu
Traditional Chinese medicine, based on theories developed and practiced for >2,000 years, is one of the most common complementary and alternative types of medicine currently used in the treatment of patients with breast cancer. Ruanjian Sanjie (RJSJ) decoction, is composed of four herbs, including Ban xia (Pinellia ternata), Xia ku cao (Prunella vulgaris), Shan ci gu (Cremastra appendiculata) and Hai zao (Sargassum pallidum), and has traditionally been used for softening hard lumps and resolving hard tissue masses...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520410/proteolytically-stable-cyclic-decapeptide-for-breast-cancer-cell-targeting
#4
Yogita Raghuwanshi, Hashem Rajab Etayash, Rania Soudy, Igor Paiva, Afsaneh Lavasanifar, Kamaljit Kaur
Starting with a previously reported linear breast cancer targeting decapeptide WxEAAYQkFL, here we report the synthesis of a novel cyclic peptide analogue cyclicWXEAAYQkFL. The N- to C-terminus amide cyclized peptide with one D-amino acid (k) displayed higher uptake by breast cancer cells, with minimal uptake by the non-cancerous cells compared to the linear peptide with two D-amino acids (x and k), and was stable toward proteolytic degradation. When immobilized on gold microcantilever surface, the cyclic peptide was able to capture breast cancer cells specifically and sense samples with ≥25 cancer cells/mL...
May 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28514723/genomic-profiling-of-pelvic-genital-type-leiomyosarcoma-in-a-woman-with-a-germline-chek2-c-1100delc-mutation-and-a-concomitant-diagnosis-of-metastatic-invasive-ductal-breast-carcinoma
#5
My Linh Thibodeau, Caralyn Reisle, Eric Zhao, Lee Ann Martin, Yazeed Alwelaie, Karen L Mungall, Carolyn Ch'ng, Ruth Thomas, Tony Ng, Stephen Yip, Howard Lim, Sophie Sun, Sean S Young, Aly Karsan, Yongjun Zhao, Andrew J Mungall, Richard A Moore, Daniel Renouf, Karen Gelmon, Yussanne P Ma, Malcolm Hayes, Janessa Laskin, Marco A Marra, Kasmintan A Schrader, Steven J M Jones
INTRODUCTION: We describe a woman with the known pathogenic germline variant CHEK2:c.1100delC and synchronous diagnoses of both pelvic genital type leiomyosarcoma and metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a tumour suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved in double-strand DNA break repair and cell cycle arrest. The CHEK2:c.1100delC variant is a moderate penetrance allele resulting in an approximate 2-fold increase in breast cancer risk...
May 16, 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28507022/loss-of-e-cadherin-dependent-cell-cell-adhesion-and-the-development-and-progression-of-cancer
#6
Heather C Bruner, Patrick W B Derksen
Classical cadherins are the key molecules that control cell-cell adhesion. Notwithstanding this function, it is also clear that classical cadherins are more than just the "glue" that keeps the cells together. Cadherins are essential regulators of tissue homeostasis that govern multiple facets of cellular function and development, by transducing adhesive signals to a complex network of signaling effectors and transcriptional programs. In cancer, cadherins are often inactivated or functionally inhibited, resulting in disease development and/or progression...
May 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28506052/-renal-cell-carcinoma-with-retroperitoneal-metastases-and-renal-invasion-from-breast-cancer-a-case-report
#7
Go Noguchi, Yoko Saito, Taku Mitome, Susumu Umemoto, Ayano Kakazu, Tomoko Sugiyama, Teiichiro Ueki
A 67-year-old female was hospitalized with back pain. Computed tomography (CT) incidentally revealed a tumor in her left kidney tumor (33 mm) and bilateral breast tumors. She underwent a breast biopsy and was diagnosed with breast cancer (invasive lobular cancer, cT2N0M0). The renal tumor was suspected to be clear cell carcinoma, cT1aN0M0, based on contrast-enhanced CT. Surgery was considered necessary for both the breast cancer and renal tumor. First, laparoscopic radical nephrectomy was performed for the renal tumor...
April 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28496363/prognostic-value-of-histone-chaperone-fact-subunits-expression-in-breast-cancer
#8
Kristopher Attwood, Daria Fleyshman, Laura Prendergast, Geraldine Paszkiewicz, Angela R Omilian, Wiam Bshara, Katerina Gurova
Understanding the underlying reasons for tumor aggressiveness, such as why some tumors grow slowly and locally, while others rapidly progress to a lethal metastatic disease, is still limited. This is especially critical in breast cancer (BrCa) due to its high prevalence and also due to the possibility that it can be detected early. Several oncogenes and tumor suppressors have been identified and are used in the prognosis and treatment of BrCa. However, even with these markers, the outcome within BrCa subtypes is highly variable...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28493713/cetuximab-prevents-methotrexate-induced-cytotoxicity-in-vitro-through-epidermal-growth-factor-dependent-regulation-of-renal-drug-transporters
#9
Pedro Caetano-Pinto, Amer Jamalpoor, Janneke Ham, Anastasia Goumenou, Monique Mommersteeg, Dirk Pijnenburg, Rob Ruijtenbeek, Natalia Sánchez-Romero, Bertrand van Zelst, Sandra Heil, Jitske Jansen, Martijn J Wilmer, Carla M L van Herpen, Rosalinde Masereeuw
The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells over-expressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4) and P-glycoprotein (P-gp) in methotrexate handling upon EGF and/or cetuximab treatment...
May 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28484492/relationships-between-global-dna-methylation-in-circulating-white-blood-cells-and-breast-cancer-risk-factors
#10
REVIEW
Nayha Chopra-Tandon, Haotian Wu, Kathleen F Arcaro, Susan R Sturgeon
It is not yet clear whether white blood cell DNA global methylation is associated with breast cancer risk. In this review we examine the relationships between multiple breast cancer risk factors and three markers of global DNA methylation: LINE-1, 5-mdC, and Alu. A literature search was conducted using Pubmed up to April 1, 2016, using combinations of relevant outcomes such as "WBC methylation," "blood methylation," "blood LINE-1 methylation," and a comprehensive list of known and suspected breast cancer risk factors...
2017: Journal of Cancer Epidemiology
https://www.readbyqxmd.com/read/28483691/3d-tumor-microtissues-as-an-in-vitro-testing-platform-for-microenvironmentally-triggered-drug-delivery-systems
#11
Virginia Brancato, Filomena Gioiella, Martina Profeta, Giorgia Imparato, Daniela Guarnieri, Francesco Urciuolo, Pietro Melone, Paolo A Netti
Therapeutic approaches based on nanomedicine have garnered great attention in cancer research. In vitro biological models that better mimic in vivo conditions are crucial tools to more accurately predict their therapeutic efficacy in vivo. In this work, a new 3D breast cancer microtissue has been developed to recapitulate the complexity of the tumor microenvironment and to test its efficacy as screening platform for drug delivery systems. The proposed 3D cancer model presents human breast adenocarcinoma cells and cancer-associated fibroblasts embedded in their own ECM, thus showing several features of an in vivo tumor, such as overexpression of metallo-proteinases (MMPs)...
May 5, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28475868/glucocorticoid-receptor-megatrans-switching-mediates-the-repression-of-an-er%C3%AE-regulated-transcriptional-program
#12
Feng Yang, Qi Ma, Zhijie Liu, Wenbo Li, Yuliang Tan, Chunyu Jin, Wubin Ma, Yiren Hu, Jia Shen, Kenneth A Ohgi, Francesca Telese, Wen Liu, Michael G Rosenfeld
The molecular mechanisms underlying the opposing functions of glucocorticoid receptors (GRs) and estrogen receptor α (ERα) in breast cancer development remain poorly understood. Here we report that, in breast cancer cells, liganded GR represses a large ERα-activated transcriptional program by binding, in trans, to ERα-occupied enhancers. This abolishes effective activation of these enhancers and their cognate target genes, and it leads to the inhibition of ERα-dependent binding of components of the MegaTrans complex...
May 4, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28474358/e2f1interactive-with-brca1-pathway-induces-hcc-two-different-small-molecule-metabolism-or-cell-cycle-regulation-via-mitochondrion-or-cd4-t-to-cytosol
#13
Qingchun Chen, Lin Wang, Minghu Jiang, Juxiang Huang, Zhenfu Jiang, Haitao Feng, Zhili Ji
Breast cancer 1 (BRCA1) and E2F transcription factor 1 (E2F1) are related to metabolism and cell cycle regulation. However, the corresponding mechanism is not clear in HCC. High BRCA1 direct pathway was constructed with 11 molecules from E2F1 feedback-interactive network in HCC by GRNInfer based on 39 Pearson mutual positive corelation CC >0.25 molecules with E2F1. Integration of GRNInfer with GO, KEGG, BioCarta, GNF_U133A, UNIGENE_EST, Disease, GenMAPP databases by DAVID and MAS 3.0, E2F1 feedback-interactive BRCA1 indirect mitochondrion to cytosol pathway was identified as upstream LAPTM4B activation, feedback UNG, downstream BCAT1-HIST1H2AD-TK1 reflecting protein and DNA binding with enrichment of small molecule metabolism; The corresponding BRCA1 indirect membrane to cytosol pathway as upstream CCNB2-NUSAP1 activation, feedback TTK-HIST1H2BJ-CENPF, downstream MCM4-TK1 reflecting ATP and microtubule binding with enrichment of CD4+T-related cell cycle regulation in HCC...
May 5, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28455002/treatment-schedule-and-estrogen-receptor-status-influence-acquisition-of-doxorubicin-resistance-in-breast-cancer-cells
#14
Logeswari Ponnusamy, Prathap Kumar S Mahalingaiah, Kamaleshwar P Singh
Breast cancer is the most common cancer in women for which doxorubicin is still the mainstay treatment. However, chemotherapy resistance is a major limitation in breast cancer treatment. Role of treatment schedule and estrogen receptor (ER) status in subtypes of breast cancers in acquired resistance development is not clear. Therefore, objective of this study was to evaluate whether the treatment schedule and ER status in breast cancer cells influence the doxorubicin resistance. To address these questions, ER-positive MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines were given either continuous or intermittent exposure with clinically relevant concentration of doxorubicin and the influence of these two treatment strategies on resistance to drug sensitivity was evaluated...
April 26, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28454301/immunohistochemical-profile-of-ing3-protein-in-normal-and-cancerous-tissues
#15
Wen-Feng Gou, Xue-Feng Yang, Dao-Fu Shen, Shuang Zhao, Hong-Zhi Sun, Jun-Sheng Luo, Hua-Chuan Zheng
The inhibitor of growth family, member 3 (ING3) protein may be capable of blocking the cell cycle via activating p53-transactivated promoters of p21 and Bcl2-associated X protein, and may induce apoptosis via a Fas/caspase-8-dependent signaling pathway. In the present study, immunohistochemistry was performed in order to characterize the expression profile of ING3 protein in tissue microarrays containing mouse and human normal tissue, human hepatocellular (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196), colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung carcinoma (n=192)...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454214/genome-wide-analysis-of-gynecologic-cancer-the-cancer-genome-atlas-in-ovarian-and-endometrial-cancer
#16
Moito Iijima, Kouji Banno, Ryuichiro Okawa, Megumi Yanokura, Miho Iida, Takashi Takeda, Haruko Kunitomi-Irie, Masataka Adachi, Kanako Nakamura, Kiyoko Umene, Yuya Nogami, Kenta Masuda, Eiichiro Tominaga, Daisuke Aoki
Cancer typically develops due to genetic abnormalities, but a single gene abnormality cannot completely account for the onset of cancer. The Cancer Genome Atlas (CGA) project was conducted for the cross-sectional genome-wide analysis of numerous genetic abnormalities in various types of cancer. This approach has facilitated the identification of novel AT-rich interaction domain 1A gene mutations in ovarian clear cell carcinoma, frequent tumor protein 53 (TP53) gene mutations in high-grade ovarian serous carcinoma, and Kirsten rat sarcoma and B-rapidly accelerated fibrosarcoma proto-oncogene, serine/threonine kinase gene mutations in low-grade ovarian serous carcinoma...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28446320/-advances-in-diagnosis-and-treatment-of-primary-breast-lymphoma-review
#17
Zhong-Ling Wei, Dong-Ping Huang
Primary breast lymphoma(PBL) is a rare and unique type of lymphoma. Female patients are the majority, but its pathogenesis is not clear, and the estrogen may be related with the pathoganesis. Women who have breast implants have more chance to be suffered. The painless breast masses are the most common clinical manifestations, which is similar to breast cancer. Surgical resection of the mass and core needle biopsy are helpful for the diagnosis. The most common pathological type of PBL is diffuse large B cell type, with non GCB type, and it is prone to extranodal relapse in which central nervous system relapse is common which has poor prognosis...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28442560/obesity-and-menopause-modify-the-epigenomic-profile-of-breast-cancer
#18
Ana B Crujeiras, Angel Díaz-Lagares, Olafur A Stefansson, Manuel Macias, Juan Sandoval, Juan Cueva, Rafael López-López, Sebastian Moran, Jon G Jonasson, Laufey Tryggvadottir, Elinborg Olafsdottir, Francisco J Tinahones, Marcos C Carreira, Felipe F Casanueva, Manel Esteller
Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumor were coupled with information on BMI and menopausal status. Additionally, DNA methylation results were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising in either pre- or postmenopausal women stratified by BMI or menopausal status alone were not associated with a specific DNA methylation pattern...
April 25, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28435289/long-noncoding-rna-nbat-1-suppresses-tumorigenesis-and-predicts-favorable-prognosis-in-ovarian-cancer
#19
Changsheng Yan, Yi Jiang, Yicong Wan, Lin Zhang, Jinhui Liu, Shulin Zhou, Wenjun Cheng
Long noncoding RNA (lncRNA) has been proven to be involved in many biological processes in ovarian cancer (OC). However, the mechanism still remains unknown. In this study, we screened significantly downregulated NBAT-1, which has been proven to play a significant role in breast cancer, clear cell renal cell carcinoma, and neuroblastoma, but not in OC, in two independent datasets with relatively more samples (GSE18520 and GSE38666) from Gene Expression Omnibus. We found that lncRNA NBAT-1 was obviously downregulated in OC tissue compared to normal ovarian tissue (P<0...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28431881/design-and-synthesis-of-1-2-3-triazolo-phenanthrene-hybrids-as-cytotoxic-agents
#20
Niggula Praveen Kumar, Shalini Nekkanti, S Sujana Kumari, Pankaj Sharma, Nagula Shankaraiah
A series of new 1,2,3-triazolo-phenanthrene hybrids has been synthesized by employing Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. These compounds were evaluated for their in vitro cytotoxic potential against various human cancer cell lines viz. lung (A549), prostate (PC-3 and DU145), gastric (HGC-27), cervical (HeLa), triple negative breast (MDA-MB-231, MDA-MB-453) and breast (BT-549, 4T1) cells. Among the tested compounds, 7d displayed highest cytotoxicity against DU145 cells with IC50 value of 1...
April 7, 2017: Bioorganic & Medicinal Chemistry Letters
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