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https://www.readbyqxmd.com/read/28944452/nano-pulse-stimulation-induces-potent-immune-responses-eradicating-local-breast-cancer-while-reducing-distant-metastases
#1
Siqi Guo, Yu Jing, Niculina I Burcus, Brittany P Lassiter, Royena Tanaz, Richard Heller, Stephen J Beebe
Nano-Pulse Stimulation (NPS) as a developing technology has been studied for minimally invasive, non-thermal local cancer elimination for more than a decade. Here we show that a single NPS treatment results in complete regression of the poorly immunogenic, metastatic 4T1-Luc mouse mammary carcinoma. Impressively, spontaneous distant organ metastases were largely prevented, even in those animals with incomplete tumor regression. All tumor-free mice were protected from secondary tumor cell challenge, demonstrating a vaccine-like effect...
September 25, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28944088/loss-of-the-vitamin-d-receptor-in-human-breast-and-prostate-cancers-strongly-induces-cell-apoptosis-through-downregulation-of-wnt-%C3%AE-catenin-signaling
#2
Yu Zheng, Trupti Trivedi, Ruby Cy Lin, Colette Fong-Yee, Rick Nolte, Jeline Manibo, Yunzhao Chen, Musharraf Hossain, Konstantin Horas, Colin Dunstan, Hong Zhou, Markus J Seibel
Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D, 1,25-dihydroxy-vitamin D [1,25(OH)2D] are mediated through binding to the vitamin D receptor (VDR). Here, we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation in vitro...
2017: Bone Research
https://www.readbyqxmd.com/read/28941142/coordination-accelerated-iron-extraction-enables-fast-biodegradation-of-mesoporous-silica-based-hollow-nanoparticles
#3
Liying Wang, Minfeng Huo, Yu Chen, Jianlin Shi
Biodegradation behavior of inorganic silica-based nanoplatforms is of critical importance in their clinical translations, but still remains a great challenge in achieving this goal by composition regulation of biocompatible silica framework. In the present work, a chemical coordination-accelerated biodegradation strategy to endow hollow mesoporous silica nanoparticles (HMSNs) with unique coordination-responsive biodegradability, on-demand coordination-responsive drug releasing behavior, and significantly enhanced chemotherapeutic efficacy by directly doping iron (Fe) ions into the framework of mesoporous silica is reported...
September 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28938604/inflammation-and-stem-markers-association-to-pim1-pim2-kinase-induced-tumors-in-breast-and-uterus
#4
Manuel-Pedro Jiménez-García, Antonio Lucena-Cacace, María-José Robles-Frías, Irene Ferrer, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938563/a-novel-immunotherapy-targeting-mmp-14-limits-hypoxia-immune-suppression-and-metastasis-in-triple-negative-breast-cancer-models
#5
Binbing Ling, Kathleen Watt, Sunandan Banerjee, Daniel Newsted, Peter Truesdell, Jarrett Adams, Sachdev S Sidhu, Andrew W B Craig
Matrix metalloproteinase-14 (MMP-14) is a clinically relevant target in metastatic cancers due to its role in tumor progression and metastasis. Since active MMP-14 is localized on the cell surface, it is amenable to antibody-mediated blockade in cancer, and here we describe our efforts to develop novel inhibitory anti-MMP-14 antibodies. A phage-displayed synthetic humanized Fab library was screened against the extracellular domain of MMP-14 and a panel of MMP14-specific Fabs were identified. A lead antibody that inhibits the catalytic domain of MMP-14 (Fab 3369) was identified and treatment of MDA-MB-231 breast cancer cells with Fab 3369 led to significant loss of extracellular matrix degradation and cell invasion abilities...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938483/varying-susceptibility-of-the-female-mammary-gland-to-in-utero-windows-of-bpa-exposure
#6
Andrea R Hindman, Xiaokui Molly Mo, Hannah L Helber, Claire E Kovalchin, Nanditha Ravichandran, Alina R Murphy, Abigail M Fagan, Pamela M St John, Craig J Burd
In utero exposure to the endocrine disrupting compound bisphenol A (BPA) is known to disrupt mammary gland development and increase tumor susceptibility in rodents. It is unclear if there are different periods of in utero development that may be more susceptible to BPA exposure. Herein, pregnant CD-1 mice were exposed to BPA at different times during gestation that correspond to specific milestones of in utero mammary gland development. Mammary glands of early-life and adult female mice, exposed in utero to BPA, were morphologically and molecularly (ERα and Ki67) evaluated for developmental abnormalities...
August 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938159/lunatic-fringe-and-p53-cooperatively-suppress-mesenchymal-stem-like-breast-cancer
#7
Wen-Cheng Chung, Shubing Zhang, Lavanya Challagundla, Yunyun Zhou, Keli Xu
Claudin-low breast cancer (CLBC) is a poor prognosis molecular subtype showing stemness and mesenchymal features. We previously discovered that deletion of a Notch signaling modulator, Lunatic Fringe (Lfng), in the mouse mammary gland induced a subset of tumors resembling CLBC. Here we report that deletion of one copy of p53 on this background not only accelerated mammary tumor development but also led to a complete penetrance of the mesenchymal stem-like phenotype. All mammary tumors examined in the Lfng/p53 compound mutant mice displayed a mesenchymal/spindloid pathology...
September 19, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28934904/clonal-deletion-of-t-cell-repertoires-with-specific-t-cell-receptor-v%C3%AE-chains-by-two-endogenous-superantigens-in-nc-nga-mice
#8
Kozo Ohkusu-Tsukada, Teruyo Tsukada, Kimimasa Takahashi
Superantigens (SAgs) are powerful T-cell stimulatory proteins. Because an atopic dermatitis (AD) model NC/Nga mice had two endogenous SAgs, namely minor lymphocyte-stimulating locus-1(a) (Mls-1(a)) and mouse mammary tumor virus (MMTV)(SHN), SAg-responsive T-cells bearing Vβ5.1, Vβ6, Vβ8.1, Vβ8.2, Vβ8.3, Vβ9, and Vβ11 should be endogenously deleted. Here, we discuss that the endogenous SAgs-expression may be involved in AD-sensitivity in NC/Nga mice.
September 22, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28932764/antisense-oligonucleotide-mediated-knockdown-in-mammary-tumor-organoids
#9
Sarah D Diermeier, David L Spector
Primary mammary tumor organoids grown in 3D are an excellent system to study tumor biology. They resemble the organization and physiology of native epithelia more closely than cancer cell lines grown in 2D, and additionally model interactions with the ECM (Boj et al., 2015; Clevers, 2016; Shamir and Ewald, 2014). Mammary tumor organoids are therefore a promising model system to identify and characterize novel drivers of breast cancer that would be unlikely to be identified using 2D cell lines. Antisense oligonucleotides can be used to efficiently and specifically knockdown target genes in the cell (Bennett et al...
August 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28931070/atrazine-induced-epigenetic-transgenerational-inheritance-of-disease-lean-phenotype-and-sperm-epimutation-pathology-biomarkers
#10
Margaux McBirney, Stephanie E King, Michelle Pappalardo, Elizabeth Houser, Margaret Unkefer, Eric Nilsson, Ingrid Sadler-Riggleman, Daniel Beck, Paul Winchester, Michael K Skinner
Ancestral environmental exposures to a variety of environmental toxicants and other factors have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The current study examined the potential transgenerational actions of the herbicide atrazine. Atrazine is one of the most commonly used herbicides in the agricultural industry, in particular with corn and soy crops. Outbred gestating female rats were transiently exposed to a vehicle control or atrazine. The F1 generation offspring were bred to generate the F2 generation and then the F2 generation bred to generate the F3 generation...
2017: PloS One
https://www.readbyqxmd.com/read/28929038/drainage-after-modified-radical-mastectomy-a-methodological-mini-review
#11
REVIEW
George S Stoyanov, Dragostina Tsocheva, Katerina Marinova, Emil Dobrev, Rumen Nenkov
Breast cancer is a socially relevant group of malignant conditions of the mammary gland, affecting both males and females. Most commonly the surgical approach of choice is a modified radical mastectomy (MRM), due to it allowing for both the removal of the main tumor mass and adjacent glandular tissue, which are suspected of infiltration and multifocality of the process, and a sentinel axillary lymph node removal. Most common post-surgical complications following MRM are the formation of a hematoma, the infection of the surgical wound and the formation of a seroma...
July 10, 2017: Curēus
https://www.readbyqxmd.com/read/28927257/differential-and-correlated-expression-of-p16-p21-p27-p38-in-mammary-gland-tumors-of-aged-dogs
#12
Hyun-Woo Kim, Jong-Il Shin, Byung-Joon Seung, Jung-Hyung Ju, Jung-Hyang Sur
The inhibitory effect of neutering on mammary gland tumor development in dogs is well known. However, we found that the effect of neutering on tumor malignancy may be altered by aging. Therefore, we aimed to characterize mammary tumors in aged dogs by analyzing the expression of cellular senescence markers, from the viewpoint of senescence. The expression of p16, p38, p21, and p27 antibodies, which are senescence-associated markers, was detected in canine mammary tumors of aged dogs via immunohistochemistry...
September 20, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/28927255/innate-immune-response-of-bovine-mammary-epithelial-cells-to-mycoplasma-bovis
#13
Satoshi Gondaira, Hidetoshi Higuchi, Hidetomo Iwano, Koji Nishi, Takanori Nebu, Keiichi Nakajima, Hajime Nagahata
Mycoplasma species are contagious bacteria and Mycoplasma bovis mastitis is a serious productivity problem on dairy farms. Bovine mammary epithelial cells (bMEC) play an important role in the elimination of pathogens, but the effect of M. bovis on bMEC has not been fully clarified. To better understand the immune response against intramammary infection by M. bovis, we used microarray analysis to examine and profile mRNA expression in bMEC after stimulation with M. bovis. We also compared the effects of M. bovis, Staphylococcus aureus and Escherichia coli on immune-related mRNA expression in bMEC...
September 20, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/28927044/isolation-and-characterization-of-adult-mammary-stem-cells-from-breast-cancer-adjacent-tissues
#14
Ai-Ping Shi, Zhi-Min Fan, Ke-Wei Ma, Yan-Fang Jiang, Lei Wang, Ke-Wei Zhang, Shi-Bo Fu, Ning Xu, Zhi-Ru Zhang
Normal adult mammary stem cells (AMSCs) are promising sources for breast reconstruction, particularly following the resection of breast tumors. However, carcinogenic events can potentially convert normal AMSCs to cancer stem cells, posing a safety concern for the use of AMSCs for clinical tissue regeneration. In the present study, AMSCs and autologous primary breast cancer cells were isolated and compared for their ability to differentiate, their gene expression profile, and their potential to form tumors in vivo...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28924054/immunosurveillance-and-immunoediting-of-breast-cancer-via-class-i-mhc-receptors
#15
Megan M Tu, Mir Munir A Rahim, Celine Sayed, Ahmad Bakur Mahmoud, Andrew P Makrigiannis
Ly49 receptors, which recognize 'self' class I major histocompatibility complex (MHC-I) molecules, enable natural killer (NK) cells to detect loss of MHC-I expression on transformed and virally-infected cells. The impact of NK cell-mediated MHC-I surveillance on immunoediting of breast cancer is still not fully understood. This work assesses the impact of Ly49 receptors on tumor development in terms of cancer control and in driving immune-evading cancer mutations. Genetically modified Ly49-deficient mice and those lacking NK cells through antibody depletion were less able to control E0771-derived mammary tumors in an MHC-I-dependent fashion...
September 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28919995/mammary-tumor-derived-ccl2-enhances-pro-metastatic-systemic-inflammation-through-upregulation-of-il1%C3%AE-in-tumor-associated-macrophages
#16
Kelly Kersten, Seth B Coffelt, Marlous Hoogstraat, Niels J M Verstegen, Kim Vrijland, Metamia Ciampricotti, Chris W Doornebal, Cheei-Sing Hau, Max D Wellenstein, Camilla Salvagno, Parul Doshi, Esther H Lips, Lodewyk F A Wessels, Karin E de Visser
Patients with primary solid malignancies frequently exhibit signs of systemic inflammation. Notably, elevated levels of neutrophils and their associated soluble mediators are regularly observed in cancer patients, and correlate with reduced survival and increased metastasis formation. Recently, we demonstrated a mechanistic link between mammary tumor-induced IL17-producing γδ T cells, systemic expansion of immunosuppressive neutrophils and metastasis formation in a genetically engineered mouse model for invasive breast cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919040/heme-binding-biguanides-target-cytochrome-p450-dependent-cancer-cell-mitochondria
#17
Zhijun Guo, Irina F Sevrioukova, Ilia G Denisov, Xia Zhang, Ting-Lan Chiu, Dafydd G Thomas, Eric A Hanse, Rebecca A D Cuellar, Yelena V Grinkova, Vanessa Wankhede Langenfeld, Daniel S Swedien, Justin D Stamschror, Juan Alvarez, Fernando Luna, Adela Galván, Young Kyung Bae, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Beverly Norris, Craig M Flory, Robert J Schumacher, M Gerard O'Sullivan, Qing Cao, Haitao Chu, John D Lipscomb, William M Atkins, Kalpna Gupta, Ameeta Kelekar, Ian A Blair, Jorge H Capdevila, John R Falck, Stephen G Sligar, Thomas L Poulos, Gunda I Georg, Elizabeth Ambrose, David A Potter
The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs...
August 29, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28916248/breast-cancer-vaccines-delivered-by-dendritic-cell-targeted-lentivectors-induce-potent-antitumor-immune-responses-and-protect-mice-from-mammary-tumor-growth
#18
Paul D Bryson, Xiaolu Han, Norman Truong, Pin Wang
Breast cancer immunotherapy is a potent treatment option, with antibody therapies such as trastuzumab increasing 2-year survival rates by 50%. However, active immunotherapy through vaccination has generally been clinically ineffective. One potential means of improving vaccine therapy is by delivering breast cancer antigens to dendritic cells (DCs) for enhanced antigen presentation. To accomplish this in vivo, we pseudotyped lentiviral vector (LV) vaccines with a modified Sindbis Virus glycoprotein so that they could deliver genes encoding the breast cancer antigen alpha-lactalbumin (Lalba) or erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) directly to resident DCs...
September 12, 2017: Vaccine
https://www.readbyqxmd.com/read/28916201/targeting-heparanase-to-the-mammary-epithelium-enhances-mammary-gland-development-and-promotes-tumor-growth-and-metastasis
#19
Ilanit Boyango, Uri Barash, Liat Fux, Inna Naroditsky, Neta Ilan, Israel Vlodavsky
Heparanase is an endoglucuronidase that uniquely cleaves the heparan sulfate side chains of heparan sulfate proteoglycans. This activity ultimately alters the structural integrity of the ECM and basement membrane that becomes more prone to cellular invasion by metastatic cancer cells and cells of the immune system. In addition, enzymatically inactive heparanase was found to facilitate the proliferation and survival of cancer cells by activation of signaling molecules such as Akt, Src, signal transducer and activation of transcription (Stat), and epidermal growth factor receptor...
September 13, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28916002/characterization-of-immune-response-in-staphylococcus-aureus-chronically-infected-bovine-mammary-glands-during-active-involution
#20
Carolina S Andreotti, Celina Baravalle, Sofía C Sacco, Melisa Lovato, Elizabet A L Pereyra, María S Renna, Hugo H Ortega, Luis F Calvinho, Bibiana E Dallard
The aim of this study was to characterize the immune response in Staphylococcus aureus chronically infected bovine mammary glands during active involution. Twenty-one Holstein non-pregnant cows in late lactation either uninfected or with chronic naturally acquired S. aureus intramammary infections (IMI) were included in this study. Cows were slaughtered at 7, 14 and 21 d after cessation of milking and samples for immunohistochemical analysis were taken. Protein expression of toll-like receptor 2 (TLR2) and TLR4 was significantly higher in S...
October 2017: Comparative Immunology, Microbiology and Infectious Diseases
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