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Evalynn Vasquez, Vivian Cristofaro, Stefan Lukianov, Fiona C Burkhard, Ali Hashemi Gheinani, Katia Monastyrskaya, Diane R Bielenberg, Maryrose P Sullivan, Rosalyn M Adam
Chronic urethral obstruction and the ensuing bladder wall remodeling can lead to diminished bladder smooth muscle (BSM) contractility and debilitating lower urinary tract symptoms. No effective pharmacotherapy exists to restore BSM contractile function. Neuropilin 2 (Nrp2) is a transmembrane protein that is highly expressed in BSM. Nrp2 deletion in mice leads to increased BSM contraction. We determined whether genetic ablation of Nrp2 could restore BSM contractility following obstruction. Partial bladder outlet obstruction (pBOO) was created by urethral occlusion in mice with either constitutive and ubiquitous, or inducible smooth muscle-specific deletion of Nrp2, and Nrp2-intact littermates...
February 9, 2017: JCI Insight
Johannes Wedel, Hironao Nakayama, Nora M Kochupurakkal, Josephine Koch, Michael Klagsbrun, Diane R Bielenberg, David M Briscoe
PURPOSE OF REVIEW: Chronic rejection is associated with persistent mononuclear cell recruitment, endothelial activation and proliferation, local tissue hypoxia and related biology that enhance effector immune responses. In contrast, the tumor microenvironment elicits signals/factors that inhibit effector T cell responses and rather promote immunoregulation locally within the tissue itself. The identification of immunoregulatory check points and/or secreted factors that are deficient within allografts is of great importance in the understanding and prevention of chronic rejection...
February 2017: Current Opinion in Organ Transplantation
Patrick Mucka, Nicholas Levonyak, Elena Geretti, Bernadette M M Zwaans, Xiaoran Li, Irit Adini, Michael Klagsbrun, Rosalyn M Adam, Diane R Bielenberg
The vasculature influences the progression and resolution of tissue inflammation. Capillaries express vascular endothelial growth factor (VEGF) receptors, including neuropilins (NRPs), which regulate interstitial fluid flow. NRP2, a receptor of VEGFA and semaphorin (SEMA) 3F ligands, is expressed in the vascular and lymphatic endothelia. Previous studies have demonstrated that blocking VEGF receptor 2 attenuates VEGFA-induced vascular permeability. The inhibition of NRP2 was hypothesized to decrease vascular permeability as well...
November 2016: American Journal of Pathology
Kai Song, Hao Wu, H N Ashiqur Rahman, Yunzhou Dong, Aiyun Wen, Megan L Brophy, Scott Wong, Sukyoung Kwak, Diane R Bielenberg, Hong Chen
VEGF-driven tumor angiogenesis has been validated as a central target in several tumor types deserving of continuous and further considerations to improve the efficacy and selectivity of the current therapeutic paradigms. Epsins, a family of endocytic clathrin adaptors, have been implicated in regulating endothelial cell VEGFR2 signaling, where its inactivation leads to nonproductive leaky neo-angiogenesis and, therefore, impedes tumor development and progression. Targeting endothelial epsins is of special significance due to its lack of affecting other angiogenic-signaling pathways or disrupting normal quiescent vessels, suggesting a selective modulation of tumor angiogenesis...
February 2017: Cellular and Molecular Life Sciences: CMLS
Lindsay L Wong, Nahyoung Grace Lee, Dhanesh Amarnani, Catherine J Choi, Diane R Bielenberg, Suzanne K Freitag, Patricia A D'Amore, Leo A Kim
PURPOSE: The human orbit is an environment that is vulnerable to inflammation and edema in the setting of autoimmune thyroid disease. Our study investigated the tenet that orbital adipose tissue lacks lymphatic vessels and analyzed the clinicopathologic differences between patients with acute and chronic thyroid eye disease (TED). The underlying molecular mediators of blood and lymphatic vessel formation within the orbital fat also were evaluated. DESIGN: Retrospective cohort study...
September 2016: Ophthalmology
Suming Wang, Anna Blois, Tina El Rayes, Joyce F Liu, Michelle S Hirsch, Karsten Gravdal, Sangeetha Palakurthi, Diane R Bielenberg, Lars A Akslen, Ronny Drapkin, Vivek Mittal, Randolph S Watnick
The vast majority of ovarian cancer-related deaths are caused by metastatic dissemination of tumor cells, resulting in subsequent organ failure. However, despite our increased understanding of the physiological processes involved in tumor metastasis, there are no clinically approved drugs that have made a major impact in increasing the overall survival of patients with advanced, metastatic ovarian cancer. We identified prosaposin (psap) as a potent inhibitor of tumor metastasis, which acts via stimulation of p53 and the antitumorigenic protein thrombospondin-1 (TSP-1) in bone marrow-derived cells that are recruited to metastatic sites...
March 9, 2016: Science Translational Medicine
Shokoufeh Shahrabi-Farahani, Marina Gallottini, Fabiana Martins, Erik Li, Dayna R Mudge, Hironao Nakayama, Kyoko Hida, Dipak Panigrahy, Patricia A D'Amore, Diane R Bielenberg
Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis...
April 2016: American Journal of Pathology
Nancy A Haug, Jennifer Bielenberg, Steven H Linder, Anna Lembke
BACKGROUND: As opioid overdose rates continue to pose a major public health crisis, the need for naloxone treatment by emergency first responders is critical. Little is known about the views of those who administer naloxone. The current study examines attitudes of health professionals on the social media platform Twitter to better understand their perceptions of opioid users, the role of naloxone, and potential training needs. METHODS: Public comments on Twitter regarding naloxone were collected for a period of 3 consecutive months...
2016: Substance Abuse
Jacqueline Banyard, Diane R Bielenberg
Metastatic cancer cells are lethal. Understanding the molecular mechanisms that bolster the conversion from benign to malignant progression is key for treating these heterogeneous and resistant neoplasms. The epithelial-mesenchymal transition (EMT) is a conserved cellular program that alters cell shape, adhesion and movement. The shift to a more mesenchymal-like phenotype can promote tumor cell intravasation of surrounding blood vessels and emigration to a new organ, yet may not be necessary for extravasation or colonization into that environment...
2015: Connective Tissue Research
Diane R Bielenberg, Bruce R Zetter
The role of angiogenesis in tumor growth has been studied continuously for over 45 years. It is now appreciated that angiogenesis is also essential for the dissemination and establishment of tumor metastases. In this review, we focus on the role of angiogenesis as a necessity for the escape of tumor cells into the bloodstream and for the establishment of metastatic colonies in secondary sites. We also discuss the role of tumor lymphangiogenesis as a means of dissemination of lymphatic metastases. Appropriate combination therapies may be used in the future to both prevent and treat metastatic disease through the rational use of antiangiogenic and antilymphangiogenic therapies in ways that are informed by the current and future work in the field...
July 2015: Cancer Journal
Christina E Wells, Elisa Vendramin, Sergio Jimenez Tarodo, Ignazio Verde, Douglas G Bielenberg
BACKGROUND: MADS-box genes encode a family of eukaryotic transcription factors distinguished by the presence of a highly-conserved ~58 amino acid DNA-binding and dimerization domain (the MADS-box). The central role played by MADS-box genes in peach endodormancy regulation led us to examine this large gene family in more detail. We identified the locations and sequences of 79 MADS-box genes in peach, separated them into established subfamilies, and broadly surveyed their tissue-specific and dormancy-induced expression patterns using next-generation sequencing...
2015: BMC Plant Biology
Christina E Wells, Elisa Vendramin, Sergio Jimenez Tarodo, Ignazio Verde, Douglas G Bielenberg
BACKGROUND: MADS-box genes encode a family of eukaryotic transcription factors distinguished by the presence of a highly-conserved ~58 amino acid DNA-binding and dimerization domain (the MADS-box). The central role played by MADS-box genes in peach endodormancy regulation led us to examine this large gene family in more detail. We identified the locations and sequences of 79 MADS-box genes in peach, separated them into established subfamilies, and broadly surveyed their tissue-specific and dormancy-induced expression patterns using next-generation sequencing...
December 2015: BMC Plant Biology
Diane R Bielenberg, Patricia A D'Amore
No abstract text is available yet for this article.
November 2014: Microvascular Research
Matthew T Migliozzi, Patrick Mucka, Diane R Bielenberg
Metastasis is the leading cause of cancer-related deaths. Understanding how the lymphatic system responds to its environment and local stimuli may lead to therapies to combat metastasis and other lymphatic-associated diseases. This review compares lymphatic vessels and blood vessels, discusses markers of lymphatic vasculature, and elucidates some of the signaling motifs involved in lymphangiogenesis. Recent progress implicating the neuropilin and semaphorin axes in this process is discussed.
November 2014: Microvascular Research
Jan-Marcus Daniel, Daniela Penzkofer, Rebecca Teske, Jochen Dutzmann, Alexander Koch, Wiebke Bielenberg, Angelika Bonauer, Reinier A Boon, Ariane Fischer, Johann Bauersachs, Eva van Rooij, Stefanie Dimmeler, Daniel G Sedding
AIMS: MicroRNA (miR)-92a is an important regulator of endothelial proliferation and angiogenesis after ischaemia, but the effects of miR-92a on re-endothelialization and neointimal lesion formation after vascular injury remain elusive. We tested the effects of lowering miR-92a levels using specific locked nucleic acid (LNA)-based antimiRs as well as endothelial-specific knock out of miR-92a on re-endothelialization and neointimal formation after wire-induced injury of the femoral artery in mice...
September 1, 2014: Cardiovascular Research
Dipak Panigrahy, Irit Adini, Roni Mamluk, Nicholas Levonyak, Christiane J Bruns, Patricia A D'Amore, Michael Klagsbrun, Diane R Bielenberg
Neuropilin-1 (NRP1) is a receptor for vascular endothelial growth factor (VEGF). A soluble isoform of Nrp1 (sNrp1) has not been described in the mouse. Our goal was to examine the expression of mouse sNrp1 during liver development and regeneration.sNrp1 was cloned from mouse liver. The expression of sNrp1 and VEGF was examined in mouse liver during post-natal development and regeneration using northern blot, western blot, in situ hybridisation, and immunohistochemical analyses. HGF/NRP1 binding was examined in vitro...
August 2014: Pathology
Jacqueline Banyard, Ivy Chung, Matthew Migliozzi, Derek T Phan, Arianne M Wilson, Bruce R Zetter, Diane R Bielenberg
BACKGROUND: Understanding the complex, multistep process of metastasis remains a major challenge in cancer research. Metastasis models can reveal insights in tumor development and progression and provide tools to test new intervention strategies. METHODS: To develop a new cancer metastasis model, we used DU145 human prostate cancer cells and performed repeated rounds of orthotopic prostate injection and selection of subsequent lymph node metastases. Tumor growth, metastasis, cell migration and invasion were analyzed...
2014: BMC Cancer
Shokoufeh Shahrabi-Farahani, Lili Wang, Bernadette M M Zwaans, Jeans M Santana, Akio Shimizu, Seiji Takashima, Michael Kreuter, Leigh Coultas, Patricia A D'Amore, Jeffrey M Arbeit, Lars A Akslen, Diane R Bielenberg
Neuropilins (NRPs) are cell surface receptors for vascular endothelial growth factor (VEGF) and SEMA3 (class 3 semaphorin) family members. The role of NRPs in neurons and endothelial cells has been investigated, but the expression and role of NRPs in epithelial cells is much less clear. Herein, the expression and localization of NRP1 was investigated in human and mouse skin and squamous cell carcinomas (SCCs). Results indicated that NRP1 mRNA and protein was expressed in the suprabasal epithelial layers of the skin sections...
July 2014: Laboratory Investigation; a Journal of Technical Methods and Pathology
Irit Adini, Kaustabh Ghosh, Avner Adini, Zai-Long Chi, Takeru Yoshimura, Ofra Benny, Kip M Connor, Michael S Rogers, Lauren Bazinet, Amy E Birsner, Diane R Bielenberg, Robert J D'Amato
Studies have established that pigmentation can provide strong, protective effects against certain human diseases. For example, angiogenesis-dependent diseases such as wet age-related macular degeneration and infantile hemangioma are more common in light-skinned individuals of mixed European descent than in African-Americans. Here we found that melanocytes from light-skinned humans and albino mice secrete high levels of fibromodulin (FMOD), which we determined to be a potent angiogenic factor. FMOD treatment stimulated angiogenesis in numerous in vivo systems, including laser-induced choroidal neovascularization, growth factor-induced corneal neovascularization, wound healing, and Matrigel plug assays...
January 2014: Journal of Clinical Investigation
Jacqueline Banyard, Ivy Chung, Arianne M Wilson, Guillaume Vetter, Antony Le Béchec, Diane R Bielenberg, Bruce R Zetter
Using an in vivo cycling strategy, we selected metastatic cancer cells from the lymph nodes (LN) of mice bearing orthotopic DU145 human prostate tumors. Repeated rounds of metastatic selection (LN1-LN4) progressively increased the epithelial phenotype, resulting in a new model of tumor cell mesenchymal-epithelial transition (MET). DU145-LN4 showed increased cell-cell adhesions, higher expression of multiple epithelial markers, such as E-cadherin, EpCAM and cytokeratin 18, and reduced expression of mesenchymal markers such as vimentin...
November 6, 2013: Scientific Reports
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