Extensive accumulation of the glycosaminoglycan hyaluronan is found in pancreatic cancer. The role synthases 2 and 3 (HAS2, 3) was investigated cancer growth tumor microenvironment. Overexpression HAS3 increased synthesis BxPC-3 cells. In vivo, overexpression led to faster growing xenograft tumors with abundant extracellular accumulation. Treatment pegylated human recombinant hyaluronidase (PEGPH20) removed dramatically decreased rate compared parental tumors. PEGPH20 had a weaker effect on...

Immunotherapies targeting immune checkpoint inhibitors have changed the landscape of cancer treatment, however, many patients are resistant or refractory to immunotherapy. The sensitivity tumor cells immunotherapy may be influenced by hyaluronan (HA) accumulation in microenvironment (TME). Enzymatic degradation HA pegvorhyaluronidase alfa (PEGPH20; PVHA) remodels TME. This leads reduced interstitial pressure and decompressed blood vessels, which both associated with increased exposure...

DNA sequences corresponding to gene segments that code for the nonstructural protein, matrix and hemagglutinin of influenza A virus [strain A/Udorn/72 (H3N2)] were cloned in Escherichia coli pBR 322. Initially, positive negative cDNA strands prepared separately by reverse transcription. The transcribed from genomic RNA using a specific dodecamer sequence as primer; cytoplasmic viral mRNA an oligo(dT) primer. duplexes size then purified, inserted into plasmid DNA, used transformation E. coli....

// Chunmei Zhao 1 , Benjamin J. Thompson * Kelly Chen Feng Gao Barbara Blouw Mathieu Marella Susan Zimmerman Trevor Kimbler Sheryl Garrovillo Jesse Bahn Lei Huang Zhongdong H. Michael Shepard Sanna Rosengren Christopher D. Thanos and Daniel C. Maneval Halozyme Therapeutics, Inc., San Diego, CA, 92121, USA Formerly of Correspondence to: Zhao, email: czhao@halozyme.com Keywords: hyaluronan; breast cancer; xenograft; tumor microenvironment; CD44 Received: August 05, 2019 Accepted: October 19,...

Abstract Hyaluronan (HA), a major extracellular matrix component in many solid tumors, has been proposed to contribute tumor progression, and play complex role T lymphocyte biology. Its depletion by intravenous PEGylated recombinant human hyaluronidase PH20 (PEGPH20) remodels the stroma, reduces intratumoral pressure, decompresses blood vessels, facilitates drug delivery. However, impact of HA removal on intra-tumoral immune responses efficacy checkpoint inhibitors is unknown. To evaluate...

Abstract Hyaluronan (HA) accumulates in the extracellular matrix (ECM) of many solid tumors, including those prostate, colon, breast, stomach, ovary, and pancreas. This accumulation is associated with tumor progression a negative clinical outcome. Accordingly, an HA-degrading enzyme, pegylated recombinant human hyaluronidase PH20 (PEGPH20), was developed to target tumor-associated HA ECM. Preclinical studies demonstrated that PEGPH20-mediated removal from HA-rich xenograft tumors mice...

Abstract Hyaluronan (HA) over-accumulation in the extracellular matrix (ECM) of many solid tumors is associated with tumor progression and poor prognosis. Accordingly, an HA-degrading enzyme, PEGPH20, being developed to deplete tumor-associated HA ECM. In preclinical animal models, enzymatic removal ECM PEGPH20 remodeling stroma, reduction interstitial fluid pressure, expansion blood vessels facilitated delivery chemotherapy. As pancreatic ductal adenocarcinoma (PDA) has been identified as a...

Abstract Multiple solid tumor types over-express epidermal growth factor receptor (EGFR). Antibodies that target the are often accompanied by adverse skin reactions due to interaction with receptors expressed in normal tissue. Additionally, downstream mutations (KRAS, BRAF) within tumors can result EGFR-independent activation and resistance treatment. We have previously described HTI-1511, an antibody-drug conjugate pre-clinical development targets EGFR. HTI-1511 carries potent cytotoxin...

Abstract Pancreatic cancer is one of most deadly cancers with a 5-year survival rate 6%. Accumulation hyaluronan (HA) found in about 87% human pancreatic adenocarcinomas, and removal HA suppresses tumor growth HA-rich preclinical models. In transgenic mouse model (LSL-KrasG12D/+;LSLTrp53R172H/+;Pdx-1-Cre, KPC), by pegylated recombinant PH20 hyaluronidase (PEGPH20) inhibits increases combination gemcitabine compared to monotherapy. this study, we explored the role synthesizing (HAS) enzymes...

Abstract Hyaluronan (hyaluronic acid, HA), a glycosaminoglycan found in tissue throughout the body, overaccumulates tumor microenvironment (TME) of many non-hematologic malignancies, including breast cancer. HA overaccumulation cancer patients correlates with progression and decreased survival (Tammi 2008). Pegylated recombinant human hyaluronidase PH20 (PEGPH20), an investigational therapeutic agent entering Phase 3 clinical development pancreatic cancer, enzymatically removes from TME. In...

Abstract Hyaluronan (also known as hyaluronic acid or HA) is a megadalton sized glycosaminoglycan present in the extracellular matrix. The abnormal accumulation of HA solid tumor microenvironment (TME) several human cancers, including pancreatic, breast, colon and prostate, has been well studied associated with poor prognosis. In certain breast cancer specimens HA-high status, found to be significantly stromal compartment rather than cells. To understand interaction between cells containing...

Abstract Hyaluronan (HA) accumulates in the tumor microenvironment (TME) of many solid tumors, including prostate, colon, breast, stomach, ovary, pancreas and lung, HA accumulation is associated with progression a negative clinical outcome. Accordingly, degrading enzyme pegylated recombinant human hyaluronidase PH20 (PEGPH20) was developed to allow systemic therapy enable treatment HA-high tumors. Preclinical studies have demonstrated that PEGPH20-mediated removal from HA-rich xenograft...

Abstract Hyaluronan (HA) accumulates in the extracellular matrix of many solid tumors, and is associated with poor prognosis pancreatic ductal adenocarcinoma. In non-clinical models, enzymatic degradation HA PEGylated recombinant human hyaluronidase PH20 (PEGPH20) has been shown to remodel tumor stroma, reduce interstitial fluid pressure, expand blood vessels, resulting enhanced delivery therapeutic imaging agents, such as monoclonal antibodies. 89Zr-DFO-HuMab-5B1 (MVT-2163) a targeted...

Abstract Hyaluronan (also known as hyaluronic acid or HA) is a nonsulfated glycosaminoglycan in the extracellular matrix. Elevated levels of HA tumor microenvironment have been associated with poor prognosis several human cancers, including pancreatic, breast, colon and prostate. In many cases breast cancer, found to be stromal compartment. To understand interaction between cells containing compartment, we engineered HA-high cell line by overexpressing HAS3 gene Balb/c 3T3 fibroblast cells....

Abstract Hyaluronan (HA) over-accumulation in the extracellular matrix (ECM) of many solid tumors is associated with tumor progression and poor prognosis (Tammi 2008). In preclinical animal models, enzymatic removal ECM HA pegylated recombinant human hyaluronidase PH20 (PEGPH20) remodeling stroma, reduction interstitial fluid pressure, expansion blood vessels facilitated delivery chemotherapy (Thompson 2010, Jacobetz 2012, Provenzano 2012). Additionally, epidermal growth factor receptor...

Abstract Introduction: Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that has been shown to accumulate at high levels in several cancers, including non-small cell lung cancer (NSCLC). The accumulation of HA NSCLC associated with a more aggressive phenotype and shortened overall survival. In prevalence analysis using tissue microarrays archival human specimens (N = 194) stained by affinity histochemistry, we demonstrated 55% adenocarcinomas, 74% squamous carcinomas 83% large...

Abstract Hyaluronan (HA), which accumulates in the tumor microenvironment of many solid tumors, is associated with progression and negative clinical outcomes. Preclinical studies have demonstrated that PEGPH20-mediated HA removal from HA-rich xenograft tumors mice decreases interstitial fluid pressure water content, resulting decompression vasculature, increased perfusion enhanced chemotherapeutic activity. Accordingly, degrading enzyme, pegylated recombinant human hyaluronidase PH20...

Abstract Accumulation of hyaluronan (HA) is correlated with poor prognosis in many human cancer including breast and pancreatic cancer. Hyaluronan synthase 2 (HAS2) one the three HA genes (HAS1-3) found mammals. Up-regulation HAS2 gene has been observed patients; expression correlates incidence metastasis lower rate overall patient survival (Okuda et al 2012). Interestingly, a recent study suggested that naked mole rat (nmr) enzyme may function differently than proteins from mice humans, its...

Abstract The tumor microenvironment is crucial for cancer cell survival and spreading. glycosaminoglycan hyaluronan (HA) accumulated in 50% of malignant breast tumors its accumulation correlates with poor patients. HA synthesized at the surface by synthase enzymes (HAS1-3) extruded to extracellular space where molecules can be attached via interactions receptors or HAS proteins. also interact binding proteins incorporated into surrounding ECM. However, origin exact functions are still...

Abstract Accumulation of Hyaluronan (HA), an important glycosaminoglycan the extracellular matrix (ECM), has been detected in about 25% human tumors, and 56% breast cancers1-2. HA is produced by malignant stromal cells acts to cross-link ECM proteins, contributing desmoplastic phenotype. Aberrant accumulation tumors associated with more aggressive malignancy1-2. We have observed that >50% epidermal growth factor receptor 2 (HER2) triple-positive a high (HA3+). Monoclonal antibodies...

Background/issues: Acute Ischemic stroke is a time sensitive disease. The only approved treatment t-PA. Prior studies have demonstrated faster Door-to-Needle (DTN) times for t-PA treated patients were associated with fewer complications and lower risk adjusted mortality. In conjunction to these findings the American Stroke Association has adopted in 2011 goal decrease door needle on all eligible patients. Georgia Professional Alliance (GA-SPA) continued encourage its members achieve...