Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multicellular resistance, a subtype of therapeutic resistance manifested in cancer cells grown as three-dimensional multicellular masses, such as spheroids in vitro and solid tumors in vivo, occurs with respect to a variety of anticancer treatment strategies including chemotherapy, ionizing radiation, and even host-mediated antibody-dependent cellular cytotoxicity. Previous studies from our laboratory have shown that multicellular resistance to chemotherapy demonstrated by aggregates of EMT-6 murine mammary carcinoma cells can be overcome by using hyaluronidase to disrupt intercellular adhesive interactions and associated patterns of protein expression. In this proof of principle study, we explored the concept of antiadhesive chemosensitization in the context of human cancer cells by using a monoclonal antibody to disrupt E-cadherin-mediated cell-cell interactions in multicellular spheroids of HT29 human colorectal adenocarcinoma. In so doing, we found that disruption of E-cadherin-mediated adhesion sensitizes multicellular spheroids of HT29 in vitro to treatment with 5-fluorouracil, paclitaxel, vinblastine, and etoposide but not cisplatin. Furthermore, we have found that antibody-mediated blockage of E-cadherin function leads to decreased expression and activity of protein kinase C alpha and beta1, both of which have previously been implicated in chemoresistance exhibited by HT29 cells; however, we have found that the chemosensitization effects of the anti-E-cadherin antibody are independent of its influence on protein kinase C beta1.
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PMID:Antiadhesive antibodies targeting E-cadherin sensitize multicellular tumor spheroids to chemotherapy in vitro. 1498 55

Preventing mucosal transmission of HIV is critical to halting the HIV epidemic. Novel approaches to preventing mucosal transmission are needed. Hyaluronic acid (HA) is a major extracellular component of mucosa and the primary ligand for the cell surface receptor CD44. CD44 enhances HIV infection of CD4(+) T cells, but the role of HA in this process is not clear. To study this, virions were generated with CD44 (HIVCD44) or without CD44 (HIVmock). Exogenous HA reduced HIV infection of unstimulated CD4(+) T cells in a CD44-dependent manner. Conversely, hyaluronidase-mediated reduction of endogenous HA on the cell surface enhanced HIV binding to and infection of unstimulated CD4(+) T cells. Exogenous HA treatment reduced activation of protein kinase C alpha via CD44 on CD4(+) T cells during infection with HIVCD44. These results reveal new roles for HA during the interaction of HIV with CD4(+) T cells that may be relevant to mucosal HIV transmission and could be exploitable as a future strategy to prevent HIV infection.
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PMID:Exogenous and endogenous hyaluronic acid reduces HIV infection of CD4(+) T cells. 2515 64