Brock Fisher Named Distinguished College Administrator

Bergen Community College Vice President of Academic Affairs Brock Fisher was recognized with this prestigious honor from Phi Theta Kappa (PTK), the two-year college honor society. Bergen PTK Alpha Epsilon Phi members nominated Brock as they recognized his contributions to students and the higher education community.

Hepatocyte Growth Factor (HGF)

Hepatocyte growth factor (HGF) is an autocrine mitogen that promotes hepatocyte proliferation by activating specific cytokines such as VEGF. Furthermore, HGF acts as an anti-fibrotic factor and critical regulator of cell turnover; HGF concentrations tend to be highest in tissues under regeneration or stress, such as livers; it serves as a Met receptor ligand and provides essential signaling throughout various organs.

Numerous studies have demonstrated the HGF/c-Met signaling pathway is essential in protecting and regenerating damaged tissues and cells. Conditional c-Met knockout mice show reduced proliferative response following hepatocellular injury, suggesting HGF/c-Met signaling is required for normal hepatocyte functions and liver regeneration; moreover, regeneration in HGF-treated hepatocellular carcinoma patients is enhanced.

HGF is a natural hormone with multiple therapeutic effects, including combatting insulin resistance and diabetes. It promotes glucose metabolizability in insulin-sensitive cells, reduces plasma triglyceride levels and plasma insulin levels, improves whole-body glucose tolerance in obese mice, and muscle-specific expression of HGF, producing similar results – decreasing muscle insulin resistance while increasing tolerance in mice.

HGF protects animals with severe, acute hepatitis from lethal liver cell destruction by blocking Fas-mediated hepatocyte apoptosis; the c-Met tyrosine kinase mediates this action. Furthermore, HGF accelerates DNA synthesis rates in hepatectomized livers via its effect on c-Met ligand receptors – another benefit mediated by HGF.

HGF is increasingly seen as effective at treating various organ diseases due to its regenerative, anti-apoptotic, and anti-fibrotic properties. Mainly, it helps prevent sepsis in acute renal failure patients, boosts hepatocyte regrowth and recovery, lessens lung fibrosis and myocardial infarction severity, and promotes neuronal survival in the brain. Furthermore, angiogenesis stimulation encourages neuronal survival. HGF also helps combat inflammation disorders by suppressing T cells and encouraging angiogenesis-associated endothelial cells to grow into angiogenesis-associated endothelial cells. Additionally, TGF-b may increase extracellular matrix-degrading enzyme levels, reverse tissue fibrosis in hepatic cirrhosis, kidney fibrosis, scleroderma, and cardiac fibrosis, and suppress TGF-b-induced fibronectin accumulation and cell death.

c-Met Receptor

c-Met is an intracellular tyrosine kinase receptor that mediates the activation of multiple downstream signaling pathways when exposed to the Hepatocyte Growth Factor (HGF). C-Met plays an integral part in cell-cell interactions, migration, invasion, and angiogenesis; it is an essential regulator in tumor progression and metastasis – it has even become a target therapy against cancer! Various inhibitors have been designed to interfere with HGF binding to inhibit its signaling cascade.

The Hepatocyte Growth Factor is encoded by the human hepatocyte growth factor gene, which contains 18 exons and 17 introns. The mature protein is a disulfide-linked heterodimer composed of an extracellular A chain linked with four transmembrane B chains and six domains on each A chain, including hairpin and four Kringle domains; its B chain counterpart features a serine protease analog domain lacking catalytic activity as well as the c-Met binding site.

NK1 forms a head-to-tail dimer that binds two c-Met molecules symmetrically (Fig. 6a,b). This complex interacts with the SEMA, PSI, and IPT1 domains of c-Met; its IPT2 domain can be reached from both sides of this complex; two molecules are located near one another, making optimal receptor activation.

The SEMA and PSI domains of c-MET combine to form a long loop (Fig. 2e), which is disordered in its crystal structure of the c-Met/InlB complex24 but exhibits well-defined density in our cryo-EM map of c-MET/HGF holo-complex (Fig. 2g and Supplementary Fig 7)24-25. Residues within this loop, including Glu302, Lys303, and Arg373, form numerous salt bridges with charged residues in Hepatocyte growth factor, which activates this loop via its tyrosine kinase domain activation25

As well as increasing tumor cell migration and angiogenesis, c-Met can stimulate cellular apoptosis by activating the phosphatidylinositol 3-kinase pathway. Cytoskeletal protein paxillin activation by c-Met causes cells to adhere together; knowledge of its biology and any dysregulated pathways caused by its binding with HGF will enable researchers to create inhibitors to block its binding with HGF and thus block activation of these pathways.

Cell-Matrix Adhesion

Cells interact with their environment in ways that play a fundamental role in biological functions such as growth and development, tissue remodeling, wound healing, and immune response. One form of such interaction is cell adhesion mediated by integrin receptors and ECM ligands; its regulation by complex signaling pathways modulating cell behavior further complicates this picture.

Cell adhesion depends on developing cell surface structures that closely associate with their matrix environment, known as cell-matrix adhesions, that serve as traction points and enable cells to alter their surrounding matrix environment. Their formation requires striking a balance between binding between integrins and their ligands and tension force exerted by cytoskeletal elements.

Though forming cell-matrix adhesions is essential in many physiological processes, a complete understanding of their formation and integration remains elusive. However, matrix components like fibronectin and laminin and non-matrix proteins, such as growth factors, are known to regulate cell adhesion. When binding with these molecules through integrin receptors, binders can trigger adhesion formation, which differs depending on the biological process or cell type involved, resulting in the assembly of numerous adhesion structures whose structure and functions depend on the natural process or cell type involved.

Fibroblasts adhering to 2D fibronectin mats will form adhesion structures rich in the integrin subunit a5b1, while those adhering to 3D fibronectin mats will form more diffuse structures that contain less of this subunit, with both effects correlating with downstream pathways that regulate matrix protease activity and cell migration.

Attracting ECM molecules requires specific adhesion sites called focal adhesions (FAs). FAs are large complexes of cytoskeletal and signaling proteins that mediate adhesion to the matrix while serving as traction centers for cell movement, believed to integrate multiple physical and biochemical matrix signals for coherent response – crucial for embryonic development, tissue homeostasis and pathological conditions such as cancer, inflammation, and hemophilia. Mutations to components regulating cell-matrix adhesion can result in serious pathologies such as cancer, rash, or hemophilia.

Bone Metastasis

Bone metastases are one of the most prevalent forms of cancer spreading to bones, as cancer cells from other areas reach them and travel. Once there, cancerous cells may cause irreparable damage by breaking down tissue in a room and creating osteolytic lesions within bones, increasing pain and your chances of breaking one.

Cancer cells that metastasize to bone often don’t show symptoms, and many don’t realize they have it until a fracture or other issues develop. Depending on where and the size of the tumor, symptoms of bone metastases could include pain, changes in sensation, or weakness; bone metastases could even lead to spinal cord compression, causing pressure on nerves that travel from the brain to the rest of the body.

Diagnosing bone metastases requires an imaging evaluation and a thorough medical history review, including any prior cancer diagnosis. X-rays and CT scans help identify where tumors lie in the bones, while magnetic resonance imaging (MRI) uses large magnets and radiofrequency waves to produce detailed images of bones and other structures without using radiation as part of its imaging process.

Blood tests can assist in diagnosing bone metastasis by revealing increased calcium levels in the blood, also known as hypercalcemia. Other indicators of bone metastasis may include anemia, low red blood cell count (anemia), low platelet counts (thrombocytopenia and pancytopenia), and elevated bone turnover markers that indicate bone resorption.

Treatment options depend on the symptoms and extent of bone metastasis. Chemotherapy, targeted therapy, and radiation can reduce the chances of cancer metastasizing to bones. Bisphosphonates provide additional bone protection by decreasing calcium reabsorption into the bloodstream.

Though metastatic bone cancer cannot be cured, early diagnosis and treatment can reduce complications such as spinal cord compression, skeletal-related events (SREs), and fractures. A multidisciplinary team of physicians can ensure patients with metastasis live the highest possible quality of life.