Efficient Targeting of Head and Neck Squamous Cell Carcinoma by Systemic Administration of a Dual uPA and MMP-Activated Engineered Anthrax Toxin

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Although considerable progress has been made in elucidating the etiology of the disease, the prognosis for individuals diagnosed with HNSCC remains poor, underscoring the need for development of additional treatment modalities. HNSCC is characterized by the upregulation of a large number of proteolytic enzymes, including urokinase plasminogen activator (uPA) and an assortment of matrix metalloproteinases (MMPs) that may be expressed by tumor cells, by tumor-supporting stromal cells or by both. Here we explored the use of an intercomplementing anthrax toxin that requires combined cell surface uPA and MMP activities for cellular intoxication and specifically targets the ERK/MAPK pathway for the treatment of HNSCC. We found that this toxin displayed strong systemic anti-tumor activity towards a variety of xenografted human HNSCC cell lines by inducing apoptotic and necrotic tumor cell death, and by impairing tumor cell proliferation and angiogenesis. Interestingly, the human HNSCC cell lines were insensitive to the intercomplementing toxin when cultured ex vivo, suggesting that either the toxin targets the tumor-supporting stromal cell compartment or that the tumor cell requirement for ERK/MAPK signaling differs in vivo and ex vivo. This intercomplementing toxin warrants further investigation as an anti-HNSCC agent

Widely tunable bottom-emitting vertical-cavity SOAs

We present bottom-emitting tunable vertical-cavity semiconductor optical amplifiers (VCSOAs) with an effective wavelength tuning range of > 20 nm. These devices utilize a high reflectivity micromechanically tunable Bragg mirror as the back reflector. Compared with our first generation tunable VCSOAs, the bottom-emitting devices exhibit a two-fold increase in the effective tuning range as well as a five-fold reduction in the required tuning voltage

Stable polarization operation of 1.3-mu m wavelength vertical-cavity surface-emitting laser (VCSEL) fabricated by orientation-mismatched wafer bonding

We present stable polarization of a long-wavelength vertical-cavity surface-emitting laser (LW VCSEL). The polarization control was achieved through growing its active region on a (113)B InP substrate, which was integrated to (001) GaAs-based distributed Bragg reflectors by a wafer-bonding technique. Theoretical investigation showed that to achieve high polarization stability, a large dichroism such as an anisotropic gain is needed. It was also shown that the (113)B and other planes of the (11n) family have asymmetry, which results in asymmetric stress and anisotropic optical gain in a strained multiquantum well. An index-guiding mesa structure was fabricated in an asymmetric shape. The index guiding either enhanced or distracted the polarization stability originating from gain anisotropy, depending on its orientation of the asymmetry, as was confirmed by a statistical summary. Using a VCSEL with an appropriate index-guiding structure, we performed 1-Gb/s modulation and confirmed single polarization under large-signal modulation

Complaint management and the role of the chief executive

Complaints, Service recovery, Complaint management, Chief executive, Financial services,