Metadherin Regulates Inflammatory Breast Cancer Invasion and Metastasis.

Inflammatory breast cancer (IBC) is one of the most lethal subtypes of breast cancer (BC), accounting for approximately 1-5% of all cases of BC. Challenges in IBC include accurate and early diagnosis and the development of effective targeted therapies. Our previous studies identified the overexpression of metadherin (MTDH) in the plasma membrane of IBC cells, further confirmed in patient tissues. MTDH has been found to play a role in signaling pathways related to cancer. However, its mechanism of action in the progression of IBC remains unknown. To evaluate the function of MTDH, SUM-149 and SUM-190 IBC cells were edited with CRISPR/Cas9 vectors for in vitro characterization studies and used in mouse IBC xenografts. Our results demonstrate that the absence of MTDH significantly reduces IBC cell migration, proliferation, tumor spheroid formation, and the expression of NF-κB and STAT3 signaling molecules, which are crucial oncogenic pathways in IBC. Furthermore, IBC xenografts showed significant differences in tumor growth patterns, and lung tissue revealed epithelial-like cells in 43% of wild-type (WT) compared to 29% of CRISPR xenografts. Our study emphasizes the role of MTDH as a potential therapeutic target for the progression of IBC.

Cost analysis of treatment strategies for the control of HSV-2 infection in the U.S.: A mathematical modeling-based case study.

Infection of Herpes Simplex Virus type 2 (HSV-2) is a lifelong sexually transmitted disease. According to the Center for Disease Control and Prevention (CDC), 11.9% of the United States (U.S.) population was infected with HSV-2 in 2015-2016. The HSV-2 pathogen establishes latent infections in neural cells and can reactivate causing lesions later in life, a strategy that increases pathogenicity and allows the virus to evade the immune system. HSV-2 infections are currently treated by Acyclovir only in the non-constitutional stage, marked by genital skin lesions and ulcers. However, patients in the constitutional stage expressing mild and common (with other diseases) symptoms, such as fever, itching and painful urination, remain difficult to detect and are untreated. In this study, we develop and analyze a mathematical model to study the transmission and control of HSV-2 among the U.S. population between the ages of 15-49 when there are options to treat individuals in different stages of their pathogenicity. In particular, the goals of this work are to study the effect on HSV-2 transmission dynamics and to evaluate and compare the cost-effectiveness of treating HSV-2 infections in both constitutional and non-constitutional stages (new strategy) against the current conventional treatment protocol for treating patients in the non-constitutional stage (current strategy). Our results distinguish model parameter regimes where each of the two treatment strategies can optimize the available resources and consequently gives the long-term reduced cost associated with each treatment and incidence. Moreover, we estimated that the public health cost of HSV-2 with the proposed most cost-effective treatment strategy would increase by approximately 1.63% in 4 years of implementation. However, in the same duration, early treatment via the new strategy will reduce HSV-2 incidence by 42.76% yearly and the reproduction number will decrease to 0.84 from its current estimate of 2.5. Thus, the proposed new strategy will be significantly cost-effective in controlling the transmission of HSV-2 if the strategy is properly implemented.