Drug Repurposing Screening Identifies Tioconazole as an ATG4 Inhibitor that Suppresses Autophagy and Sensitizes Cancer Cells to Chemotherapy.

Tumor cells require proficient autophagy to meet high metabolic demands and resist chemotherapy, which suggests that reducing autophagic flux might be an attractive route for cancer therapy. However, this theory in clinical cancer research remains controversial due to the limited number of drugs that specifically inhibit autophagy-related (ATG) proteins. We screened FDA-approved drugs using a novel platform that integrates computational docking and simulations as well as biochemical and cellular reporter assays to identify potential drugs that inhibit autophagy-required cysteine proteases of the ATG4 family.

Blocking the interaction between S100A9 and RAGE V domain using CHAPS molecule: A novel route to drug development against cell proliferation.

Human S100A9 (Calgranulin B) is a Ca(2+)-binding protein, from the S100 family, that often presents as a homodimer in myeloid cells. It becomes an important mediator during inflammation once calcium binds to its EF-hand motifs. Human RAGE protein (receptor for advanced glycation end products) is one of the target-proteins.

ErbB3-dependent motility and intravasation in breast cancer metastasis.

A better understanding of how epidermal growth factor receptor family members (ErbBs) contribute to metastasis is important for evaluating ErbB-directed therapies. Activation of ErbB3/ErbB2 heterodimers can affect both proliferation and motility. We find that increasing ErbB3-dependent signaling in orthotopic injection models of breast cancer can enhance intravasation and lung metastasis with no effect on primary tumor growth or microvessel density.

Epidermal growth factor receptor overexpression results in increased tumor cell motility in vivo coordinately with enhanced intravasation and metastasis.

Although overexpression of the epidermal growth factor receptor (EGFR; ErbB1) has been correlated with poor prognosis in breast and other cancers, clinical trials of ErbB1 inhibitors have shown limited efficacy in inhibiting tumor proliferation. To evaluate other possible roles of ErbB1 in tumor malignancy besides proliferation, we have developed a series of tools for analysis of intravasation. Overexpression of ErbB1 in MTLn3 mammary adenocarcinoma cells results in increased intravasation and lung metastasis from tumors formed by injection of cells in the mammary fat pad.

Pulmonary atelectasis: a frequent alternative diagnosis in patients undergoing CT-PA for suspected pulmonary embolism.

The purpose of the study was to evaluate the prevalence of atelectasis as an alternative diagnosis in patients who underwent computed tomographic pulmonary angiography (CT-PA) for suspected pulmonary embolism (PE), and to contrast the pathophysiology of pulmonary atelectasis and PE, both of which are associated with dyspnea and hypoxemia. We retrospectively identified 144 consecutive emergency department patients (n=49) and inpatients (n=95) admitted between July 2001 and June 2002 who were evaluated with CT-PA for suspected PE. There were 98 women and 46 men with a mean age of 58 years (range 27-95 years).

Tuberculous meningitis in infancy.

The lack of specific symptoms and signs in patients with tuberculous meningitis makes early diagnosis difficult. To our knowledge, there has been no report in the literature focusing on tuberculous meningitis patients younger than 1 year of age. In this report, we reviewed the clinical features and laboratory findings of seven infants with tuberculous meningitis encountered during a 15-year period.