Design, synthesis, and biological evaluation of benzo[b]thiophene 1,1-dioxide derivatives as potent STAT3 inhibitors.

As a member of the signal transducer and activator of transcription (STAT) family, STAT3 plays a critical role in several biological pathways such as cell proliferation, migration, survival, and differentiation. Due to abnormal continuous activation in tumors, inhibition of STAT3 has emerged as an attractive approach for the treatment of various cancer cells. Herein, we report a series of novel STAT3 inhibitors based on benzo[b]thiophene 1,1-dioxide scaffold and evaluated their anticancer potency. Among them, compound 8b exhibited the best activity against cancer cells. Compound 8b induced apoptosis and blocked the cell cycle. Meanwhile, 8b reduced intracellular ROS content and caused the loss of mitochondrial membrane potential. Further research revealed that 8b significantly blocked STAT3 phosphorylation and STAT3-dependent dual-luciferase reporter gene experiments showed that compound 8b has a marked inhibition of STAT3-mediated Firefly luciferase activity. Molecular modeling studies revealed compound 8b occupied the pocket well with the SH2 domain in a favorable conformation.

Mycobacterium abscessus granulomatous prostatitis.

Infectious granulomatous prostatitis is uncommon, and most cases of granulomatous prostatitis are classified as nonspecific granulomatous prostatitis. From 2007 to 2009, 5 patients experienced poor wound healing after radical prostatectomy for prostate cancer at a specialist cancer center. Mycobacterium abscessus was cultured from the debridement specimens, and acid-fast-positive bacilli were identified histologically within the prostates. All 180 radical prostatectomy specimens from May 2007 to June 2009 were reviewed, and 7 additional cases with morphologies suspicious of M. abscessus granulomatous prostatitis (MAGP) were identified. The characteristic morphologic feature of MAGP was suppurative necrotizing granulomatous inflammation extensively (10% to 80% of the gland; mean, 39%) involving the prostate. The centers of MAGP were large areas of neutrophilic abscess and necrotic debris, which were surrounded by histiocytes, lymphocytes, plasma cells, scattered multinucleated giant cells, and eosinophils. In the adjacent areas, there was a lobular extension of mixed inflammatory infiltrates into dilated and ruptured ducts. Involvement of extraprostatic soft tissue and seminal vesicles/vas deferens was found in 9 and 4 cases, respectively. Acid-fast-positive bacilli were identified in 5 radical prostatectomies. Eleven patients had fresh tissue specimens stored at -150°C, and M. abscessus was cultured from 8 prostates. Random amplified polymorphic DNA-polymerase chain reaction showed the same clone for all isolates. After prostatectomy, 8 patients experienced prolonged wound healing, with urethrorectal fistula formation in 1 patient and a pelvic abscess in another. It is critical for pathologists to recognize MAGP and to distinguish it from the more common nonspecific granulomatous prostatitis and other granulomatous lesions within the prostate.

Improving diagnosis of central venous catheter-related bloodstream infection by using differential time to positivity as a hospital-wide approach at a cancer hospital.

OBJECTIVES: Considering the difficulty of diagnosing catheter-related bloodstream infection (CRBSI), Koo Foundation Sun Yat-Sen Cancer Center uses differential time to positivity (DTP) as a hospital-wide approach to improve the diagnosis of CRBSI in febrile patients with indwelling central venous catheters (CVCs). This study describes the result of a hospital-wide use of DTP in a real practice setting. METHODS: During January 2003-August 2007, 142 positive paired blood cultures from 125 patients without infection focus other than CVC were included. These were evaluated by DTP and semi-quantitative catheter culture (SQCC) to confirm the diagnosis of CRBSI, and were further divided into two groups: confirmed (either by DTP or SQCC) and non-confirmed CRBSI (neither DTP nor SQCC positive). RESULTS: Fifty-nine point two percent (84/142) of episodes were confirmed as CRBSI, of which DTP was positive in 83.3% (n=70). Non-confirmed CRBSI was associated with hematologic malignancy, neutropenia status, previous antibiotics exposure and a lower CVC removal rate. CONCLUSIONS: A hospital-wide approach of DTP was practical and feasible in improving the diagnosis of CRBSI in a real practice setting.