Structural and diffusion weighted MRI demonstrates responses to ibrutinib in a mouse model of follicular helper (Tfh) T-cell lymphoma.

Recent analyses of the genetics of peripheral T-cell lymphoma (PTCL) have shown that a large proportion of cases are derived from normal follicular helper (Tfh) T-cells. The sanroque mouse strain bears a mutation that increases Tfh cell number and heterozygous animals (Roquinsan/+) develop lymphomas similar to human Tfh lymphoma. Here we demonstrate the usefulness of Roquinsan/+ animals as a pre-clinical model of Tfh lymphoma. Long latency of development and incomplete penetrance in this strain suggests the lymphomas are genetically diverse. We carried out preliminary genetic characterisation by whole exome sequencing and detected tumor specific mutations in Hsp90ab1, Ccnb3 and RhoA. Interleukin-2-inducible kinase (ITK) is expressed in Tfh lymphoma and is a potential therapeutic agent. A preclinical study of ibrutinib, a small molecule inhibitor of mouse and human ITK, in established lymphoma was carried out and showed lymphoma regression in 8/12 (67%) mice. Using T2-weighted MRI to assess lymph node volume and diffusion weighted MRI scanning as a measure of function, we showed that treatment increased mean apparent diffusion coefficient (ADC) suggesting cell death, and that change in ADC following treatment correlated with change in lymphoma volume. We suggest that heterozygous sanroque mice are a useful model of Tfh cell derived lymphomas in an immunocompetent animal.

Total inhibition of (1)O2-induced oxidative damage to guanine bases of DNA/RNA by turmeric extracts.

The guanine base of nucleic acids is known to be very reactive towards degradation by (1)O2-induced oxidative stress. Oxidative reactions of DNA are linked to many human diseases including cancer. Among the various forms of reactive O2 species (OH, (1)O2 or O2(-)), the oxidative stress caused by (1)O2 is of particular physiologic importance because of its selectively long life in aqueous medium and its ability to diffuse through a cell membrane. In this study we investigated the degradation of a model compound guanosine (Guo) by (1)O2, which was generated by riboflavin-induced photosensitization and by molybdate ion catalyzed disproportionation of H2O2. We observed the remarkable ability of an aqueous and alcoholic extracts of Turmeric (Curcuma longa) as an extraordinary scavenger of (1)O2 to completely inhibit the degradation of Guo. The alcoholic extracts were more effective in their antioxidant activity than the corresponding water extract. This naturally occurring antioxidant offers a most economical supplement to protect biologically significant molecules from the oxidative stress induced by (1)O2.

Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance.

CONTEXT: We wanted to investigate vitamin D in low-risk prostate cancer. OBJECTIVES: The objective of the study was to determine whether vitamin D(3) supplementation at 4000 IU/d for 1 yr is safe and would result in a decrease in serum levels of prostate-specific antigen (PSA) or in the rate of progression. DESIGN: In this open-label clinical trial (Investigational New Drug 77,839), subjects were followed up until repeat biopsy. SETTING: All subjects were enrolled through the Medical University of South Carolina and the Ralph H. Johnson Veterans Affairs Medical Center, both in Charleston, SC. PATIENTS AND OTHER PARTICIPANTS: All subjects had a diagnosis of low-risk prostate cancer. Fifty-two subjects were enrolled in the study, 48 completed 1 yr of supplementation, and 44 could be analyzed for both safety and efficacy objectives. INTERVENTION: The intervention included vitamin D(3) soft gels (4000 IU). MAIN OUTCOME MEASURES: Adverse events were monitored throughout the study. PSA serum levels were measured at entry and every 2 months for 1 yr. Biopsy procedures were performed before enrollment (for eligibility) and after 1 yr of supplementation. RESULTS: No adverse events associated with vitamin D(3) supplementation were observed. No significant changes in PSA levels were observed. However, 24 of 44 subjects (55%) showed a decrease in the number of positive cores or decrease in Gleason score; five subjects (11%) showed no change; 15 subjects (34%) showed an increase in the number of positive cores or Gleason score. CONCLUSION: Patients with low-risk prostate cancer under active surveillance may benefit from vitamin D(3) supplementation at 4000 IU/d.

Community-acquired methicillin-resistant Staphylococcus aureus prostatic abscess.

We present a 43-year-old man with a history of intravenous drug abuse who presented to the emergency department with a 5-week history of lower urinary tract symptoms. On digital rectal examination, a firm prostate with exquisite tenderness was noted. Computed tomography scan of the pelvis with contrast demonstrated a 4.4 by 2.7-cm prostatic abscess in the right lobe. Suppurative fluid was expressed from the right prostatic lobe during transurethral resection of the prostate. Cultures of blood and suppurative prostatic fluid grew methicillin-resistant Staphylococcus aureus.