Macrophage migration inhibitory factor expression in ovarian cancer.

OBJECTIVE: We evaluated the hypothesis that ovarian cancer patients have significantly higher levels of serum macrophage migration inhibitory factor (MIF). STUDY DESIGN: MIF levels were determined by enzyme-linked immunosorbent assay (ELISA) in epithelial ovarian cancer cell lines and immortalized normal ovarian surface epithelial cells and in serum of ovarian cancer patients (n = 54) and age-matched healthy women (n = 60). To determine the impact of Toll-like receptor-4 ligation on MIF levels, cells were treated for 48 hours with lipopolysaccharide. RESULTS: Cancer cells, but not normal cells, secrete significant amounts of MIF. This correlates in vivo, where serum MIF levels are significantly higher in ovarian cancer patients. Treatment of cancer cells with lipopolysaccharide induced a significant increase in MIF secretion. CONCLUSION: MIF may be relevant in the process of ovarian cancer formation and progression. The events leading to the induction of MIF expression and its contribution to ovarian cancer progression may open new venues for targeted therapy.

Asymptomatic free-floating vitreous cyst masquerading as cysticercosis.

A male patient aged 37 years, referred with the diagnosis of right eye intravitreal cysticercosis, was diagnosed as asymptomatic free-floating vitreous cyst after thorough evaluation. The patient was kept under observation, since baseline visual acuity was unaffected. No change was noted over the period of 6 months.

Institutional experience using interstitial brachytherapy for the treatment of primary and recurrent pelvic malignancies.

PURPOSE: The study assessed the outcomes of patients at a single institution with locally advanced primary and recurrent pelvic malignancies treated with interstitial high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy (BT), using a modified Syed-Neblett template. MATERIAL AND METHODS: Between 1996 and 2010, 60 patients with primary or recurrent pelvic malignancies were treated with interstitial BT. Thirty three patients had primary malignancies with 6.1% being stage I, 33.3% stage II, 45.5% stage III, and 15.2% stage IV; the remaining 27 patients were recurrent malignancies. Fifty four patients received external beam radiotherapy (EBRT) as part of their treatment course. The median EBRT, BT, and EBRT + BT doses were 45 Gy, 20 Gy, and 65 Gy, respectively. Thirty eight patients received concurrent chemotherapy with EBRT. Complete response (CR) was defined by absence of clinical and radiographic disease on first follow-up. Toxicity was graded as per Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The median follow-up was 37 months (4-234 months) and initial CR was achieved in 91%. For primary cancers at diagnosis, 5-year local control (LC), 5-year progression-free survival (PFS), 5-year overall survival (OS) were 65%, 64%, and 42% respectively. For recurrent cancers at diagnosis, 5-year LC, 5-year PFS, and 5-year OS were 80%, 51%, and 37%, respectively. There was a significant difference in both OS and PFS among different tumor sites (p < 0.05), with vaginal cancers having the best 5-year OS (55%) and PFS (84%). There was a total of 1 acute toxicity ≥ grade 3, 6 late grade 3 toxicities, and late grade 4 toxicity. CONCLUSIONS: Our series suggests that interstitial BT using a modified Syed-Neblett template is a safe and effective treatment for primary or recurrent pelvic malignancies. This technique allowed effective LC and 97% of patients had preservation of both bladder and rectal function.

The effect of surface charge on in vivo biodistribution of PEG-oligocholic acid based micellar nanoparticles.

To systematically elucidate the effect of surface charge on the cellular uptake and in vivo fate of PEG-oligocholic acid based micellar nanoparticles (NPs), the distal PEG termini of monomeric PEG-oligocholic acid dendrimers (telodendrimers) are each derivatized with different number (n = 0, 1, 3 and 6) of anionic aspartic acids (negative charge) or cationic lysines (positive charge). Under aqueous condition, these telodendrimers self-assemble to form a series of micellar NPs with various surface charges, but with similar particle sizes. NPs with high surface charge, either positive or negative, were taken up more efficiently by RAW 264.7 murine macrophages after opsonization in fresh mouse serum. Mechanistic studies of cellular uptake of NPs indicated that several distinct endocytic pathways (e.g., clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis) were involved in the cellular uptake process. After their cellular uptake, the majority of NPs were found to localize in the lysosome. Positively charged NPs exhibited dose-dependent hemolytic activities and cytotoxicities against RAW 264.7 cells proportional to the positive surface charge densities; whereas negatively charged NPs did not show obvious hemolytic and cytotoxic properties. In vivo biodistribution studies demonstrated that undesirable liver uptake was very high for highly positively or negatively charged NPs, which is likely due to active phagocytosis by macrophages (Kupffer cells) in the liver. In contrast, liver uptake was very low but tumor uptake was very high when the surface charge of NPs was slightly negative. Based on these studies, we can conclude that slightly negative charge may be introduced to the NPs surface to reduce the undesirable clearance by the reticuloendothelial system (RES) such as liver, improve the blood compatibility, thus deliver the anti-cancer drugs more efficiently to the tumor sites.

Inherited predisposition to gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract and are a relatively recently identified category of mesenchymal tumors. Germline mutations in a number of different genes predispose to GIST. This article discusses familial GIST syndrome, Carney triad, Carney-Stratakis syndrome, and neurofibromatosis type 1, and addresses the recognition of an inherited predisposition in GIST patients.

Ethical and legal implications of cancer genetic testing: do physicians have a duty to warn patients' relatives about possible genetic risks?

This vignette raises questions about the extent of physicians' obligations to warn relatives of a patient about a hereditary cancer risk.