Mesenchymal Stem Cells and Co-stimulation Blockade Enhance Bone Marrow Engraftment and Induce Immunological Tolerance.

BACKGROUND: Organ transplantation currently requires long-term immunosuppression. This is associated with multiple complications including infection, malignancy and other toxicities. Immunologic tolerance is considered the optimal solution to these limitations. OBJECTIVE: To develop a simple and non-toxic regimen to induce mixed chimerism and tolerance using mesenchymal stem cell (MSC) in a murine model. METHODS: Wild type C57BL6 (H2D(k)) and Bal/C (H2D(d)) mice were used as donors and recipients, respectively. We studied to achieve tolerance to skin grafts (SG) through mixed chimerism (MC) by simultaneous skin graft and non-myeloablative donor bone marrow transplantation (DBMT) +/- MSC. All recipients received rapamycin and CTLA-4 Ig without radiation. RESULTS: DBMT+MSC combined with co-stimulation blockage and rapamycin led to stable mixed chimerism, expansion of Tregs population and donor-specific skin graft tolerance. The flow cytometry analysis revealed that recipient mice developed 15%-85% chimerism. The skin allografts survived for a long time. Elimination of MSC failed to induce mixed chimerism and tolerance. CONCLUSION: Our results demonstrate that donor-specific immune tolerance can be effectively induced by non-myeloablative DBMT-MSC combination without any additional cytoreductive treatment. This approach provides a promising and non-toxic allograft tolerance strategy.

Carnoy's in Aggressive Lesions: Our Experience.

Carnoy's solution is used in the treatment of various aggressive cysts and tumors in the maxillofacial region as a chemical cauterizing agent. Its use has been extensively studied in case of odontogenic keratocysts. It is used in the management of unicystic ameloblastomas and ossifying fibromas. In our institution from 2006 to 2010 we have treated 14 cases of maxillofacial lesions using carnoy's solution. Among these cases 7 were of odontogenic keratocyst, 4 cases were of amelobalstoma and one case was of juvenile ossifying fibroma. So here we share our experience of treating these lesions with the carnoy's solution.

A review of odontogenic keratocyst with a report of unusual occurrence in the maxilla.

Odontogenic keratocysts (OKC) are keratinizing epithelium-lined cycts of the jaws with well-defined histologic criteria and possessing one clinical feature warranting their recognition and separation as a distinctive entity, due to their exceedingly high recurrence rate. This report describes a case of OKC which occurred in the anterior maxilla in a 12 year old female child, with its treatment. These lesions are normally seen in the mandible, and are rare in the maxilla.

Docetaxel, estramustine, and short-term androgen withdrawal for patients with biochemical failure after definitive local therapy for prostate cancer.

Over the past 10 years, men with prostate cancer have received earlier diagnoses and are undergoing prostatectomy and/or radiation therapy with curative intent; however, many men have increasing prostate-specific antigen (PSA) levels without evidence of local progression or metastatic disease during the first 2 years after definitive local therapy. Optimal treatment of men with PSA-only recurrent prostate cancer has not been established. This ongoing phase II trial is evaluating docetaxel (70 mg/m(2) administered intravenously over 1 hour on day 2 every 21 days for four cycles) and estramustine (10 mg/kg/d orally on days 1 to 5 every 21 days for four cycles) followed by bicalutamide and goserelin acetate in men with increasing PSA levels after prostatectomy and/or radiation therapy. Patients received pretreatment with dexamethasone, and after the third patient enrolled, patients received warfarin for prophylaxis against thrombosis. Colony-stimulating factor support was allowed. In preliminary results, 11 of 15 patients completed protocol chemotherapy; 12 of 15 patients achieved complete response (ie, normalization of PSA) after four cycles of chemotherapy. In addition, testosterone levels were reduced to the castrate range in all patients after chemotherapy. The regimen was generally well tolerated, and toxicities were mostly hematologic, with grade (3/4) neutropenia reported in approximately half of patients. Preliminary results of this phase II trial are encouraging, and enrollment is ongoing.

Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist.

The role of androgen receptor (AR) mutations in androgen-independent prostate cancer (PCa) was determined by examining AR transcripts and genes from a large series of bone marrow metastases. Mutations were found in 5 of 16 patients who received combined androgen blockade with the AR antagonist flutamide, and these mutant ARs were strongly stimulated by flutamide. In contrast, the single mutant AR found among 17 patients treated with androgen ablation monotherapy was not flutamide stimulated. Patients with flutamide-stimulated AR mutations responded to subsequent treatment with bicalutamide, an AR antagonist that blocks the mutant ARs. These findings demonstrate that AR mutations occur in response to strong selective pressure from flutamide treatment.