We explored the effectiveness of ejaculatory hood sparing technique to Holmium laser enucleation of the prostate (HoLEP) for ejaculation preservation. From June 2010 to July 2011, 52 sexually active patients with sufficient ejaculate underwent HoLEP. Twenty-six patients received the ejaulatory hood sparing technique during HoLEP (EH-HoLEP group). The other 26 patients underwent conventional HoLEP (conventional-HoLEP group). In the EH-HoLEP group, paracollicular and supracollicular tissue >1 cm proximal to the verumontanum was preserved. The mean follow-up period was 9.7 months (range 3-12). There was no significant difference in patient characteristics and perioperative parameters, including age, prostate volume, International Index of Erectile Function score, operation time, weight of the enucleated tissue and the amount of laser energy. Semen was unchanged, decreased or vanished in 4 (15.4%), 8 (30.8%) and 17 (53.8%) EH-HoLEP patients, respectively. In the conventional-HoLEP group, semen was unchanged, decreased or vanished in 0 (0.0%%), 7 (26.9%) and 19 (73.1%) patients, respectively. Overall success rate of ejaculation preservation was 46.2% in the EH-HoLEP group and 26.9% in the conventional-HoLEP group (P = 0.249). Application of an ejaculatory hood sparing technique to HoLEP could not improve the success rate for ejaculation preservation. This was likely due to the surgical characteristics of HoLEP, which enable complete removal of the apical tissue. In this condition, simply preserved ejaculatory hood tissue seems not to be sufficient to obviate retrograde ejaculation. For the maintenance of antegrade ejaculation, it is postulated that a part of apical tissue should be preserved as well.
Pediatric brainstem glioma is an incurable malignancy because of its inoperability. As a result of their extensive tropism toward cancer and the possibility of autologous transplantation, human adipose-derived mesenchymal stem cells (hAT-MSC) are attractive vehicles to deliver therapeutic genes to brainstem gliomas. In this study, in a good manufacturing practice (GMP) facility, we established clinically applicable hAT-MSCs expressing therapeutic genes and investigated their therapeutic efficacy against brainstem glioma in mice. For feasible clinical applications, (1) primary hAT-MSCs were cultured from human subcutaneous fat to make autologous transplantation possible, (2) hAT-MSCs were genetically engineered to express carboxyl esterase (CE) and (3) a secreted form of the tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) expression vector for synergistic effects was delivered by a gene transfer technology that did not result in genomic integration of the vector. (4) Human CE and sTRAIL sequences were utilized to avoid immunological side effects. The hAT-MSCs expressing CE±sTRAIL showed significant therapeutic effects against brainstem gliomas in vitro and in vivo. However, the simultaneous expression of CE and sTRAIL had no synergistic effects in vivo. The results indicate that non-viral transient single sTRAIL gene transfer to autologous hAT-MSCs is a clinically applicable stem cell-based gene therapy for brainstem gliomas in terms of therapeutic effects and safety.
The prognosis of medulloblastoma has improved significantly because of advances in multi-modal treatments; however, metastasis remains one of the prognostic factors for a poor outcome and is usually associated with tumor recurrence. We evaluated the migratory potential and therapeutic efficacy of genetically engineered human neural stem cells (NSCs) that encode a prodrug enzyme in the subdural medulloblastoma model. We genetically modified HB1.F3 (F3) immortalized human NSCs to express rabbit carboxylesterase (rCE) enzyme, which efficiently converts the prodrug CPT-11 (Irinotecan) into an active anti-cancer agent (SN-38). To simulate clinical metastatic medulloblastomas, we implanted human medulloblastoma cells into the subdural spaces of nude mice. rCE expressing NSCs (F3.rCE) were labeled with fluorescence magnetic nanoparticle for in vivo imaging. The therapeutic potential of F3.rCE was confirmed using a mouse subdural medulloblastoma model. The majority of intravenously (i.v.) injected, F3.rCE cells migrated to the subdural medulloblastoma site and a small number of F3.rCE cells were found in the lungs, pancreas, kidney and liver. Animals that received F3.rCE cells in combination with prodrug CPT-11 survived significantly longer (median survival: 142 days) than control mice that received F3.rCE cells only (median survival: 80 days, Po0.001) or CPT-11 only (median survival: 118 days, Po0.001). In conclusion, i.v. injected F3.rCE NSCs were able to target subdural medulloblastomas and demonstrate therapeutic efficacy. Our study provides data that supports further investigation of stem-cell-based gene therapy against metastatic medulloblastomas.
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