Mitomycin C Injection Research Articles

50% Ethanol extract of Orthosiphon stamineus modulates genotoxicity and clastogenicity induced by mitomycin C

Herbal products contain a variety of compounds which may be useful in protecting against cellular damage caused by mutagens. Orthosiphon stamineus (O.s) also known as Cat whiskers. The herb has been shown anti-oxidative properties and can modulate key cellular proteins that have cytoprotective effect. The study aimed to evaluate the effects of different doses (250, 500 and 1000 mg kg−1) of 50% ethanol extract of O.s (Et. O.s) on micro-nucleated polychromatic erythrocytes (MNPCE), Polychromatic to normachromatic erythrocytes ratio (PCE/NCE), Mitotic index (MI), and Chromosomal aberration (CA) in Bab/c mice. Moreover, these parameters were used to evaluate the anti-genotoxic and clastogenic potencies of (Et. O.s) against mitomycin c (MMC) that interact with biological molecules and induce genotoxic and clastogenic disorders in non-tumor cells. MMC (4 mg kg−1) was injected intraperitoneally (i.p.) to the mice before and after treatment with three different doses of (Et. O.s). The results indicated that the extract at different doses did not show significant (p ≥ 0.05) differences in (MNPCE), (PCE/NCE) ratios, and (CA) values. The higher doses sowed high (MI) values compared with untreated control group. MMC showed significant increase (p ≤ 0.001) in (MNPCE), (CA) and reduce (PCE/NCE) and (MI) values compared with untreated control group. Treatment with (Et. O.s) at different doses before and after MMC injection showed to modulate MNPCE, PCE/NCE ratios, CA and MI values in mice bone marrow cells suggesting genoprotective potential of this plant extract.

Preoperative subconjunctival combined injection of bevacizumab and mitomycin C before the surgical excision of primary pterygium: clinical and histological results

PurposeThe aim of this study was to detect the clinical and histological effects of preoperative subconjunctival injection of both bevacizumab and mitomycin C (MMC) 1 month before the surgical excision of primary pterygium using a bare sclera technique.Patients and methodsA total of 20 patients with primary pterygium underwent subconjunctival combined injection of 0.1 mL of MMC (0.1 mg/mL) and 0.1 mL of bevacizumab (1.25 mg/0.1 mL) 1 month before bare sclera excision of the pterygium. The excised pterygium tissues were examined histologically and immunohistologically by CD31 staining, and the patients were followed up clinically for at least 2 years. The excised pterygia of two patients without preoperative injection were used for histological comparison.ResultsClinically, there were no intraoperative or postoperative complications. No recurrence was noted during the follow-up period. Histologically, the previously injected pterygia showed a decreased number of epithelial cells and stromal fibroblasts. The latter were rounded or oval and swollen rather than spindle shaped, and some were degenerating or apoptotic. Collagen and elastic fibers were degenerated, distorted, and decreased in density, while blood capillaries were obliterated. There was a significant decrease in CD31-positive cells in previously injected pterygia.ConclusionPreoperative subpterygium combined injection of bevacizumab and MMC is safe and effective in reducing the postoperative recurrence of primary pterygium. Histological and immunohistological changes in the form of decreased fibrovascular activity and degeneration of the extracellular matrix and nerve axons were noted.

Mitomycin C-augmented trabeculectomy: subtenon injection versus soaked sponges: a randomised clinical trial

Background/aimsTo compare the efficacy and safety of subtenon injection of mitomycin C (MMC) with that of conventional application of MMC-soaked sponges in trabeculectomy.MethodsIn this multicentre randomised clinical trial, 80 consecutive...

Intraoperative Injection vs Sponge-applied Mitomycin C during Trabeculectomy: One-year Study.

AimTo determine the safety and efficacy of intraoperative injection of mitomycin C (MMC) against conventional sponge-applied MMC during trabeculectomy.Materials and methodsThis study was a retrospective, comparative case series. Thirty eyes with primary open-angle glaucoma underwent consecutive trabeculectomies with MMC injection (injection group), and thirty eyes with sponge-applied MMC were as controls (sponge group). Data were collected preoperatively and postoperatively at 1 day, 1 week, 1 month, 3 months, 6 months, and 1 year after surgery. Demographic data, applanation intraocular pressure (IOP), best-corrected visual acuity (VA), number of glaucoma medications, postoperative interventions, postoperative complications, and number of visits within 3 months were recorded. In order to stratify data, proportion of eyes achieving >30% IOP reduction from baseline with or without glaucoma medications was calculated and defined as surgical success.ResultsMean IOP reduction at 1 year was significant in both the injection and sponge groups from baseline (46.8 and 37.8% respectively). The injection group had overall lower postoperative IOP and comparable complete treatment success, defined as achieving >30% IOP reduction without glaucoma medications (p = 0.941). The number of postoperative visits within 3 months and the proportion of eyes needing 5-fluorouracil (5-FU) intervention were significantly lower in the injection group (p = 0.03, p = 0.04 respectively).ConclusionInjection of MMC was as safe and effective as sponge application with comparable estimated complete treatment success, less need for visits within 3 months, and 5-FU intervention.Clinical significanceSurgeons may consider intraopera-tive injection of MMC in appropriate patient cohorts given comparable safety and efficacy and several advantages over traditional sponge application. Further study in a prospective, larger, long-term manner is necessary to assess this modality.How to cite this article: Khouri AS, Huang G, Huang LY. Intraoperative Injection vs Sponge-applied Mitomycin C during Trabeculectomy: One-year Study. J Curr Glaucoma Pract 2017;11(3):101-106.

Preclinical Evaluation of Promitil, a Radiation-Responsive Liposomal Formulation of Mitomycin C Prodrug, in Chemoradiotherapy

Toexamine the effect of radiation on invitro drug activation and release of Promitil, apegylated liposomal formulation of a mitomycin C (MMC) lipid-based prodrug; and examine the efficacy and toxicity of Promitil with concurrent radiation in colorectal cancer models. Promitil was obtained from Lipomedix Pharmaceuticals (Jerusalem, Israel). We tested the effects of radiation on release of active MMC from Promitil invitro. We next examined the radiosensitization effect of Promitil invitro. We further evaluated the toxicity of a single injection of free MMC or Promitil when combined with radiation by assessing the effects on blood counts and in-field skin andhair toxicity. Finally, we compared the efficacy of MMC and Promitil in chemoradiotherapy using mouse xenograft models. Mitomycin C was activated and released from Promitil in a controlled-release profile, and the rate of release was significantly increased in medium from previously irradiated cells. Both Promitil and MMC potently radiosensitized HT-29cells invitro. Toxicity of MMC (8.4mg/kg) was substantially greater than with equivalent doses of Promitil (30mg/kg). Mice treated with human-equivalent doses of MMC (3.3mg/kg) experienced comparable levels of toxicity as Promitil-treated mice at 30 mg/kg. Promitil improved the antitumor efficacy of 5-fluorouracil-based chemoradiotherapy in mouse xenograft models of colorectal cancer, while equitoxic doses of MMC did not. We demonstrated that Promitil is an attractive agent for chemoradiotherapy because it demonstrates a radiation-triggered release of active drug. We further demonstrated that Promitil is a well-tolerated and potent radiosensitizer at doses not achievable with free MMC. These results support clinical investigations using Promitil in chemoradiotherapy.

Revisiting the Role of the Myofibroblast in Socket Surgery: An Immunohistochemical Study

Purpose:To determine the impact of a single injection of various anti-inflammatory, antimitotic, and antiangiogenic agents on the cell count of myofibroblasts in an eviscerated socket.Methods:One eye from 15 skeletally mature New Zealand white rabbits was eviscerated, and the rabbits were divided into 5 groups. Each group of 3 rabbits received a 0.1 ml subconjunctival injection of a different agent. Group I received bevacizumab 25 mg/ml, group II received triamcinolone 40 mg/ml, group III received 5-fluorouracil 50 mg/ml, group IV received mitomycin-C 0.4 mg/ml, while group V was the control group and received no injections. The animals were euthanized 19 days after evisceration and conjunctival samples were submitted for histopathological examination. Monoclonal α-smooth muscle actin antibody was applied, and the mean of 5 readings of the number of myofibroblasts was recorded in each slide.Results:The mean count of myofibroblasts was highest for the control group and all groups achieved a statistically significant reduction in myofibroblast count compared with the control group. Sorting the means showed that Group IV (mitomycin-C) achieved the lowest mean value (p = 0.000006) followed by triamcinolone (p = 0.00048), while group I (bevacizumab) achieved the least reduction in myofibroblast count (p = 0.00148).Conclusion:Until newer antimyofibroblast medications and antibodies are commercially available, a single injection of mitomycin-C or triamcinolone during surgery achieves the highest mean reduction of myofibroblast count.

Safety and efficacy of Intraurethral Mitomycin C Hydrogel for prevention of post-traumatic anterior urethral stricture recurrence after internal urethrotomy.

:Background:Evaluation of the safety and efficacy of intraurethral Mitomycin C (MMC) hydrogel for prevention of post-traumatic anterior urethral stricture recurrence after internal urethrotomy.Methods:A thermoresponsive hydrogel base consisting of 0.8 mg MMC with 1cc water and propylene glycol to PF-127 poloxamer was used in theater. 40 male patients with short, non-obliterated, urethral stricture were randomized into 2 groups: control and MMC. After internal urethrotomy, the MMC group patients received the MMC-Hydrogel while the others were just catheterized. Both groups had their catheters for at least 1 week. After surgery, they were followed up by means of medical history and physical examination, monitoring voiding patterns and retrograde urethrogram at 1 month, 6 months and 1 year after surgery.Results:40 male patients between 14 to 89 years old (Mean = 54.15) underwent internal urethrotomy. The average age for the control and MMC group was 54.55±21.25 and 53.75±24.75 respectively. In a comparison of age between the two groups, they were matched (P=0.574). Stricture length was 10.7±5.9 and 9.55±4.15 mm for the control and MMC group respectively. There were no statistically meaningful differences between the two groups (P=0.485). Fifteen patients had a history of one previous internal urethrotomy which in a comparison between the two groups meant there was no meaningful difference (P = 0.327). During postoperative follow up, total urethral stricture recurrence happened in 12 patients: 10 patients (50%) in control group and 2 patients (10%) in MMC group. The difference was statistically significant (P = 0.001). There were no significant complications associated with the MMC injection in our patients.Conclusions:Based on our results, MMC Hydrogel may have an anti-fibrotic action preventing post-traumatic anterior urethral stricture recurrence with no side effects on pre-urethral tissue. Due to our study limitations, our follow up time and the small number of patients, our results were not conclusive and further studies will be needed with a longer follow up time.

Comparison of Subconjunctival Mitomycin C and 5-Fluorouracil Injection for Needle Revision of Early Failed Trabeculectomy Blebs

Background. To compare the efficacy of needle revision with 5-fluorouracil (5-FU) and mitomycin C (MMC) on dysfunctional filtration blebs shortly after trabeculectomy. Methods. It is a prospective randomized study comparing needle revision augmented with MMC or 5-FU for failed trabeculectomy blebs. Results. To date 71 patients (75 eyes) have been enrolled, 40 eyes in the MMC group and 35 in the 5-FU group. 68 patients (72 eyes) have completed 12-month follow-up, 38 eyes in the MMC group and 34 in the 5-FU group. The mean IOP before and that after needle revision in the MMC group were 26.5 ± 4.3 mmHg and 11.3 ± 3.4 mmHg, respectively (P < 0.05), and in the 5-FU group were 27.1 ± 3.8 mmHg and 10.9 ± 3.4 mmHg, respectively (P < 0.05). At 12-month follow-up, complete success rates were 57.5% for MMC group and 34.3% for 5-FU group (P = 0.042; log-rank test) and 75% and 60% (P = 0.145; log-rank test), respectively, for the qualified success. Complication rates between the two groups were not statistically different (P > 0.05). Conclusions. Needle revision and subconjunctival MMC injection were more effective than needling and subconjunctival 5-FU injection for early dysfunctional filtration blebs after trabeculectomies.

Mitigating effect of Indian propolis against mitomycin C induced bone marrow toxicity.

A major drawback with cancer chemotherapy is its severe toxic effects on non-target tissues. Assessment of natural products for their protective effect against anticancer drugs-induced toxicity is gaining importance in cancer biology. The present study was aimed at assessing the protective effect of hydroethanolic extract of Indian propolis (HEIP) against mitomycin C (MMC)-induced genotoxicity and cytotoxicity. Swiss albino mice were injected with various doses of HEIP (100, 200, 300, 400, 600 and 800mg/kg b. wt., i.p) 1h prior to MMC (8mg/kg, i.p.) injection. The geno- and cyto-toxicities were evaluated in mice by performing bone marrow micronucleus and TUNEL assays. In vitro antioxidant and lipid peroxidation inhibitory assays were carried out to understand the mechanism of the protective effects. The significant increase in the frequency of micronculeated cells (12.51±0.48), apoptotic cells (23.43±1.86) and reduction in P/N ratio (0.69±0.04) compared with control indicated the potential geno- and cytotoxic effects of MMC in bone marrow. Pretreatment with HEIP resulted in the significant recovery of the toxic effects induced by MMC. HEIP at 400mg/kgb. wt. was found to be the optimum dose imparting the maximum protective effects. The in vitro antioxidant and lipid peroxidation inhibitory assays suggest that the extract possesses substantial free radical scavenging activities. In conclusion, HEIP possesses substantial geno- and cyto-protective properties against MMC, which could be mediated through efficient free radical scavenging and inhibitory effect on lipid peroxidation.

Deep Sclerectomy With a New Nonabsorbable Uveoscleral Implant (Esnoper-Clip): 1-Year Outcomes.

Purpose:To report the safety and the effectiveness of deep sclerectomy (DS) with a new nonabsorbable uveoscleral hema implant (Esnoper-Clip) designed to increase trabecular and uveoscleral outflow and to achieve higher intrascleral blebs.Materials and Methods:Twenty-seven eyes of 27 patients with open-angle glaucoma, who underwent DS with an Esnoper-Clip implant, were included in this study. All patients were followed up after 12 months.Results:A significant decrease in intraocular pressure was observed after surgery, changing from a preoperative mean of 26.6±5.2 mm Hg to a postoperative mean of 15.3±5 mm Hg (P<0.001) at 12 months. There was also a significant reduction in the number of glaucoma drugs needed, varying from 2.5 per patient to 0.3 (P<0.001) 1 year after surgery. The main intrascleral lake height and volume at 12 months was 0.7±0.1 mm and 3.9±1.3 mm3, respectively. No intraoperative complications occurred. The main postoperative complications were a positive Seidel test result at 24 hours in 2 eyes (7.4%), hyphema in 2 eyes (7.4%), and choroidal detachment in 1 eye (3.7%). All these complications resolved successfully. The need for additional mitomycin-C injections was recorded in 4 eyes (14.8%), twice in 2 of them. Twelve eyes (44.4%) underwent postsurgical Nd:YAG laser goniopuncture with a mean time between surgery and this procedure of 4.3 months. Mean intraocular pressure after Nd:YAG laser goniopuncture decreased from 19.2 to 15.5 mm Hg (P<0.001).Conclusion:DS with an uveoscleral hema implant (Esnoper-Clip) is a safe and effective technique for the management of open-angle glaucoma.

Visual Internal Urethrotomy With Intralesional Mitomycin C and Short-term Clean Intermittent Catheterization for the Management of Recurrent Urethral Strictures and Bladder Neck Contractures

To evaluate our longitudinal experience using visual internal urethrotomy (VIU) with intralesional mitomycin C (MMC) and short-term clean intermittent catheterization (CIC) for urethral strictures and bladder neck contractures (BNC) after failure of endoscopic management. This case series involved review of our prospectively developed database of all men who underwent VIU with MMC and CIC in a standardized fashion for urethral stricture or BNC between 2010 and 2013 at our tertiary care medical center. Etiology was identified as radiation-induced stricture (RIS) or non-RIS and analyzed by stricture location. Cold knife incisions were made in a tri or quadrant fashion followed by intralesional injection of MMC and 1 month of once daily CIC. All 37 patients previously underwent at least 1 intervention for urethral stricture or BNC before VIU with MMC and CIC. Mean stricture length was 2.0 cm (range, 1-6 cm; standard deviation, 1.0 cm). Over the median follow-up period of 23 months (range, 12-39 months), 75.7% of patients required no additional surgical intervention (RIS, 54.5%; non-RIS, 84.6%; P = .051). In those that did recur, median time to stricture recurrence was 8 months (range, 2-28 months). One patient with recurrence required urethroplasty. VIU with MMC followed by short-term CIC provides a minimally invasive and widely available tool to manage complex recurrent urethral strictures (<3 cm) and BNC without significant morbidity. This approach may be most attractive for patients who are poor candidates for open surgery.

MP15-06 BIPOLAR INCISION OF BLADDER NECK CONTRACTURE WITH INTRALESIONAL INJECTION OF MITOMYCIN C: A SINGLE INSTITUTION EXPERIENCE

INTRODUCTION AND OBJECTIVES: Transurethral incision of bladder neck contracture (TUIBNC) has high failure rates, prompting concomitant injection of a scar modulator. We present our single institution series of bipolar TUIBNC with immediate mitomycin C (MMC) injection to determine if the combination therapy could improve patency rates. METHODS: Records for all patients who underwent TUIBNC with intralesional MMC at a single institution from 2013e2014 were retrospectively reviewed. Instruments used were the biopolar Gyrus ACMI PK button electrode or PK Plasma-CISE . A total of 2mg of 40% mitomycin C solution was injected in four quadrants of the treated BNC. Postoperatively, patients were monitored for stricture recurrence using a combination of serial postvoid residuals, uroflowometry and flexible cystoscopy. Failure was defined as the need for subsequent intervention. RESULTS: Fifteen patients underwent bipolar TUIBNC with MMC. All were Caucasian males with a median age of 66 years (IQR 6). Etiologies included radical prostatectomy (8), transurethral prostate resection (3), radical cystoprostatectomy (2), and prostate brachytherapy (2). Fourteen (93%) patients had failed at least one prior intervention. Overall, 7 (47%) patients recurred following an initial TUIBNC with MMC at a median follow up of 9.9 months (IQR 9.2). Six of the 7 chose to undergo repeat TUIBNC with MMC, 2 (33%) of whom recurred during median follow up of 7 months (IQR 11). Likelihood of BNC recurrence was not significantly associated with history of prior pelvic radiation (33% vs 56%, p 1⁄4 0.4). Two patients experienced a postoperative complication but no serious adverse events occurred. CONCLUSIONS: Bipolar TUIBNC with MMC injection had lower than expected efficacy with a 10-month failure rate near 50%.

Bipolar Transurethral Incision of Bladder Neck Stenoses with Mitomycin C Injection.

Introduction. To determine the efficacy of bipolar transurethral incision with mitomycin C (MMC) injection for the treatment of refractory bladder neck stenosis (BNS). Materials and Methods. Patients who underwent bipolar transurethral incision of BNS (TUIBNS) with MMC injection at our institution from 2013 to 2014 were retrospectively reviewed. A total of 2 mg of 40% mitomycin C solution was injected in four quadrants of the treated BNS. Treatment failure was defined as the need for subsequent intervention. Results. Thirteen patients underwent 17 bipolar TUIBNS with MMC injection. Twelve (92%) patients had failed a mean of 2.2 ± 1.1 prior endoscopic procedures. Median follow-up was 16.5 months (IQR: 14–18.4 months). Initial success was 62%; five (38%) patients had a recurrence with a median time to recurrence of 7.3 months. Four patients underwent a repeat procedure, 2 (50%) of which failed. Overall success was achieved in 77% (10/13) of patients after a mean of 1.3 ± 0.5 procedures. BNS recurrence was not significantly associated with history of pelvic radiation (33% versus 43%, p = 0.9). There were no serious adverse events. Conclusions. Bipolar TUIBNS with MMC injection was comparable in efficacy to previously reported techniques and did not result in any serious adverse events.

English

INTRODUCTION: Direct visual internal urethrotomy (DVIU) is the most commonly performed procedure for bulbar urethral stricture disease of length 10mm or less. DVIU alone, classically, has a poor long-term success rate. The objective of this prospective study conducted at VIMS Bellary from Sep 2012 to Aug 2013 is to compare the effect of submucosal injection of mitomycin-C after DVIU on recurrence rate of bulbar urethral stricture with DVIU alone. MATERIALS AND METHODS: Forty five male patients with bulbar urethral strictures of 10mm or less were included in the study with every alternate patient undergoing DVIU was injected urethral submucosal Mitomycin-C(0.1mg) at the urethrotomy site. Mitomycin C injected in 23 patients. Mean stricture length, as measured by retrograde urethrography (RUG) was 0.75 cm. Mean preoperative uroflow was 10.5ml/sec. The patients were re-evaluated after 6 months and 1 year by uroflow, USG abdomen and RGU, and the stricture recurrence rate was compared between the two groups. RESULTS: Analysis of the results revealed a stricture recurrence rate of 47% in the DVIU only group while the recurrence rate in the Mitomycin C group was only 13%. This difference was statistically significant. The mean uroflow of the recurrences in the Mitomycin C group was 13 ml/sec,and DVIU group 11.75 ml/sec. CONCLUSIONS: Submucosal injection of Mitomycin C after DVIU is effective in reducing the rate of early recurrence in our short term follow up study.However further studies are required to know the long term results. In our study aetiology of stricture has no relation to the recurrence rate after DVIU.

Single-step assembly of polymer-lipid hybrid nanoparticles for mitomycin C delivery.

Mitomycin C is one of the most effective chemotherapeutic agents for a wide spectrum of cancers, but its clinical use is still hindered by the mitomycin C (MMC) delivery systems. In this study, the MMC-loaded polymer-lipid hybrid nanoparticles (NPs) were prepared by a single-step assembly (ACS Nano 2012, 6:4955 to 4965) of MMC-soybean phosphatidyhlcholine (SPC) complex (Mol. Pharmaceutics 2013, 10:90 to 101) and biodegradable polylactic acid (PLA) polymers for intravenous MMC delivery. The advantage of the MMC-SPC complex on the polymer-lipid hybrid NPs was that MMC-SPC was used as a structural element to offer the integrity of the hybrid NPs, served as a drug preparation to increase the effectiveness and safety and control the release of MMC, and acted as an emulsifier to facilitate and stabilize the formation. Compared to the PLA NPs/MMC, the PLA NPs/MMC-SPC showed a significant accumulation of MMC in the nuclei as the action site of MMC. The PLA NPs/MMC-SPC also exhibited a significantly higher anticancer effect compared to the PLA NPs/MMC or free MMC injection in vitro and in vivo. These results suggested that the MMC-loaded polymer-lipid hybrid NPs might be useful and efficient drug delivery systems for widening the therapeutic window of MMC and bringing the clinical use of MMC one step closer to reality.

Therapeutic effect of folate-targeted and PEGylated phytosomes loaded with a mitomycin C-soybean phosphatidyhlcholine complex.

A mitomycin C (MMC)-soybean phosphatidyhlcholine complex loaded in phytosomes was previously reported for the purpose of developing a MMC drug delivery system (Mol. Pharmaceutics 2013, 10, 90-101), but this approach was limited by rapid elimination from the body and lack of target specificity. In this article, to overcome these limitations, MMC-soybean phosphatidyhlcholine complex-loaded phytosomes (MMC-loaded phytosomes) as drug carriers were surface-functionalized with folate-PEG (FA-PEG) to achieve reduced toxicity and a superior MMC-mediated therapeutic effect. For this purpose, FA was conjugated to DSPE-PEG-NH2, and the resultant DSPE-PEG-FA was introduced into the lipid moiety of the phytosomes via a postinsertion technique. The prepared FA-PEG-functionalized MMC-loaded phytosomes (FA-PEG-MMC-loaded phytosomes) have a particle size of 201.9 ± 2.4 nm, a PDI of 0.143 ± 0.010, a zeta potential of -27.50 ± 1.67 mV, a spherical shape, and sustained drug release. The remarkable features of FA-PEG-MMC-loaded phytosomes included increased cellular uptake in HeLa cells and higher accumulation in H22 tumor-bearing mice over that of the PEG-MMC-loaded phytosomes. Furthermore, FA-PEG-MMC-loaded phytosomes were associated with enhanced cytotoxic activity in vitro and an improved antitumor effect in vivo compared to that resulting from free MMC injection. These results suggest that FA-PEG-MMC-loaded phytosomes may be useful drug delivery systems for widening the therapeutic window of MMC in clinical trials.

Early Postoperative Results and Complications of using the EX-PRESS Shunt in uncontrolled Uveitic Glaucoma: A Case Series of Preliminary Results.

ABSTRACTPurpose: The purpose of this case series is to describe the efficacy of the EX-PRESS shunt in uveitic glaucoma.Methods: This prospective case series sequentially recruited uveitic glaucoma subjects with intraocular pressure (IOP) > 21 mm Hg despite maximal topical antiglaucoma medications from July 2012 to July 2013 in Hong Kong. All subjects received a trabeculectomy with mitomycin C (MMC) and EX-PRESS shunt implantation. The primary outcome measures included preope-rative IOP and postoperative IOP on day 1, 1 week, 1 month, and every 3 months thereafter. The secondary outcome measures included postoperative complications and follow-up procedures, pre- and postoperative Snellen best corrected visual acuity and cup-disc ratio, as well as the number of antiglaucoma medication required.Results: In a case series of five subjects with uncontrolled uveitic glaucoma, two had inactive anterior uveitis, and three had active panuveitis. The mean preoperative IOP was 35.4 ± 12.6 mm Hg on 3.8 ± 0.5 antiglaucoma eye drops. The mean day 1, 1 week and 1 month IOP's were 6.6 ± 3.7 mm Hg, 7.2 ± 3.2 mm Hg, and 12.6 ± 8.2 mm Hg, respectively. One case required subconjunctival MMC injections postoperatively; two required conjunctival resuture for leakage; and two had early postoperative hypotony that resolved after oral prednisolone. At 6 months, the mean IOP was 13.2 ± 4.6 mm Hg. Four out of five subjects had IOP < 21 mm Hg without medication, and all had IOP < 21 mm Hg with antiglaucoma medication.Conclusion: The EX-PRESS shunt demonstrates good IOP control with a propensity for hypotony in the early postoperative period in this small uveitic glaucoma series.How to cite this article: Lee JWY, Chan JCH, Qing L, Lai JSM. Early Postoperative Results and Complications of using the EXPRESS Shunt in uncontrolled Uveitic Glaucoma: A Case Series of Preliminary Results. J Current Glau Prac 2014;8(1):20-24.

Effect and Mechanism of Mitomycin C Combined with Recombinant Adeno-Associated Virus Type II against Glioma

The effect of chemotherapy drug Mitomycin C (MMC) in combination with recombinant adeno-associated virus II (rAAV2) in cancer therapy was investigated, and the mechanism of MMC affecting rAAV2’s bioactivity was also studied. The combination effect was evaluated by the level of GFP and TNF expression in a human glioma cell line, and the mechanism of MMC effects on rAAV mediated gene expression was investigated by AAV transduction related signal molecules. C57 and BALB/c nude mice were injected with rAAV-EGFP or rAAV-TNF alone, or mixed with MMC, to evaluate the effect of MMC on AAV-mediated gene expression and tumor suppression. MMC was shown to improve the infection activity of rAAV2 both in vitro and in vivo. Enhancement was found to be independent of initial rAAV2 receptor binding stage or subsequent second-strand synthesis of target DNA, but was related to cell cycle retardation followed by blocked genome degradation. In vivo injection of MMC combined with rAAV2 into the tumors of the animals resulted in significant suppression of tumor growth. It was thus demonstrated for the first time that MMC could enhance the expression level of the target gene mediated by rAAV2. The combination of rAAV2 and MMC may be a promising strategy in cancer therapy.

Dual Role Of MERIT40 In Hematopoietic Stem and Progenitor Cells

The balance between self-renewal and differentiation of hematopoietic stem cells (HSCs) is maintained by cell intrinsic and extrinsic mechanisms, including tight regulation of signaling pathways such as Tpo-Mpl and SCF-ckit. Posttranslational modifications, such as phosphorylation and ubiquitination, regulate these pathways. While the role of protein phosphorylation is well established, the importance of ubiquitination in HSC self-renewal has not been well addressed. It is known that of the seven different lysines on ubiquitin, Lys48 polyubiquitination is a marker for protein degradation, and Lys63 polyubiquitination is associated with regulation of kinase activity, protein trafficking, and localization. In this study, we provide evidence that the adaptor protein MERIT40 has multiple roles in hematopoietic stem/progenitor cells (HSPCs). MERIT40 is a scaffolding protein shared by two distinct complexes with Lys63 deubiquitinase (DUB) activities: the nuclear RAP80 complex with a known role in DNA damage repair in breast/ovarian cancer cells, whereas the functions of the cytoplasmic BRISC remains less characterized. MERIT40 is important for integrity of both complexes, and its deficiency leads to their destabilization and a >90% reduction in deubiquitinase activity. By using MERIT40 knockout (M40-/-) mice, we found that lack of MERIT40 leads to a two-fold increase in phenotypic and functional HSCs determined by FACS and limiting dilution bone marrow transplantation (BMT), respectively. More importantly, M40-/- HSCs have increased regenerative capability demonstrated by increased chimerism in the peripheral blood after BMT of purified HSCs. The higher self-renewal potential of these HSCs provides a survival advantage to M40-/- mice and HSCs after repetitive administration of the cytotoxic agent 5-flurouracil (5FU). MERIT40 deficiency also preserves HSC stemness in culture as judged by an increase in peripheral blood chimerism in recipient mice transplanted with M40-/- Lin-Sca1+Kit+ (LSK) cells cultured in cytokines for nine days compared to recipient mice receiving cultured wildtype (WT) LSK cells. In contrast to the increased HSC homeostasis and superior stem cell activity due to MERIT40 deficiency, M40-/- mice are hypersensitive to DNA damaging agents caused by inter-cross linking (ICL), such as Mitomycin C (MMC) and acetaldehydes that are generated as side products of intracellular metabolism. MMC injection caused increased mortality in M40-/- mice compared to WT controls attributable to DNA damage-induced bone marrow failure. MMC-treated M40-/- mice showed marked reduction in LSK progenitor numbers accompanied by increased DNA damage, in comparison to WT mice. Consistent with the in vivo studies, M40-/- progenitor cells are hypersensitive to MMC and acetaldehyde treatment in a cell-autonomous manner in colony forming assays. ICL repair is known to require Fanconi Anemia (FA) proteins, an ICL repair network of which mutations in at least 15 different genes in humans cause bone marrow failure and cancer predisposition. Thus, M40-/- mice represent a novel mouse model to study ICL repair in HSPCs with potential relevance to bone marrow failure syndromes. Taken together, our data establishes a complex role of MERIT40 in HSPCs, warranting future investigation to decipher functional events downstream of two distinct deubiquitinating complexes associated with MERIT40 that may regulate distinct aspects of HSPC function. Furthermore, our findings reveal novel regulatory pathways involving a previously unappreciated role of K63-DUB in stem cell biology, DNA repair regulation and possibly bone marrow failure. DUBs are specialized proteases and have emerged as potential “druggable” targets for a variety of diseases. Hence, our work may provide insights into novel therapies for the treatment of bone marrow failure and associated malignancies that occur in dysregulated HSCs. Disclosures:No relevant conflicts of interest to declare.

Modulatory Role of Pre- And Post- Treatment of Spirulina platensis on Mitomycin C Drug Induced Genotoxicity and Pathological Changes in Ehrlich Ascites Carcinoma Bearing Mature Female Swiss Albino Mice

Mitomycin C (MMC) is a potent antitumor agent used against many cancers. It has a clastogenic and aneugenic effects. The protective effect of pre- and post- addition of Spirulina platensis (Sp) to the diet on MMC induced genotoxic effect and histopathological changes were evaluated in Erlich Acites Carcinoma Cell (EAC) bearing mature female Swiss albino mice. The sixty EAC bearing female albino mice weighted 30-40 gm were observed along the experimental period and classified into six equal groups. The first kept as negative control fed on Sp powder free diet. the second kept as control positive fed on Sp powder 1% in their diet 3 weeks before tumor induction (Sp1), the third group fed on Sp powder 1% 3 weeks pre and one week post – tumor induction (Sp1+Sp2), while the fourth group intraperitonealy (i.p) injected with MMC (1mg/kg b.wt) on the third day post tumor induction and for 7 consecutive days, while the fifth group fed on Sp1 in diet for 24 days before MMC injection (Sp1+MMC) and the six group fed on Sp1 for 24 days pre- and 7 days post MMC injection (Sp1+MMC+Sp2) as the same previous dose and manner. The end of experimental period, 7 days from MMC injection, 3 animals from each group were sacrificed after 90 minutes from I.M injection of colchicine. MMC exhibited a significant increase in the frequency of micronucleated (MN) erythrocytes concomitant with several chromosomal aberrations and multiple histopathological changes in the bone marrow, liver and kidney. Pre- and post- treatment with Sp showed potent anticlastogenic effect, regeneration of liver and kidney with restoration of bone marrow to the normal state. It can be concluded that Sp can minimize and mitigate the side effects of MMC on the normal cells and tissues of the body, so it can be pre- or post- treatment with MMC chemotherapy.