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1.  Interleukin-1β, Calcium-Sensing Receptor, and Urokinase Gene Polymorphisms in Korean Patients with Urolithiasis 
Korean Journal of Urology  2011;52(5):340-344.
Purpose
There are various causes of ureter calculi, and genetic factors are known to play a role. Interleukin-1β (IL-1β) and calcium-sensing receptor (CaSR) genes are related to hypercalciuria, and urokinase is related to the formation of calcium oxalate stones. This study investigated polymorphisms in IL-1β, CaSR, and urokinase in patients with urolithiasis and healthy controls.
Materials and Methods
Urolithiasis patients treated at Chung-Ang University Hospital were enrolled from January 2007 to December 2008. The control group of volunteers displayed normal urinalysis findings in the health screening, no stones identified by ultrasonography, and no history of urolithiasis. DNA extracted from peripheral blood was analyzed by the polymerase chain reaction. Patients were genetically screened for mutations in IL-1β (484 urolithiasis patients, 208 controls), CaSR (433 urolithiasis patients, 197 controls), and urokinase (370 urolithiasis patients, 167 controls). Stone metabolic study was done to see the differences between the metabolic factors and to discern normal genes from polymorphic genes.
Results
According to the genotype frequency and allele frequency analysis, there were no statistically significant differences between IL-1β, CaSR, and urokinase genes. Also, the analysis between genotypes and metabolic factors did not show statistically significant differences between the three genes.
Conclusions
In Korean urolithiasis patients, IL-1β, CaSR, and urokinase gene polymorphisms do not differ from those of healthy individuals. A larger-scale study is needed to confirm the need for other genetic markers of urolithiasis.
doi:10.4111/kju.2011.52.5.340
PMCID: PMC3106167  PMID: 21687394
Calcium sensing receptor; Genetic polymorphism; Interleukin-1beta; Urokinase; Urolithiasis
2.  Significance of S100A2 and S100A4 Expression in the Progression of Prostate Adenocarcinoma 
Korean Journal of Urology  2010;51(7):456-462.
Purpose
The aim of this study was to investigate the expression pattern of calcium-binding proteins S100A2 and S100A4. We also sought to determine the prognostic value of these markers for patients with prostate adenocarcinoma.
Materials and Methods
Immunohistochemical staining was performed to detect S100A2 and S100A4 expression in 26 tissue samples obtained during transurethral resection from patients with benign prostatic hyperplasia (BPH) and in 67 tissue samples obtained during prostate biopsy and radical prostatectomy from patients with prostate carcinoma. The immunoreactivity of these proteins was stratified on a scale of 0 to 3 and was correlated with the pathologic features of prostate adenocarcinoma.
Results
High expression of S100A2 was observed in the tissue of patients with BPH, whereas low or no expression was observed in prostate cancer (CaP) cells. The protein level of S100A4 was significantly higher in CaP than in BPH cells. The higher level of S100A4 observed in CaP tissue correlated with increasing tumor grade.
Conclusions
Decreased expression of S100A2 and increased expression of S100A4 may be important in the progression of CaP. This finding could aid in identifying aggressive CaP. The simultaneous analysis of S100A2 and S100A4 expression in prostate tissues may be a useful prognostic marker for CaP.
doi:10.4111/kju.2010.51.7.456
PMCID: PMC2907493  PMID: 20664777
Prostatic hyperplasia; Prostatic neoplasms; S100A2 protein, human; S100A4 protein, human
3.  Effectiveness of Flexible Ureteroscopic Stone Removal for Treating Ureteral and Ipsilateral Renal Stones: A Single-Center Experience 
Korean Journal of Urology  2013;54(6):377-382.
Purpose
The aim of this study was to evaluate the effectiveness of simultaneous flexible ureteroscopic removal of stones (URS) for ureteral and ipsilateral renal stones and to analyze the predictive factors for renal stone-free status.
Materials and Methods
We retrospectively reviewed the records of patients who underwent simultaneous flexible URS of ureteral and ipsilateral renal stones from January 2010 to May 2012. All operations used a flexible ureteroscope. We identified 74 cases of retrograde intrarenal surgery and 74 ureteral stones (74 patients). Stone-free status was respectively defined as no visible stones and clinically insignificant residual stones <3 mm on a postoperative image study. Predictive factors for stone-free status were evaluated.
Results
The immediate postoperative renal stone-free rate was 70%, which increased to 83% at 1 month after surgery. The immediate postoperative ureteral stone-free rate was 100%. Among all renal stones, 15 (20.3%) were separately located in the renal pelvis, 11 (14.8%) in the upper calyx, 15 (20.3%) in the mid calyx, and 33 (44.6%) in the lower calyx. The mean cumulative stone burden was 92.22±105.75 mm2. In a multivariate analysis, cumulative stone burden <100 mm2 was a significant predictive factor for postoperative renal stone-free status after 1 month (p<0.01).
Conclusions
Flexible URS can be considered simultaneously for both ureteral and renal stones in selected patients. Flexible URS is a favorable option that promises high stone-free status without significant complications for patients with a stone burden <100 mm2.
doi:10.4111/kju.2013.54.6.377
PMCID: PMC3685637  PMID: 23789046
Kidney calculi; Lithotripsy; Treatment outcome
4.  Transurethral Procedures for Lower Urinary Tract Symptoms Resulting From Benign Prostatic Enlargement: A Quality and Meta-Analysis 
Purpose
Thanks to advancements in surgical techniques and instruments, many surgical modalities have been developed to replace transurethral resection of the prostate (TURP). However, TURP remains the gold standard for the surgical treatment of benign prostatic hyperplasia (BPH). We conducted a meta-analysis on the efficacy and safety of minimally invasive surgical therapies for BPH compared with TURP.
Methods
This meta-analysis used a Medline search assessing the period from 1997 to 2011. A total of 784 randomized controlled trials were identified in an electronic search. Among the 784 articles, 36 randomized controlled trials that provided the highest level of evidence (level 1b) were included in the meta-analysis. We also conducted a quality analysis of selected articles.
Results
Only 2 articles (5.56%) were assessed as having a low risk of bias by use of the Cochrane collaboration risk of bias tool. On the other hand, by use of the Jadad scale, there were 26 high-quality articles (72.22%). Furthermore, 28 articles (77.78%) were assessed as high-quality articles by use of the van Tulder scale. Holmium laser enucleation of the prostate (HoLEP) showed the highest reduction of the International Prostate Symptom Score compared with TURP (P<0.0001). Bipolar TURP, bipolar transurethral vaporization of the prostate, HoLEP, and open prostatectomy showed superior outcome in postvoid residual urine volume and maximum flow rate. The intraoperative complications of the minimally invasive surgeries had no statistically significant inferior outcomes compared with TURP. Also, there were no statistically significant differences in any of the modalities compared with TURP.
Conclusions
The selection of an appropriate surgical modality for BPH should be assessed by fully understanding each patient's clinical conditions.
doi:10.5213/inj.2013.17.2.59
PMCID: PMC3713243  PMID: 23869269
Prostatic hyperplasia; Holmium; Lasers; Potassium titanylphosphate; Transurethral resection of prostate; Meta-analysis
5.  Delayed Presentation of Intravesical Bone Penetration after Pelvic Ring Fracture 
Korean Journal of Urology  2012;53(12):887-889.
Retrograde cystography and computed tomography (CT) are considered the gold standard for investigating bladder and pelvic bone injury. However, these methods can miss extraperitoneal bladder rupture caused by a penetrating bone fragment from a pelvic bone fracture. We experienced a routine conventional cystography and CT scan that failed to identify penetration of the bladder by a bone fragment, which thus delayed optimal treatment. Therefore, different diagnostic methods such as CT cystography or cystoscopy should be considered to rule out penetrating injury by a bony fragment in patients with extraperitoneal bladder rupture.
doi:10.4111/kju.2012.53.12.887
PMCID: PMC3531646  PMID: 23301137
Delayed diagnosis; Injuries; Pelvic bones; Urinary bladder
6.  Influence of Overweight on 24-Hour Urine Chemistry Studies and Recurrent Urolithiasis in Children 
Korean Journal of Urology  2012;53(4):268-274.
Purpose
We investigated the influence of overweight on 24-hour urine chemistry studies and recurrent urolithiasis (UL) in children.
Materials and Methods
A retrospective cohort study was designed to assess children who presented with UL at a pediatric institution between 1985 and 2010. We calculated body mass index percentile (BMIp) adjusted for gender and age according to the 2007 Korean Children and Adolescents Growth Chart and stratified the children into 3 BMI categories: lower body weight (LBW, BMIp≤10), normal BW (NBW, 10
Results
A total of 125 patients were included. The age of the patients in the NBW group was older than that of patients in the LBW group, but 24-hour urine chemistry studies did not differ significantly between the three groups. Mean urine citrate levels were lower (0.273±0.218 mg/mg/d vs. 0.429±0.299 mg/mg/d, p<0.05) and the incidence of hypocitraturia was higher (81.5% vs. 45.7%, p<0.05)) in the recurrent stone former group. In the univariate analysis, hypocitraturia and acidic urinary pH were risk factors, but in the multivariate analysis, only hypocitraturia was a risk factor for stone recurrence (hazard ratio, 3.647; 95% confidence interval, 1.047 to 12.703). In the Kaplan-Meier curve, the hypocitraturia group showed higher recurrence than did the normocitraturia group (p<0.05).
Conclusions
Unlike in adults, in children, overweight adjusted for gender and age was not associated with 24-hour urine chemistry studies and was not a risk factor for recurrent UL. Hypocitraturia was the only risk factor for UL in children.
doi:10.4111/kju.2012.53.4.268
PMCID: PMC3332139  PMID: 22536471
Body mass index percentile; Overweight; Pediatric urolithiasis
Asian Spine Journal  2012;6(1):15-21.
Study Design
This is a retrospective study.
Purpose
To evaluate the advantages and effects of posterior lumbar interbody fusion (PLIF) using allograft and posterior instrumentation in the lumbar pyogenic discitis, which are resistant to antibiotics.
Overview of Literature
To present preliminary results of PLIF using a compressive bone graft with allograft and pedicle screw fixation in the lumbar pyogenic discitis.
Methods
Fifteen patients who had lumbar pyogenic discitis were treated by posterior approach from May 2004 to July 2008. The mean follow-up duration was 27.2 ± 18.68 months. The standing radiographs of the lumbar spine and clinical results were compared and analyzed in order to assess the bony union, the changes in the distance between the two vertebral bodies and the changes in the lordotic angle formed between the fused bodies immediately after surgery and at the final follow-up.
Results
Fifteen solid unions at an average of 15.2 ± 3.5 weeks after operation. The mean preoperative lordotic angle of the affected segments was 14.3 ± 15.1°, compared to 20.3 ± 12.3° after surgery and 19.8 ± 15.2° at last follow-up. For the functional result according to the Kirkaldy-Willis criteria, the outcome was excellent in 9, good in 5, fair in 1, and there were no poor cases. The average visual analogue scale score was decreased from 7.4 before surgery to 3.4 at 2 weeks postoperative.
Conclusions
The main advantage in the procedure of PLIF using compressive bone graft with allograft and post instrumentation is early ambulation. We believe that this is another good procedure for patients with poor general condition because a further autograft bone harvest is not required.
doi:10.4184/asj.2012.6.1.15
PMCID: PMC3302910  PMID: 22439083
Lumbar spine; Discitis; Posterior lumbar interbody fusion; Homologous transplantation
Korean Journal of Urology  2012;53(1):23-28.
Purpose
Following the introduction of medical therapy for benign prostatic hyperplasia (BPH), we determined the effect of the change in trends in medical therapy on the indication and outcome of surgical intervention for BPH.
Materials and Methods
We compared the basic characteristics of, weight of resected tissue of, transfusions in, and postoperative complications of patients who underwent surgery between 1985 and 1989 (before the advent of medical therapy for BPH), between 1995 and 1999 (when medical therapy was developed and became widely used as alternative treatment), and between 2005 and 2009 (when medical therapy superseded surgical intervention to become first-line treatment and when combination therapy became widely adopted).
Results
At our institution, the mean age and BMI of patients increased over the past two decades (p<0.001). Hypertension, operation history, and other comorbidities also increased significantly (p<0.001, p=0.005, and p<0.001, respectively). The indications for surgery in 1985 to 1989, 1995 to 1999, and 2005 to 2009 were as follows: acute urinary retention in 34.7%, 20.2%, and 15.1% of patients and symptomatic deterioration in 61.1%, 72.3%, and 73.0% of patients, respectively. Prostate volume and the weight of resected tissue increased from 34.4±14.5 ml to 61.3±32.4 ml and from 7.2±6.4 g to 10.8±7.6 g, respectively, over two decades. Patients who underwent surgery in 2005 to 2009 had their catheters removed earlier (p<0.001). Secondary hemorrhage within four postoperative weeks and repeat transurethral resection of the prostate within 1 year decreased significantly (p=0.03 and p=0.003, respectively). No statistically significant change in impaired detrusor contractility was found (p=0.523).
Conclusions
Although patients who underwent surgery were older after widespread use of medical therapy for BPH, advancements in surgical techniques have benefitted these patients.
doi:10.4111/kju.2012.53.1.23
PMCID: PMC3272552  PMID: 22323970
Benign prostatic hyperplasia; Medical therapy; Surgical intervention
Korean Journal of Urology  2011;52(10):674-680.
Purpose
To retrospectively evaluate the effect of post-prostate-biopsy hemorrhage on the interpretation of magnetic resonance diffusion-weighted (MRDW) and magnetic resonance spectroscopic (MRS) imaging in the detection of prostate cancer. We also investigated the optimal timing for magnetic resonance examination after prostate biopsy.
Materials and Methods
We reviewed the records of 135 men. All patients underwent prostate magnetic resonance imaging (MRI). The prostate was divided into eight regions according to the biopsy site. Subsequently, we measured hemorrhage on apparent diffusion coefficient (ADC) values and (choline+creatinine)/citrate ([Cho+Cr]/Cit) ratios in the same regions on the MRI. We investigated the effect of hemorrhage at ADC values and (Cho+Cr)/Cit ratios on MRI and the relationship between prostate biopsy results and MRI findings.
Results
The mean patient age was 68.7 years and the mean time between biopsy and MRI was 23.5 days. The total hemorrhagic score demonstrated no significant associations with intervals from biopsy to MRI. Higher hemorrhagic scores were associated with higher ADC values, prostate cancer, and noncancer groups, respectively (p<0.001). ADC values were lower in tumors than in normal tissue (p<0.001), and ADC values were inversely correlated with tumor Gleason score in biopsy cores (p<0.001). However, (Cho+Cr)/Cit ratios did not exhibit any association with prostate biopsy results and hemorrhage.
Conclusions
Hemorrhage had no significant associations with the interval from biopsy to MRI. ADC values may help to detect prostate cancer and predict the aggressiveness of cancer; however, it is important to consider the bias effect of hemorrhage on the interpretation of MRDW imaging given that hemorrhage affects ADC values.
doi:10.4111/kju.2011.52.10.674
PMCID: PMC3212661  PMID: 22087361
Hemorrhage; Magnetic resonance imaging; Magnetic resonance spectroscopy; Prostatic neoplasms
Korean Journal of Urology  2011;52(8):548-553.
Purpose
To analyze the independent effect of metabolic syndrome (MS) on nephrolithiasis (NL) despite differences in gender compared with the known lithogenic factors.
Materials and Methods
From 1995 to 2009, 40,687 Koreans were enrolled in the study and observed for the development of NL at a health promotion center. The examination included anthropometric and biochemical measurements as well as kidney ultrasonography. A student's t-test or chi-square test was used to characterize the participants and a standard Cox proportional hazards model was used to calculate the adjusted odds ratio of lithogenic risk factors in the NL model.
Results
The mean age of the study cohort was 44.9 years (range, 13-100 years), and 22,540 (55.4%) of the cohort was male. The incidence of NL was 1.5% (609 participants), with males exhibiting a higher incidence than females (1.9% vs 1.0%, p<0.01). Among the total cohort, MS as well as each trait of MS were risk factors for NL. In males, high body mass index (BMI), high blood pressure, and abnormal glucose metabolism were significant lithogenic factors, whereas in females, lithogenic factors included only high BMI and abnormal glucose metabolism.
Conclusions
MS is a significant lithogenic factor compared with other lithogenic factors. There was a correlated change in the prevalence of MS and NL and MS traits in Korea.
doi:10.4111/kju.2011.52.8.548
PMCID: PMC3162221  PMID: 21927702
Body mass index; Gender identity; Metabolic syndrome X; Nephrolithiasis; Obesity
Korean Journal of Urology  2011;52(3):194-199.
Purpose
We aimed to investigate the detection of nanobacteria (NB) from expressed prostatic secretions (EPS) in patients with category III chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and from vaginal swabs in patients with vaginitis by reverse transcriptase polymerase chain reaction (RT-PCR) and to evaluate the association between NB and Neisseria gonorrhea, Chlamydia trachomatis, Ureaplasma urealyticum (U. urealyticum), Mycoplasma hominis, Trichomonas vaginalis, and Mycoplasma genitalium.
Materials and Methods
A group of 11 men attending a specialized CP/CPPS clinic and a group of 157 women who reported symptoms of lower genital tract infection were enrolled in this study. NB were detected by RT-PCR. A Seeplex Sexually Transmitted Disease Detection assay (Seegene Inc., Seoul, Korea) was used that could detect DNA for 6 types of sexually transmitted pathogens.
Results
In EPS samples, the detection rate of NB in patients with CP/CPPS was 9.1%, and 9 (5.7%) of 157 vaginitis patients showed positive results in RT-PCR for NB in vaginal swabs. Associations observed among the 7 microorganisms included 6 (54.5%) patients who tested positive on EPS and 75 (47.8%) patients who tested positive on vaginal swabs. Five patients with vaginitis were found to have monoinfection of NB (6.7%).
Conclusions
We found that conventional RT-PCR for NB was rapid, simple, low in cost, and easily available for the detection of NB, and that NB may be a possible etiological factor for vaginitis and CP/CPPS. The prevalence of U. urealyticum among the four patients with NB coinfection was 75%; the presence of U. urealyticum might therefore raise suspicion for nanobacterial infection.
doi:10.4111/kju.2011.52.3.194
PMCID: PMC3065132  PMID: 21461284
Nanoparticles; Prostatitis; Reverse transcriptase polymerase chain reaction; Vaginitis
Korean Journal of Urology  2010;51(9):657-659.
The synthetic, tension-free midurethral sling procedure using transobturator tape (TOT) was introduced in 2001 and has become the most widely used procedure for the treatment of female urinary incontinence worldwide. However, infectious complications associated with erosions have occasionally been reported because of a foreign body reaction to the polypropylene mesh. We observed a case of a bilateral recurrent thigh abscess manifesting 5 years after a TOT sling procedure. The patient had recurrent thigh abscesses with repeated incisions and drainages in the past 1 year. Five months earlier, she had undergone a procedure to remove the eroded suburethral mesh, but incompletely. The right thigh abscess recurred, and ultimately the residual mesh was completely excised with abscess drainage. Complete mesh removal is very important to prevent abscess recurrence, and it is necessary for any urologist treating women who have undergone the TOT procedure to be aware of the possibility of abscesses occurring for a long time after the operation.
doi:10.4111/kju.2010.51.9.657
PMCID: PMC2941817  PMID: 20856653
Abscess; Stress urinary incontinence; Suburethral slings
Journal of Gynecologic Oncology  2009;20(2):113-116.
Objective
Platinum (Pt) based drugs including cisplatin and carboplatin are widely used as anticancer drugs in various human cancers. Many studies have shown that chemotherapeutic agents synergistically enhance cell death induced by death ligands. However it has been recently reported that cisplatin may inhibit tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death through inactivation of caspases. Thus, we investigated whether carboplatin also inhibits TRAIL-induced cell death.
Methods
HeLa cells were treated with TRAIL in the presence of cisplatin or carboplatin, and cell death was analyzed using the crystal violet staining method. Caspase activation was checked through detection of Bid cleavage by Western blotting using anti-Bid antibody.
Results
Cisplatin inhibits TRAIL-induced cell death in HeLa cells; however, carboplatin enhanced TRAIL-induced cell death. Whereas cisplatin inhibited caspase-8-mediated Bid cleavage, carboplatin had no effect on caspase-8 activity.
Conclusion
Although cisplatin and carboplatin are platinum-containing cancer therapeutic agents, they have the opposite effects on TRAIL-induced cell death.
doi:10.3802/jgo.2009.20.2.113
PMCID: PMC2704992  PMID: 19590723
Carboplatin; Caspase-8; Cisplatin; TRAIL
Experimental & Molecular Medicine  2008;40(3):294-303.
Even though there is no direct evidence to prove the cellular and molecular changes induced by radiofrequency (RF) radiation itself, we cannot completely exclude the possibility of any biological effect of mobile phone frequency radiation. We established a carousel-type exposure chamber for 849 MHz or 1763 MHz of mobile phone RF radiation to expose RF to the heads of C57BL mice. In this chamber, animals were irradiated intermittently at 7.8 W/kg for a maximum of 12 months. During this period, the body weights of 3 groups-sham, 849 MHz RF, and 1763 MHz RF-did not show any differences between groups. The brain tissues were obtained from 3 groups at 6 months and 12 months to examine the differences in histology and cell proliferation between control and RF exposure groups, but we could not find any change upon RF radiation. Likewise, we could not find changes in the expression and distribution of NeuN and GFAP in hippocampus and cerebellum, or in cell death by TUNEL assay in RF exposure groups. From these data, we conclude that the chronic exposure to 849 MHz and 1763 MHz RF radiation at a 7.8 W/kg specific absorption rate (SAR) could not induce cellular alterations such as proliferation, death, and reactive gliosis.
doi:10.3858/emm.2008.40.3.294
PMCID: PMC2679292  PMID: 18587267
brain; cellular phone; radiation; radiation injuries; gliosis
Interleukin-6 (IL-6) can stimulate a variety of tumors including prostatic carcinoma. Research has recently shown that IL-6 may act to stimulate the progression of prostatic cancer. To date, little research has been performed to better understand the nature of granulocyte macrophage colony-stimulating factor (GM-CSF) and the expression of IL-6. The aim of this study was to evaluate the effects of GM-CSF on the expression of IL-6 in prostate cancer-3 (PC-3) cells. The bone-derived PC-3 cell line was used in this study. Reverse transcription polymerase chain reaction (RT-PCR) and real- time PCR were performed to detect IL-6 mRNA expression. The IL-6 protein was measured by enzyme-linked immunosorbent assay (ELISA) after treatment with hGM-CSF. Our data indicated that IL-6 mRNA expression did not increase after treatment with hGM-CSF in comparison to the control group. However, the expression of IL-6 protein was increased compared to the control group. GM-CSF may modulate the post-transcription pathway of IL-6 expression in prostate carcinoma cells. Our data suggest that GM-CSF may have a role in IL-6-mediated development of prostate cancer.
doi:10.3346/jkms.2008.23.1.94
PMCID: PMC2526505  PMID: 18303206
Prostatic Neoplasms; Interleukin-6; Granulocyte-Macrophage Colony-Stimulating Factor
Molecular Biology of the Cell  2004;15(7):3061-3072.
Release of cytochrome c from the mitochondrial intermembrane space is critical to apoptosis induced by a variety of death stimuli. Bid is a BH3-only prodeath Bcl-2 family protein that can potently activate this efflux. In the current study, we investigated the mitochondrial localization of Bid and its interactions with mitochondrial phospholipids, focusing on their relationships with Bid-induced cytochrome c release. We found that Bid binding to the mitochondria required only three of its eight helical structures (α4-α6), but not the BH3 domain, and the binding could not be inhibited by the antideath molecule Bcl-xL. Membrane fractionations indicated that tBid bound to mitochondrial outer membranes at both contact and noncontact sites. Bid could interact with specific cardiolipin species on intact mitochondria as identified by mass spectrometry. Like the binding to the mitochondria, this interaction could not be blocked by the mutation in the BH3 domain or by Bcl-xL. However, a cardiolipin-specific dye, 10-N-nonyl acridine orange, could preferentially suppress Bid binding to the mitochondrial contact site and inhibit Bid-induced mitochondrial cristae reorganization and cytochrome c release. These findings thus suggest that interactions of Bid with mitochondrial cardiolipin at the contact site can contribute significantly to its functions.
doi:10.1091/mbc.E03-12-0864
PMCID: PMC452564  PMID: 15107464
PLoS ONE  2014;9(1):e80050.
Bacterial cancer therapy relies on the fact that several bacterial species are capable of targeting tumor tissue and that bacteria can be genetically engineered to selectively deliver therapeutic proteins of interest to the targeted tumors. However, the challenge of bacterial cancer therapy is the release of the therapeutic proteins from the bacteria and entry of the proteins into tumor cells. This study employed an attenuated Salmonella typhimurium to selectively deliver the mitochondrial targeting domain of Noxa (MTD) as a potential therapeutic cargo protein, and examined its anti-cancer effect. To release MTD from the bacteria, a novel bacterial lysis system of phage origin was deployed. To facilitate the entry of MTD into the tumor cells, the MTD was fused to DS4.3, a novel cell-penetrating peptide (CPP) derived from a voltage-gated potassium channel (Kv2.1). The gene encoding DS4.3-MTD and the phage lysis genes were placed under the control of PBAD, a promoter activated by L-arabinose. We demonstrated that DS4.3-MTD chimeric molecules expressed by the Salmonellae were anti-tumoral in cultured tumor cells and in mice with CT26 colon carcinoma.
doi:10.1371/journal.pone.0080050
PMCID: PMC3885380  PMID: 24416126

Results 1-17 (17)