Activation of p53-regulated pro-survival signals and hypoxia-independent mitochondrial targeting of TIGAR by human papillomavirus E6 oncoproteins.

The high-risk subtype human papillomaviruses (hrHPVs) infect and oncogenically transform basal epidermal stem cells associated with the development of squamous-cell epithelial cancers. The viral E6 oncoprotein destabilizes the p53 tumor suppressor, inhibits p53 K120-acetylation by the Tat-interacting protein of 60 kDa (TIP60, or Kat5), and prevents p53-dependent apoptosis. Intriguingly, the p53 gene is infrequently mutated in HPV + cervical cancer clinical isolates which suggests a possible paradoxical role for this gatekeeper in viral carcinogenesis. Here, we demonstrate that E6 activates the TP53-induced glycolysis and apoptosis regulator (TIGAR) and protects cells against oncogene-induced oxidative genotoxicity. The E6 oncoprotein induces a Warburg-like stress response and activates PI3K/PI5P4K/AKT-signaling that phosphorylates the TIGAR on serine residues and induces its hypoxia-independent mitochondrial targeting in hrHPV-transformed cells. Primary HPV + cervical cancer tissues contain high levels of TIGAR, p53, and c-Myc and our xenograft studies have further shown that lentiviral-siRNA-knockdown of TIGAR expression inhibits hrHPV-induced tumorigenesis in vivo. These findings suggest the modulation of p53 pro-survival signals and the antioxidant functions of TIGAR could have key ancillary roles during HPV carcinogenesis.

Balloon dilation performs poorly as a salvage management strategy for recurrent bulbar urethral strictures following failed urethroplasty.

BACKGROUND: The optimal management strategy for recurrent urethral stricture disease (USD) following urethroplasty remains undefined. We aim to evaluate the role and efficacy of endoscopic urethral balloon dilation in temporizing recurrent USD after failed urethroplasty. METHODS: Between 2007-2018 at our institution, 80 patients underwent balloon dilation procedures for bulbomembranous urethral strictures. Balloon dilation was performed with an 8-cm, 24-French UroMax Ultra™ balloon dilator, under direct vision, guided by a 16-French flexible cystoscope. Patients who underwent concomitant open or endoscopic urethral procedures were excluded. Treatment failure was defined as the need for subsequent surgical intervention for stricture recurrence. Stricture characteristics including etiology, length, location, severity stage, and prior surgical procedures were compared between patients with and without treatment failure. RESULTS: Failure cases were more likely to have strictures following urethroplasty (21/27, 78%) [vs. the no-failure group (27/53, 51%)]. Among the 27/80 (33.8%) failures with a median follow-up of 8.4 months (IQR, 3.9-22.5 months), median time to recurrence was 4 months (IQR, 2-12 months). These patients had a greater incidence of prior stricture intervention in general (P=0.01) and prior urethroplasty specifically (P=0.03). On multivariable analysis, the number of prior treatments specifically independently remained associated with treatment failure. Complications of balloon dilation were uncommon (6/80, 7.5%) and minor in nature. CONCLUSIONS: Endoscopic balloon dilation performs poorly as a salvage strategy after failed open urethral reconstruction in addition to prior urethral dilations.

Age ≤40 is an independent predictor of anastomotic urethroplasty and successful repair of bulbar urethral strictures.

BACKGROUND: Among men with bulbar strictures, we aimed to analyze stricture characteristics, repair type, and treatment success in younger versus older patient cohorts. METHODS: We retrospectively reviewed our single surgeon database with patients undergoing bulbar urethroplasty from 2007 to 2017. This population was then age-stratified into ≤40 and >40-year-old cohorts. Exclusion criteria included patients with penile strictures and those with history of hypospadias. Patient characteristics, surgical approach, and outcome were compiled by medical record and database review. Criterion for success included functional emptying and lack of repeat surgical intervention. Parameters associated with failure were included in multivariate logistic regression models. RESULTS: Eight hundred and fifty-three patients with bulbar strictures were identified, 231 patients (27.1%) ≤40 years old and 622 patients (72.9%) >40 years old. Mean stricture length was significantly longer in older men (2.3 vs. 2.7 cm, P=0.005). Excision and primary anastomosis (EPA) were more commonly utilized when managing younger compared to older patient groups (87% in ≤40 group, 77% in >40, P=0.0009). Younger men underwent significantly fewer endoscopic stricture treatments than older men (2.1 vs. 4.9, P=0.001). Traumatic etiology was more commonly attributable in the younger group (48% vs.17%, P<0.0001). Younger men presented less frequently with diabetes (1.7% vs. 21.7%, P<0.0001), coronary artery disease (0.4% vs. 19.1%, P<0.0001), and erectile dysfunction (11.5% vs. 29.2%, P<0.0001) relative to older men. Over a median follow-up of 52.4 months, success rates were higher in the ≤40 cohort (97.4%) than the >40 cohort (87.3%, P<0.0001). On multivariate logistic regression, independent predictors of urethroplasty success include younger age), utilization of EPA, and lack of pelvic radiation. CONCLUSIONS: Although men ≤40 years old have a higher incidence of traumatic etiology, bulbar urethroplasty has a higher success rate when compared to patients >40 years old. Bulbar strictures are more amenable to EPA in the younger population, likely due to fewer endoscopic treatments and favorable tissue characteristics.

Outpatient buccal mucosal graft urethroplasty outcomes are comparable to inpatient procedures.

BACKGROUND: We sought to compare outcomes between inpatient and outpatient buccal mucosal graft (BMG) urethroplasty among a large tertiary referral center series. METHODS: A retrospective review of consecutive patients who underwent BMG urethroplasty between 2007 and 2018 was performed, including only first stage and one stage graft procedures. Patients were divided into inpatient and outpatient groups. Demographic and outcome data were collected and analyzed, with success defined as no need for further endoscopic or open reoperative management. RESULTS: Of 143 patients undergoing BMG urethroplasty during the study period, 87 cases (60.8%) were performed on an inpatient basis, and 56 (39.2%) on an outpatient basis. Patient characteristics such as age, BMI, prior endoscopic procedures and co-morbid factors were similar between inpatient and outpatient groups. Perioperative characteristics such as estimated blood loss were also similar between groups, but the inpatient cohort had a longer operative time (157.6 vs. 123.1 min, P<0.0001). Operative success was comparable in the two groups (74.7% inpatient vs. 76.8% outpatient, P=0.7) as were rates of complications (29.9% inpatient vs. 26.8% outpatient, P=0.07). CONCLUSIONS: BMG urethroplasty can be safely performed in an ambulatory setting without increased complications or compromised outcomes.

Long-term sequelae of inflatable penile prosthesis: clinical characteristics of patients who develop distal cylinder tip extrusion.

BACKGROUND: Impending distal cylinder tip extrusions (DCTE) make up approximately 5-33% of all inflatable penile prosthesis (IPP) reoperations. While there have been a few case reports of DCTE in patients with diabetes and trauma, the current literature regarding risk factors for DCTE is limited. In this study, we examined the long-term sequelae among a large cohort of IPP patients to identify clinical risk factors for impending DCTE. METHODS: A retrospective review was completed of our single surgeon IPP database of 797 IPP placement cases from the years 2007 to 2018. We identified those who had a surgical intervention for a confirmed DCTE. Infected prostheses were excluded. The primary clinical end point of this study was to identify the time to extrusion repair from original penile prosthesis placement. Secondary clinical end points included location of extrusion and presence of corporal fibrosis. RESULTS: Between the years 2007 to 2018, 26 cases (3%) of impending or complete cylinder extrusions were identified in our IPP database (n=797). The mean age at initial IPP placement was 58 years, compared to a mean of 66 years at the time of extrusion. The mean time from initial placement to extrusion repair surgery was 8.4 years (median 5.5 years). Most patients (15/26, 57.7%) had a history of prior IPP placement, five of whom had two or more prior prostheses. Location among the 26 extrusions varied-12 (46.2%) lateral, 9 (34.6%) distal urethra, 2 (7.7%) glanular, 2 (7.7%) mid-shaft, and 1 (3.8%) coronal sulcus. Concomitant pathologies identified include Peyronie's disease (7, 26.9%), idiopathic corporal fibrosis (7, 26.9%) and sickle cell disease with priapism induced erectile dysfunction (3, 11.5%). CONCLUSIONS: The risk of IPP extrusion appears to be associated with increased time from initial prosthesis placement, prior history of IPP placement, and the presence of corporal fibrosis or deformity. Patients should be counseled to recognize this important long-term sequela of IPP surgery.

Urethral atrophy is now a rare cause for artificial urinary sphincter revision surgery in the contemporary 3.5 cm cuff era.

BACKGROUND: Urethral atrophy has long been suggested as the leading cause of artificial urinary sphincter (AUS) revision. Since the introduction of the 3.5 cm AUS cuff in 2010, precise cuff sizing primarily has been suggested to reduce revisions due to urethral atrophy. We evaluated a large contemporary series of reoperative AUS cases to determine reasons for revision surgery. METHODS: We retrospectively reviewed our tertiary referral center database of male AUS procedures performed by a single surgeon from 2007-2019. AUS revision or replacement procedures were included for analysis. Cuff sizes and reasons for reoperation were recorded based on intraoperative findings and evaluated for temporal trends. Patients with cuff erosion or lacking follow-up were excluded. RESULTS: Among 714 AUS cases, 177 revisions or replacements were identified. Of these, 137 met inclusion criteria [mean age 71.7 years, median follow-up 52.7 months (IQR 22.3-94.6 months)]. Urethral atrophy was cited as the cause of AUS failure in 8.0% (11/137) of cases overall, virtually never among those with a 3.5 cm cuff placement (1/51, 2.0%). In those with ≥4.0 cm cuffs, urethral atrophy was the reason for revision in 10/86 (11.6%). Pressure regulating balloon (PRB) failure was the most frequently cited cause of failure (47/137, 34.3%). Cuff-related failure (23/137, 16.8%) and mechanical failure of unspecified device component (16/137, 11.8%) were the next most frequent causes of failure. CONCLUSIONS: Urethral atrophy has become a rare cause of AUS revision surgery since the availability of smaller cuffs. PRB-related failure is now the leading cause of AUS reoperation.

Comparison of 3.5 cm and transcorporal cuffs in high-risk artificial urinary sphincter populations.

BACKGROUND: The transcorporal (TC) artificial urinary sphincter (AUS) has traditionally been utilized in high-risk patients with urethral atrophy or prior urethral erosion. The 3.5 cm AUS cuff has been developed for use in a similar population. We compared the outcomes of TC AUS and 3.5 cm cuff patients to assess whether the TC approach was protective against urethral complications. METHODS: We performed a retrospective review for all men who underwent TC AUS and 3.5 cm AUS implantation by a single surgeon from 2007 to 2018 at a tertiary medical center. Demographic and outcomes data were collected and analyzed after database review to evaluate for rates of urethral erosion. Multivariate logistic regression was performed to identify co-morbid factors associated with urethral erosion. RESULTS: In our database of 625 AUS patients, we identified 59 (9%) men with TC AUS and 168 (27%) having a 3.5 cm cuff. Over a median follow-up time of 49 months, 28 (47%) men with TC cuffs developed urethral erosion compared with 25 (15%) men with a 3.5 cm cuff. On univariate analysis, a TC cuff was associated with increased odds of erosion (OR 6.65, 95% CI: 3.20-14.4, P<0.0001) when compared with a 3.5 cm cuff. On multivariate analysis, TC cuffs continued to portend significantly increased odds of cuff erosion. CONCLUSIONS: With longer follow up, TC AUS may not be as protective against urethral complications as previously described.

Preventing the need for revision surgery after penile plication reconstruction of Peyronie's deformities.

BACKGROUND: The need for repeat penile plication (PP) for persistent penile deformity has previously been associated with (I) poor initial erectile response to intracavernosal injection (ICI), (II) an inadequate number of corrective sutures, and (III) a lack of sutures along the proximal shaft of the penis. We present our current experience with PP after implementing corrective measures to assess whether our need for revision surgery was reduced. METHODS: We performed a retrospective review of patients who underwent PP for Peyronie's disease (PD) between 2009-2018 and had a minimum follow-up of 6 months. We updated our surgical technique in 2016 by (I) using supplemental intracorporal saline injections if the initial erection response to prostaglandin E1 injection was inadequate, (II) increasing numbers of corrective plication sutures, and (III) emphasizing more proximal suture placement. Patients were stratified into two groups and outcomes compared (prior technique versus current technique). RESULTS: Of 472 PP patients who met inclusion criteria, 340 (72%) plication patients before 2016 were compared to 132 (28%) performed after 2016. The revision rate in the current cohort (1.5%, 2/132) decreased by more than half compared to the previous cohort (3.8%, 13/340). Mean preoperative angle of curvature was similar between the two groups (50.4 vs. 51.4 degrees, P=0.64), while the average residual postoperative degree was smaller in the current group (7.36 vs. 2.14 degrees, P<0.001). Fewer sutures were used in the early cohort than in the current (7.63 vs. 8.38, P=0.04). After revision, all cases were functionally straight, with a mean postoperative curvature of 4 degrees at a median follow-up of 10.6 months (IQR, 2.08-20.7). CONCLUSIONS: Ensuring adequate rigidity with additional ICI and focusing a greater number of corrective sutures in a more proximal location appears to help prevent the need for revision plication surgery.

Dutasteride in the long-term management of stuttering priapism.

BACKGROUND: The objective of this study is to review our 12-year experience with the 5-α reductase inhibitor dutasteride as a potential long-term treatment option for stuttering priapism. Dutasteride has a uniquely long half-life of 35 days which offers a theoretical advantage as a chronic therapy for management of stuttering priapism. METHODS: We retrospectively reviewed patients with stuttering priapism in our database from 2006-2018 treated with dutasteride. Men with concurrent use of medications other than dutasteride to treat stuttering priapism were excluded. Patients were started on a dose of 0.5 mg daily and tapered to a more infrequent dosing schedule, ranging from 0.5 mg every other day to once weekly. The frequency of priapism episodes before and after initiation of dutasteride therapy was analyzed. RESULTS: Among 21 cases, 13 patients met our inclusion criteria (mean age 43 years). Median follow-up on daily dutasteride was 79 days, and median follow-up on tapered dutasteride was 607 days. A total of 11/13 (85%) men treated with dutasteride had some degree of improvement-5/13 (38%) had complete resolution of their symptoms and 6/13 (46%) had reduced frequency and/or severity of their episodes. Among 5/13 (38%) men who had >2 emergency room (ER) visits for ischemic priapism prior to therapy, most (3/5, 60%) did not require any ER visits while on dutasteride therapy. Among the five men who received chronic, tapered-dose therapy, all reported continued suppression of priapistic episodes. Among 4 patients with sickle cell disease (SCD), 3/4 (75%) ultimately chose more invasive therapy including androgen deprivation therapy (ADT) and penile prosthesis. Side effects were minimal and included gynecomastia (8%), decreased libido (8%), and fatigue (8%). CONCLUSIONS: In patients with stuttering priapism, daily dutasteride therapy is a promising treatment option to reduce the frequency and severity of priapistic episodes without significant side effects. Therapy can effectively be tapered to once weekly dosing without a reduction in efficacy.

Strong correlation between standing cough test and 24-hour pad weights in the evaluation of male stress urinary incontinence.

AIMS: We sought to compare in-office physical exam findings via standing cough test (SCT) versus 24-hour pad weights among men seeking treatment for postprostatectomy stress urinary incontinence (SUI). METHODS: A retrospective review of a single surgeon database of incontinence procedures was performed. Documentation of SUI severity (grades 0-4) was completed by SCT preoperatively utilizing the Male Stress Incontinence Grading Scale (MSIGS). All patients had pads per day (PPD) and 24-hour pad weights obtained. We determined the Spearman's correlation coefficient between these variables. RESULTS: We identified 104 men who underwent anti-incontinence surgery (AdVance Sling or artificial urinary sphincter [AUS]). In the sling group (65 patients), nearly all (97%) had minimal incontinence with SCT (MSIGS = 0-2). In the AUS group (39 patients), most patients (69%) had an MSIGS 3 or 4 with SCT. Spearman's coefficient between quantification of SCT and pad weight for the overall group was ρ = .68 (P < .0001) demonstrating a strong positive correlation. PPD was also strongly correlated with pad weight (ρ = .55, P < .0001). As seen previously, SCT and PPD were correlated (ρ = .47, P < .0001). In a multivariable model predicting pad weight, the effect of SCT was greater than PPD (ß = 83 [54-111], P < .0001 vs 45 [2169], P = .0004). CONCLUSIONS: SCT findings strongly correlate to 24-hour pad weights in the evaluation of male SUI. The SCT shows promise as a rapid, reliable, noninvasive measure of SUI severity before anti-incontinence surgery.

Long-term outcomes of anastomotic urethroplasty for radiation-induced strictures.

PURPOSE: To present our experience with excision and primary anastomosis (EPA) of radiation-induced urethral strictures (RUS) in men, including risk factors for stricture recurrence and long-term recurrence rates. METHODS: A retrospective review was performed of patients who underwent EPA of RUS between 2007 and 2018 at a single tertiary referral center. Demographic information, stricture location and length, complications, and stricture recurrence were analyzed. Univariate and multivariate Cox regression analyses were performed to identify variables impacting recurrence. RESULTS: EPA was performed in 116 patients with RUS. The majority of patients (86.2%, 100/116) underwent at least one prior urologic intervention. Mean stricture length was 2.3 cm. Stricture recurrence occurred in 19.0% (22/116) at a mean of 8.6 months. For patients with at least 1 year of postoperative follow-up (mean 30.7 months), stricture recurrence significantly increased to 36.6% (15/41; p = 0.03). On univariate and multivariate analyses, postoperative complications were associated with stricture recurrence (p < 0.001). CONCLUSION: EPA remains a viable option for men with RUS. Nearly two-thirds of RUS patients remain recurrence-free with long-term follow-up following EPA.

The human T-cell leukemia virus type-1 tax oncoprotein dissociates NF-κB p65RelA-Stathmin complexes and causes catastrophic mitotic spindle damage and genomic instability.

Genomic instability is a hallmark of many cancers; however, the molecular etiology of chromosomal dysregulation is not well understood. The human T-cell leukemia virus type-1 (HTLV-1) oncoprotein Tax activates NF-κB-signaling and induces DNA-damage and aberrant chromosomal segregation through diverse mechanisms which contribute to viral carcinogenesis. Intriguingly, Stathmin/oncoprotein-18 (Op-18) depolymerizes tubulin and interacts with the p65RelA subunit and functions as a cofactor for NF-κB-dependent transactivation. We thus hypothesized that the dissociation of p65RelA-Stathmin/Op-18 complexes by Tax could lead to the catastrophic destabilization of microtubule (MT) spindle fibers during mitosis and provide a novel mechanistic link between NF-κB-signaling and genomic instability. Here we report that the inhibition of Stathmin expression by the retroviral latency protein, p30II, or knockdown with siRNA-stathmin, dampens Tax-mediated NF-κB transactivation and counters Tax-induced genomic instability and cytotoxicity. The Tax-G148V mutant, defective for NF-κB activation, exhibited reduced p65RelA-Stathmin binding and diminished genomic instability and cytotoxicity. Dominant-negative inhibitors of NF-κB also prevented Tax-induced multinucleation and apoptosis. Moreover, cell clones containing the infectious HTLV-1 ACH. p30II mutant provirus, impaired for p30II production, exhibited increased multinucleation and the accumulation of cytoplasmic tubulin aggregates following nocodozole-treatment. These findings allude to a mechanism whereby NF-κB-signaling regulates tubulin dynamics and mitotic instability through the modulation of p65RelA-Stathmin/Op-18 interactions, and support the notion that p30II enhances the survival of Tax-expressing HTLV-1-transformed cells.

Synchronous Urethral Repair During Prosthetic Surgery: Safety of Planned and Damage Control Approaches Using Suprapubic Tube Urinary Diversion.

BACKGROUND: Urethral injury during inflatable penile prosthesis (IPP) or artificial urinary sphincter (AUS) placement is rare, and traditionally most prosthetic surgeons abort prosthetic implantation when urethral repair is necessary. AIM: To report our experience with synchronous urethroplasty (SU) as a planned or damage control surgery during urologic prosthetic surgery, to evaluate the safety and outcomes of the procedure. METHODS: A retrospective review of our IPP and AUS database was completed to identify patients who underwent an SU between 2007 and 2018. We included patients who underwent an SU during prosthetic surgery in either a planned procedure for known stricture or diverticulum or a "damage control" procedure after intraoperative injury. OUTCOME: Patient characteristics and surgical outcomes were assessed, with success defined as the absence of urethral stricture and revision surgery. RESULTS: From our database of 1,508 prosthetic cases, we identified 7 patients (0.46%) who had an SU in the same setting as complete prosthesis placement (4 AUS and 3 IPP [1 combined IPP/AUS], and 1 sling). Three patients underwent planned repair of a known urethral abnormality (urethral diverticulum, urethrocutaneous fistula, and urethral stricture), and 4 underwent repair of an intraoperative urethral injury. Among the patients who experienced an intraoperative urethral injury, contributing etiologies included previous anti-incontinence surgery with periurethral fibrosis (n = 2), severe corporal fibrosis from priapism, and previous urethral disruption from pelvic fracture. Nearly all of the urethroplasties (6 of 7; 86%) were completed with a primary closure. The average indwelling duration of suprapubic tube (SPT) catheters was 4.1 weeks (range, 7 to 47 days). The average duration of follow-up was 21.5 months, and all patients were continent at follow-up. No device infections or urethral complications were identified. CLINICAL IMPLICATIONS: Our study illustrates the safety of concomitant urethral repair at time of prosthetic placement as an option to avoid the use of 2 anesthetics and prevent further scarring in high-risk patients. STRENGTHS & LIMITATIONS: This is the first study to address definitive urethral reconstruction during anti-incontinence procedures along with planned concomitant urethroplasty during IPP placement. This promising initial experience is relevant for surgeons who may encounter concomitant urethral pathology in the setting of complex reoperative prosthetic cases. The need for SU is rare, and thus our cohort size was limited in this retrospective, single-institution experience. CONCLUSION: SU with prolonged SPT urinary diversion offers a safe damage control approach for men with concomitant urethral pathology during prosthetic surgery without conferring an increased risk of infection or stricture. Yi YA, Fuchs JS, Davenport MT, et al. Synchronous Urethral Repair During Prosthetic Surgery: Safety of Planned and Damage Control Approaches Using Suprapubic Tube Urinary Diversion. J Sex Med 2019;16:1106-1110.

The TP53-Induced Glycolysis and Apoptosis Regulator mediates cooperation between HTLV-1 p30II and the retroviral oncoproteins Tax and HBZ and is highly expressed in an in vivo xenograft model of HTLV-1-induced lymphoma.

The human T-cell leukemia virus type-1 (HTLV-1) is an oncoretrovirus that infects and transforms CD4+ T-cells and causes adult T-cell leukemia/lymphoma (ATLL) -an aggressive lymphoproliferative disease that is highly refractive to most anticancer therapies. The HTLV-1 proviral genome encodes several regulatory products within a conserved 3' nucleotide sequence, known as pX; however, it remains unclear how these factors might cooperate or dynamically interact in virus-infected cells. Here we demonstrate that the HTLV-1 latency-maintenance factor p30II induces the TP53-induced glycolysis and apoptosis regulator (TIGAR) and counters the oxidative stress, mitochondrial damage, and cytotoxicity caused by the viral oncoproteins Tax and HBZ. The p30II protein cooperates with Tax and HBZ and enhances their oncogenic potential in colony transformation/foci-formation assays. Further, we have shown that TIGAR is highly expressed in HTLV-1-induced tumors associated with oncogene dysregulation and increased angiogenesis in an in vivo xenograft model of HTLV-1-induced T-cell lymphoma. These findings provide the first evidence that p30II likely collaborates as an ancillary factor for the major oncoproteins Tax and HBZ during retroviral carcinogenesis.

The human T-cell leukemia virus type-1 p30II protein activates p53 and induces the TIGAR and suppresses oncogene-induced oxidative stress during viral carcinogenesis.

In normal cells, aberrant oncogene expression leads to the accumulation of cytotoxic metabolites, including reactive oxygen species (ROS), which can cause oxidative DNA-damage and apoptosis as an intrinsic barrier against neoplastic disease. The c-Myc oncoprotein is overexpressed in many lymphoid cancers due to c-myc gene amplification and/or 8q24 chromosomal translocations. Intriguingly, p53 is a downstream target of c-Myc and hematological malignancies, such as adult T-cell leukemia/lymphoma (ATL), frequently contain wildtype p53 and c-Myc overexpression. We therefore hypothesized that p53-regulated pro-survival signals may thwart the cell's metabolic anticancer defenses to support oncogene-activation in lymphoid cancers. Here we show that the Tp53-induced glycolysis and apoptosis regulator (TIGAR) promotes c-myc oncogene-activation by the human T-cell leukemia virus type-1 (HTLV-1) latency-maintenance factor p30II, associated with c-Myc deregulation in ATL clinical isolates. TIGAR prevents the intracellular accumulation of c-Myc-induced ROS and inhibits oncogene-induced cellular senescence in ATL, acute lymphoblastic leukemia, and multiple myeloma cells with elevated c-Myc expression. Our results allude to a pivotal role for p53-regulated antioxidant signals as mediators of c-Myc oncogenic functions in viral and non-viral lymphoid tumors.

Uncomplicated E. coli urinary tract infection in college women: a follow-up study of E. coli sensitivities to commonly prescribed antibiotics.

Treatment of uncomplicated urinary tract infections (UTIs) has changed in the past few years with researchers advocating empiric treatment for shorter periods of time without the use of cultures. Researchers report that antibiotic resistance of Escherichia coli (E. coli) to commonly prescribed antibiotics in uncomplicated UTIs has been increasing. Trimethoprim/sulfamethoxazole (TMP/SMX) is 1 of these antibiotics. Researchers also report that resistance patterns may differ depending on the geographic area of the United States. In this study, the authors present the results of a 7-month retrospective chart analysis of 98 E. coli sensitivities to commonly prescribed antibiotics in the treatment of uncomplicated UTIs at a college health service. They examined the more common antibiotic choices and analyzed their in vitro responses. Of these antibiotics, ciprofloxacin, nitrofurantoin, amoxicillin/clavulanate, and TMP/SMX had the highest sensitivity rates. The authors compared the results with a previous study that they performed at the same institution in 1993. The results of this study show a sensitivity rate of 86% for TMP/SMX. When compared with the previous result of 87%, this represented a 1% change. Because of this slight decrease in sensitivity and the increasing concern over resistance, the authors suggest that they will continue to reevaluate the resistance pattern in their population on a regular basis. This will help determine if there is a need for modifying choices of empiric therapy for UTIs.