Impact of gene expression profiling on diagnosis and survival after metastasis in patients with uveal melanoma.

Surveillance frequency for metastasis is guided by gene expression profiling (GEP). This study evaluated the effect of GEP on time to diagnosis of metastasis, subsequent treatment and survival. A retrospective study was conducted of 110 uveal melanoma patients with GEP (DecisionDx-UM, Castle Biosciences, Friendswood, Texas, USA) and 110 American Joint Committee on Cancer-matched controls. Surveillance testing and treatment for metastasis were compared between the two groups and by GEP class. Rates of metastasis, overall survival and melanoma-related mortality were calculated using Kaplan-Meier estimates. Baseline characteristics and follow-up time were balanced in the two groups. Patients' GEP classification was 1A in 41%, 1B in 25.5% and 2 in 33.6%. Metastasis was diagnosed in 26.4% ( n  = 29) in the GEP group and 23.6% ( n  = 26) in the no GEP group ( P  = 0.75). Median time to metastasis was 30.5 and 22.3 months in the GEP and no GEP groups, respectively ( P  = 0.44). Median months to metastasis were 34.7, 75.8 and 26.1 in class 1A, 1B and 2 patients, respectively ( P  = 0.28). Disease-specific 5-year survival rates were 89.4% [95% confidence interval (CI): 81.0-94.2%] and 84.1% (95% CI: 74.9-90.1%) in the GEP and no GEP groups respectively ( P  = 0.49). Median time to death from metastasis was 10.1 months in the GEP group and 8.5 months in the no GEP group ( P  = 0.40). There were no significant differences in time to metastasis diagnosis and survival outcomes in patients with and without GEP. To realize the full benefit of GEP, more sensitive techniques for detection of metastasis and adjuvant therapies are required.

Perioperative outcomes of laparoscopic low anterior resection using ArtiSential® versus robotic approach in patients with rectal cancer: a propensity score matching analysis.

BACKGROUND: Total mesorectal excision using conventional straight fixed devices may be technically difficult because of the narrow and concave pelvis. Several laparoscopic articulating tools have been introduced as an alternative to robotic systems. The aim of this study was to compare perioperative outcomes between laparoscopic low anterior resection using ArtiSential® and robot-assisted surgery for rectal cancer. METHODS: This retrospective study included 682 patients who underwent laparoscopic or robotic low anterior resection  for rectal cancer from September 2018 to December 2021. Among them, 82 underwent laparoscopic surgery using ArtiSential® (group A) and 201 underwent robotic surgery (group B). A total of 73 [group A; 66.37 ± 11.62; group B 65.79 ± 11.34] patients were selected for each group using a propensity score matching analysis. RESULTS: There was no significant difference in the baseline characteristics between group A and B. Mean operative time was longer in group B than A (163.5 ± 61.9 vs 250.1 ± 77.6 min, p < 0.001). Mean length of hospital stay was not significantly different between the two groups (6.2 ± 4.7 vs 6.7 ± 6.1 days, p = 0.617). Postoperative complications, reoperation, and readmission within 30 days after surgery were similar between the two groups. Pathological findings revealed that the circumferential resection margins were above 10 mm in both groups (11.00 ± 7.47 vs 10.17 ± 6.25 mm, p = 0.960). At least 12 lymph nodes were sufficiently harvested, with no significant difference in the number harvested between the groups (20.5 ± 9.9 vs 19.7 ± 7.3, p = 0.753). CONCLUSIONS: Laparoscopic low anterior resection using ArtiSential® can achieve acceptable clinical and oncologic outcomes. ArtiSential®, a multi-joint and articulating device, may serve a feasible alternative approach to robotic surgery in rectal cancer.

Revisiting straight-line repair in unilateral complete cleft lip: a comparison with rotation-advancement repair.

Rotation-advancement repair (RAR) has been the most widely used technique for unilateral cleft lip repair. We recently used a straight-line repair with medial orbicularis muscle lengthening (SLR-ml) technique, based on the hypothesis that it could minimize the postoperative scar appearance without causing s short-lip deformity when muscle reorientation is performed correctly. A retrospective cohort study was conducted on unilateral complete cleft lip patients who underwent cheiloplasty between 2009 and 2017. Two cheiloplasty techniques were compared: RAR and SLR-ml. Outcomes were evaluated by assessing follow-up photographs using three methods: (1) glance impression on a five-point scale, (2) Manchester Scar Scale, and (3) indirect anthropometry. Seventy-one patients were analysed: 41 in the RAR group (28 male, 13 female) and 30 in the SLR-ml group (15 male, 15 female). The glance impression (P=0.506) and Manchester Scar Scale (P=0.347) scores did not differ between the groups. According to the symmetry ratio (cleft side value/non-cleft side value), vertical lip height (P=0.804), horizontal lip length (P=0.881), and Cupid's bow width (P=0.122) did not differ significantly between the groups. The preoperative lip height discrepancy was not correlated with the postoperative vertical lip height. The SLR-ml method can be regarded as a successful tool for symmetric repair of unilateral cleft lip.

Liver Transplantation for Severe Alcoholic Hepatitis: Report of a Single Center Pilot Program.

BACKGROUND: Liver transplantation (LT) can significantly improve mortality for severe alcoholic hepatitis (AH). However, this practice remains controversial. Our aim is to report the findings from our institution regarding outcomes for LT in severe AH and to discuss the results of a pilot program for discharging selected patients with close follow-up, in order to demonstrate sustained outpatient sobriety before listing. METHODS: Patient records were reviewed retrospectively from January 1, 2015 to January 17, 2018. The primary outcomes were patient and graft survival after LT. Secondary outcomes included relapse rates after LT, survival for those not transplanted, and reasons for denial among those not approved for transplant listing. RESULTS: A total of 18 patients with severe AH were considered for LT, of which 10 were transplanted and 8 were either denied transplantation or died before completing the evaluation. Patient and graft survival rates were 100% among those transplanted, and only 1 of the 10 patients (10%) returned to harmful drinking. In comparison, 6 of 8 (75%) of patients not transplanted died. Among the 10 patients transplanted, 4 were initially not approved for listing and were discharged with close follow-up, to demonstrate outpatient sobriety. All 4 of those patients demonstrated short-term abstinence and ultimately underwent transplantation, with no instances of relapse post-LT. CONCLUSIONS: Liver transplantation for AH can achieve excellent outcomes with low rates of relapse. Carefully selected patients can be discharged with close monitoring to demonstrate commitment to outpatient sobriety prior to transplant listing.

Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Failure in a Liver Transplant Patient: A Case Report.

Intraoperative extracorporeal membrane oxygenation (ECMO) support, both venoarterial and venovenous (VV), have been used sparingly and with limited success in the setting of liver transplantation. Here, we report the successful use of VV-ECMO in the resuscitation and pulmonary bridging support after severe systemic inflammatory response in a combined liver and kidney transplant recipient who suffered primary nonfunction of both allografts. Where conventional ventilator maneuvers may prove ineffective, the implementation of VV-ECMO should be considered as a therapeutic option in limited, short-lived acute pulmonary injury.

Impact of Early Hospital Readmissions After Kidney Transplantation on Graft Function.

Early hospital readmissions are common after kidney transplantation. This single-center retrospective study investigated the relationship between early hospital readmissions and clinical outcomes. All adult patients receiving a kidney transplant at this center between March 2009 and June 2015 were included. The early hospital readmissions within the first 30 days were numbered, and the diagnosis was ascertained. The patients were divided into None and Readmission groups. Clinical outcomes and patient- and death-censored graft survival were compared. Among the 103 patients included in the study, 32 (31.1%) had 1 or more readmissions within 30 days. Surgical complications, electrolyte imbalance, and acute rejection were common causes of readmission. No differences were observed in baseline characteristics between the two groups. Patients with early readmissions exhibited low renal function at 3, 6, and 12 months postoperatively (P = .002, .020, and .013, respectively). No difference in graft function was found 12 months after transplantation between the None and Readmission groups. Five-year graft and patient survival also showed no difference between the two groups (P = .424 and .442, respectively). In conclusion, early readmission after kidney transplantation affected lower graft function until 1 year after kidney transplantation. However, the long-term effect on graft function is limited in this study.

Outcomes of Highly Sensitized Patients Undergoing Simultaneous Liver and Kidney Transplantation: A Single-Center Experience With Desensitization.

BACKGROUND: Preformed donor-specific human leukocyte antigen antibodies (DSAs) in patients undergoing simultaneous liver and kidney transplantation (SLKT) are an independent risk factor for poorer patient and renal allograft survival. The outcomes of patients highly sensitized (HS) against HLA antigens undergoing SLKT and select HS SLKT recipients undergoing desensitization at a high-volume desensitization center were investigated. METHODS: Seventy-five patients undergoing SLKT at a high-volume desensitization center between January 1, 2001, and December 31, 2015, were retrospectively reviewed. HS patients were defined by panel-reactive antibody (PRA) >30% (n = 17 patients), 11 of whom received pre- or perioperative desensitization with high-dose intravenous immunoglobulin (IVIG) ± rituximab. RESULTS: HS patients had significantly higher class I and class II PRA (class I = 41.3% ± 40.0% vs 2.5% ± 6.3%; class II = 45.7% ± 36.4% vs 1.0% ± 2.9%; P < .001), were more likely to be female (P = .05), and more likely to have had a prior transplant (P = .03). HS patients demonstrated greater susceptibility to renal cell-mediated rejection (CMR) (23.5% vs 5.2%, P = .02) compared to nonsensitized patients. Higher renal antibody-mediated rejection (ABMR) was also observed in HS patients, 11.8% vs 3.4%, but did not reach significance (P = .18). Desensitization in select HS SLKT patients was well tolerated but did not improve patient and allograft survival or significantly curtail rejection. CONCLUSION: HS SLKT recipients demonstrated increased allograft rejection, particularly CMR, but patient and graft survival were not impacted in the first year post-transplant. Select HS SLKT patients tolerated desensitization with high-dose IVIG ± rituximab and may have received additional immunoprotection against ABMR but survival was not affected.

Health-Related Quality of Life and Psychologic Distress in Korean Kidney Transplant Recipients.

BACKGROUND: Little is known about the extent to which transplant recipients face psychologic distress with the receipt of a transplanted organ. The purpose of this study was to investigate health-related quality of life (HRQoL) and psychologic distress in 105 adults who had undergone kidney transplantation (KT). METHODS: HRQoL was measured with the use of the Korean version of Medical Outcome Study Short Form 36 version 2, and psychologic distress with the use of the Transplant Effects Questionnaire (TEQ). Clinical and demographic data were collected from questionnaires. The data were collected from August 2014 to November 2014 at 2 medical centers in Korea. RESULTS: Of the 105 patients, 53.3% were male and the overall mean age was 46.99 years. The mean score of each of the TEQ subscales ranged from 2.45 to 4.62. In the subscales of HRQoL, the mean score of physical component summary (PCS) was 50.23, and the mean score of mental component summary (MCS) was 46.19. MCS was negatively correlated with worry (P = .001) and guilt (P = .037) and positively correlated with adherence (P = .006) in the TEQ subscales, whereas there was no significant correlation between PCS and the TEQ subscales. CONCLUSIONS: The study indicates that mental HRQoL is correlated with psychologic distress. Therefore, to increase the HRQoL, continuous attention is needed in kidney transplant recipients who experience psychologic distress and adherence problem. In addition, further empirical studies should be conducted to explain the mechanisms underlying this relationship.

Early Weight Gain After Transplantation Can Cause Adverse Effect on Transplant Kidney Function.

BACKGROUND: The outcomes of kidney transplant recipients with increased body mass index (BMI) remain controversial. We studied the relationship between changes in BMI and kidney transplant function, especially during the first year after transplantation. METHODS: We performed an observational cohort study of all kidney transplant recipients at our center from March 2009 to June 2014 to determine whether changes in BMI were associated with kidney transplant function, as measured by estimated glomerular filtration rate (eGFR). Recipient BMI and eGFR were calculated pre-transplant and at 1, 3, 6, 9, and 12 postoperative months (POM) after transplantation. The correlation between changes in BMI and eGFR was then evaluated. RESULTS: Eighty-one patients were studied. There was a strong negative correlation between changes in BMI and eGFR from pre-transplant to POM 1 (correlation coefficient, -0.406; P < .0001) and from POM 1 to POM 3 (r = -0.324, P = .004). CONCLUSIONS: We found that increased BMI caused a significant decline in renal function as measured by eGFR, especially in the initial 3 months after kidney transplantation.

Intravitreal aflibercept for macular oedema secondary to central retinal vein occlusion in patients with prior treatment with bevacizumab or ranibizumab.

PurposeTo report the visual and anatomic outcomes in eyes with macular oedema (MO) secondary to central retinal vein occlusion (CRVO) that were switched from either intravitreal bevacizumab or ranibizumab to intravitreal aflibercept.MethodsTwo-center retrospective chart review. Eyes with MO secondary to CRVO that received a minimum of three intravitreal injections of bevacizumab or ranibizumab and were switched to intravitreal aflibercept for persistent or recurrent MO not responding to either bevacizumab and/or ranibizumab.ResultsIn all 42 eyes of 42 patients were included in the study. The median visual acuity before the switch was 20/126, 1 month after the first injection of aflibercept 20/89 (P=0.0191), and at the end of the follow-up 20/100 (P=0.2724). The median CRT before the switch was 536 µm, 1 month after the first injection of aflibercept 293.5 µm (P=0.0038), and at the end of the follow-up 279 µm (P=0.0013 compared to before the switch). The median number of weeks between injections before the switch was 5.6 and after the switch was 7.6 (P<0.0001).ConclusionConverting eyes with refractory MO due to CRVO to aflibercept can result in stabilization of the vision, improved macular anatomy, and extension of the injection interval.

Successful Treatment of Mitochondrial Toxicity in an HIV-Positive Patient After Liver Transplantation.

Liver transplantation in patients infected with the human immunodeficiency virus (HIV) has been increasingly performed with reasonable outcomes; however, medical management of both immunosuppression and antiretroviral therapy can be challenging owing to drug toxicities and interactions. Nucleoside reverse transcriptase inhibitors (NRTIs), a common backbone of highly active antiretroviral therapy (HAART), were the first class of effective antiretroviral drugs developed. NRTIs are commonly used for posttransplant HAART therapy and have a rare but fatal complication of mitochondrial toxicity, manifesting as severe lactic acidosis, hepatic steatosis, and lipoatrophy. Herein, we have reported on the first known successful treatment of severe mitochondrial toxicity secondary to NRTIs in an HIV-infected transplant recipient.

Future Direction of IMIA Standardization. Report from the IMIA Standardization Working Group.

OBJECTIVES: Standardization in the field of health informatics has increased its importance and global alliance for establishing interoperability and compatibility internationally. Standardization has been organized by standard development organizations (SDOs) such as ISO (International Organization for Standardization), CEN (European Committee for Standardization), IHE (Integrating the Healthcare Enterprise), and HL7 (Health Level 7), etc. This paper reports the status of these SDOs' activities. METHODS: In this workshop, we reviewed the past activities and the current situation of standardization in health care informatics with the standard development organizations such as ISO, CEN, IHE, and HL7. Then we discussed the future direction of standardization in health informatics toward "future medicine" based on standardized technologies. RESULTS: We could share the status of each SDO through exchange of opinions in the workshop. Some WHO members joined our discussion to support this constructive activity. CONCLUSION: At this meeting, the workshop speakers have been appointed as new members of the IMIA working groups of Standards in Health Care Informatics (WG16). We could reach to the conclusion that we collaborate for the international standardization in health informatics toward "future medicine".

The burden of influenza-like illness in the US workforce.

BACKGROUND: The disease burden of influenza-like illnesses (ILIs) on the working population has been documented in the literature, but statistical evidence of ILI-related work absenteeism in the USA is limited due to data availability. AIMS: To assess work absenteeism due to ILIs among privately insured employees in the USA in 2007-8 and 2008-9. METHODS: We used the 2007-9 MarketScan® research databases. Full-time employees aged 18-64 years, with the ability to incur work absence and continuously enrolled in the same insurance plan during each season were included. We identified ILI episodes using ICD-9 codes for influenza and pneumonia (480-487). For each season, we calculated the mean work-loss hours per ILI episode and the proportion of employees who had at least one ILI episode. Work-loss hours and ILI rates were examined by subgroups. RESULTS: The mean number of work hours lost per ILI episode was 23.6 in 2007-8 and 23.9 in 2008-9. The proportion of employees with at least one ILI was 1.7% in 2007-8 and 1.2% in 2008-9. In both seasons, the proportion with ILI was higher among older (2.1 and 1.5%) and hourly workers (2.0 and 1.3%), workers in the southern region (1.9 and 1.3%) and those in oil, gas or mining industries (1.9 and 1.4%). CONCLUSIONS: Our results indicate that the disease burden associated with ILIs in the working population is not trivial and deserves attention from policymakers and health care professionals to design effective strategies to reduce this burden.

NF-κB mediated miR-21 regulation in cardiomyocytes apoptosis under oxidative stress.

Oxidative stress, defined as an excess production of reactive oxygen species (ROS), is shown to play an important role in the pathophysiology of cardiac remodeling including cell death and contractile dysfunction. Therefore, the balance between ROS production and removal of excess ROS is essential in maintaining the redox state and homeostasis balance in the cell. The increased ROS further activates nuclear factor-κB (NF-κB), a redox-sensitive transcription factor and promotes cell death. Recently, microRNAs (miRNAs) have been identified as critical regulators of various pathophysiological processes of cardiac remodeling; however, NF-κB-mediated miRNA's role in cardiomyocytes under oxidative stress remains undetermined. The miR-21 has been implicated in diverse cardiac remodeling; but, NF-κB-mediated miR-21 modulation in oxidative stress is currently unknown. Neonatal cardiomyocytes were transfected with IκBα mutant, miR-21 mimetic, and inhibitors separately, and were challenged with H2O2. The target gene, programmed cell death 4 (PDCD4), ROS activity, and NF-κB translocation were analyzed. Our results indicated that NF-κB positively regulated miR-21 expression under oxidative stress, and PDCD4 was a direct target for miR-21. NF-κB further regulated the expression of PDCD4 in H2O2-induced oxidative stress. Moreover, H2O2-induced ROS activity and cardiomyocytes apoptosis were partly protected by overexpression of miR-21 and displayed an important role in ROS-mediated cardiomyocytes injury. We evaluated a critical role of NF-κB-mediated miR-21 modulation in H2O2-induced oxidative stress in cardiomyocytes by targeting PDCD4. Our data may provide a new insight of miR-21's role in cardiac diseases primarily mediated by ROS.

Protective effects of peroxiredoxin 6 overexpression on amyloid ß-induced apoptosis in PC12 cells.

Oxidative stress triggered by amyloid beta (Aß) accumulation contributes substantially to the pathogenesis of Alzheimer's disease (AD). In the present study, we examined the involvement of the antioxidant activity of peroxiredoxin 6 (Prdx 6) in protecting against Aß25-35-induced neurotoxicity in rat PC12 cells. Treatment of PC12 cells with Aß25-35 resulted in a dose- and time-dependent cytotoxicity that was associated with increased accumulation of intracellular reactive oxygen species (ROS) and mitochondria-mediated apoptotic cell death, including activation of Caspase 3 and 9, inactivation of poly ADP-ribosyl polymerse (PARP), and dysregulation of Bcl-2 and Bax. This apoptotic signaling machinery was markedly attenuated in PC12 cells that overexpress wild-type Prdx 6, but not in cells that overexpress the C47S catalytic mutant of Prdx 6. This indicates that the peroxidase activity of Prdx 6 protects PC12 cells from Aß25-35-induced neurotoxicity. The neuroprotective role of the antioxidant Prdx 6 suggests its therapeutic and/or prophylactic potential to slow the progression of AD and limit the extent of neuronal cell death caused by AD.

Influence of serum leptin levels on future overweight risk in Korean children.

BACKGROUND AND AIMS: Leptin is an important regulator of energy metabolism. It is considered to be positively related to body adiposity and metabolic disorders in obese adults and children. The purpose of this study was to evaluate the relationship between baseline circulating leptin, insulin and adiponectin levels and future overweight and metabolic risks in a paediatric population-based cohort. METHODS AND RESULTS: First-grade students, who entered elementary school at age 7 years in Gwacheon, a Korean city, were enrolled in this cohort study, and followed from 1st grade to 5th grade. Annual physical examinations from 2005 to 2009 were performed. In 2006, the levels of serum glucose, insulin, leptin and adiponectin and lipid profiles were examined. In 2008, the above parameters, except for adiponectin, were measured again in 381 children (202 boys and 179 girls) who participated. In 2006, 10.2% of the children were overweight (body mass index (BMI) ≥ 85th percentile), and after 2 years, an additional 3% became overweight. Compared with insulin and adiponectin, leptin was most highly associated with current and future BMI, and percent body fat. Boys in the highest tertile for initial leptin (T3) showed the highest prevalence of overweight and metabolic risk scores among three leptin tertile groups. Girls showed the same trends as boys. High initial leptin levels could be predictive of greater future BMI and metabolic risk score (p < 0.001). CONCLUSION: These results suggest that elevated serum leptin concentrations among the childhood population could be a marker for future BMI and metabolic disorders.

Relationship of serum retinol-binding protein 4 with weight status and lipid profile among Korean children and adults.

BACKGROUND/OBJECTIVES: Although some studies have suggested that retinol-binding protein 4 (RBP4), a fat-derived adipokine, is positively related to overweight and obesity-related disorders, these claims have been disputed. This study investigated relationships between RBP4 level and weight status and metabolic disorders in a Korean population including confounding factors, age and gender. SUBJECTS/METHODS: From 2005 to 2007, we recruited 570 children and 241 of their parents living in Korean urban areas. We analyzed anthropometrical parameters, blood pressure, lipid profiles, and levels of serum glucose, insulin, leptin and RBP4, and estimated dietary intake based on a self-reported 3-day food diary. RESULTS: Levels of RBP4 were high for men (226.2 µg/ml), mid-range among women (143.2 µg/ml) and low among boys and girls (boys 71.4, girls 66.9 µg/ml). After adjusting for age, gender differences among adults were consistently maintained (P<0.0001), and gender differences among children were detected minimally (P=0.05). On the basis of Cole's body mass index cutoff points, the prevalence of overweight among children was 19.3%. The prevalence among adults was 32.0%, based on World Health Organization criteria. Overweight children had higher RBP4 concentrations than normal. Overweight women had higher RBP4 levels than those of normal weight. Higher RBP4 levels were observed among overweight men, but the results were not statistically significant. Triglyceride (TG) levels were significantly correlated with RBP4 in all groups. CONCLUSIONS: Our results indicate that RBP4 concentrations in a Korean population varied with age, gender and overweight status. TG levels could be strongly correlated with RBP4 concentration.

Effect of bath temperature on the properties of nanocrystalline ZnO thin films.

The nanocrystalline zinc oxide (ZnO) thin films have been prepared by chemical bath deposition (CBD) method from aqueous zinc nitrate solution at room temperature (25 degrees C) and at higher temperature (75 degrees C). The changes in structural, morphological and optical properties were studied by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), and optical absorption. The structural studies revealed that the film deposited at room temperature showed mixed phases of ZnO and Zn(OH)2 with wurtzite and orthorhombic crystal structure whereas at higher temperature, the deposited film is ZnO with wurtzite crystal structure. After air annealing at 400 degrees C, all the films converted into pure ZnO with wurtzite crystal structure. The films deposited at room temperature showed fibrous surface morphology with interconnected flakes while films deposited at higher temperature shows well-developed nano-rod morphology. Optical study shows that band gap energy (E(g)) of as-deposited thin films deposited at room temperature and at higher temperature are 3.81 and 3.4 eV, decreases up to 3.20 eV, after annealing treatment.

Ribosomal protein S6 is a selective mediator of TRAIL-apoptotic signaling.

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a potent inducer of apoptosis in tumor cells and holds a promise as a therapeutic agent against cancer. To elucidate the death signaling evoked by TRAIL, we performed a functional genetic screening and rescued TRAIL-resistant Jurkat clones harboring ribosomal protein S6 (rpS6) cDNA in anti-sense frame. Reduction of rpS6 expression in Jurkat and HeLa cells attenuated apoptosis induced by TRAIL, but not those by other cell death signals, including tumor necrosis factor-alpha and cycloheximide, etoposide, doxorubicin, tunicamycin and staurosporine. Death receptor (DR) 4, but not DR5, was downregulated in rpS6 knockdown cells. Conversely, the sensitivity to TRAIL was increased by the ectopic expression of wild-type rpS6 and further by phospho-defective rpS6 mutant (S6-SS235,6AA), but not by phospho-mimic rpS6 mutant (S6-SS235,6DD). Also, unphosphorylatable rpS6 knock-in mouse embryo fibroblasts (rpS6(P-/-) MEFs) were more sensitive to TRAIL than control MEFs. In addition, SKHep-1 tumor cells, which express less phospho-rpS6 and are more sensitive to TRAIL than other tumor cells, became effectively desensitized to TRAIL after rpS6 knockdown. These results suggest that rpS6, especially in its unphosphorylated form, is a selective mediator of TRAIL-induced apoptosis.