NPFFR2 Contributes to the Malignancy of Hepatocellular Carcinoma Development by Activating RhoA/YAP Signaling.

G protein-coupled receptors (GPCRs) are a diverse family of cell surface receptors implicated in various physiological functions, making them common targets for approved drugs. Many GPCRs are abnormally activated in cancers and have emerged as therapeutic targets for cancer. Neuropeptide FF receptor 2 (NPFFR2) is a GPCR that helps regulate pain and modulates the opioid system; however, its function remains unknown in cancers. Here, we found that NPFFR2 is significantly up-regulated in liver cancer and its expression is related to poor prognosis. Silencing of NPFFR2 reduced the malignancy of liver cancer cells by decreasing cell survival, invasion, and migration, while its overexpression increased invasion, migration, and anchorage-independent cell growth. Moreover, we found that the malignant function of NPFFR2 depends on RhoA and YAP signaling. Inhibition of Rho kinase activity completely restored the phenotypes induced by NPFFR2, and RhoA/F-Actin/YAP signaling was controlled by NPFFR2. These findings demonstrate that NPFFR2 may be a potential target for the treatment of hepatocellular carcinoma.

Impact of Donor-Recipient Age Difference on Graft Function and Survival After Deceased Donor Kidney Transplantation.

BACKGROUND: Donor-recipient age difference (DRAD) is one of the reasons why patients on kidney waiting lists refuse to receive the offered organ. However, its impact on deceased donor kidney transplantation (DDKT) outcomes is still controversial. METHODS: One hundred fifty-three kidney transplant recipients (KTRs) who received their first-time DDKT were enrolled. The KTRs were divided into groups by DRAD: group 1 (n = 74) (DRAD < 0) and group 2 (n = 79) (DRAD ≥ 0). The KTRs in group 2 were divided into 3 subgroups: DRAD 0 to 10 (n = 35), 10 to 20 (n = 32), and ≥ 20 (n = 12). The outcome measures included estimated glomerular filtration rate (eGFR), delayed graft function (DGF), acute rejection (AR), and graft and patient survival. RESULTS: There were no significant differences in clinical outcomes between group 1 and 2 except eGFR until 5 years after DDKT. Among the subgroups of group 2, DGF, AR, patient survival, and eGFR until 5 years showed no significant differences. However, graft survival was significantly different (P = .015); in addition, in the DRAD ≥ 20 subgroup, graft survival decreased compared with that in the DRAD 10 to 20 subgroup and DRAD 0 to 10 subgroup (P = .020, P = .012, respectively). In a multivariate Cox proportional hazards analysis, the DRAD ≥ 20 subgroup showed a higher risk for graft failure than the DRAD 0 to 10 subgroup. CONCLUSIONS: Although donors were of the same age or older than recipients, DDKT showed acceptable graft outcomes. However, because donors over 20 years older than recipients showed a decreased graft survival, it might be important to consider this point in donor-recipient matching of DDKT.

Analysis of Clinical Outcomes According to the Definition of Slow Graft Function in Deceased Donor Kidney Transplantation.

BACKGROUND: Slow graft function (SGF) is considered to be an intermediate state between immediate graft function (IGF) and delayed graft function (DGF). However, the criteria of SGF is still arbitrary, and the clinical outcomes of SGF are not fully understood. METHODS: A total of 212 deceased donor kidney transplantation recipients were enrolled. Three schemas were adopted, which classified SGF according to the serum creatinine (Cr) level by a given postoperative day (POD). SGF was defined as Cr ≥ 3.0 mg/dL on POD5, Cr ≥ 2.5 mg/dL on POD7, and Cr ≥ 1.5 mg/dL on POD14 without dialysis in schema I, II, and III, respectively. Estimated glomerular filtration rate (eGFR) after transplantation, acute rejection, and graft survival were compared in each schema. Decreased renal function, defined as eGFR less than 30.0 mL/min/1.73m2, was also compared. RESULTS: In schema I and III, SGF had significantly lower eGFR at 3 months after transplantation compared with IGF (P < .017), and only schema III maintained the difference until 36 months after transplantation. The incidence of decreased renal function showed significant difference among groups in schema I and III (P < .05). Graft survival did not show significant difference among groups in all schemas. However, SGF and DGF groups showed a higher probability of decreased renal function than the IGF group (P < .017) in schema I and III. CONCLUSIONS: In deceased donor kidney transplantation, certain definitions of SGF identified significantly worse clinical outcomes compared with IGF, suggesting similar impact with DGF. It is necessary to reach a consensus on a clearer definition of SGF with further studies.

Sequencing and characterization of Varicella-zoster virus vaccine strain SuduVax.

BACKGROUND: Varicella-zoster virus (VZV) causes chickenpox in children and shingles in older people. Currently, live attenuated vaccines based on the Oka strain are available worldwide. In Korea, an attenuated VZV vaccine has been developed from a Korean isolate and has been commercially available since 1994. Despite this long history of use, the mechanism for the attenuation of the vaccine strain is still elusive. We attempted to understand the molecular basis of attenuation mechanism by full genome sequencing and comparative genomic analyses of the Korean vaccine strain SuduVax. RESULTS: SuduVax was found to contain a genome that was 124,759 bp and possessed 74 open reading frames (ORFs). SuduVax was genetically most close to Oka strains and these Korean-Japanese strains formed a strong clade in phylogenetic trees. SuduVax, similar to the Oka vaccine strains, underwent T- > C substitution at the stop codon of ORF0, resulting in a read-through mutation to code for an extended form of ORF0 protein. SuduVax also shared certain deletion and insertion mutations in ORFs 17, 29, 56 and 60 with Oka vaccine strains and some clinical strains. CONCLUSIONS: The Korean VZV vaccine strain SuduVax is genetically similar to the Oka vaccine strains. Further comparative genomic and bioinformatics analyses will help to elucidate the molecular basis of the attenuation of the VZV vaccine strains.

Comparison of clinical effects between total vaginal hysterectomy and total laparoscopic hysterectomy on large uteruses over 300 grams.

OBJECTIVE: To compare intra- and postoperative complications, operation time, and duration of hospital stay, and to evaluate cost-effectiveness between total vaginal hysterectomy (TVH) and total laparoscopic hysterectomy (TLH) groups. MATERIAL & METHODS: Patients undergoing TVH or TLH for a large uterus weighing more than 300 g were recruited from January to December 2007: 150 cases of TVH and 100 cases of TLH, were used. Evaluated variables are as follows: age, parity, previous surgical history, intra- and postoperative complications, hysterectomy specimen weight, operation time, duration of hospital stay and total cost. Total cost ($US) include admission, anesthesia and operation costs. RESULTS: There was no difference in demographics, intra- and postoperative complications, and uterine weight. However, operation time in TLH (mean, 179.9 min) was significantly longer than TVH (mean, 93.8 min; P < 0.05). The mean length of hospital stay was 6.13 days in TVH group and 5.78 days in TLH group, respectively (P < 0.05). TVH was more cost-effective than TLH. There was significant difference in total cost between the two groups (TVH, mean $1815.7 vs TLH, mean $2560.5; P < 0.05). When the total cost was analyzed in detail, there was no difference in admission cost. However, the significant mean differences in anesthesia cost (TVH, $165 vs TLH, $245) and operation cost (TVH, $30.3 vs TLH, $768) were demonstrated (P < 0.05). CONCLUSION: TVH should not be abandoned for cases with a large uterus, and skilled surgeons for vaginal approach should preferentially perform TVH rather than TLH for the management of large uteruses.