Predictive Value of Ultrasound-Measured Quadriceps Depth and Frailty Status for Hypotension in Older Patients Undergoing Reverse Total Shoulder Arthroplasty in the Beach Chair Position under General Anesthesia.

The beach chair position (BCP) is widely used in shoulder surgery; however, it frequently leads to hypotension. Hypotension in BCP is prevalent among older patients who are at risk of secondary complications such as ischemic injuries. Therefore, this prospective study aimed to investigate the association and predictive value of frailty, as assessed by ultrasound-measured quadriceps depth and questionnaire, in patients aged ≥65 years undergoing elective shoulder surgery under general anesthesia. A multivariable logistic regression analysis was performed to identify independent risk factors for hypotension in BCP under general anesthesia. Receiver operating characteristic curves were constructed to assess the predictive values of various parameters. The results indicated that a quadriceps depth < 2.3 cm and BCP for an extended period significantly increased the risk of hypotension. The combined consideration of quadriceps depth < 2.3 cm and frailty demonstrated markedly superior predictive power compared with each factor individually. In conclusion, the study findings facilitate the screening and identification of risk factors for older patients undergoing surgery in BCP, thereby enhancing perioperative management.

A Cell-Penetrant Peptide Disrupting the Transcription Factor CP2c Complexes Induces Cancer-Specific Synthetic Lethality.

Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof-of-principle evidence is presented that a cell-penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene-addicted cancer cells through transcription activity-independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2-p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome-wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C-resistant cancers. This study enhances the understanding of ACP52C-induced cancer-specific apoptosis induction and supports the use of ACP52C in anticancer drug development.

Intravenous Versus Perineural Dexamethasone for Reducing Rebound Pain After Interscalene Brachial Plexus Block: A Randomized Controlled Trial.

BACKGROUND: Interscalene brachial plexus block (ISB) is a common regional technique to manage acute postoperative pain for arthroscopic rotator cuff tear repair. However, rebound pain may compromise its overall benefit. Our aim was to investigate the primary hypothesis that perineural and intravenous dexamethasone have different effects on rebound pain after resolution of ISB for arthroscopic rotator cuff tear repair. METHODS: Patients aged ≥ 20 years scheduled for elective arthroscopic rotator cuff tear repair under general anesthesia with preoperative ISB were included. The participants were randomized to receive dexamethasone either perineurally (perineural group) or intravenously (intravenous group). In the perineural group, patients received ISB with 12 mL of 0.5% ropivacaine containing 5 mg of dexamethasone; simultaneously, 1 mL of 0.9% normal saline was administered intravenously. In the intravenous group, patients received ISB with 12 mL of 0.5% ropivacaine; simultaneously, 1 mL of dexamethasone 5 mg was administered intravenously. The primary outcome was the difference in the pain score (0-10 on numeric rating scale) between before and after ISB resolution. The secondary outcomes were the incidence of rebound pain; onset, duration, and intensity of rebound pain; time to the first analgesic request; and pain-related sleep disturbance. RESULTS: A total of 71 patients were randomized to either perineural group (n = 36) or intravenous group (n = 35). After block resolution, pain scores increased significantly more in the perineural group (mean ± standard deviation, 4.9 ± 2.1) compared to the intravenous group (4.0 ± 1.7, P = 0.043). The duration of ISB was more prolonged in the perineural group (median [interquartile range], 19.9 [17.2-23.1] hours) than the intravenous group (15.1 [13.7-15.9] hours, P < 0.001). The incidence of rebound pain and pain-related sleep disturbance during the first postoperative week was significantly higher in the perineural group than in the intravenous group (rebound pain: 44.4% vs. 20.0%, P = 0.028; sleep disturbance: 55.6% vs. 25.7%, P = 0.011). The duration and intensity of rebound pain were similar between the two groups. CONCLUSION: Although perineural dexamethasone provided longer postoperative analgesia, intravenous dexamethasone was more beneficial in reducing pain increase after ISB resolution, incidence of rebound pain, and pain-related sleep disturbance. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0006795.

Cancer cachexia: molecular mechanisms and treatment strategies.

Muscle wasting is a consequence of physiological changes or a pathology characterized by increased catabolic activity that leads to progressive loss of skeletal muscle mass and strength. Numerous diseases, including cancer, organ failure, infection, and aging-associated diseases, are associated with muscle wasting. Cancer cachexia is a multifactorial syndrome characterized by loss of skeletal muscle mass, with or without the loss of fat mass, resulting in functional impairment and reduced quality of life. It is caused by the upregulation of systemic inflammation and catabolic stimuli, leading to inhibition of protein synthesis and enhancement of muscle catabolism. Here, we summarize the complex molecular networks that regulate muscle mass and function. Moreover, we describe complex multi-organ roles in cancer cachexia. Although cachexia is one of the main causes of cancer-related deaths, there are still no approved drugs for cancer cachexia. Thus, we compiled recent ongoing pre-clinical and clinical trials and further discussed potential therapeutic approaches for cancer cachexia.

Predictability of Radiologically Measured Psoas Muscle Area for Intraoperative Hypotension in Older Adult Patients Undergoing Femur Fracture Surgery.

This retrospective study aimed to determine the predictive value of radiologically measured psoas muscle area (PMA) for intraoperative hypotension (IOH) using receiver operating characteristic (ROC) curves in older adult patients with hip fractures. The cross-sectional axial area of the psoas muscle was measured by CT at the level of the 4th lumbar vertebrae and normalized by body surface area (BSA). The modified frailty index (mFI) was used to assess frailty. IOH was defined as an absolute threshold of mean arterial blood pressure (MAP) < 65 mmHg or a relative decrease in MAP > 30% from baseline MAP. Among the 403 patients, 286 (71.7%) had developed IOH. PMA normalized by BSA in male patients was 6.90 ± 0.73 in the no-IOH group and 4.95 ± 1.20 in the IOH group (p < 0.001). PMA normalized by BSA in female patients was 5.18 ± 0.81 in the no-IOH group and 3.78 ± 0.75 in the IOH group (p < 0.001). The ROC curves showed that the area under the curve for PMA normalized by BSA and modified frailty index (mFI) were 0.94 for male patients, 0.91 for female patients, and 0.81 for mFI (p < 0.001). In multivariate logistic regression, low PMA normalized by BSA, high baseline systolic blood pressure, and old age were significant independent predictors of IOH (adjusted odds ratio: 3.86, 1.03, and 1.06, respectively). PMA measured by computed tomography showed an excellent predictive value for IOH. Low PMA was associated with developing IOH in older adult patients with hip fractures.

SUMOylation-mediated PSME3-20S proteasomal degradation of transcription factor CP2c is crucial for cell cycle progression.

Transcription factor CP2c (also known as TFCP2, α-CP2, LSF, and LBP-1c) is involved in diverse ubiquitous and tissue/stage-specific cellular processes and in human malignancies such as cancer. Despite its importance, many fundamental regulatory mechanisms of CP2c are still unclear. Here, we uncover an unprecedented mechanism of CP2c degradation via a previously unidentified SUMO1/PSME3/20S proteasome pathway and its biological meaning. CP2c is SUMOylated in a SUMO1-dependent way, and SUMOylated CP2c is degraded through the ubiquitin-independent PSME3 (also known as REGγ or PA28)/20S proteasome system. SUMOylated PSME3 could also interact with CP2c to degrade CP2c via the 20S proteasomal pathway. Moreover, precisely timed degradation of CP2c via the SUMO1/PSME3/20S proteasome axis is required for accurate progression of the cell cycle. Therefore, we reveal a unique SUMO1-mediated uncanonical 20S proteasome degradation mechanism via the SUMO1/PSME3 axis involving mutual SUMO-SIM interaction of CP2c and PSME3, providing previously unidentified mechanistic insights into the roles of dynamic degradation of CP2c in cell cycle progression.

Effects of Local Anesthetics With or Without Steroids in High-Volume Transforaminal Epidural Blocks for Lumbar Disc Herniation: A Randomized, Double-Blind, Controlled Trial.

BACKGROUND: Lumbar transforaminal epidural block (TFEB) is an effective treatment modality for radicular pain due to lumbar disc herniation (LDH). The addition of steroids is more effective than local anesthetic alone in TFEBs for patients with LDH. Moreover, the efficacy of TFEBs has been reported to be positively correlated with the volume of injectate. We hypothesized that high-volume TFEBs without steroids effectively alleviate axial back and radicular pain associated with LDH. This study compared the efficacy of high-volume TFEBs with vs. without steroids for the management of the axial and radicular pain caused by LDH. METHODS: A total of 54 patients were randomly assigned to either group L or group D. Patients in group L received 8-mL injections of 0.33% lidocaine only. Patients in group D received 8-mL injections of 0.33% lidocaine with 5 mg of dexamethasone. The primary outcomes were pain intensity at baseline and 4 weeks after the procedure. The secondary outcomes included the change of functional disability between baseline and 4 weeks after the procedure, pain scores during injection, and adverse effects. RESULTS: Both groups showed a significant reduction in axial and radicular pain and improvement in the functional status at the outpatient visit 4 weeks after TFEB. However, there were no significant differences between the groups in terms of changes in back pain (10.00 [20.00] vs. 10.00 [22.50]; P = 0.896) or radicular pain (5.00 [20.00] vs. 10.00 [12.50]; P = 0.871). CONCLUSION: High-volume TFEBs with and without steroid administration yielded similar significant pain reductions and functional improvements among LDH patients 4 weeks after the procedure.

Strategy to Reduce Hypercapnia in Robot-Assisted Radical Prostatectomy Using Transcutaneous Carbon Dioxide Monitoring: A Prospective Observational Study.

Purpose: Monitoring end-tidal carbon dioxide partial pressure (PETCO2) is a noninvasive, continuous method, but its accuracy is reduced by prolonged capnoperitoneum and the steep Trendelenburg position in robot-assisted radical prostatectomy (RARP). Transcutaneous carbon dioxide partial pressure (PTCCO2) monitoring, which is not affected by ventilator-perfusion mismatch, has been suggested as a suitable alternative. We compared the agreement of noninvasive measurements with the arterial carbon dioxide partial pressure (PaCO2) over a long period of capnoperitoneum, and investigated its sensitivity and predictive power for detecting hypercapnia. Patients and Methods: The patients who underwent RARP were enrolled in this study prospectively. Intraoperative measurements of PETCO2, PTCCO2, and PaCO2 were analyzed. The primary outcome was the agreement of noninvasive monitoring with PaCO2 during prolonged capnoperitoneum. Bias and precision between noninvasive measurements and PaCO2 were assessed using Bland-Altman analysis. The bias and mean absolute difference were compared using a two-tailed Wilcoxon signed-rank test for pairs. The secondary outcome was the sensitivity and predictive power for detecting hypercapnia. To assess this, the Yates corrected chi-square test and the area under the receiver operating characteristic curve were used. Results: The study analyzed 219 datasets from 46 patients. Compared with PETCO2, PTCCO2 had lower bias, greater precision, and better agreement with PaCO2 throughout the RARP. The mean absolute difference in PETCO2 and PaCO2 was larger than that of PTCCO2 and PaCO2, and continued to exceed the clinically acceptable range of 5 mmHg after 1 hour of capnoperitoneum. The sensitivity during capnoperitoneum and overall predictive power of PTCCO2 for detecting hypercapnia were significantly higher than those of PETCO2, suggesting a greater contribution to ventilator adjustment, to treat hypercapnia. Conclusion: PTCCO2 monitoring measured PaCO2 more accurately than PETCO2 monitoring during RARP requiring prolonged capnoperitoneum and a steep Trendelenburg position. PTCCO2 monitoring also provides more sensitive measurements for ventilator adjustment and detects hypercapnia more effectively than PETCO2 monitoring.

Autophagy induction promotes renal cyst growth in polycystic kidney disease.

BACKGROUND: Polycystic kidney disease (PKD) involves renal cysts arising from proliferating tubular cells. Autophagy has been recently suggested as a potential therapeutic target in PKD, and mammalian target of rapamycin (mTOR) is a key negative regulator of autophagy. However, the effect of autophagy regulation on cystogenesis has not been elucidated in PKD mice. METHODS: Clinical validation was performed using GEO datasets and autosomal dominant polycystic kidney disease (ADPKD) patient samples. Newly established PKD and LC3 transgenic mice were used for in vivo verifications, and additional tests were performed in vitro and in vivo using multiple autophagy drugs. FINDINGS: Neither autophagy stimulation nor LC3 overexpression alleviated PKD. Furthermore, we observed the inhibitory effect of an autophagy inhibitor on cysts, indicating its possible therapeutic use in a specific group of patients with ADPKD. INTERPRETATION: Our findings provide a novel insight into the pathogenesis related to autophagy in PKD, suggesting that drugs related to autophagy regulation should be considered with caution for treating PKD. FUNDING SOURCES: This work was supported by grants from the Bio & Medical Technology Development Program; the Collaborative Genome Program for Fostering New Post-Genome Industry of the NRF; the Basic Science Program.

Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts.

Osteoclasts (OCs) are bone-resorbing cells that originate from hematopoietic stem cells and develop through the fusion of mononuclear myeloid precursors. Dysregulation of OC development causes bone disorders such as osteopetrosis, osteoporosis, and rheumatoid arthritis. Although the molecular mechanisms underlying osteoclastogenesis have been well established, the means by which OCs maintain their survival during OC development remain unknown. We found that Ninjurin1 (Ninj1) expression is dynamically regulated during osteoclastogenesis and that Ninj1-/- mice exhibit increased trabecular bone volume owing to impaired OC development. Ninj1 deficiency did not alter OC differentiation, transmigration, fusion, or actin ring formation but increased Caspase-9-dependent intrinsic apoptosis in prefusion OCs (preOCs). Overexpression of Ninj1 enhanced the survival of mouse macrophage/preOC RAW264.7 cells in osteoclastogenic culture, suggesting that Ninj1 is important for the survival of preOCs. Finally, analysis of publicly available microarray data sets revealed a potent correlation between high NINJ1 expression and destructive bone disorders in humans. Our data indicate that Ninj1 plays an important role in bone homeostasis by enhancing the survival of preOCs.

Comparison of micro-computed tomography and histomorphometry in the measurement of bone-implant contact ratios.

OBJECTIVE: The purpose of this study was to measure the 3-dimensional (3D) bone-to-implant contact (BIC) ratios calculated with an associated software algorithm on 3D micro-computed tomography (µCT) scans and compare them with measurements made with 2-dimensional histomorphometry. STUDY DESIGN: For uncomplicated calculation of the 3D BIC ratios, 16 implants (8 grade 2 titanium and 8 grade 4 titanium) with simple cylindrical geometry were inserted into 8 rabbit tibiae; 2 implants were inserted into each tibia. The experimental animals were sacrificed at 2 weeks after surgery. The implants were surgically removed en bloc with surrounding bone. 3D µCT images were acquired and reconstructed, and histomorphometric procedures were performed. The calculated 3D BIC ratios were compared with the histomorphometrically measured BIC ratios. RESULTS: When the 3D BIC ratios calculated in this study were compared with the BIC ratios measured conventionally by using histologic slides for light microscopy, no significant statistical correlation was found between the 2 ratios (P ≥ .35). CONCLUSIONS: This study indicated that 3D µCT should be used for more accurate BIC assessment to produce an overall 3D picture for the bone-implant interface.

Multi-Spectral Fluorescence Imaging of Colon Dysplasia InVivo Using a Multi-Spectral Endoscopy System.

BACKGROUND AND STUDY AIM: To develop a molecular imaging endoscopic system that eliminates tissue autofluorescence and distinguishes multiple fluorescent markers specifically on the cancerous lesions. METHODS: Newly developed multi-spectral fluorescence endoscope device has the potential to eliminate signal interference due to autofluorescence and multiplex fluorophores in fluorescent probes. The multiplexing capability of the multi-spectral endoscope device was demonstrated in the phantom studies and multi-spectral imaging with endoscopy and macroscopy was performed to analyze fluorescence signals after administration of fluorescent probe that targets cancer in the colon. Because of the limitations in the clinical application using rigid-type small animal endoscope, we developed a flexible channel insert-type fluorescence endoscope, which was validated on the colonoscopy of dummy and porcine model. RESULTS: We measured multiple fluorescent signals simultaneously, and the fluorescence spectra were unmixed to separate the fluorescent signals of each probe, in which multiple fluorescent probes clearly revealed spectral deconvolution at the specific targeting area in the mouse colon. The positive area of fluorescence signal for each probe over the whole polyp was segmented with analyzing software, and showed distinctive patterns and significantly distinguishable values: 0.46 ±â€¯0.04, 0.39 ±â€¯0.08 and 0.73 ±â€¯0.12 for HMRG, CET-553 and TRA-675 probes, respectively. The spectral unmixing was finally demonstrated in the dummy and porcine model, corroborating the targeted multi-spectral fluorescence imaging of colon dysplasia. CONCLUSION: The multi-spectral endoscopy system may allow endoscopists to clearly identify cancerous lesion that has different patterns of various target expression using multiple fluorescent probes.

The effect of anesthetic agents on cerebral vasospasms after subarachnoid hemorrhage: A retrospective study.

Cerebral vasospasm is the most important cause of morbidity after an aneurysm clipping in the early postoperative period. The aim of this retrospective study was to evaluate whether the incidence of vasospasms differs when using propofol or desflurane for an emergent aneurysm clipping.The data from 102 patients (50 in the propofol group, 52 in the desflurane group) were analyzed. The occurrence of vasospasm based on daily transcranial Doppler, angiography, and cerebral infarction during 14 days after surgery were compared by anesthetic agents. Postoperative data including Glasgow Coma Scale (GCS) score on day 14 after surgery, and the Glasgow Outcome Scale (GOS) score at 3 months were documented.Patients that intraoperatively received propofol for anesthesia maintenance, had higher incidence of transcranial Doppler (TCD)-evident vasospasm than those that received desflurane (54% vs 30.8%, P = .027). The occurrence of TCD-evident vasospasm was still higher (odds ratio: 2.84; 95% confidence interval: 1.12-7.20) in the propofol group than in the desflurane group after adjusting for confounding factors. However, the incidence of angiographic vasospasm, cerebral infarction, and interventions to treat cerebral vasospasms were similar between both groups. GCS score on day 14 after surgery and the GOS score at 3 months were similar between groups.No effect of anesthetic agents on angiographic vasospasm, cerebral infarction, or clinical outcome was observed, whereas desflurane anesthesia was associated with a lower incidence of TCD-evident vasospasms compared to propofol anesthesia. Our study provides a basis for further randomized controlled studies in a larger patient population to clarify the effects of anesthetic agents on the occurrence of cerebral vasospasms.

Compression stockings reduce the incidence of hypotension but not that of cerebral desaturation events in the beach-chair position: a randomized controlled trial.

BACKGROUND: The beach-chair position (BCP) results in decreases in venous return, cardiac output, and cerebral perfusion pressure. In this randomized, prospective study, we investigated whether applying thigh-high compression stockings affected the maintenance of regional cerebral tissue oxygen saturation (rSO2) in the BCP. METHODS: Patients undergoing orthopedic surgery in the BCP under general anesthesia were included and assigned randomly to the control or the compression stocking group. Appropriately sized thigh-high compression stockings were applied to the patients in the stockings group. All patients were tilted, up to 45°, throughout the operation. Non-invasive blood pressure, invasive arterial blood pressure zeroed at the external auditory meatus, and rSO2 were recorded. RESULTS: Data were analyzed from 19 patients per group. In the BCP, the values of rSO2 and blood pressure decreased significantly compared with those at baseline, with no significant difference between the groups. The incidences of cerebral desaturation events (CDEs) were similar between the groups; however, that of hypotension was significantly lower in the compression stocking group. During 36 CDEs, the levels of rSO2 and blood pressure decreased significantly compared with those at baseline in both groups. No significant correlation was found between rSO2 and blood pressure. CONCLUSIONS: Thigh-high compression stockings reduced the incidence of hypotension but not that of CDEs. Our results suggest that other factors, beyond hypotension itself, contribute to CDEs and in other words, efforts just to reduce the incidence of hypotension may not mainly contribute to a reduction of CDEs occurrence in the BCP under general anesthesia.

Diagnostic and prognostic relevance of CP2c and YY1 expression in hepatocellular carcinoma.

Recent studies have demonstrated an oncogenic role of the transcription factor (TF) CP2c in hepatocellular carcinoma (HCC) based on a strong correlation between CP2c expression, tumor grade, and aggressiveness. We recently found that CP2c directly interacts with another TF, YY1, which is also overexpressed in multiple cancers, including HCC. To evaluate if these proteins are co-regulated in carcinogenesis, we analyzed the expression of CP2c and YY1 in HCC (n = 136) tissues and examined the correlation between their expression and clinicopathological characteristics of HCC. Receiver operating characteristic analysis exhibited the validity of CP2c and nuclear YY1 expression as a diagnostic factor in HCC tissues. High expression of CP2c was significantly correlated with patient age, and higher histological grade, American Joint Committee on Cancer (AJCC) stage, and small and large vessel invasion in HCC tissues, whereas high expression of nuclear YY1 was significantly associated with higher AJCC stage and small vessel invasion. In univariate and multivariate analyses, high expression of CP2c was significantly correlated with disease free survival (DFS), indicating that CP2c expression is an independent prognostic factor for DFS in HCC patients. Patients with high expression of both CP2c and nuclear YY1 usually had a shorter median survival time and worse DFS prognosis than other patients, suggesting that combined detection of CP2c and nuclear YY1 is a useful prognostic marker in HCC patients.

The Outcome of Multiple Slit on Plaque with Plication Technique for the Treatment of Peyronie's Disease.

PURPOSE: To evaluate the postoperative outcome of the multiple slit on plaque plication technique for the treatment of Peyronie's disease. MATERIALS AND METHODS: We retrospectively evaluated 22 patients who underwent plaque incision with penile plication for the surgical treatment of Peyronie's disease, who had failed medical treatment between 2009 and 2014. Patients were grouped by preoperative degree of penile curvature into Group I: mild (n=5, 22.7%), Group II: moderate (n=11, 50.0%), and Group III: severe (n=6, 27.3%). After a thorough review of the medical records, we evaluated (a) the correction of the curvature; (b) sexual function; and (c) any penile shortening or other complications. RESULTS: The mean postoperative follow-up period was 39 months. Complete correction of the curvature was attained in 21 patients (95.5%). As an inevitable complication, minimal penile shortening (<1.5 cm) was reported by 14 patients (82.4%) but did not adversely affect sexual intercourse (0%), and all patients found the extent of penile shortening to be acceptable. Nineteen patients had good erectile function (International Index of Erectile Function >21). The most frequent complication was subcutaneous penile edema in three patients (13.6%), which was resolved within about 3 months following surgery. CONCLUSIONS: As a modified technique, multiple slit on plaque with plication is a simple, minimally-invasive and effective technique for correcting penile curvature regardless of curvature severity. The degree of penile curvature does not significantly predict the amount of penile length loss.

Wunderlich syndrome as the first manifestation of an extraskeletal Ewing sarcoma.

We recently encountered an extremely rare case of spontaneous perirenal hemorrhage in a 34-year-old man. He initially had undergone radical nephrectomy owing to suspicion of renal cell carcinoma. The final diagnosis was extraskeletal Ewing sarcoma.

Inhibition of cisplatin-resistance by RNA interference targeting metallothionein using reducible oligo-peptoplex.

Effective intracellular level of a platinum anti-cancer drug, cisplatin, following repeated injections can be decreased either by the active efflux via ATP pump or by interactions with glutathione and metallothionein. Cisplatin in cytoplasm preferably binds to cysteine-rich proteins such as glutathione and metallothionein (MT). Detoxification of cisplatin by intracellular thiol-containing proteins has been considered to be major hurdles to overcome. The short hairpin RNA targeting MT (shMT) was tested to down-regulate MT and recover cisplatin resistance. A reducible polymer, poly(oligo-d-arginine) (rPOA), formed stable complex with shMT and demonstrated superior transfection efficiency. Efficient transfection of shMT/rPOA oligo-peptoplexes was found to significantly inhibit MT over-expression, resulting in 45% decrease of cell viability compared to the cisplatin alone group. This decrease was mediated by the synergistic effect of shMT/rPOA oligo-peptoplex and cisplatin. Co-administration of shMT/rPOA oligo-peptoplex and cisplatin in in vivo tumor model showed noticeable tumor-suppressing effect by inducing reversal of cisplatin resistance following effective intracellular delivery of shMT by rPOA. Combination therapy through co-administration of shMT/rPOA oligo-peptoplex and cisplatin was found to effectively reverse cisplatin resistance by RNA interference and consequently improve anti-cancer activity of cisplatin.

Decreased ARID1A expression correlates with poor prognosis of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (CCRCC) is the most common renal cell carcinoma. It has a relatively unfavorable prognosis compared to other common renal cell carcinomas. Recently, comprehensive molecular studies in CCRCC revealed important genetic alterations, including changes in the VHL, PBRM1, and ARID1A genes. The expression of ARID1A protein is associated with tumor progression and prognosis in many cancers. This study aimed to evaluate the nuclear expression of ARID1A in CCRCC and to assess its expression with the clinical prognosis. The nuclear expression of ARID1A was evaluated in 290 cases of CCRCC by immunohistochemistry. To determine the clinicopathological association with ARID1A, each of the cases was divided into 2 groups, low- and high-expression groups, according to the average proportion of nuclear staining. Decreased ARID1A expression was associated with the higher nuclear grade and higher pTNM stage (P < .001 and P = .013, respectively). The ARID1A low-expression group revealed significantly shorter cancer-specific and progression-free survival times (P = .001 and P < .001, respectively). Furthermore, Cox regression analysis showed that ARID1A expression was an independent prognostic factor for progression-free survival (P = .009). These results suggest that nuclear expression of ARID1A may serve as a new prognostic marker in CCRCC patients.

GAGE12 mediates human gastric carcinoma growth and metastasis.

The spontaneous metastasis from human gastric carcinoma (GC) remains poorly reproduced in animal models. Here, we established an experimental mouse model in which GC progressively developed in the orthotopic stomach wall and metastasized to multiple organs; the tumors colonized in the ovary exhibited typical characteristics of Krukenberg tumor. The expression of mesenchymal markers was low in primary tumors and high in those in intravasating and extravasating veins. However, the expression of epithelial markers did not differ, indicating that the acquisition of mesenchymal markers without a concordant loss of typical epithelial markers was associated with metastasis. We identified 35 differentially expressed genes (DEGs) in GC cells metastasized to ovary, among which overexpression of GAGE12 family genes, the top-ranked DEGs, were validated. In addition, knockdown of the GAGE12 gene family affected transcription of many of the aforementioned 35 DEGs and inhibited trans-well migration, tumor sphere formation in vitro and tumor growth in vivo. In accordance, GAGE12 overexpression augmented migration, tumor sphere formation and sustained in vivo tumor growth. Taken together, the GAGE12 gene family promotes GC growth and metastasis by modulating the expression of GC metastasis-related genes.