Prediction of Oncotype DX Recurrence Score Based on Systematic Evaluation of Ki-67 Scores in Hormone Receptor-Positive Early Breast Cancer.

PURPOSE: Oncotype DX (ODX) predicts the risk of recurrence and benefits of adding chemotherapy for patients with estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer. We aimed to develop a simplified scoring system using readily available clinicopathological parameters to predict a high-risk ODX recurrence score (RS) while minimizing reproducibility issues regarding Ki-67 index evaluation methods. METHODS: We enrolled 300 patients with ER+/HER2- early breast cancer, for whom ODX RS data were available in the test set. Using the QuPath image analysis platform, we systematically evaluated the average, hotspot, and hottest spot Ki-67 scores in the test set. Logistic regression analyses were conducted to establish a predictive scoring system for high-risk ODX RS. An independent validation set comprising 117 patients over different periods was established. RESULTS: Factors such as age ≤ 50 years, invasive ductal carcinoma tumor type, histologic grade 2 or 3, tumor necrosis, progesterone receptor negativity, and a high Roche-analyzed Ki-67 score (> 20) were associated with high-risk ODX RS. These variables were incorporated into our scoring system. The area under the curve of the scoring system was 0.8057. When applied to both the test and validation sets with a cutoff value of 3, the sensitivity of our scoring system was 92%. CONCLUSION: We successfully developed a scoring system based on the systematic evaluation of Ki-67 scoring methods. We believe that our user-friendly predictive scoring system for high risk ODX RS could help clinicians in identifying patients who may or may require additional ODX testing.

Histopathologic image-based deep learning classifier for predicting platinum-based treatment responses in high-grade serous ovarian cancer.

Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image-based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model's decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.

An exploratory clinical trial of preoperative non-invasive localization before breast-conserving surgery using augmented reality technology.

PURPOSE: This single-center, randomized, prospective, exploratory clinical trial was conducted to assess the clinical efficacy of an augmented reality (AR)-based breast cancer localization imaging solution for patients with breast cancer. METHODS: This clinical trial enrolled 20 women who were diagnosed with invasive breast cancer between the ages of 19 and 80, had a single lesion with a diameter ≥ 5 mm but ≤ 30 mm, had no metastases to other organs, and had not received prior chemotherapy. All patients underwent mammography, ultrasound, computed tomography, and magnetic resonance imaging for preoperative assessment. Patients were randomly assigned to ultrasound-guided skin marking localization (USL) and AR-based localization (ARL) groups (n = 10 in each group). Statistical comparisons between USL and ARL groups were made based on demographics, radiologic features, pathological outcomes, and surgical outcomes using chi-square and Student t-tests. RESULTS: Two surgeons performed breast-conserving surgery on 20 patients. Histopathologic evaluation of all patients confirmed negative margins. Two independent pathologists evaluated the marginal distances, and there were no intergroup differences in the readers' estimates (R1, 6.20 ± 4.37 vs. 5.04 ± 3.47, P = 0.519; R2, 5.10 ± 4.31 vs. 4.10 ± 2.38, P = 0.970) or the readers' average values (5.65 ± 4.19 vs. 4.57 ± 2.84, P = 0.509). In comparing the tumor plane area ratio, there was no statistically significant difference between the two groups in terms of either reader's mean values (R1, 15.90 ± 9.52 vs. 19.38 ± 14.05, P = 0.525; R2, 15.32 ± 9.48 vs. 20.83 ± 12.85, P = 0.290) or the overall mean values of two readers combined (15.56 ± 9.11 vs. 20.09 ± 13.38, P = 0.388). Convenience, safety, satisfaction, and reusability were all superior in the AR localization group (P < 0.001) based on the two surgeons' responses. CONCLUSION: AR localization is an acceptable alternative to ultrasound-guided skin marking with no significant differences in surgical outcomes.

Initial experience with the enhanced recovery after surgery (ERAS) protocols in gynecologic surgery at an urban academic tertiary medical center.

Background: The enhanced recovery after surgery (ERAS) protocols have been consistently associated with improved patient experience and surgical outcomes. Despite the release of ERAS Society guidelines specific to gynecologic oncology, the adoption of ERAS in gynecology on global level has been disappointingly low and some centers have shown minimal improvement in clinical outcomes after adopting ERAS. The aim of this study is to describe the development and early experience of ERAS protocols in gynecologic surgery at an urban academic tertiary medical center. Methods: This was an observational prospective cohort study. The target patient population included those with low comorbidities who were scheduled to undergo various types of gynecologic surgeries for both benign and malignant diseases between October 2020 and February 2021. Two attending surgeons implemented the protocols for their patients (ERAS cohort) while three attending surgeons maintained the conventional perioperative care for their patients (non-ERAS cohort). Baseline characteristics, surgical outcomes and patients' answers to a 12-question survey were compared. A case-matched comparative analysis was also performed between the ERAS cohort and the historical non-ERAS cohort (those who received the same types of surgical procedures from the two ERAS attending surgeons prior to the implementation of the protocols). Results: A total of 244 patients were evaluated (122 in the ERAS cohort vs. 122 in the non-ERAS cohort). The number of vials of opioid analgesia used during the first two postoperative days was significantly lower whereas the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen was more frequent in the ERAS cohort group. The patients in the ERAS group reported less postoperative pain, feelings of hunger and thirst, and greater amount of exercise postoperatively. These benefits of the ERAS cohort were more pronounced in the patients who underwent laparotomic surgeries than those who underwent laparoscopic surgeries. The case-matched comparative analysis also showed similar results. The length of hospital stay did not differ between those who underwent the ERAS protocols and those who did not. Conclusions: The results of the study demonstrated the safety, clinical feasibility and benefits of the ERAS protocols for patients undergoing gynecologic surgeries for both benign and malignant indications.

Does Bladder Cancer Subtype Influence Pathologic Complete Response (pCR) and Pelvic Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Response Evaluation After Neoadjuvant Chemotherapy? Pathological Perspective.

INTRODUCTION: We aimed to provide a pathological perspective on the management of muscle-invasive bladder cancer (MIBC) by correlating the prechemotherapy transurethral resection of bladder tumor findings and postchemotherapy radiologic evaluation with final radical cystectomy (RC) findings. MATERIALS AND METHODS: This retrospective study included 79 MIBC patients treated with neoadjuvant chemotherapy (NAC) and RC. Pelvic diffusion-weighted magnetic resonance imaging (DW-MRI) and pathologic reports were retrieved from our institutional database. All pathology slides were reviewed based on diagnostic criteria with high interobserver reproducibility. RESULTS: Pathologic complete response (pCR) was confirmed in 32 patients (40.5%). The concordance and discordance between MRI and RC findings occurred in 68.3% and 31.7% of cases, respectively. The 21.5% of cases that were clinical CR (cCR) on MRI actually achieved pCR on RC specimens and 46.8% of cases that were non-cCR on MRI were actually non-pCR on RC specimens. In 19.0% of cases, RC findings were pCR, but MRI demonstrated residual tumor and the opposite was 12.7%. The greatest discrepancy between the 2 methods (75%, 3/4) was for the plasmacytoid subtype. Plasmacytoid histology was the most common histological subtype identified in RC specimens after NAC, followed by micropapillary and squamous histologies. CONCLUSIONS: We found that all cases with plasmacytoid and micropapillary subtypes, and squamous differentiation did not show pCR. In particular, the largest discrepancy between MRI findings and RC pathology after NAC was seen in the plasmacytoid subtype. An accurate pathologic diagnosis based on strict criteria to identify histological subtypes of MIBC is necessary for proper treatment.

Anti-Inflammatory Effect of Cinnamomum japonicum Siebold's Leaf through the Inhibition of p38/JNK/AP-1 Signaling.

Cinnamomum japonicum Siebold (CJ) branch bark, commonly known as Japanese cinnamon, has been used for various culinary and medicinal applications for many centuries. Although the efficacy of CJ branch bark's anti-inflammatory and antioxidant activity for the treatment of various diseases has been confirmed, the efficacy of CJ leaves (CJLs) has not been examined. We therefore investigated whether CJL3, an ethyl acetate extract of a 70% ethanol CJL extract, exerts anti-inflammatory effects on lipopolysaccharide (LPS)-activated Kupffer cells, specialized macrophages found in the liver. Liver inflammation can activate Kupffer cells, inducing the release of pro-inflammatory molecules that contribute to tissue damage. We found that CJL3 has high 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) radical-scavenging activity. Among the CJL extracts, CJL3 exhibited the greatest polyphenol content, with protocatechuic acid and 4-hydroxybenzoic acid being the most abundant. In addition, we verified that CJL3, which has strong antioxidant properties, ameliorates LPS-induced pro-inflammatory responses by inhibiting p38/JNK/AP-1 signaling. CJL3 therefore has potential for treating liver disease, including hepatitis.

Invasive urothelial carcinoma with chordoid features or abundant myxoid stroma: A reappraisal of morphologic spectrum and risk stratification based on molecular classification.

Urothelial carcinoma (UC) with myxoid stroma or chordoid features is a rare diagnosis. We retrospectively collected data from 17 cases of diagnosed UC with myxoid stroma, mucin production, or chordoid features. We aimed to investigate the molecular subtypes of this neoplasm and to assess subtype correlations with clinical outcomes. Immunohistochemical (IHC) staining with a panel composed of markers for basal subtypes (CK5/6, CK14, and CD44) and luminal subtypes (GATA3, FOXA1, and CK20) was performed. Morphologically, all cases included an at least partial conventional UC component, with the first histologic pattern, named as "typical", characterized by a small- or medium-sized tumor cell nest. The second histologic pattern, named as "chordoid", was characterized by tumor cells with cording that mimic extra-skeletal myxoid chondrosarcoma or chordoma, and the third histologic pattern, named as "sarcomatoid", was characterized by non-cohesive spindle tumor cells with a mucin-producing or myxoid stroma background. The "typical" cases showed [CK5/6- CK14- CD44-] [GATA3 + FOXA1 + CK20-] IHC results and was classified as lumina subtype. The "chordoid" cases showed [CK5/6 + CK14 + CD44-] [GATA3- FOXA1- CK20-] IHC results and was classified as basal subtype, and the "sarcomatoid" cases showed [CK5/6- CK14- CD44+] [GATA3- FOXA1- CK20-] IHC results and was "not classified". All pT3 cases and all cases with lymph node (LN) metastasis belonged to the "sarcomatoid" pattern. All patients who had metastasis or died showed the "chordoid" or "sarcomatoid" morphology. Our findings suggest that UC with myxoid stroma/chordoid features shows characteristic expression of luminal and basal markers and different prognosis according to the morphologic pattern spectrum.

Application of The Paris System in neobladder washing cytology: Comparison between the original diagnosis and correlation with histopathology.

BACKGROUND: In urinary diversion after radical cystectomy, the incidence of recurrent urothelial carcinoma (UC) in upper urinary tract or urethra are reported in 2%-17% of the patients. Urine cytology plays a pivotal role in detecting the recurrence of UC. However, cytologic diagnosis in urinary diversion including neobladder is often challenging due to significant degenerative changes and necro-inflammatory background. Since the proposal of The Paris System (TPS) for reporting cytology, the utility of TPS in urinary diversion specimen has not been studied yet. The objective of this study is to evaluate the diagnostic usefulness of TPS compared with the original diagnosis and correlate with the matched histopathological results. METHODS: Urinary diversion cytology specimens with concurrent or subsequent biopsy or resection at EUMC in recent 16 years (from January 2002 to December 2018) are retrospectively reviewed and reclassified according to TPS criteria. The TPS categories and the original diagnoses were compared and correlated with follow-up histology. RESULTS: Concurrent or subsequent biopsy or resection within a 6-month period was available in 45 cases from 28 patients. When applying TPS, the rate of atypical and suspicious categories decreased by 13.4% and 11.1%. Using TPS increased the value of sensitivity, NPV, and accuracy to 93.75%, 93.75%, and 90.91%, respectively. CONCLUSION: Application of TPS reduced the rate of indeterminate diagnoses and moreover, improved the sensitivity and accuracy of urinary diversion cytology. Therefore, we believe that diversion urine cytology diagnosis according to TPS is useful to screen patients for detection of recurrence in routine clinical practice.

Proliferation-Related Features of the Human Mesenchymal Stem Cells Derived from Palatine Tonsils, Adipose Tissues, and Bone Marrow.

BACKGROUND: Mesenchymal stem cells (MSCs) are widely used in regenerative medicine and cell-based transplantations. However, an in-depth comparison of the different MSC origins is lacking. This study aimed to compare the expression of adipose-derived (AMSCs), bone marrow-derived (BMSCs), and tonsil-derived (TMSCs) and evaluate whether TMSCs are good alternatives for AMSCs or BMSCs. METHODS: We analyzed the expression levels of 47,000 transcripts in AMSCs (n = 4), BMSCs (n = 4), and TMSCs (n = 4) using GeneChip. Microarray data were analyzed using the LIMMA package to compare the TMSCs, AMSCs, and BMSCs. Hub genes were analyzed using STRING and Cytoscape. To ascertain the functional roles of AURKA and AURKB, small interfering RNA (siRNA) molecules specifically targeting AURKA and AURKB mRNA were synthesized and employed to induce knockdown of AURKA and AURKB in TMSC and AMSC. We analyzed the expression level of OCT4, SOX-2, and NANOG genes in TMSC and AMSCs by cell culture and real-time PCR. RESULTS: We identified commonly increased 256 and decreased 160 genes in TMSCs from the differentially expressed genes (DEGs) between the TMSCs, AMSCs, and BMSCs. In the DEG-based protein-protein interaction and gene set enrichment analysis, hub genes (AURKA, AURKB, CDC20, and BUB1) highly expressed in TMSCs were enriched for development- and progression-related oocyte meiosis, the cell cycle, and ubiquitin-mediated proteolysis. In vitro analysis demonstrated that cells with downregulated expression of AURKA and AURKB exhibited a significant reduction in proliferation compared to control cells. However, silencing of the genes did not affect the differentiation capacity in TMSCs and AMSCs. CONCLUSION: Our study compared MSCs of different origins to better understand the similarities and differences among these cell types.

The Effect of Complete Prostate Examination of Radical Cystoprostatectomy Specimen on the Final Stage of Urothelial Carcinoma of the Urinary Bladder and the Detection of Prostate Cancer.

CONTEXT.­: The prostate sampling methods for radical cystoprostatectomy (RCP) specimens may affect pathologic results. OBJECTIVE.­: To investigate the impact on the tumor stage and clinicopathologic features according to the prostate sampling method for RCP specimens. DESIGN.­: From 2016 to 2017, the prostate in RCP was minimally and conventionally embedded (group 1, n = 98). From 2017 to 2018, it was completely embedded (group 2, n = 102). RESULTS.­: Group 2 was more likely to have prostatic ducts or acini involvement by urothelial carcinoma in situ component (27% versus 10%, P = .002) and prostate involvement (30% versus 13%, P = .003) than group 1. Although there were cases with prostatic stromal invasion in group 2 (14% versus 7%, P = .13), this was not statistically significant. In all, 6 cases were upstaged by subepithelial prostatic stromal invasion through intraurethral extension according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. Tumor location and the presence of concurrent carcinoma in situ were strongly associated with prostate involvement of urothelial carcinoma. Prostatic adenocarcinoma (PA) was incidentally identified in 47 cases (23.5%). Incidental PA and clinically significant PA were more often identified in group 2 than group 1 (38% versus 8%, P < .01 and 15% versus 6%, P = .048, respectively). CONCLUSIONS.­: A complete prostate examination in RCP specimens can be suggested, since the final pathologic stage can be changed through a thorough prostate examination especially in accord with the AJCC staging manual 8th edition. In addition, the complete prostate analysis could detect more incidental and clinically significant PA.

Age-Dependent Clinicopathological Characteristics of Patients with T1b Papillary Thyroid Carcinoma: Implications for the Possibility of Active Surveillance.

BACKGROUND: Active surveillance (AS) of low-risk T1a papillary thyroid carcinoma (PTC) is generally accepted as an alternative to immediate surgery. The cut-off in the size criterion for AS has recently been extended in select individuals, especially older patients. We evaluated the clinicopathological differences of T1b PTC according to age to investigate the possibility of AS in older patients. PATIENTS AND METHODS: From a cohort study of 1269 patients undergoing lobectomy for PTC, 1223 PTC patients with T1 stage disease (tumor ≤ 2 cm) were enrolled. The clinicopathological characteristics between T1a and T1b patients according to age were analyzed. RESULTS: Among the 1223 T1 cases, 918 (75.1%) were T1a (≤ 1 cm) and 305 (34.9%) T1b (> 1 and ≤ 2 cm). T1b PTC was associated with male sex, minimal extrathyroidal extension, lymphovascular invasion, occult central lymph node (LN) metastasis, and a higher number of metastatic LNs than T1a. However, in patients over 55 years of age, the clinicopathological features of the patients with T1a and T1b PTC were not significantly different except for minimal extrathyroidal extension, although many clinicopathological differences were observed in patients under 55 years of age. CONCLUSION: The clinicopathological features of patients with T1b PTC over 55 years of age are similar to those with T1a PTC and less aggressive than those with T1b PTC under 55 years of age. These findings suggest that AS may be possible in patients with T1b PTC over 55 years of age without high-risk features on preoperative examinations.

Effect of Echinochrome A on Submandibular Gland Dysfunction in Ovariectomized Rats.

Post-menopausal dry mouth or xerostomia is caused by reduced salivary secretion. This study aimed to investigate the efficacy of echinochrome A (Ech A) in alleviating submandibular gland dysfunctions in ovariectomized rats that mimic menopause. Female rats that were eight-weeks-old were randomly divided into SHAM-6, -12; OVX-6, -12; and ECH-6, -12 groups (consisting of 6- and 12-weeks post-sham-operated, ovariectomized, and Ech A-treated ovariectomized rats, respectively). The ECH groups had lower body weight than OVX but similar food intake and estradiol or estrogen receptor ß expression. However, the ECH groups had lower mRNA expression of sterol-regulatory element binding protein-1c (Srebp-1c), acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), cluster of differentiation 36 (Cd36), and lipid vacuole deposition than OVX mice. Moreover, reactive oxygen species (ROS), malondialdehyde (MDA), and iron accumulation were lower in the ECH than in the OVX groups. Fibrosis markers, transforming growth factor ß (Tgf-ßI and Tgf-ßII mRNA) increased in the OVX than SHAM groups but decreased in the ECH groups. Aquaporin (Aqp-1 and Aqp-5 mRNA) and mucin expressions were downregulated in the OVX groups but improved with Ech A. In addition, Ech A prevented post-menopausal salivary gland dysfunction by inhibiting lipogenesis and ferroptosis. These findings suggest Ech A as an effective remedy for treating menopausal dry mouth.

Comparison of Patients Satisfaction with Direct to Implant versus Latissimus Dorsi Flap with Implant Breast Reconstruction Using Breast-Q.

Background The latissimus musculocutaneous flap (LD flap) is a useful option for breast reconstruction following mastectomy. It has the advantage of obtaining sufficient tissue padding and natural shape by using autologous tissue. However, with the emergence of the skin-sparing mastectomy technique and artificial dermis matrix, direct-to-implant (DTI) breast reconstruction has become the first choice of surgery. The purpose of this study was to compare the satisfaction levels of patients who underwent DTI and LD flap with implant using patient-reported Breast-Q results. Methods A retrospective study was performed reviewing the records of 49 women who underwent immediate breast reconstruction with DTI or LD flap with implant and responded to the BREAST-Q questionnaire after the operation. The patient-reported breast-Q results were analyzed and correlated to the demographic information and intraoperative information. Results A total of 26 patients who underwent reconstruction with LD flap with implant and 23 patients with DTI were identified and responded to the questionnaire after an average of 32.3 and 10.4 months postoperation, respectively. According to the patient response to the breast-q values, satisfaction with breast was 60.0 and 57.0 points, psychosocial well-being 61.0 and 60.0 points, and sexual well-being 41.0 and 43.0 points in the two groups. Overall, there was no significant difference in the breast-Q score between the two groups. Conclusion Patients who underwent DTI breast reconstruction seemed equally satisfied with the appearance and outcome of their breast reconstruction compared with LD flap with implant. Therefore, it appears that DTI is adequately replacing LD with implant.

OR2AT4, an Ectopic Olfactory Receptor, Suppresses Oxidative Stress-Induced Senescence in Human Keratinocytes.

Olfactory receptors (ORs) are the largest protein superfamily in mammals. Certain ORs are ectopically expressed in extranasal tissues and regulate cell type-specific signal transduction pathways. OR2AT4 is ectopically expressed in skin cells and promotes wound healing and hair growth. As the capacities of wound healing and hair growth decline with aging, we investigated the role of OR2AT4 in the aging and senescence of human keratinocytes. OR2AT4 was functionally expressed in human keratinocytes (HaCaT) and exhibited co-expression with G-protein-coupled receptor signaling components, Golfα and adenylate cyclase 3. The OR2AT4 ligand sandalore modulates the intracellular calcium, inositol phosphate, and cyclic adenosine monophosphate (cAMP) levels. The increased calcium level induced by sandalore was attenuated in cells with OR2AT4 knockdown. OR2AT4 activation by sandalore inhibited the senescent cell phenotypes and restored cell proliferation and Ki-67 expression. Sandalore also inhibited the expression of senescence-associated ß-galactosidase and increased p21 expression in senescent HaCaT cells in response to hydrogen peroxide. Additionally, sandalore activated the CaMKKß/AMPK/mTORC1/autophagy signaling axis and promoted autophagy. OR2AT4 knockdown attenuated the increased in the intracellular calcium level, cell proliferation, and AMPK phosphorylation induced by sandalore. These findings demonstrate that the effects of sandalore are mediated by OR2AT4 activation. Our findings suggest that OR2AT4 may be a novel therapeutic target for anti-aging and anti-senescence in human keratinocytes.

Indirect Clinical Validation of a Programmed Death-Ligand 1 Laboratory-Developed Test for Gastric/Gastroesophageal Junction Adenocarcinoma with 22C3 Antibody Concentrate.

BACKGROUND: The PD-L1 IHC 22C3 pharmDx used on the Dako Autostainer Link 48 (ASL48) staining platform is an established method for assessing programmed death-ligand 1 (PD-L1) expression in tumor tissue and determining patient eligibility for pembrolizumab treatment; however, the availability of this platform is limited in Europe and Asia. OBJECTIVES: The aims of this study were to develop and optimize protocols for the PD-L1 22C3 antibody concentrate with multiple immunohistochemistry staining platforms and to validate these protocols using PD-L1 combined positive score (CPS) with a cut-off of ≥ 1 in gastric or gastroesophageal junction adenocarcinoma. DESIGN: The 22C3 antibody concentrate was tested and optimized protocols were developed for use with three staining platforms: Dako ASL48, Ventana BenchMark ULTRA, and Leica BOND-MAX. Tumor specimens (N = 120) from patients with gastric or gastroesophageal junction adenocarcinoma were used for the validation study; these specimens were evaluated independently by three pathologists for PD-L1 CPS as a continuous variable and using a cut-off of ≥ 1. PD-L1 IHC 22C3 pharmDx used on the Dako ASL48 platform served as the reference or gold standard. RESULTS: The intraclass correlation coefficient of CPS as a continuous variable between the gold standard and each staining platform assessed was 0.910-0.989. When CPS was dichotomized based on a cut-off of ≥ 1, depending on the pathologist and the platform used, positive percentage agreement was 81-99% and negative percentage agreement was 90-100%. Interobserver agreement using the gold standard showed substantial agreement (κ = 0.779). CONCLUSION: The PD-L1 22C3 antibody concentrate can potentially be used with the laboratory-developed test on three commercially available immunohistochemistry staining platforms to determine PD-L1 expression in tumor samples from patients with gastric or gastroesophageal junction adenocarcinoma.

Effect of cholesterol-lowering agents on soluble epidermal growth factor receptor level in type 2 diabetes and hypercholesterolemia.

Soluble epidermal growth factor receptor (sEGFR) levels are elevated in patients with type 2 diabetes mellitus (T2DM) and positively correlate with blood glucose and cholesterol levels. However, how cholesterol-lowering treatment in patients with T2DM affects the sEGFR level is unknown. Therefore, we investigated the change of serum sEGFR after cholesterol-lowering treatment in type 2 diabetic patients with hypercholesterolemia. This study is a non-randomized, prospective observational study. A total of 115 patients were treated in either the rosuvastatin monotherapy group (R group, 5 mg/day, n = 59) or the rosuvastatin/ezetimibe combination therapy group (RE group, 5 mg/10 mg/day, n = 56) for 12 weeks. We measured serum levels of lipids and sEGFR using an ELISA kit before and after 12 weeks of treatment in each group. The low-density lipoprotein cholesterol (LDL-C) level was significantly reduced (from 130.27 ± 27.09 to 76.24 ± 26.82 mg/dL; P < .001) after 12 weeks of treatment and more so in the RE group than in the R group (from 131.68 ± 28.72 to 87.13 ± 27.04 mg/dL, P < .001 in the R group; from 128.78 ± 25.58 to 64.75 ± 21.52 mg/dL, P < .001 in the RE group; R vs RE group, P < .001). The sEGFR level was significantly decreased after 12 weeks of treatment (from 50.34 ± 13.31 to 45.75 ± 11.54 ng/mL; P = .007). The RE group only showed a significant reduction in the sEGFR level after treatment (from 50.94 ± 12.10 to 44.80 ± 11.36 ng/mL; P = .007). Moreover, the sEGFR level was significantly reduced only when the LDL-C level was significantly reduced (from 50.46 ± 10.66 to 46.24 ± 11.86 ng/mL; P = .043). The serum sEGFR level was significantly reduced by cholesterol-lowering treatment with rosuvastatin alone or rosuvastatin/ezetimibe. We suggested that sEGFR may play a significant role in insulin resistance (IR) and inflammation, which are central pathophysiological mechanisms. We confirmed the possibility of using sEGFR as a biomarker to predict a good response to lipid-lowering treatment in type 2 diabetes patients with hypercholesterolemia.

Data on the evaluation of the relation between ß-arrestin 2 and YAP phosphorylation in patient-derived colon cancer organoids.

The data presented in this article is related to a rapid communication entitled "ß-arrestin 2 suppresses the activation of YAP by promoting LATS kinase activity". This article describes the correlation of ß-arrestin 2 and YAP phosphorylation in patient-derived organoid models. Here, we analyzed 45 colon cancer organoids (CCOs) selected in the related research article to investigate the role of ß-arrestin 2 in YAP phosphorylation. Hematoxylin and eosin (H&E) staining and immunohistochemistry data showed that the CCOs maintained tissue architecture and histological features of their original cancer tissues. Moreover, mutation data detected from RNA-seq (RNA-sequencing) analysis showed that these CCOs retained the genetic features of their original colon cancer tissues as well. We also confirmed at the protein level that organoids expressing ß-arrestin 2 showed high expression of phosphorylated YAP. These organoid model studies strongly support the related research article that ß-arrestin 2 suppresses the activation of YAP in colon cancer.

Tensin Regulates Fundamental Biological Processes by Interacting with Integrins of Tonsil-Derived Mesenchymal Stem Cells.

Human tonsil-derived mesenchymal stem cells (TMSCs) have a superior proliferation rate and differentiation potential compared to adipose-tissue-derived MSCs (AMSCs) or bone-marrow-derived MSCs (BMSCs). TMSCs exhibit a significantly higher expression of the tensin3 gene (TNS3) than AMSCs or BMSCs. TNS is involved in cell adhesion and migration by binding to integrin beta-1 (ITG ß1) in focal adhesion. Here, we investigated the roles of four TNS isoforms, including TNS3 and their relationship with integrin in various biological processes of TMSCs. Suppressing TNS1 and TNS3 significantly decreased the cell count. The knockdown of TNS1 and TNS3 increased the gene and protein expression levels of p16, p19, and p21. TNS1 and TNS3 also have a significant effect on cell migration. Transfecting with siRNA TNS3 significantly reduced Oct4, Nanog, and Sox-2 levels. Conversely, when TNS4 was silenced, Oct4 and Sox-2 levels significantly increase. TNS1 and TNS3 promote osteogenic and adipogenic differentiation, whereas TNS4 inhibits adipogenic differentiation of TMSCs. TNS3 is involved in the control of focal adhesions by regulating integrin. Thus, TNS enables TMSCs to possess a higher proliferative capacity and differentiation potential than other MSCs. Notably, TNS3 plays a vital role in TMSC biology by regulating ITGß1 activity.

Effect of oligonol, a lychee-derived polyphenol, on skeletal muscle in ovariectomized rats by regulating body composition, protein turnover, and mitochondrial quality signaling.

Oligonol is a low-molecular-weight polyphenol product derived from lychee (Litchi chinensis Sonn.) fruits. This study was focused on the effects of oligonol on the skeletal muscle of ovariectomized rats. We randomly divided female Sprague-Dawley rats into three groups: a sham surgery control group (Sham), an ovariectomy (OVX) group, and an OVX group treated with oligonol (OVX + Oligonol). Oligonol was intraperitoneally administrated at 30 mg/kg daily for 6 weeks. Oligonol treatment after OVX decreased body weight and fat mass, regulated lipid metabolism in skeletal muscle, without loss of lean mass and bone. Bone turnover was not affected by oligonol. In protein synthesis and degradation, oligonol increased the levels of the mammalian target of rapamycin and its downstream targets, eukaryotic initiation factor 4E-binding protein 1 and 70-kDa ribosomal protein S6 kinase, and it stimulated the expression of ubiquitin-proteasome pathway proteins, the forkhead box transcription factors of the class O and the muscle ring-finger protein-1. Moreover, oligonol treatment enhanced mitochondrial biogenesis and dynamics. Thus, our results indicated that oligonol treatment had beneficial effects on the skeletal muscle in an estrogen-deficiency rat model.