Phenolic changes in a combined herbal extract of Lithospermum erythrorhizon, Houttuynia cordata, and Spirodela polyrhiza and alleviation of DNCB-induced atopic dermatitis in BALB/c mice.

Atopic dermatitis (AD) is an inflammatory skin disease showing skin barrier dysfunction, eczematous lesions, severe itching, and abnormal immune responses. The aim of this study was to determine whether an herb combination of Lithospermum erythrorhizon (LE), Houttuynia cordata (HC), and Spirodela polyrhiza (SP) has a superior anti-AD effect. Forty-two compounds were identified in LE, HC, SP, and a combined herb extract of LE, HC, and SP (LHS) using ultra-high-pressure liquid chromatography (UHPLC)-Orbitrap mass spectrometer (MS). The concentration of flavonoid glycosides including orientin (luteolin-8-C-glucoside), quercetin-3-O-rhamnoside, and luteolin-7-O-glucoside in the LHS was increased than in individual extracts. Furthermore, the treatment of LHS most effectively inhibited the increase of epidermal thickness, the number of mast cells, and the release of immunoglobulin E compared with that with each extract. These results suggest that the potential anti-AD effects of the LHS are due to the changes of bioactive compounds by the combination of herbs. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01329-7.

Nontuberculous mycobacterial myositis in dermatomyositis with long-term use of immunosuppressant: a case report.

Inflammatory myopathies, such as polymyositis and dermatomyositis, are systemic inflammatory disorders that affect skeletal muscles and internal organs. The treatment of inflammatory myopathies usually involves long-term use of high doses of steroids and/or immunosuppressants, making patients susceptible to opportunistic infections. Unfortunately, infections are a leading cause of morbidity and mortality in patients with inflammatory myopathies. Musculoskeletal nontuberculous mycobacterial infections are rare. Nontuberculous mycobacterial infections are easily overlooked owing to their rarity, leading to delayed diagnosis and treatment, indolent clinical course, and difficulty isolating the pathogen. Nontuberculous mycobacterial infections are a growing health concern because of their increasing incidence and the need for prolonged treatment. In patients with connective tissue diseases, immunosuppressant use may lead to an increased risk of nontuberculous mycobacterial infection with a poor prognosis, which highlights the need for early diagnosis and treatment. Herein, we report the case of a 59-year-old man diagnosed with dermatomyositis, who had prolonged use of immunosuppressants and developed a disseminated soft tissue infection in both thighs caused by Mycobacterium abscessus. Multimodal images were obtained using magnetic resonance imaging, ultrasonography, and computed tomography. A strong suspicion of possible combined opportunistic infections and appropriate staining is essential in diagnosing nontuberculous mycobacterial myositis.

Effects of Cortactin Expression on Prognosis in Patients with Breast Cancer.

BACKGROUND: Cortactin is overexpressed in several types of invasive cancers. However, the role of cortactin expression in breast cancer prognosis has not been sufficiently elucidated. Therefore, we investigated the clinicopathological significance of cortactin in breast cancer. METHODS: Tissue microarrays were prepared from a cohort of 506 patients with breast cancer, and cortactin expression was evaluated using immunohistochemistry. The cortactin immunoreactivity score (IRS) was quantified as the product of the intensity score and the percentage of immunoreactive cells. Cortactin expression was classified as low or high using the IRS (IRS ≤ 4 as a cortactin-low value and IRS > 4 as a cortactin-high value). We compared cortactin expression and clinicopathological factors according to the molecular subtypes of breast cancer. RESULTS: Of 506 breast cancer cases, 333 and 173 showed high and low cortactin expression, respectively. Of the 333 patients with high cortactin expression, 204, 58, and 71 had luminal, HER2, and triple-negative breast cancer (TNBC), respectively. In the univariate and multivariate analyses of patients with TNBC, cortactin expression was found to be a significant prognostic factor for overall survival (OS). However, in all patients with non-TNBC, cortactin expression had no significant association with prognosis or overall survival. Survival curves revealed that among patients with TNBC, the high-cortactin group had a better prognosis in disease-free survival and OS. CONCLUSIONS: Cortactin expression may be a good biomarker for predicting the prognosis of patients with TNBC.

ASAP1 Expression in Invasive Breast Cancer and Its Prognostic Role.

Breast cancer is a major global health burden with high morbidity and mortality rates. Previous studies have reported that increased expression of ASAP1 is associated with poor prognosis in various types of cancer. This study was conducted on 452 breast cancer patients who underwent surgery at Hanyang University Hospital, Seoul, South Korea. Data on clinicopathological characteristics including molecular pathologic markers were collected. Immunohistochemical staining of ASAP1 expression level were used to classify patients into high and low groups. In total, 452 cases low ASAP1 expression group was associated with significantly worse recurrence-free survival (p = 0.029). In ER-positive cases (n = 280), the low ASAP1 expression group was associated with significantly worse overall survival (p = 0.039) and recurrence-free survival (p = 0.029). In multivariate cox analysis, low ASAP1 expression was an independent significant predictor of poor recurrence-free survival in the overall patient group (hazard ratio = 2.566, p = 0.002) and ER-positive cases (hazard ratio = 4.046, p = 0.002). In the analysis of the TCGA dataset, the low-expression group of ASAP1 protein demonstrated a significantly poorer progression-free survival (p = 0.005). This study reports that low ASAP1 expression was associated with worse recurrence-free survival in invasive breast cancer.

Immunohistochemical Analysis of Single-Stranded DNA Binding Protein 2 in Non-Melanoma Skin Cancers.

Single-stranded DNA binding protein 2 (SSBP2) is a tumor suppressor candidate. In this study, the expression level and clinicopathological significance of SSBP2 in squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were evaluated. We also identified biological pathways associated with a set of genes potentially related to SSBP2. Immunohistochemistry (IHC) was performed on 70 SCC and 146 BCC cases to assess SSBP2 expression semi-quantitatively. In addition, the associations between SSBP2 expression and clinicopathological characteristics were analyzed. Gene ontology (GO) enrichment analysis was performed using publicly available data and web-based bioinformatics tools. Compared with BCC, SCC had a significantly low SSBP2 expression (p < 0.001). In total, 12 (17.1%) of the 70 SCC cases and 30 (20.5%) of the 146 BCC cases showed low SSBP2 expression. Among SCC cases, ulceration (p = 0.005) and a deep level of invasion (p = 0.012) showed an association with low SSBP2 expression. Local recurrence was slightly more common in the SCC subgroup with low SSBP2 expression, although the difference was not significant (p = 0.058). Using GO enrichment analysis, we identified several biological functions performed by a set of 36 genes in SCC. SSBP2 evaluation using IHC can be helpful in the differential diagnosis of SCC and BCC. SSBP2 expression was associated with tumor invasiveness in SCC.

Prognostic Implication of YY1 and CP2c Expression in Patients with Primary Breast Cancer.

Yin Yang 1 (YY1) is a transcription factor that regulates epigenetic pathways and protein modifications. CP2c is a transcription factor that functions as an oncogene to regulate cell proliferation. YY1 is known to interact with CP2c to suppress CP2c's transcriptional activity. This study aimed to investigate YY1 and CP2c expression in breast cancer and prognostic implications. In this study, YY1 and CP2c expression was evaluated using immunohistochemical staining, Western blot and RT-PCR assays. Of 491 patients with primary breast cancer, 138 patients showed YY1 overexpression. Luminal subtype and early stage were associated with overexpression (p < 0.001). After a median follow-up of 68 months, YY1 overexpression was found to be associated with a better prognosis (disease-free survival rates of 92.0% vs. 79.2%, p = 0.014). In Cox proportional hazards model, YY1 overexpression functioned as an independent prognostic factor after adjustment of hormone receptor/HER2 status and tumor size (hazard ratio of 0.50, 95% CI 0.26-0.98, p = 0.042). Quantitative analysis of YY1 and CP2c protein expression in tumors revealed a negative correlation between them. In conclusion, YY1 overexpression is a favorable prognostic biomarker in patients with breast cancer, and it has a negative correlation with CP2c at the protein level.

Clinicopathological Significance of Cell Adhesion Molecule 4 Expression in Gallbladder Cancer and Its Prognostic Role.

Cell adhesion molecule 4 (CADM4) is involved in intercellular interactions and is a tumor-suppressor candidate. The role of CADM4 in gallbladder cancer (GBC) has not been reported. Therefore, the clinicopathological significance and prognostic value of CADM4 expression in GBC were evaluated in the present study. Immunohistochemistry (IHC) was performed on 100 GBC tissues to assess CADM4 expression at the protein level. The association between CADM4 expression and the clinicopathological characteristics of GBC was analyzed, and the prognostic significance of CADM4 expression was evaluated. Low CADM4 expression was significantly associated with advanced T category (p = 0.010) and high AJCC stage (p = 0.019). In a survival analysis, low CADM4 expression was associated with shorter overall survival (OS; p = 0.001) and recurrence-free survival (RFS; p = 0.018). In univariate analyses, low CADM4 expression was associated with shorter OS (p = 0.002) and RFS (p = 0.023). In multivariate analyses, low CADM4 expression was an independent prognostic factor of OS (p = 0.013). Low CADM4 expression was associated with tumor invasiveness and poor clinical outcomes in patients with GBC. CADM4 may play an important role in cancer progression and patient survival and can be used as a potential prognostic marker of GBC.

Low MTUS1 Protein Expression Is Associated with Poor Survival in Patients with Colorectal Adenocarcinoma.

INTRODUCTION: Microtubule-associated tumor suppressor 1 (MTUS1) is a novel tumor suppressor protein involved in cell proliferation, migration, and tumor growth. MTUS1 is thought to be downregulated in various human cancers and associated with poor prognosis. We evaluated the clinicopathologic significance and prognostic value of MTUS1 in colorectal adenocarcinoma. METHODS: Immunohistochemical staining for MTUS1 was performed on tissue microarrays of 393 colorectal adenocarcinoma cases, and MTUS1 staining was classified into high- and low-expression groups. Then, we investigated the correlations between MTUS1 protein expression and various clinicopathological parameters and patient survival. RESULTS: MTUS1 protein was expressed at various grade levels in the cytoplasm of tumor cells, which showed loss or decreased expression of MTUS1. A total of 253 cases (64.4%) were classified into the low MTUS1 protein expression group and 140 cases (35.6%) into the high MTUS1 expression group. A low level of MTUS1 protein significantly correlated with tumor size (p = 0.047), histological grade (p < 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p = 0.047), and lymph node metastasis (p < 0.001). Survival analyses showed that patients with low MTUS1 protein expression had worse overall survival (p = 0.007, log-rank test) and worse recurrence-free survival (p = 0.019, log-rank test) than those with high MTUS1 expression. CONCLUSIONS: Low MTUS1 protein expression is associated with adverse clinicopathological characteristics and poor survival outcomes in patients with colorectal adenocarcinoma. These results suggest that MTUS1 functions as a tumor suppressor in colorectal adenocarcinoma and could be a potential prognostic biomarker.

Extranodal extension influences prognosis in pancreatic head cancer: A retrospective cohort study.

BACKGROUND: Extranodal extension (ENE) is an established prognostic factor in several gastrointestinal cancers. However, the prognostic impact remains unclear. Here, we investigated the prognostic implications of ENE in patients with surgically resected pancreatic cancer. METHODS: We retrospectively reviewed 476 surgically resected pancreatic head cancer patients who consecutively underwent upfront pancreaticoduodenectomy for pathologically confirmed pancreatic ductal adenocarcinoma between January 2009 and December 2013. We compared the disease-free survival (DFS) rates of the patients according to ENE status. RESULTS: Among the 476 patients, patients with ENE had lower DFS rates than those without ENE (N0, 13 months; LN+/ENE-, 7 months; LN+/ENE+, 6 months; P < .001). In addition, even in the same N stage, patients with ENE had lower DFS rates than those without ENE (N0, 13 months; N1/ENE- 8 months; N1/ENE+, 7 months; N2/ENE-, 7 months; N2/ENE+, 4 months, P < .001). However, there was no significant difference in survival rates between patients in the N1/ENE+ group and those in the N2/ENE- group. Additionally, ENE was an independent prognostic factor for pancreatic cancer. CONCLUSIONS: Extranodal extension significantly predicted a poor prognosis among patients with pancreatic head cancer, especially those with nodal metastasis. Therefore, ENE should be considered a prognostic factor in future editions of the staging system.

Naringin enhances long-term potentiation and recovers learning and memory deficits of amyloid-beta induced Alzheimer's disease-like behavioral rat model.

Alzheimer's disease (AD), as the most typical type of dementia, is a chronic neurodegenerative disorder characterized by progressive learning and memory impairment. It is known that the main causes of AD are the accumulation of ß-amyloid (Aß) plaques and neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Naringin is a flavonoid from citrus fruits, especially in grapefruit, which has anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective activities. However, the effect of naringin in AD caused by Aß has not been clearly studied, and there are few studies on the electrophysiological aspect. Thus, we investigated the ex vivo neuroprotective effect of naringin through the long-term potentiation (LTP) on organotypic hippocampal slice cultures. We evaluated the in vivo effects of naringin (100 mg/kg/day) orally treated for 20 days on learning, memory, and cognition which was impaired by bilateral CA1 subregion injection of Aß. Cognitive behaviors were measured 2 weeks after Aß injection using behavioral tests and the hippocampal expression of apoptotic and neurotrophic regulators were measured by immunoblotting. In hippocampal tissue slices, naringin dose-dependently increased the field excitatory postsynaptic potential (fEPSP) after theta burst stimulation and attenuated Aß-induced blockade of fEPSP in the hippocampal CA1 area. In Aß injected rats, naringin improved object recognition memory in the novel object test, avoidance memory in the passive avoidance test and spatial recognition memory in the Morris water maze test. In the hippocampus, naringin attenuated the Aß-induced cyclooxygenase-2, Bax activation and Bcl-2, CREB, BDNF and TrkB inhibition. These results suggest that naringin has therapeutic potential to reduce neuronal inflammation and apoptosis induced by Aß related with the BDNF/TrkB/CREB signaling.

CD47 Expression Predicts Unfavorable Prognosis in Clear Cell Renal Cell Carcinoma after Curative Resection.

The role of CD47 expression as a 'do not eat me' signal that inhibits phagocytosis of tumor cells by macrophages is well established. Immune checkpoint therapy that targets CD47 has been successful in preclinical trials and is currently undergoing clinical investigation for various human malignancies. Here, the clinicopathological correlation with CD47 expression in clear cell renal cell carcinoma (ccRCC) was explored. CD47 expression was evaluated by immunohistochemical staining in tissue microarray sections of 235 ccRCC tissues. CD47 expression was observed in 28 (11.9%) of 235 ccRCC tissues and was significantly associated with higher WHO/ISUP grade (p = 0.001), frequent lymphovascular invasion (p = 0.036), frequent renal vein thrombus (p = 0.018), frequent sinus fat invasion (p = 0.004), frequent sarcomatous change (p = 0.001), higher pT stage (p = 0.002), higher pN stage (p = 0.002), higher pM stage (p < 0.001), and advanced American Joint Committee on Cancer stage (p = 0.002). In the survival analyses, positive CD47 expression was associated with cancer-specific survival (p = 0.003). However, positive CD47 expression was not associated with recurrence-free survival. In conclusion, CD47 expression was associated with adverse clinicopathological parameters and cancer-specific survival in patients with ccRCC.

Low expression of DUSP4 expression predicts unfavorable prognosis in gallbladder adenocarcinoma.

Background: Dual specificity phosphatase 4 (DUSP4), which regulates the mitogen activated protein kinases, has emerged as a tumor suppressor gene in several human malignancies. Aims and Objectives: In this study, we investigated the clinicopathologic significance and the prognostic role of DUSP4 in gallbladder adenocarcinoma. Materials and methods: DUSP4 expression was evaluated immunohistochemically in tissue microarray from 110 gallbladder adenocarcinoma samples and scored by H score system. The cut off (H score <170) was determined by ROC curve analysis. Results: Low expression of DUSP4 expression was observed in 57 (51.8%) out of 110 gallbladder adenocarcinoma samples. Low expression of DUSP4 expression was significantly associated with high histologic grade (P = 0.017), high pT stage (P = 0.002) and high AJCC stage (P = 0.007). Kaplan Meier survival curves revealed that patients with low expression of DUSP4 expression had significantly worse cancer specific survival (P = 0.024, log rank test). However, there was no significant association between DUSP4 expression and recurrence free survival. Conclusions: In conclusion, gallbladder adenocarcinoma with low expression of DUSP4 expression was associated with adverse clinicopathologic characteristics and poor patient outcome.patient outcome.

Clinicopathological Implications of ASAP1 Expression in Hepatocellular Carcinoma.

Background: The expression of ArfGAP with SH3 domain ankyrin repeat and PH domain 1 (ASAP1) is increased in various types of cancer, showing potential as a prognostic marker. The clinicopathological implications of ASAP1 expression in patients with hepatocellular carcinoma (HCC) remain unclear. We thus investigated the clinicopathological significance and prognostic effect of ASAP1 expression in HCC patients. Materials and Methods: ASAP1 expression was assessed in 149 HCC tissue samples using immunohistochemistry (IHC). The associations between ASAP1 expression and clinicopathological characteristics were analyzed. The prognostic effect of ASAP1 expression in patients with HCC was evaluated based on survival analyses and confirmed using a web-based tool. Results: ASAP1 expression was observed in the cytoplasm of tumor cells. High ASAP1 expression was observed in 89 (59.7%) of 149 cases. High ASAP1 expression was significantly associated with male patients (p = 0.018), higher histological grade (p = 0.013), vessel invasion (p = 0.021), and higher stage (p = 0.020). High ASAP1 expression was associated with shorter overall survival (OS; p = 0.041) and recurrence-free survival (RFS; p = 0.008) based on Kaplan-Meier survival analyses. Web-based analysis using Kaplan-Meier (KM) plotter showed high mRNA ASAP1 expression to be associated with short OS (p = 0.001). Conclusion: High ASAP1 expression was associated with aggressive clinicopathological characteristics and poor clinical outcomes in patients with HCC. ASAP1 can be considered a prognostic biomarker in HCC patients.

CD47 Expression in Non-Melanoma Skin Cancers and Its Clinicopathological Implications.

CD47 is a cell surface molecule and regulates diverse cellular responses. CD47 is highly expressed in cancer cells and has potential as a therapeutic target and prognostic factor in cancer patients. The expression patterns of CD47 in basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and its precursor lesions, and its clinicopathological significance were investigated. CD47 expression was evaluated by immunohistochemistry in 152 cases of BCC and 71 cases of SCC. For comparison of CD47 expression, actinic keratosis (AK), squamous cell carcinoma in situ (SCCIS), keratoacanthoma (KA), and normal skin (NS) tissue were used. CD47 expression in BCC was significantly lower than that of SCC (p < 0.001). CD47 expression levels in SCC and KA were significantly higher than those of NS and AK (p < 0.05). High CD47 expression was significantly associated with the presence of ulceration (p = 0.005) and a deeper level of invasion (p = 0.011) in BCC. In addition, high CD47 expression was significantly associated with the presence of ulceration (p = 0.019) and larger tumor size (p = 0.004) in SCC. CD47 expression was associated with tumorigenesis and tumor progression in non-melanoma skin cancers.

Decreased Expression of Cell Adhesion Molecule 4 in Gastric Adenocarcinoma and Its Prognostic Implications.

Cell adhesion molecule 4 (CADM4) is a novel tumor suppressor candidate. The prognostic implications of CADM4 in gastric cancer have not been conclusively elucidated. Therefore, we evaluated the clinicopathological significance and prognostic value of CADM4 expression in a large series of patients with gastric adenocarcinoma. Immunohistochemical staining for CADM4 was performed on 534 gastric adenocarcinomas. We evaluated the associations between CADM4 expression and the clinicopathological and molecular characteristics of the adenocarcinomas. The prognostic effect of CADM4 expression was evaluated by survival analyses. Low CADM4 expression was significantly associated with young age (p = 0.046), aggressive histological type (p < 0.001), high pT category (p < 0.001), nodal metastasis (p < 0.001), high stage (p = 0.002), lymphovascular invasion (p = 0.001), and perineural invasion (p = 0.001). Low CADM4 expression was more frequently observed in tumors without human epidermal growth factor receptor 2 (HER2) amplification (p = 0.002). Low CADM4 expression was associated with worse overall survival (p = 0.007) and recurrence-free survival (p = 0.005) in the survival analyses. Low CADM4 expression was associated with aggressive clinicopathological features and poor clinical outcomes. CADM4 can act as a tumor suppressor in gastric adenocarcinoma and can be considered a prognostic biomarker.

EPHB2 expression is associated with intestinal phenotype of gastric cancer and indicates better prognosis by suppressing gastric cancer migration.

The protein tyrosine kinase Ephrin type-B receptor 2 (EPHB2) belongs to one of the intestinal stem cell signature genes and plays a crucial role in maintaining the crypt-villous axis. Herein, we aimed to investigate the expression of EPHB2 during gastric carcinogenesis and evaluated its prognostic and functional significance in gastric cancer (GC). EPHB2 expression was upregulated in intestinal metaplasia and GCs compared to normal antral and fundic glands. EPHB2 mRNA levels were strongly correlated with the intestinal stem cell markers OLFM4, LGR5, and EPHB3. Notably, EPHB2 expression was significantly correlated with CDX2 expression, and in vitro studies demonstrated that CDX2 expression increased both EPHB2 transcription and protein levels. In a large cohort of GC patients, EPHB2 positivity was observed in 39% of 704 GCs and was negatively correlated with tumor differentiation, lymphovascular invasion, and tumor-node-metastasis stages. Notably, EPHB2 positivity was associated with better overall survival, and it was an independent prognostic marker in intestinal-type GCs. Overexpression of EPHB2 in GC cell lines, MKN-28 and MKN-74, reduced migration activity by suppressing phosphorylation of focal adhesion kinase, whereas no significant difference was observed in proliferation rates. Thus, we suggest that EPHB2 acts as a tumor suppressor in GCs and can be a prognostic marker in intestinal-type GCs.

Loss of Single-Stranded DNA Binding Protein 2 Expression Is Associated with Aggressiveness and Poor Overall Survival in Patients with Invasive Breast Carcinoma.

BACKGROUND: Single-stranded DNA binding protein 2 (SSBP2) is involved in the DNA damage response and the maintenance of genome stability. Previous studies have suggested that SSBP2 has a tumor suppressor function or oncogenic function. Loss of SSBP2 expression has been reported in various tumors. However, the role of SSBP2 expression in invasive breast carcinoma has not been reported. METHODS: Immunohistochemical staining for SSBP2 was performed on tissue microarrays consisting of 491 invasive breast carcinoma cases. The result of nuclear SSBP2 staining was stratified as either negative or positive. Then, we investigated the correlations between SSBP2 expression and various clinicopathological parameters and patient outcomes. RESULTS: Loss of nuclear SSBP2 expression was observed in 61 cases (12.4%) of 491 invasive breast carcinomas. Loss of nuclear SSBP2 expression was significantly correlated with larger tumor size (p < 0.001, chi-squared test), higher histological grade (p = 0.016, Cochran-Armitage trend test), higher pathological T stage (p < 0.001, Cochran-Armitage trend test), estrogen receptor status (p < 0.001, chi-squared test), and molecular subtype (p < 0.001, chi-squared test). Kaplan-Meier survival analysis revealed that patients with loss of nuclear SSBP2 expression had worse overall survival (p = 0.013, log-rank test). However, loss of nuclear SSBP2 expression was not correlated with recurrence-free survival (p = 0.175, log-rank test). CONCLUSIONS: Loss of nuclear SSBP2 expression was associated with adverse clinicopathological characteristics and poor patient outcomes. SSBP2 acts as a tumor suppressor in invasive breast carcinoma and may be used as a prognostic biomarker.

Loss of DUSP4 Expression as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma.

Dual-specificity protein phosphatase 4 (DUSP4) is a negative regulator of mitogen-activated protein kinases. The prognostic impact of DUSP4 expression in renal cell carcinoma is not well studied. Therefore, we evaluated the clinicopathological implications of DUSP4 expression in clear cell renal cell carcinoma by performing immunohistochemistry (IHC). The clinical outcome according to DUSP4 expression was evaluated through survival analyses, and the association between mRNA expression and prognosis was confirmed by online analysis (Kaplan-Meier plotter). Loss of DUSP4 expression was noted in most histological subtypes of renal cell carcinoma. Loss of DUSP4 expression in clear cell renal cell carcinoma was significantly correlated with old age (p = 0.033), high histologic grade (p < 0.001), tumor necrosis (p < 0.001), and high pT category (p < 0.001). In survival analysis, loss of DUSP4 expression was associated with poor clinical outcomes in cancer-specific survival and recurrence-free survival (p = 0.010 and p = 0.007, respectively). Upon TCGA data analysis, patients with low DUSP4 mRNA expression showed a shorter overall survival (p = 0.023). These results suggest that loss of DUSP4 expression can be used as a potential biomarker for predicting clinical outcomes in clear cell renal cell carcinoma patients.

Loss of YY1 expression predicts unfavorable prognosis in stage III colorectal cancer.

BACKGROUND: Yin Yang 1 (YY1), the multifunctional transcription factor, has recently been assigned biological properties related to human malignancies. YY1 can facilitate both tumor suppression and tumor growth. The conflicting role of YY1 in human malignancies is not yet fully explained. OBJECTIVE: In this study, we determined the clinicopathologic significance and prognostic role of YY1 in stage III colorectal cancer (CRC). MATERIALS AND METHODS: YY1 expression was evaluated immunohistochemically in tissue microarray from 345 CRCs. YY1 expression was scored by the proportion of tumor cells with nuclear staining into 4 scores (0, none; 1+, ≤10%; 2+, 10 to ≤25%; 3+, >25%). A score of 0 and 1 were considered as loss of expression. RESULTS: Loss of YY1 expression was observed in 49 (14.2%) out of 345 CRCs and was associated with larger tumor size (P = 0.004), tumor deposit (P = 0.008), and higher pathologic tumor (pT) stage (P = 0.004). In stage III group, loss of YY1 expression was associated with larger tumor size (P = 0.027) and tumor deposit (P = 0.011). Kaplan-Meier survival curves revealed no significant difference between patients with YY1 loss and patients with intact YY1 in both cancer-specific survival and recurrence-free survival (P = 0.330 and P = 0.470, respectively). In American Joint Committee on Cancer (AJCC) stage subgroup, loss of YY1 expression was associated with poor recurrence-free survival in AJCC stage III CRC (P = 0.038). CONCLUSION: Loss of YY1 expression was significantly associated with aggressive phenotypes and poor patient outcome in AJCC stage III CRC.

Sulforaphane enhances long-term potentiation and ameliorate scopolamine-induced memory impairment.

Increases in human life expectancy have led to increases in the prevalence of senile dementia and neurodegenerative diseases. This is a major problem because there are no curative treatments for these diseases, and patients with unmanaged cognitive and neurodegenerative symptoms experience many social problems. Sulforaphane is a type of organosulfur compound known as an isothiocyanate. It is derived from glucoraphanin, a compound found in cruciferous vegetables such as broccoli, brussels sprouts, and cabbages, via an enzymatic reaction that is triggered by plant damage (e.g., chewing). Sulforaphane exhibits activity against cancer, inflammation, depression, and severe cardiac diseases. It can also alleviate oxidative stress and neural dysfunction in the brain. However, there is insufficient knowledge about the electrophysiological and behavioral basis of the effects of sulforaphane on learning and memory. Therefore, we evaluated whether acute sulforaphane administration affected long-term potentiation (LTP) in organotypic cultured rat hippocampal tissues. We also measured the effect of sulforaphane on the performance of three behavioral tests, the Y-maze test, the passive avoidance test, and the Morris water maze, which assess short-term memory, avoidance memory, and short and long-term spatial memory, respectively. We found that sulforaphane increased the total field excitatory postsynaptic potential (fEPSP) in a dose-dependent manner after high frequency stimulation and attenuated scopolamine-induced interference of the fEPSP in the hippocampal CA1 area. Sulforaphane also restored cognitive function and inhibited memory impairment as indicated by the alleviation of the negative neurological effects of scopolamine, i.e, a lowered ratio of spontaneous alternation in the Y-maze, a reduced step-through latency in the passive avoidance test, and an increased navigation time in the Morris water maze. These results indicate that sulforaphane can effectively prevent the attenuation of LTP and cognitive abilities induced by cholinergic and muscarinic receptor blockade. Further research is warranted to explore the potential therapeutic and prophylactic utility of sulforaphane for improving learning and memory, especially in those suffering from neurodegenerative disorders.