P63 and P73 Activation in Cancers with p53 Mutation.

The members of the p53 family comprise p53, p63, and p73, and full-length isoforms of the p53 family have a tumor suppressor function. However, p53, but not p63 or p73, has a high mutation rate in cancers causing it to lose its tumor suppressor function. The top and second-most prevalent p53 mutations are missense and nonsense mutations, respectively. In this review, we discuss possible drug therapies for nonsense mutation and a missense mutation in p53. p63 and p73 activators may be able to replace mutant p53 and act as anti-cancer drugs. Herein, these p63 and p73 activators are summarized and how to improve these activator responses, particularly focusing on p53 gain-of-function mutants, is discussed.

Major Plant in Herbal Mixture Gan-Mai-Da-Zao for the Alleviation of Depression in Rat Models.

Gan-Mai-Da-Zao (GMDZ) is a well-known product in Chinese traditional medicine and includes three major plants: blighted wheat (Fu Mai), licorice (Gan Cao), and jujube (Da Zao). GMDZ is widely used as an efficacious and well-tolerated prescription for depression in clinics. The present study was designed to investigate the main plant of GMDZ for its antidepressant-like effect using the unpredictable chronic mild stress (UCMS) model on rats who received an injection with p-chlorophenylalanine (PCPA) to produce the chemical model. In rats subjected to the UCMS model, forced swim tests, open field tests, and sucrose preference tests were applied to estimate the chronic effect of GMDZ. We found that the oral administration of GMDZ for 21 days significantly alleviated the behavior in rats with depression induced by either UCMS or PCPA. The expression levels of the serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) in the hippocampus of the rats with depression were markedly increased by GMDZ. Additionally, rats that received the herbal mixture without licorice showed a markedly lower response than GMDZ. These results suggest that GMDZ may alleviate the depressive-like behaviors in depressive rats, possibly via licorice (Gan Cao), to increase 5-HTT and BDNF signals in the hippocampus. The present study confirmed the antidepressant-like effects of GMDZ. Additionally, licorice (Gan Cao) may play a key role in the effectiveness of GMDZ.

Assessment of tumor extension to the ductal system of submucosal glands in patients with superficial esophageal squamous neoplasms: Implications for endoscopic resection.

BACKGROUND: Endoscopic submucosal dissection (ESD) has become the standard treatment for superficial esophageal squamous cell neoplasia (SESCN); however, local recurrence still occurs occasionally even in patients who meet the current curative criteria. Esophageal ducts of the submucosal gland may serve as a pathway for the spread of SESCN to a deeper layer. However, the clinical impact of ductal involvement (DI) in patients undergoing ESD has yet to be investigated. METHODS: We consecutively enrolled patients with SESCN who were treated with ESD. The resected specimens were meticulously reviewed in multiple section slices for the presence and resected margins of DI, and their correlations with clinical factors were evaluated. RESULTS: A total of 210 lesions were analyzed, of which 78 (37.1%) presented with DI. The presence of submucosal invasion, lymphovascular invasion (LVI), and DI were indicators of worse prognosis (P < .05). Deep extended DIs were misdiagnosed as deep submucosal invasive cancer in 4 cases (2%). Of the 185 patients who met the criteria for curative ESD (ie, R0 resection and no deep submucosal invasion or LVI), 11 (5.9%) developed local recurrence/metastasis during a mean follow-up of 55.2 months (range, 6 to 140) months. Compared with patients with without DI, patients with DI had worse recurrence-free survival (P = .008, log-rank test) and a higher local risk of recurrence (12.7% vs 2.5%) after curative ESD (hazard ratio, 4.20; P = .038). CONCLUSIONS: A precise histological assessment of DI in SESCN is crucial after ESD, given that DI is common and associated with worse outcome. Whether total removal of esophageal glands/ducts can improve outcome requires future study.

Immunohistochemistry Helps to Distinguish Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features/Noninvasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma with Other Follicular Thyroid Lesions.

Background and Objectives: We aimed to assess the diagnostic value of various immunohistochemical (IHC) markers and panels for differentiation among benign follicular nodules (BFNs), noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), noninvasive encapsulated follicular variants of papillary thyroid carcinoma (NEFVPTCs), and infiltrative FVPTC (IFVPTC). Materials and Methods: Sixty-three cases were classified as BFNs, NIFTPs, NEFVPTCs, or IFVPTCs and were evaluated using the following markers: CK19, CD56, galectin-3, CITED1, HBME-1, VE1, and TROP-2. Results: The IHC results for NIFTP and NEFVPTC exhibited no statistically significant differences. In differentiating IFVPTCs from BFNs and NIFTPs/NEFVPTCs, galectin-3 and TROP-2 were the markers with the highest sensitivity plus high specificity, respectively. In various combinations, panel co-expression of two markers, including galectin-3 and/or HBME-1 and/or TROP-2, and the combination of galectin-3 and TROP-2 co-expression could achieve 100% in all aspects. In terms of discrimination of BFNs from NIFTP/NEFVPTC, CK19 was the single most sensitive marker (81.3%), while CD56 was the most specific (100%). The panel consisting of CK19 and/or HBME-1 exhibited the greatest sensitivity (96.9%), but the panel with CD56 and/or HBME-1 exhibited the greatest specificity (90.5%). Conclusions: Our results broaden the use of IHC markers for differential diagnoses among the four groups of follicular-based lesions. In addition, the similar IHC profiles of NIFTP and NEFVPTC also suggest the original criterion of <1% papillae within tumors, providing a reliable NIFTP diagnosis. Their close relationship may represent a spectrum of progressing neoplasia.

Ovarian Folliculogenesis and Uterine Endometrial Receptivity after Intermittent Vaginal Injection of Recombinant Human Follicle-Stimulating Hormone in Infertile Women Receiving In Vitro Fertilization and in Immature Female Rats.

The uterine first-pass effect occurs when drugs are delivered vaginally. However, the effect of vaginally administered recombinant human follicle-stimulating hormone (rhFSH) on ovarian folliculogenesis and endometrial receptivity is not well established. We aimed to compare the efficacy of rhFSH administered vaginally and abdominally in clinical in vitro fertilization (IVF) treatment, pharmacokinetic study, and animal study. In IVF treatment, the number of oocytes retrieved, endometrial thickness and uterine artery blood perfusion were not different between women who received the rhFSH either vaginally or abdominally. For serum pharmacokinetic parameters, significantly lower Tmax, clearance, and higher AUC and T1/2_elimination of rhFSH were observed in women who received rhFSH vaginally, but urine parameters were not different. Immature female rats that received daily abdominal or vaginal injections (1 IU twice daily for 4 days) or intermittent vaginal injections (4 IU every other day for two doses) of rhFSH had more total follicles than the control group. In addition, the serum progesterone and progesterone receptors in the local endometrium were significantly higher in the groups treated with intermittent abdominal or vaginal injection of rhFSH, compared with those who recieved daily injection. In summary, vaginal administration of rhFSH may provide an alternative treatment regimen in women receiving IVF.

Etanercept Ameliorates Cardiac Fibrosis in Rats with Diet-Induced Obesity.

Diet-induced obesity (DIO) is considered the main risk factor for cardiovascular diseases. Increases in the plasma levels of tumor necrosis factor alpha (TNF-α) is associated with DIO. Etanercept, a TNF-α inhibitor, has been shown to alleviate cardiac hypertrophy. To investigate the effect of etanercept on cardiac fibrosis in DIO model, rats on high fat diet (HFD) were subdivided into two groups: the etanercept group and vehicle group. Cardiac injury was identified by classic methods, while fibrosis was characterized by histological analysis of the hearts. Etanercept treatment at 0.8 mg/kg/week twice weekly by subcutaneous injection effectively alleviates the cardiac fibrosis in HFD-fed rats. STAT3 activation seems to be induced in parallel with fibrosis-related gene expression in the hearts of HFD-fed rats. Decreased STAT3 activation plays a role in the etanercept-treated animals. Moreover, fibrosis-related genes are activated by palmitate in parallel with STAT3 activation in H9c2 cells. Etanercept may inhibit the effects of palmitate, but it is less effective than a direct inhibitor of STAT3. Direct inhibition of STAT3 activation by etanercept seems unlikely. Etanercept has the ability to ameliorate cardiac fibrosis through reduction of STAT3 activation after the inhibition of TNF-α and/or its receptor.

Coexistence of disseminated Kaposi sarcoma and multicentric Castleman disease in an HIV-infected patient under viral suppression.

Coexistence of multicentric Castleman disease and Kaposi sarcoma is rare and might be missed without an experienced pathologists' interpretation. A 46-year-old man had been diagnosed with HIV infection and treated with combination antiretroviral therapy of dolutegravir/abacavir/lamivudine (Triumeq) for one year. The latest viral load was 49 copies/mL and CD4 T-cell count was 192 cells/uL. He was admitted due to fever off and on, splenomegaly, general lymphadenopathy, and severe thrombocytopenia for two months. Biopsy of a purplish skin lesion and gastric tissue showed Kaposi sarcoma. The pathology of inguinal lymph nodes revealed coexistence of Kaposi sarcoma and multicentric Castleman disease. The plasma Kaposi sarcoma herpesvirus viral load was 365,000 copies/mL. During hospitalization, progressive pancytopenia and spiking fever persisted, and he died of multi-organ failure before completion of chemotherapeutic treatments with rituximab plus liposomal doxorubicin.

Connective tissue growth factor in hepatocytes is elevated by carbon tetrachloride via STAT3 activation.

Carbon tetrachloride (CCl4) is widely used to induce hepatic fibrosis. Therapeutic agents alleviate hepatic fibrosis by inhibiting signal transducer and activator of transcription 3 (STAT3) activation. To understand the direct effects of CCl4 on STAT3 expression in the liver, the present study incubated cultured hepatocytes expressing connective tissue growth factor (CTGF) with CCl4. Rats exposed to CCl4 for 8 weeks exhibited hepatic fibrosis, which was confirmed through the assessment of plasma biomarkers. Isolated liver samples were used to determine the protein levels of CTGF and STAT3 using western blotting. In addition, STAT3 expression was silenced in α mouse liver 12 (AML­12) cells using small interfering RNA transfection. In addition, a pharmacological inhibitor, stattic, was used to inhibit STAT3 expression. The incubation of AML­12 cells with CCl4 induced a dose­dependent increase in CTGF expression and STAT3 activation. Notably, silymarin, an extract from milk thistle, inhibited these changes in AML­12 cells and the antioxidant tiron produced similar effects. Silencing of STAT3 reduced the CTGF expression promoted by CCl4 in the hepatocytes. Additionally, similar to tiron, stattic inhibited CTGF expression induced by CCl4. In conclusion, CCl4 may activate STAT3 through oxidative stress to promote CTGF expression, which is one of the main factors contributing to the risk of hepatic fibrosis.

ECE-1 overexpression in head and neck cancer is associated with poor tumor differentiation and patient outcome.

BACKGROUND: Endothelin-converting enzyme-1 (ECE-1) primarily converts big endothelins (ETs) into active endothelin-1 (ET-1). However, the expression pattern and prognostication status of ECE-1 in head and neck cancer (HNC) are enigmatic. In this study, we investigated ECE-1 expression and assessed the roles of ECE-1 as a predictor for HNC differentiation and prognosis. MATERIALS AND METHODS: ECE-1 expressions were evaluated by immunohistochemical analysis using a tissue microarray (TMA) composed of 100 cases of head and neck squamous cell carcinoma. The correlation of ECE-1 expression with clinicopathologic variables and patient outcomes was analyzed. RESULTS: ECE-1 may be overexpressed in HNC carcinoma cells. Higher ECE-1 level was detected more frequently in moderately to poorly differentiated tumors and showed a lower differentiation category compared to the G1 cases (p = 0.015); this finding was further confirmed by an adjusted odds ratio (OR) of 4.071 (p = 0.042). Moreover, Kaplan-Meier survival analyses showed that a higher ECE-1 expression was associated with a poorer survival in patients with HNC (p < 0.0001). On multivariate Cox proportional hazards models analysis, ECE-1 of high expression proved to be an independent prognostic factor with a hazard ratio (HR) of 3.985 (p < 0.001). CONCLUSION: Our data provide the first evidence that overexpression of ECE-1 in HNC is a predictor of poor tumor differentiation and prognosis.

Ginsenoside Rh2 Improves Cardiac Fibrosis via PPARδ-STAT3 Signaling in Type 1-Like Diabetic Rats.

Ginsenoside Rh2 (Rh2) is an active principal ingredient contained in ginseng (Panax ginseng Meyer), a medicinal herb used to enhance health worldwide. The present study is designed to investigate the effect of Rh2 on myocardial fibrosis in diabetic rats. In a streptozotocin-induced model of type-1 diabetic rats (STZ-diabetic rats), the increased fasting blood glucose levels and heart weight/body weight (HW/BW) ratio were substantially alleviated by Rh2. Moreover, Rh2 improved cardiac performance in STZ-diabetic rats. Histological results from Masson staining showed that Rh2 attenuated cardiac fibrosis in STZ-diabetic rats. The effects of Rh2 were reversed by GSK0660 at a dose sufficient to inhibit peroxisome proliferator-activated receptor δ (PPARδ) in STZ-diabetic rats. The role of PPARδ was subsequently investigated in vitro. Rh2 restored the decreased PPARδ expression level in high glucose-cultured cardiomyocytes. Moreover, increased protein levels of fibrotic signals, including signal transducer and activator of transcription 3 (STAT3), connective tissue growth factor (CCN2) and fibronectin, were reduced by Rh2 in high glucose-cultured cardiomyocytes. These effects of Rh2 were reversed by GSK0660 or siRNA specific for PPARδ Taken together, PPARδ activation may inhibit STAT3 activation to reduce CCN2 and fibronectin expression in diabetic rats with cardiac fibrosis. Moreover, Rh2 improves cardiac function and fibrosis by increasing PPARδ signaling. Therefore, Rh2 is suitable to develop as an alternative remedy for cardiac fibrosis.

Cryptotanshinone Inhibits STAT3 Signaling to Alleviate Cardiac Fibrosis in Type 1-like Diabetic Rats.

Cryptotanshinone is an active principal ingredient isolated from Salvia miltiorrhiza (Danshen), a medicinal plant used in China to treat cardiac disorders. The objective of this study was to investigate the effect of cryptotanshinone on myocardial fibrosis in diabetic rats. In streptozotocin-induced type 1 diabetic model hyperglycemic rats (STZ-treated rats), fasting blood glucose levels and heart weight/body weight ratio were markedly increased but both were not modified by cryptotanshinone. Additionally, cardiac performance in catheterized STZ-treated rats was improved. The histological results from Masson staining showed that cryptotanshinone attenuated cardiac fibrosis in STZ-treated rats. Moreover, both the mRNA and protein levels of the signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-9, and connective tissue growth factor were reduced by cryptotanshinone in high glucose-cultured cardiomyocytes, similar to the reductions observed in the hearts of STZ-treated rats. In conclusion, while STAT3 regulates matrix metalloproteinase-9 and connective tissue growth factor expression in diabetic rats with cardiac fibrosis, cryptotanshinone inhibited fibrosis to improve cardiac function by suppressing the STAT3 pathway. Cryptotanshinone is suitable as an alternative remedy for therapy of cardiac fibrosis. Copyright © 2017 John Wiley & Sons, Ltd.

Central Obesity and H. pylori Infection Influence Risk of Barrett's Esophagus in an Asian Population.

BACKGROUND AND AIM: The prevalence rates of Barrett's esophagus (BE) in western countries are higher than Asian ones, but little is known about their difference among risk factors of BE. The aim of this study is to investigate the associations of various risk factors including central obesity, body mass index (BMI), metabolic syndrome and H. pylori infection, with BE. METHODS: A total of 161 subjects with BE were enrolled and compared to age- and gender-matched controls randomly sampled (1:4) from check-up center in same hospital. Central obesity was defined by waist circumference (female>80cm; male>90cm), metabolic syndrome by the modified National Cholesterol Education Program Adult Treatment Panel III criteria in Taiwan. Independent risk factors for BE were identified by multiple logistic regression analyses. RESULTS: The mean age for BE was 53.8±13.7 years and 75.8% was male. H. pylori infection status was detected by the rapid urease test with the prevalence of 28.4% and 44.4% in the BE patients and controls, respectively. The univariate logistic regression analyses showed the risk was associated with higher waist circumference (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.78-3.60), metabolic syndrome (OR, 2.02; 95% CI, 1.38-2.96) and negative H. pylori infection (OR, 0.50; 95% CI, 0.34-0.74). However, multivariate logistic regression analyses revealed that BE associated with higher waist circumference (adjusted OR, 2.79; 95% CI, 1.89-4.12) and negative H. pylori infection (adjusted OR, 0.46; 95% CI, 0.30-0.70). CONCLUSIONS: Central obesity is associated with a higher risk of BE whereas H. pylori infection with a lower risk in an ethnic Chinese population.

Lung damage induced by hyperglycemia in diabetic rats: The role of signal transducer and activator of transcription 3 (STAT3).

Increased evidence has shown that diabetes can be a risk factor for pulmonary fibrosis. The objective of this study was to use streptozotocin-induced diabetic rats (STZ rats) to assess the possible signals associated with lung damage in diabetic disorders. The expression levels of signal transducer and activator of transcription 3 (STAT3) and connective tissue growth factor (CTGF) in lung tissues were measured through Western blot analysis and real-time PCR. Additionally, the potential mechanisms were confirmed in cultured rat lung cell line (L2) incubated in high-glucose (HG) medium to mimic the in vivo changes. The pathological changes in the lung tissues of STZ rats were characterized using the bleomycin-treated tissues as reference. Moreover, the higher expression levels of STAT3 and CTGF in the lung tissues of STZ rats were reversed by treating the hyperglycemia. CTGF expression increased following the higher expression of STAT3 in the cultured L2 cells exposed to HG, and this change was reversed by siRNA treatment specific for STAT3. Stattic, at a dose sufficient to inhibit STAT3, reduced the CTGF levels in the lungs of STZ rats. In conclusion, STAT3 enhanced CTGF expression in a type-1 diabetes model associated with lung damage. Thus, STAT3 inhibitors may be developed to improve diabetes-induced lung damage in the future.

Capsulated Metallic Debris Tumor Mass Mimicking Adjacent Segment Disease: A Case Report.

STUDY DESIGN: A case report. OBJECTIVE: To inform the spine surgeons another cause of late complications after instrumented spinal fusion surgery. SUMMARY OF BACKGROUND DATA: Posterior lumbar instrumented fusion has been widely applied as an effective procedure for treating patients with degenerative lumbar spine disease. The development of pathology at the mobile segment adjacent to the lumbar spinal fusion has been termed as adjacent segment disease. METHODS: Most patients with adjacent segment disease present with recurrent back pain, sciatica, intermittent claudication, or even muscle weakness. Herein, we report the case of a 58-year-old man with posterior lumbar instrumented fusion at L4-L5 who complained of recurrent neurological symptoms mimicking adjacent instability and stenosis. In addition to severe adjacent stenosis at L3-L4, preoperative magnetic resonance imaging showed an intraspinal extradural tumor-like mass with compression of the neurological elements. RESULTS: The well-capsulated tumor mass was gently dissected and meticulously excised without injury to the adhesive dura or nerve roots. The tumor specimen was fixed in formalin, and then decalcified and tinted using several special stains, which conformed metallic wear debris, resulting in foreign body reaction. CONCLUSIONS: The metallic wear particulates may initiate a cascade of immune and inflammatory responses. Therefore, attention should be paid to patients who are found to have loosening of the implants at the metal-metal or metal-bone interface.

Eucommia bark (Du-Zhong) improves diabetic nephropathy without altering blood glucose in type 1-like diabetic rats.

BACKGROUND: Eucommia bark, Eucommia ulmoides Oliver barks (Du-Zhong in Mandarin), is an herb used for renal dysfunction in Chinese traditional medicine. In an attempt to develop this herb as a treatment for diabetic nephropathy (DN), we investigated the effects of Du-Zhong on renal dysfunction in type 1-like diabetic rats. METHODS: Streptozotocin (STZ) was used to induce type 1-like diabetes in rats (STZ-diabetic rats). In addition to hyperglycemia, STZ-diabetic rats showed significant nephropathy, including higher plasma levels of blood urea nitrogen, creatinine, and renal fibrosis. Western blot analysis of renal cortical tissue was applied to characterize the changes in potential signals related to nephropathy. RESULTS: Oral administration of Du-Zhong (1 g/kg/day) to STZ-diabetic rats for 20 days not only decreased the plasma levels of blood urea nitrogen and creatinine but also improved renal fibrosis, whereas the plasma glucose level was not changed. The higher expressions of protein levels of transforming growth factor-beta (TGF-ß) and connective tissue growth factor in diabetic rats were markedly attenuated by Du-Zhong. The increased phosphorylation of Smad2/3 in STZ-diabetic rats was also reduced by Du-Zhong. However, Du-Zhong cannot reverse the hyperglycemia-induced overproduction of signal transducers and activators of transcription 3 in the diabetic kidney. CONCLUSION: Oral administration of Du-Zhong improves STZ-induced DN in rats by inhibiting TGF-ß/Smad signaling and suppressing TGF-ß/connective tissue growth factor expression. Therefore, active principle from Du-Zhong is suitable to develop as new agent for DN in the future.

The Overexpression of FEN1 and RAD54B May Act as Independent Prognostic Factors of Lung Adenocarcinoma.

Synthetic lethality arises when a combination of mutations in two or more genes leads to cell death. However, the prognostic role of concordant overexpression of synthetic lethality genes in protein level rather than a combination of mutations is not clear. In this study, we explore the prognostic role of combined overexpression of paired genes in lung adenocarcinoma. We used immunohistochemical staining to investigate 24 paired genes in 93 lung adenocarcinoma patients and Kaplan-Meier analysis and Cox proportional hazards models to evaluate their prognostic roles. Among 24 paired genes, only FEN1 (Flap endonuclease 1) and RAD54B (RAD54 homolog B) were overexpressed in lung adenocarcinoma patients with poor prognosis. Patients with expression of both FEN1 and RAD54B were prone to have advanced nodal involvement and significantly poor prognosis (HR = 2.35, P = 0.0230). These results suggest that intensive follow up and targeted therapy might improve clinical outcome for patients who show expression of both FEN1 and RAD54B.

CDCA5 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.

AIMS: Urothelial carcinoma (UC) is the most common tumor involving upper urinary tract (UTUC) and urinary bladder (UBUC) whose molecular survival determinants remains obscured. By computerizing a public transcriptomic database of UBUCs (GSE32894), we identified cell division cycle associated 5 (CDCA5) as the most significantly upregulated gene among those associated with G1-S transition of the mitotic cell cycle (GO:0000082). We therefore analyzed the clinicoptaological significance of CDCA5 expression in our well-characterized UC cohort. METHODS AND RESULTS: Quantigene assay was used to detect CDCA5 transcript levels in 36 UTUCs and 30 UBUCs. We used immunohistochemistry evaluated by H-scores to determine CDCA5 protein expression in 295 UBUCs and 340 UTUCs, respectively. CDCA5 expression was further correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS). For both groups of UCs, increments of CDCA5 transcript levels were associated with higher pT status, CDCA5 protein overexpression was also significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses. CDCA5 overexpression was predictive for worse DSS and MeFS in univariate and multivariate analysis. CONCLUSIONS: CDCA5 overexpression is associated with advanced clinical features of UC, suggesting its potential value as a prognostic biomarker and a novel therapeutic target.

HAS3 underexpression as an indicator of poor prognosis in patients with urothelial carcinoma of the upper urinary tract and urinary bladder.

Via data mining a published transcriptomic database of UBUC (GSE31684), we discovered hyaluronan synthase-3 (HAS3) as the most significant gene stepwise downregulated from early tumorigenesis to progression among those associated with hyaluronan synthase activity (GO:0050501). We consequently analyzed HAS3 protein expression and their association with clinicopathological factors and survival in our well-characterized cohort of urothelial carcinoma of upper urinary tract (UTUC) and urinary bladder (UBUC). HAS3 expression was assessed by immunohistochemistry and evaluated by using H score method in 295 UBUCs and 340 UTUCs, respectively. HAS3 protein expression statuses were further correlated with clinicopathological parameters and evaluated the prognostic significance for disease-specific survival (DSS) and metastasis-free survival (MeFS). HAS3 protein underexpression was significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses in both groups of UCs. HAS3 underexpression not only predicted poorer DSS and MeFS with univariate analysis, but also indicated dismal DSS and MeFS in multivariate analysis. HAS3 underexpression is associated with advanced tumor stage and adverse pathological features, as well as implies inferior clinical outcomes for both groups of patients with UTUCs and UBUCs, suggesting its critical role in tumor progression in UCs and may serve as a prospective prognostic biomarker and a novel therapeutic target in UCs.

Overexpression of DNAJC12 predicts poor response to neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer.

Genes associated with protein folding have been found to have certain prognostic significance in a subset of cancers. The aim of this study is to evaluate the clinical impact of DNAJC12 expression in patients with rectal cancers receiving neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery. Through data mining from a public transcriptomic dataset of rectal cancer focusing on genes associated with protein folding, we found that DNAJC12, a member of the HSP40/DNAJ family, was the most significant such gene correlated with the CCRT response. We further evaluated the expression of DNAJC12 by immunohistochemistry in the pre-treatment tumor specimens from 172 patients with rectal cancers. From this set, we statistically analyzed the association of DNAJC12 expression with various clinicopathological factors, tumor regression grade, overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS). High expression of DNAJC12 was significantly associated with advanced pre- and post-treatment tumor status (P<0.001), advanced pre- and post-treatment nodal status (P<0.001), increased vascular invasion (P=0.015), increased perineural invasion (P=0.023) and lower tumor regression grade (P=0.009). More importantly, high expression of DNAJC12 was found to be correlated with poor prognosis for OS (P=0.0012), DFS (P<0.0001) and LRFS (P=0.0001). In multivariate analysis, DNAJC12 overexpression still emerged as an independent prognosticator for shorter OS (P=0.040), DFS (P<0.001) and LRFS (P=0.016). The data indicate that DNAJC12 overexpression acts as a negative predictive factor for the response to neoadjuvant CCRT and was significantly associated with shorter survival in patients with rectal cancers receiving neoadjuvant CCRT followed by surgery.

Secondary oligodendroglioma after postoperative irradiation for medulloblastoma: a case report and review of the literature.

Medulloblastoma, a malignant, invasive embryonal tumor of the cerebellum, occurs most often in children. It has high metastatic potential and is usually treated by aggressive multimodal therapy, including surgery, chemotherapy and craniospinal irradiation. Multiple secondary tumors have been reported following craniospinal irradiation. It is rare with the occurrence of oligodendroglioma after irradiation. In this report, we described a patient with secondary oligodendroglioma after postoperative craniospinal irradiation for medulloblastoma.