Evaluating CXCL12 for Effects on Reactive Gene Expression in Primary Astrocytes.

Upon injury to the CNS, astrocytes undergo morphological and functional changes commonly referred to as astrocyte reactivity. Notably, these reactive processes include altered expression of factors that control immune processes and neuronal survival, as well as increased expression of the CXCL12 receptor, CXCR7/ACKR3. We now asked whether these events are related in that the astrocytic CXCL12 system modulates immune responses and/or neuronal survival.

Consultation on UTUC II Stockholm 2022: diagnostic and prognostic methods-what's around the corner?

Purpose: To map current literature and provide an overview of upcoming future diagnostic and prognostic methods for upper tract urothelial carcinoma (UTUC), including translational medical science.

Methods: A scoping review approach was applied to search the literature. Based on the published literature, and the experts own experience and opinions consensus was reached through discussions at the meeting Consultation on UTUC II in Stockholm, September 2022.

A randomised trial of [F]PSMA-1007-PET/CT versus NaF-PET/CT for staging primary prostate cancer: A trial protocol.

Background: Prostate-specific membrane antigen (PSMA)-positron emission tomography/contrast-enhanced computed tomography (PET/CT) is a sensitive imaging modality for prostate cancer (PCa). Due to lack of knowledge of the patient benefit, PSMA-PET/CT is not yet recommended in the European guidelines for staging and treatment planning of patients with newly diagnosed PCa. We will investigate the potential difference in progression-free survival (PFS) and quality of life (QoL) of using PSMA-PET/CT versus sodium fluoride (NaF)-PET/CT for staging and treatment planning in patients with newly diagnosed PCa.

The diagnostic challenge of suspicious or positive malignant urine cytology findings when cystoscopy findings are normal: an outpatient blue-light flexible cystoscopy may solve the problem.

Purpose: To investigate whether outpatient blue-light flexible cystoscopy could solve the diagnostic challenge of positive or suspicious urine cytology findings despite normal white-light flexible cystoscopy results and normal findings on computerized tomography urography, in patients investigated for urothelial cancer.

Material And Methods: In a multicentre study, a total of 70 examinations were performed with the use of blue-light flexible cystoscopy (photodynamic diagnosis) after intravesical instillation of the fluorescence agent hexaminolevulinate. The examination started with a conventional white-light flexible cystoscopy and then the settings were switched to use blue light.

Identification of CXCL11 as part of chemokine network controlling skeletal muscle development.

The chemokine, CXCL12, and its receptors, CXCR4 and CXCR7, play pivotal roles during development and maintenance of limb muscles. CXCR7 additionally binds CXCL11, which uses CXCR3 as its prime receptor. Based on this cross-talk, we investigate whether CXCL11 would likewise affect development and/or function of skeletal muscles.

CXCL11 promotes tumor progression by the biased use of the chemokine receptors CXCR3 and CXCR7.

The chemokine, CXCL11, is highly expressed in different solid tumors and controls tumor growth, metastasis, and lymphocyte infiltration. Although of potential clinical interest, it is presently unknown whether these tumor-promoting activities involve the CXCL11 receptors, CXCR3 and/or CXCR7. This issue is further intrigued by the fact that CXCR3 exists in the two functionally divergent splice variants, CXCR3A and CXCR3B, which exert pro- and anti-tumorigenic influences, respectively.

Molecular Mechanisms of Vaspin Action - From Adipose Tissue to Skin and Bone, from Blood Vessels to the Brain.

Visceral adipose tissue-derived serine protease inhibitor (vaspin) or SERPINA12 according to the serpin nomenclature was identified together with other genes and gene products that were specifically expressed or overexpressed in the intra-abdominal or visceral adipose tissue (AT) of the Otsuka Long-Evans Tokushima fatty rat. These rats spontaneously develop visceral obesity, insulin resistance, hyperinsulinemia and -glycemia, as well as hypertension and thus represent a well suited animal model of obesity and related metabolic disorders such as type 2 diabetes.The follow-up study reporting the cloning, expression and functional characterization of vaspin suggested the great and promising potential of this molecule to counteract obesity induced insulin resistance and inflammation and has since initiated over 300 publications, clinical and experimental, that have contributed to uncover the multifaceted functions and molecular mechanisms of vaspin action not only in the adipose, but in many different cells, tissues and organs.

Ablation of kallikrein 7 (KLK7) in adipose tissue ameliorates metabolic consequences of high fat diet-induced obesity by counteracting adipose tissue inflammation in vivo.

Vaspin is an adipokine which improves glucose metabolism and insulin sensitivity in obesity. Kallikrein 7 (KLK7) is the first known protease target inhibited by vaspin and a potential target for the treatment of metabolic disorders. Here, we tested the hypothesis that inhibition of KLK7 in adipose tissue may beneficially affect glucose metabolism and adipose tissue function.

Vaspin suppresses cytokine-induced inflammation in 3T3-L1 adipocytes via inhibition of NFκB pathway.

Vaspin expression is increased in white adipose tissue (WAT) of diet-induced obese mice and rats and is supposed to compensate HFD-induced inflammatory processes and insulin resistance in adipose tissue by counteracting pro-inflammatory gene expression in obesity. Multiple studies have also demonstrated strong anti-inflammatory effects in vascular and skin cells. Here, we used vaspin treated 3T3-L1 murine adipocytes as well as 3T3-L1 cells with stable vaspin expression to investigate the effect of exogenous and endogenous vaspin on inflammatory processes and insulin signaling in adipocytes.

Brown adipose tissue (BAT) specific vaspin expression is increased after obesogenic diets and cold exposure and linked to acute changes in DNA-methylation.

Objective: Several studies have demonstrated anti-diabetic and anti-obesogenic properties of visceral adipose tissue-derived serine protease inhibitor (vaspin) and so evoked its potential use for treatment of obesity-related diseases. The aim of the study was to unravel physiological regulators of vaspin expression and secretion with a particular focus on its role in brown adipose tissue (BAT) biology.

Methods: We analyzed the effects of obesogenic diets and cold exposure on vaspin expression in liver and white and brown adipose tissue (AT) and plasma levels.

Reducing recurrence in non-muscle-invasive bladder cancer using photodynamic diagnosis and immediate post-transurethral resection of the bladder chemoprophylaxis.

Objective: The aim of this study was to evaluate the effect of fluorescence cystoscopy and immediate post-transurethral resection of the bladder (TURB) chemoprophylaxis on the risk of recurrence of non-muscle-invasive bladder cancer (NMIBC) under routine clinical conditions.

Materials And Methods: Fluorescence cystoscopy using hexyl-aminolevulinate and post-TURB chemoprophylaxis using mitomycin C were simultaneously introduced in an effort to reduce the recurrence of NMIBC. In total, 190 consecutive patients were enrolled over a 2 year period and followed as the intervention group; 216 patients treated over a 2 year period before introduction served as controls.

Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma.

Background: The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out.

Methods: We used specific q-RT-PCR assays to analyse the expression of the CT genes MAGE-A3, NY-ESO-1 (CTAG1B), LAGE-1 (CTAG2) and PRAME in a panel of bladder tumours from 350 patients with long-term follow-up and detailed treatment information.

Results: Overall, 43% of the tumours expressed MAGE-A3, 35% expressed NY-ESO-1, 27% expressed LAGE-1 and 20% expressed PRAME.

Cathepsin E, maspin, Plk1, and survivin are promising prognostic protein markers for progression in non-muscle invasive bladder cancer.

Bladder cancer is a common cancer with particularly high recurrence after transurethral resection. In this study, we investigated the prognostic value of the protein expression of cathepsin E, maspin, polo-like kinase 1 (Plk1), and survivin in patients with stage Ta and T1 urothelial carcinomas. Transcripts from the four genes encoding these proteins were previously included in gene expression signatures for outcome prediction for Ta/T1 bladder cancer.

Long-term risk of progression of carcinoma in situ of the bladder and impact of bacille Calmette-Guérin immunotherapy on the outcome.

Objective: This study aimed to determine the long-term risk of cancer progression of carcinoma in situ (CIS) of the urinary bladder, and whether intravesical bacille Calmette-Guérin (BCG) immunotherapy can reduce the risk of progression of CIS.

Material And Methods: From a prospectively enrolled cohort of bladder cancer patients treated at Ã…rhus University Hospital Skejby, Denmark, between 1994 and 2008, all 163 cases with CIS in the bladder, and a history free of invasive bladder cancer (stage T1-4) at least 1 year prior to inclusion were included in the study.

Results: Median follow-up was 51 (0-253) months for progression.

Prediction and diagnosis of bladder cancer recurrence based on urinary content of hTERT, SENP1, PPP1CA, and MCM5 transcripts.

Background: Identification of urinary biomarkers for detection of bladder cancer recurrence would be beneficial to minimize the frequency of cystoscopy. Our objective was to determine the usability of urine content of mRNA in the detection and prediction of bladder cancer recurrence.

Methods: We analyzed 123 prospectively cross-sectional collected urine samples from 117 patients with bladder cancer (12 incident cancers and 111 control visits).

Consistent genomic alterations in carcinoma in situ of the urinary bladder confirm the presence of two major pathways in bladder cancer development.

Bladder cancer develops through different pathways, provisionally entitled "papillary" and "invasive." Carcinoma in situ (CIS) is thought to be the precursor of invasive bladder cancer. However, little is known about chromosomal alterations of these clinically important lesions, and the relationship between chromosomal alterations and the different pathways.

Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro.

microRNAs (miRNA) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Here, we profiled the expression of 290 unique human miRNAs in 11 normal and 106 bladder tumor samples using spotted locked nucleic acid-based oligonucleotide microarrays. We identified several differentially expressed miRNAs between normal urothelium and cancer and between the different disease stages.

Chromosomal imbalance in the progression of high-risk non-muscle invasive bladder cancer.

Background: Non-muscle invasive bladder neoplasms with invasion of the lamina propria (stage T1) or high grade of dysplasia are at "high risk" of progression to life-threatening cancer. However, the individual course is difficult to predict. Chromosomal instability (CI) is associated with high tumor stage and grade, and possibly with the risk of progression.

High throughput molecular diagnostics in bladder cancer - on the brink of clinical utility.

An enormous body of high-throughput genome-wide data, in particular gene expression data, has been gathered from roughly all human cancer forms in the past 10 years. This has widely increased our understanding of the cancer disease and its molecular changes and pathways, with a large contribution from studies of cancer cell lines and functional genomics. In the last three years, the focus has been moved to clinical outcome parameters as recurrence, progression, metastasis and treatment response.

Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma: a multicenter validation study.

Purpose: Clinically useful molecular markers predicting the clinical course of patients diagnosed with non-muscle-invasive bladder cancer are needed to improve treatment outcome. Here, we validated four previously reported gene expression signatures for molecular diagnosis of disease stage and carcinoma in situ (CIS) and for predicting disease recurrence and progression.

Experimental Design: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays.

Recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers.

Bladder cancer is the fifth most common neoplasm in industrialized countries. Due to frequent recurrences of the superficial form of this disease, bladder cancer ranks as one of the most common cancers. Despite the description of a large number of tumor markers for bladder cancers, none have individually contributed to the management of the disease.

Recent developments in molecular profiling of bladder cancer.

Purpose Of Review: Profiling bladder tumors using high-density microarrays has recently become possible. We review recent reports on the use of profiling for the prediction of various clinical courses in bladder cancer. We also stress the methods and materials needed to translate such molecular profiles into clinically useful tests.

Role of activating fibroblast growth factor receptor 3 mutations in the development of bladder tumors.

Purpose: Bladder tumors develop through different molecular pathways. Recent reports suggest activating mutations of the fibroblast growth factor receptor 3 (FGFR3) gene as marker for the "papillary" pathway with good prognosis, in contrast to the more malignant "carcinoma in situ" (CIS) pathway. The aim of this clinical follow-up study was to investigate the role of FGFR3 mutations in bladder cancer development in a longitudinal study.

A molecular signature in superficial bladder carcinoma predicts clinical outcome.

Purpose: Cancer of the urinary bladder is a common malignant disease in the western countries. The majority of patients presents with superficial tumors with a high recurrence frequency, a minor fraction of these patients experience disease progression to a muscle invasive stage. No clinical useful molecular markers exist to identify patients showing later disease progression.

DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis.

During the evolution of cancer, the incipient tumour experiences 'oncogenic stress', which evokes a counter-response to eliminate such hazardous cells. However, the nature of this stress remains elusive, as does the inducible anti-cancer barrier that elicits growth arrest or cell death. Here we show that in clinical specimens from different stages of human tumours of the urinary bladder, breast, lung and colon, the early precursor lesions (but not normal tissues) commonly express markers of an activated DNA damage response.