Noncancerous Conditions Research Articles

Inflammation of Prostate and Prostate-Specific Antigen

Noncancerous conditions (e.g., benign prostatic hyperplasia and prostatitis) can elevate serum prostate-specific antigen (PSA) levels, limiting the specificity of PSA screening for prostate cancer. In recent years, several studies have also demonstrated a relationship between chronic prostatitis/chronic pelvic pain syndrome and increased PSA levels. However, in asymptomatic patients, routine screening for this diagnosis is not performed before transrectal biopsy to rule out prostate cancer. These asymptomatic men with elevated PSA levels frequently show evidence of inflammation when their expressed prostatic secretions are examined, or on their prostate biopsy specimens. This raises the problem of appropriate evaluation in the presence of chronic prostatitis and elevated PSA levels not only in prostate cancer screening programs, but also in cancer-negative biopsy findings. Thus, there has been investigation into ways to decrease the confounding from inflammation, including repeat PSA measurements after a period of observation or a course of empiric antibiotics. This article reviews the evidence regarding elevations in PSA due to prostatitis and describes the controversy over the optimal approach to reduce its confounding impact on prostate cancer screening. Nowadays, it appears that in patients with prostatic inflammation and increased PSA, an antimicrobial regimen may provide more acceptable initial treatment than proceeding directly to prostate biopsy. Additional evidence is necessary in the form of a randomized clinical trial in which all patients undergo biopsy, regardless of the PSA response to antibiotic or placebo.

Potential of epigenetic therapies in non-cancerous conditions.

There has been an explosion of knowledge in the epigenetics field in the past 20 years. The first epigenetic therapies have arrived in the clinic for cancer treatments. In contrast, much of the promise of epigenetic therapies for non-cancerous conditions remains in the laboratories. The current review will focus on the recent progress that has been made in understanding the pathogenic role of epigenetics in immune and inflammatory conditions, and how the knowledge may provide much needed new therapeutic targets for many autoimmune diseases. Dietary factors are increasingly recognized as potential modifiers of epigenetic marks that can influence health and diseases across generations. The current epigenomics revolution will almost certainly complement the explosion of personal genetics medicine to help guide treatment decisions and disease risk stratification.

Genetic variants at 1q32.1, 10q11.2 and 19q13.41 are associated with prostate-specific antigen for prostate cancer screening in two Korean population-based cohort studies

Prostate-specific antigen (PSA) levels are affected by non-cancerous conditions such as benign prostatic hyperplasia, inflammations, and inherited factors. To search for genetic variants associated with PSA levels, we conducted a genome-wide association study (GWAS) using a two-stage design. A total of 554 men from the Korean Cancer Prevention Study-II were used as a discovery stage and 1575 men collected by the Korean Genome Epidemiology Study were used as a replication stage. Analysis by Genome-wide Human single-nucleotide polymorphism (SNP) array 5.0 was performed by using DNAs derived from venous blood. We analyzed the association between genetic variants and PSA levels using multivariate linear regression models, including age as a covariate. We detected 12 genome-wide significant signals on chromosome 1q32.1, 10q11.2, and 19q13.41 between PSA levels and SNPs. The top SNP associated with log PSA levels was rs2153904 in SLC45A3 (p values, 5.24×10−9 to 2.00×10−6). We also investigated GWAS using 754 subjects from KCPS-II cohort whether our genome-wide significant loci were associated with a risk of prostate cancer (PCa) (200 PCa cases and 554 controls). Three of the SNPs on 10q11.2, rs7077830, rs2611489, and rs4631830, were associated with a risk of PCa. However, two loci, 1q32.1 and 19q13, were not significantly associated with a PCa risk. We suggest that our results for some but not all PCa risk SNPs to be associated with PSA levels could be used as an evidence for the advance of individual PCa screening strategies, such as applying a personalized cutoff value for PSA.

Subjective Social Status and Depression Symptoms: A Prospective Study of Women with Noncancerous Pelvic Problems

ObjectiveSubjective social status (SSS) may be a stronger determinant of health than objective measures of socioeconomic status. We sought to examine the effect of community and national SSS on symptoms of depression in a racially/ethnically diverse sample of adult women with noncancerous uterine conditions. MethodsWe conducted a secondary analysis of data obtained from 634 women who enrolled in the Study of Pelvic Problems, Hysterectomy, and Intervention Alternatives (SOPHIA) in 2003 and 2004. SOPHIA was a longitudinal study of women aged 31 to 54 who were experiencing abnormal uterine bleeding, symptomatic fibroids, or pelvic pain. The primary outcome for this analysis consisted of symptoms suggesting major or other depressive disorder, as measured by the Patient Health Questionnaire-9, 2 years after study enrollment. We hypothesized that women who had low community and national SSS at baseline, as measured by the MacArthur SSS ladder, would be at higher risk of experiencing symptoms of depression at follow-up. ResultsWomen with low community SSS had an increased odds of experiencing depression symptoms 2 years later compared with women with high SSS, after adjusting for age, pelvic problem impact and baseline depression (odds ratio, 2.93; 95% CI, 1.11–7.77). Odds remained elevated after further adjusting for income and education. Results for the national ladder were not significant. ConclusionLow perceived community social status is predictive of symptoms suggestive of major or other depressive disorder among women with noncancerous uterine conditions. Asking about perceived community social status can help clinicians to identify patients who may be at increased risk for depressive disorders. Asking about perceived national social status does not seem to add value beyond that provided by income and education.

Development of protocol for the management of cervical cancer symptoms in resource-constrained developing countries.

Cervical cancer is the commonest malignancy of women in economically emerging countries. Patients have distressing symptoms from presentation through follow-up or end of life. Cervical cancer imposes significant burden on health care system due to distressing symptoms and associated loss of quality-adjusted life years (QALY). Multitude of drugs and surgical measures in various combinations can relieve these distressing symptoms and various clinical conditions. The protocols and guidelines for alleviation or relief of symptoms by general pharmacological and surgical measures form an important policy subject in planning cervical cancer management program. These protocol and guidelines are based on the mechanism of action of drugs, extrapolation from management of similar symptoms, and clinical situations arising out of other non-cancerous conditions and experience of health care professionals. Therefore, rigorous evaluation of effectiveness of supportive health care services in developing countries is the need of hour. However, evaluation of such protocol and guidelines are not feasible in emerging economies due to resource constraint. Industrialized affluent nations are also not able to implement and further support care guidelines despite its recognition as an integral part of multidisciplinary management of cancer. Aforementioned factors have created blind spot zone of management purview of cervical cancer. Hence, we attempt to develop protocol for management of adverse events of cervical cancer. Symptoms' and medical conditions' management guidelines evolved on the basis of empirical clinical practice in community and premier oncology centers in resource-constrained developing countries has been presented in this short report. This report should not be an end in itself but has to attract attention of policy-makers, academicians, researchers, and practitioners toward advancing supportive care needs of cancer patients in low- and middle-income countries (LMIC).

HPV vaccination in head and neck HPV-related pathologies

Recent data demonstrate that human papilloma virus (HPV) plays a role in pathologies other than ano-genital cancers, specifically head and neck malignancies, and non-cancerous conditions such as recurrent respiratory papillomatosis (RRP). High-risk HPV16 and 18, and low risk HPV6 and 11 play the main role in HPV-related pathologies. As more and more information about the role of HPV infection in non-cervical diseases is amassed, additional questions about whether prophylactic HPV vaccines will effectively prevent these conditions are raised. HPV vaccination programs for the cervical pathology are being implemented worldwide. In the United States, the US Food and Drug Administration (FDA) approved the quadrivalent HPV vaccine for girls in 2006 and for boys in 2011. These vaccination programs were aimed at the genital, HPV-related lesions, and there was not much recognition at that time of how HPV vaccination programs might affect oral HPV infection, which is a risk factor for the development of HPV-related head and neck cancers. Vaccination has proved to be a successful policy, and an extant recommendation is aimed at preventing HPV and associated cervical and other anogenital cancers with the routine use of HPV vaccines for males and females. However, HPV vaccines are presently not recommended for preventing oropharyngeal cancer (OPC), although they have been shown to be highly effective against the HPV strains that are most commonly found in the oropharynx. This review is aimed at presenting the evidence-based knowledge concerning HPV vaccination and highlighting the trials and strategies for vaccine administration in HPV-dependent head and neck pathologies.

Sleep problems among women with noncancerous gynecologic conditions

Objective: To estimate the prevalence of and identify factors associated with poor sleep quality and short sleep duration among women with noncancerous gynecologic conditions.Study design: We conducted a cross-sectional analysis of 838 pre-menopausal women aged 31–54 who enrolled in a study of pelvic problems, hysterectomy and intervention alternatives in 2003/2004. Primary outcomes were poor sleep quality and short sleep duration (six or less hours on average) in the four weeks preceding the interview; hypothesized correlates included sociodemographic characteristics, pelvic problem impact, measured by the Pelvic Problem Impact Questionnaire (PPIQ), and depression, measured by the Patient Health Questionnaire (PHQ).Results: One-third (33.7%) of the participants reported having poor sleep quality and nearly half (46.8%) reported short sleep duration. In multivariable models, women with major depressive disorder were more likely than those who were not depressed to experience poor sleep quality (adjusted odds ratio (aOR) 4.15, 95% confidence interval (CI) 2.36–7.28, p < 0.001). Women with higher PPIQ scores also were more likely to experience poor sleep quality (aOR 1.59, 95% CI 1.27–1.98, p < 0.001) and short sleep duration (aOR 1.37, 95% CI 1.11–1.69, p < 0.003). Finally, women who self-identified as African-American (aOR 2.81, 95% CI 1.83–4.32, p < 0.001) or Asian/Pacific Islander (aOR 2.32, 95% CI 1.32–4.09, p < 0.003) were more likely than White women to have short sleep duration.Conclusions: Sleep problems are prevalent among women with noncancerous gynecologic conditions, and are associated with depression and high pelvic problem impact. Providers should be proactive in inquiring about and offering solutions for sleep difficulties experienced by their patients.

Clinicopathological and Prognostic Characteristics of Hepatoid Adenocarcinoma of the Stomach

The present study was undertaken to clarify the association of the clinicopathological features of hepatoid adenocarcinoma (HAC) in the stomach, a special kind of carcinoma that histologically resembled hepatocellular carcinoma (HCC) and is characterized by large amounts of α-fetoprotein (AFP) in serum, with the clinical prognosis. We collected the data of the clinicopathological features and the follow-up information from a total of 31 HACs from January 2005 to December 2012 in our hospital. High lymphatic (54.8%) and distant (25.8%) metastasis rates before surgery, large proportion of advanced HACs (71.0%) at admission, short median overall survival time (6 months), and low three-year survival rate (22.6%) suggested that HAC in the stomach was an aggressive disease, resulting in a poor prognosis. And pTNM stages, immunohistochemical staining of AFP, CEA, CK7, and CK20 had statistically relation with the survival as the independent risk factors, P < 0.05. Therefore, early and clear differentiation of HAC from cancerous or noncancerous conditions with AFP elevation and assessment of high risk patients by histopathology may improve the clinical prognosis.

Contributions of Hysterectomy and Uterus-Preserving Surgery to Health-Related Quality of Life

To document the long-term effect of surgical interventions for noncancerous uterine conditions on health-related quality of life. The Study of Pelvic Problems, Hysterectomy and Intervention Alternatives, conducted between 1998 and 2008, was a longitudinal study of 1,503 women with intact uteri experiencing abnormal uterine bleeding with or without leiomyomas, chronic pelvic pain, or pressure resulting from leiomyomas. Baseline and follow-up questionnaires included three condition-specific measures (Pelvic Problem Resolution, Pelvic Problem Impact Overall, and Pelvic Problem Impact on Sex) and five generic measures (Short Form-12 Mental and Physical Component Summaries, Current Health Utility, Feelings about Heath, and Satisfaction with Sex). We modeled changes over time in these patient-reported outcomes stratified by the most invasive treatment undergone (hysterectomy [13.7%], uterus-preserving surgery [9.0%], or nonsurgical therapy [77.3%]). Participants in all three groups reported significant improvement on all condition-specific measures and two of the five generic measures (Current Health Utility and Feelings about Health) from enrollment to final interview (all P values <.01). In general, greater improvements were experienced by women who had surgery. Trajectories modeled around the dates of surgery showed dramatic improvements after hysterectomy and, to a lesser degree, after uterus-preserving surgery. Although women who underwent uterus-preserving surgery tended to show immediate improvement, women who underwent hysterectomy experienced a 6-month delay in improvement in some outcomes with trajectories converging by 4 years postsurgery. Women seeking care for noncancerous uterine conditions can expect to experience improvement over time. Those who opt for surgery may experience most improvement. Understanding health-related quality-of-life trajectories may enhance counseling for women deciding between hysterectomy and alternative interventions. II.

Raman spectroscopic study on classification of cervical cell specimens

Cervix-cancer is the third most common female cancer worldwide. Papanicolaou (Pap) test, a well-recognized screening tool, is labor intensive, time consuming and prone to subjective interpretations. Optical spectroscopic methods, sensitive to molecular changes are being pursued as potential diagnostics tool. In this study we have explored Raman spectroscopic approach to differentiate exfoliated cell pellets using 94 cervical cell specimens (45-normal and 49-abnormal specimens). Study was carried out by two approaches. In the first approach, spectral data from 37 cell specimens were acquired and analyzed by Principal Component-Linear Discriminant Analysis (PC-LDA), which yielded classification efficiencies of 86% and 84% for normal and abnormal specimens, respectively. Mean and difference spectra suggest presence of blood in abnormal specimen as a major cause of discrimination. However, as tumor is vascular, bleeding was observed during abnormal sample collection. Hence, spectra of abnormal specimens show heme and fibrin features, and this can lead to false interpretations, as bleeding also occur in several non-cancerous conditions. Therefore, remaining 57 specimens were treated with Red Blood Corpuscles (RBC) lysis buffer in order to remove the RBC influence. PC-LDA resulted classification efficiency of about 79% and 78% for normal and abnormal smear, respectively – comparable to Pap test. Thus finding of the study suggests feasibility of Raman spectroscopic classification of normal and cancerous exfoliated cervical cell specimens.

Comparative Analysis of the Thyrocytes and T Cells: Responses to H2O2 and Radiation Reveals an H2O2-Induced Antioxidant Transcriptional Program in Thyrocytes

Radiation is an established cause of thyroid cancer, and growing evidence supports a role for hydrogen peroxide (H2O2) in spontaneous thyroid carcinogenesis. Little is known about the molecular programs activated by these agents in thyrocytes. The purpose of this study was to compare the responses of thyrocytes and T cells to H2O2 and radiation. We profiled the DNA damage and cell death induced by γ-radiation (0.1-5 Gy) and H2O2 (0.0025-0.3 mM) in primary human thyrocytes and T cells. We next prepared thyroid and T-cell primary cultures from 8 donors operated for noncancerous thyroid pathological conditions and profiled their genome-wide transcriptional response 4 hours after (1) exposure to 1-Gy radiation, (2) treatment with H2O2 and (3) no treatment. Two H2O2 concentrations were investigated, calibrated in each cell type to elicit levels of single- and double-strand breaks equivalent to 1-Gy γ-radiation. Although thyrocytes and T cells had comparable radiation responses, 3- to 10-fold more H2O2 was needed to induce detectable DNA damage in thyrocytes. At H2O2 and radiation doses inducing double-strand breaks, cell death occurred after 24 hours in T cells but not in thyrocytes. The transcriptional responses of thyrocytes and T cells to radiation were similar, involving DNA repair and cell death genes. In addition to this transcriptional program, H2O2 also up-regulated antioxidant genes in thyrocytes, including glutathione peroxidases and heme oxygenase at the double-strand breaks-inducing concentration. In contrast, a transcriptional storm involving thousands of genes was raised in T cells. Finally, we showed that inhibiting glutathione peroxidases activity increased the DNA damaging effect of H2O2 in thyrocytes. We propose that high H2O2 production in thyrocytes is matched with specific transcriptionally regulated antioxidant protection.

Improving prostate cancer detection in veterans through the development of a clinical decision rule for prostate biopsy

BackgroundWe sought to improve prostate cancer (PC) detection through developing a prostate biopsy clinical decision rule (PBCDR), based on an elevated PSA and laboratory biomarkers. This decision rule could be used after initial PC screening, providing the patient and clinician information to consider prior to biopsy.MethodsThis case–control study evaluated men from the Tampa, Florida, James A. Haley (JH) Veteran’s Administration (VA) (N = 1,378), from January 1, 1998, through April 15, 2005. To assess the PBCDR we did all of the following: 1) Identified biomarkers that are related to PC and have the capability of improving the efficiency of PC screening; 2) Developed statistical models to determine which can best predict the probability of PC; 3) Compared each potential model to PSA alone using Receiver Operator Characteristic (ROC) curves, to evaluate for improved overall effectiveness in PC detection and reduction in (negative) biopsies; and 4) Evaluated dose–response relationships between specified lab biomarkers (surrogates for extra-prostatic disease development) and PC progression.ResultsThe following biomarkers were related to PC: hemoglobin (HGB) (OR = 1.42 95% CI 1.27, 1.59); red blood cell (RBC) count (OR = 2.52 95% CI 1.67, 3.78); PSA (OR = 1.04 95% CI 1.03, 1.05); and, creatinine (OR = 1.55 95% CI 1.12, 2.15). Comparing all PC stages versus non-cancerous conditions, the ROC curve area under the curve (AUC) enlarged (increasing the probability of correctly classifying PC): PSA (alone) 0.59 (95% CI 0.55, 0.61); PBCDR model 0.68 (95% CI 0.65, 0.71), and the positive predictive value (PPV) increased: PSA 44.7%; PBCDR model 61.8%. Comparing PC (stages II, III, IV) vs. other, the ROC AUC increased: PSA (alone) 0.63 (95% CI 0.58, 0.66); PBCDR model 0.72 (95% CI 0.68, 0.75), and the PPV increased: 20.6% (PSA); PBCDR model 55.3%.ConclusionsThese results suggest evaluating certain common biomarkers in conjunction with PSA may improve PC prediction prior to biopsy. Moreover, these biomarkers may be more helpful in detecting clinically relevant PC. Follow-up studies should begin with replicating the study on different U.S. VA patients involving multiple practices.

Prognostic and Predictive Markers in Early Detection of Different Types of Cancers for Selected Organ Sites

Background: Tumor markers are substances that are produced by cancer or by other cells of the body in response to cancer or certain benign (noncancerous) conditions. Tumor markers are used to help detect, diagnose, and manage some types of cancer. Although an elevated level of a tumor marker may suggest the presence of cancer. Aim: The aim of this review is to compare and analyze the present and newer oncogenic markers which help in diagnosis of different types of cancers. Material & Methods: An extensive literature survey was done aiming to compare and compile cancer tests makers required in diagnosis of diseases. Results: Cytoplasmic Proteins, Cell Surface Antigens, Oncofetal Antigens, Receptors, Oncogenes and their metabolic products, Acute-Phase Proteins, Enzymes, Hormones or Tumor associated antigens such as Carcino-Embryonic Antigen (CEA) and Alpha Feto Protein (AFP) are makers for routine analysis whereas several studies have confirmed and consolidated the usefulness of markers such as AFP: Alfa fetoprotein; β-hCG: Beta human chorionic;gonadotropin; CA: Carbohydrate antigen; CEA: Carcinoembryonic antigen; ER: Estrogen receptor; HIAA: Hydroxy indole acetic acid; LDH: Lactate dehydrogenase; PLAP: Placental alkaline phosphatase; PR: Progesterone receptor; PSA: Prostate-specific antigen. Conclusion: There is no ―universal‖ tumor marker that can detect any type of cancer. Further investigation is necessary to define these biomarkers in terms of usefulness in assessing diagnosing various types of cancers. Keywords: Monitoring; Recurrence; Screening; Prognosis; Diagnosis; Response to therapy. Tumor markers are substances that can often be detected in higher than normal amounts in the blood, urine, or body tissues of some patients with certain types of cancer. These substances can be proteins, enzymes, biochemicals, or antigens. Tumor markers may be produced directly by a tumor or by other tissues in response to a tumor, they can be metabolic products, acute-phase proteins, enzymes, hormones or tumor associated antigens such as Carcino-Embryonic Antigen (CEA) and Alpha Feto Protein (AFP).In general, tumor marker levels are lower in early stage disease (but still higher than normal) and higher with advanced disease. Furthermore, their levels decrease in response to treatment and increase when the cancer progresses. Tumor markers are very useful in monitoring the course of a diagnosed malignant tumor, for example pre-treatment and subsequent serial values are essential for the evaluation of the response to the treatment modality with time. When used in combination with x-rays and other tests the detection of tumour markers in the blood can be extremely useful in the detection and diagnosis of cancer. Tumor markers are often used to:  Monitor response to treatment—some tests show whether the cancer is responding to treatment  Monitor for progression—in general, an increase in some tumor markers indicates disease progression  Detect recurrence—regular monitoring of some tumor markers during a remission may help detect recurrence

New developments in treatment planning and verification of particle beam therapy.

Charged particle beam therapy has been used for almost 60 years. During the initial 40 years, the medical use of protons and heavy ions was explored at accelerator laboratories in a limited number of patients and for a limited number of cancerous and non-cancerous disease conditions. After the development of computed tomography and 3D treatment planning, it was time to move charged particle therapy into the clinical realm. This happened in October 1991 when an ocular melanoma patient became the first patient to be treated at Loma Linda University Medical Center in California. Due to the increased awareness of the advantages of charged particle therapy and promising results of single-institution experiences, one currently observes a phase of rapid expansion of proton treatment centers throughout the world. A few of these centers are combined proton/carbon ion facilities. It is very important that the technological evolution of charged particle therapy will continue during this phase of clinical expansion to ensure that the increasing number of patients exposed to therapeutic charged particles will benefit most from the advantageous dose distributions that these particles afford. This report will give an overview of translational research activities related to planning and verification of proton therapy in which the authors have been involved for a number of years. While our activities focus on protons, these developments are to a large degree also applicable to carbon ion therapy.

Commentary: Thoughts on assessing evidence for gene by environment interaction

Commentary: Thoughts on assessing evidence for gene by environment interaction

Emerging technologies in endoscopic imaging.

Endoscopic imaging is in part responsible for the recent drop in deaths from gastrointestinal cancers and also for detecting pre-cancerous and non-cancerous conditions and allowing them to be treated effectively, although techniques are far from perfect. Endoscopic imaging has evolved considerably from fiber optic systems 50 years ago to high resolution and high definition systems used at present. Moreover, image enhancement using filters and processors has led to the technique of ‘electronic chromoendoscopy’ to visualize mucosal blood vessels and surface pit patterns clearly. Magnification by optical zoom or confocal laser microscopy has enabled real time diagnosis and ‘virtual histology’. These techniques have contributed to the early detection, assessment and treatment of various gastrointestinal pathologies. The focus of future research is directed towards molecular targeted imaging.

Putting Evidence Into Practice

Radiation dermatitis, or radiodermatitis, is a significant symptom caused by radiation therapy for the treatment of cancerous and noncancerous conditions. Radiodermatitis can negatively affect patients' physical functioning and quality of life. The Oncology Nursing Society coordinated a Putting Evidence Into Practice (PEP) project team to develop a PEP resource summarizing current evidence for the management of patients with radiodermatitis. Oncology nurses play an important role in educating, assessing, and monitoring patients for this symptom. Many common nursing interventions for radiodermatitis are based on tradition or opinion and have not been researched thoroughly. In addition, evidence to support some current interventions in practice is lacking. This article presents information concerning radiodermatitis, summarizes the evidence-based review for its prevention and management, and identifies gaps in the literature, as well as opportunities for research, education, and practice.

The Mechanoreceptor TRPV4 is Localized in Adherence Junctions of the Human Bladder Urothelium: A Morphological Study

TRPV4 (transient receptor potential vanilloid 4 channel) is a nonselective cation channel involved in different sensory functions that was recently implicated in bladder mechanosensation. We investigated the cellular site of TRPV4 in bladder urothelium and explored a molecular connection between TRPV4 and urothelial adherence junctions. We obtained healthy tissues sections from cystectomy in humans due to cancer in 3 and noncancerous conditions in 2. Besides human biopsies tissues from 7 normal and 7 TRPV4-/-mice, and the urothelial cell line RT4 were also used. Experiments were done with polyclonal antibody against TRPV4 (against the N-terminus of rat TRPV4). A molecular connection between TRPV4 and different adherence junction components was investigated using immunofluorescence, Western blot and immunoprecipitation. Results revealed TRPV4 on urothelial cell membranes near adherence junctions. Results were comparable in the urothelial cell line, human bladders and mouse bladders. Subsequent immunoprecipitation experiments established a molecular connection of TRPV4 to α-catenin, an integral part of the adherence junction that catenates E-cadherin to the actin-microfilament network. Results provide evidence for the location of TRPV4 in human bladder urothelium. TRPV4 is molecularly connected to adherence junctions on the urothelial cell membrane. TRPV4 coupling to a rigid intracellular and intercellular structural network would agree with the hypothesis that TRPV4 can be activated by bladder stretch.

Clinical significance of serum levels of immune‐associated molecules, uric acid and soluble MHC class I chain‐related molecules A and B, as diagnostic tumor markers for pancreatic ductal adenocarcinoma

Immune-associated molecules play important roles in cancer development and progression. The aims of this study were to determine the diagnostic utility of uric acid (UA) and soluble MHC class I chain-related molecules A (sMICA) and B (sMICB) in pancreatic ductal adenocarcinoma (PDAC) compared with those of cancer antigen 19-9 (CA19-9), the most commonly available tumor marker for PDAC. We evaluated serum levels of UA, sMICA and sMICB along the carcinogenic process of PDAC obtained from 148 individuals composed of normal (n = 70), chronic pancreatitis (n = 23) and PDAC (n = 55), and compared them with those of CA19-9. We also evaluated the correlations of these biomarkers with tumor size, resectability or TNM stage, and tested logistic regression to ascertain the potential usability of these markers for the detection of PDAC. We also investigated the correlations among these biomarkers. Serum UA, sMICA and sMICB differed significantly according to groups (Kruskal-Wallis, P < 0.05), and were closely correlated with the development of PDAC. Serum sMICA were correlated with distant metastasis and sMICB were correlated with unresectability. Sensitivity and specificity of sMICA and sMICB were higher than CA19-9, and a multi-maker panel using all tested markers (UA, sMICA, sMICB and CA19-9) demonstrated the best potential for detecting PDAC (94.2% sensitivity at 93.3% specificity). The three tested markers also showed added diagnostic potentials to overcome the limitation of CA19-9 by differentiation of PDAC from non-cancerous conditions when CA19-9 is inappropriate. In conclusion, serum UA, sMICA and sMICB might be useful screening or differential diagnostic biomarkers for PDAC to complement CA19-9.

Germline Sequence Variants and Prostate-Specific Antigen Interpretation

Prostate-specific antigen (PSA)2 is the primary biomarker used to screen for prostate cancer. PSA has limited specificity as a marker, however, and it can be increased in multiple noncancerous conditions [e.g., prostatitis, benign prostatic hyperplasia (BPH)] and after prostatic manipulation (e.g., catheterization) (1, 2). There is now emerging evidence that PSA concentrations may also be affected by genetic variables. Through genome-wide association studies, investigators have identified >30 single-nucleotide polymorphisms (SNPs) that are associated with prostate cancer susceptibility. Eeles et al. reported a strong association of SNPs on chromosomes 10 (rs10993994) and 19 (rs2735839) with PSA concentration and prostate cancer risk (3). It is noteworthy that rs2735839 is located near the KLK3 3 (kallikrein-related peptidase 3) gene on chromosome 19, which encodes PSA, potentially underlying the relationship. In 2009, our group further explored the potential implications of these intriguing findings for prostate cancer screening (4). With 505 men from the Baltimore Longitudinal Study of Aging, we used mixed-effects models to evaluate the relationships between genotype, PSA, and prostate cancer risk. In a model with age and date, there was a 1.18-fold (18%) increased risk ratio for prostate cancer per unit increase in PSA. In an expanded model that also considered the SNP genotypes on chromosomes 10 (rs10993994) and 19 (rs2659056 and rs2735839) and the interaction between genotype and PSA, we found significant differences in prostate cancer risk by PSA that depended on genotype. Specifically, the risk ratio for prostate cancer was …