Altered JS-2 expression in colorectal cancers and its clinical pathological relevance

JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the clinicopathological features of the cancer patients. We evaluated the DNA copy number and mRNA expression of JS-2 in 176 colorectal tissues (116 adenocarcinomas, 30 adenomas and 30 non-neoplastic tissues) using real-time polymerase chain reaction. JS-2 expression was also evaluated in two colorectal cancer cell lines and a benign colorectal cell line. JS-2 amplification was noted in 35% of the colorectal adenocarcinomas. Significant differences in relative expression levels for JS-2 mRNA between different colorectal tissues were noted (p = 0.05). Distal colorectal adenocarcinoma had significantly higher copy number than proximal adenocarcinoma (p = 0.005). The relative expression level of JS-2 was different between colonic and rectal adenocarcinoma (p = 0.007). Mucinous adenocarcinoma showed higher JS-2 expression than non-mucinous adenocarcinoma (p = 0.02). Early T-stage cancers appear to have higher JS-2 copy number and lower expression of JS-2 mRNA than later stage cancers (p = 0.001 and 0.03 respectively). Colorectal cancer cell lines showed lower expression of JS-2 than the benign colorectal cell line. JS-2 copy number change and expression were shown for the first time to be altered in the carcinogenesis of colorectal cancer. In addition, genetic alteration of JS-2 was found to be related to location, pathological subtypes and staging of colorectal cancer.

Signet-ring cell carcinoma of colorectum : current perspectives and molecular biology

PURPOSE Colorectal signet-ring cell carcinoma (SRCC) is rare, and very little detailed information on the molecular biology of the disease is available. METHODS The literature on the clinical, pathological and, in particular, the molecular biology of this rare entity was critically reviewed. The reviewed articles take into account a total of 1,817 cases of SRCC, but only 143 cases have molecular data available. The characteristics of two patients with colorectal SRCC were also discussed. RESULTS Colorectal SRCC mostly occurs in younger patients, is larger and has different site predilection compared with conventional colorectal adenocarcinoma. It can occur as one of the synchronous cancers in the colorectum. The cancer is usually diagnosed at advanced stages because of the late manifestation of symptoms, and aggressive treatment strategy is required. Limited reports in the literature have shown that the variant of colorectal cancer demonstrated a different pattern of genetic alterations of common growth kinase-related oncogenes (K-ras, BRAF), tumour suppressor genes (p53, p16), gene methylation and cell adhesion-related genes related to the Wingless signalling pathway (E-cadherin and beta-catenin) from conventional colorectal adenocarcinoma. Colorectal SRCC also showed high expression of mucin-related genes and genes related to the gastrointestinal system. There was also a higher prevalence of microsatellite instability-high tumours and low Cox-2 expression in colorectal SRCC as opposed to conventional adenocarcinoma. CONCLUSIONS Colorectal SRCC has unique molecular pathological features. The unique molecular profiles in SRCC may provide molecular-based improvements to patient management in colorectal SRCC.

Beliefs about infant regulation, early infant behaviors and maternal postnatal depressive symptoms

Background: Young infants may have irregular sleeping and feeding patterns. Such regulation difficulties are known correlates of maternal depressive symptoms. Parental beliefs regarding their role in regulating infant behaviours also may play a role. We investigated the association of depressive symptoms with infant feeding/sleeping behaviours, parent regulation beliefs, and the interaction of the two. Method: In 2006, 272 mothers of infants aged up to 24 weeks completed a questionnaire about infant behaviour and regulation beliefs. Participants were recruited from general medical practices and child health clinics in Brisbane, Australia. Depressive symptomology was measured using the Edinburgh Postnatal Depression Scale (EPDS). Other measures were adapted from the ALSPAC study. Results: Regression analyses were run controlling for partner support, other support, life events, and a range of demographic variables. Maternal depressive symptoms were associated with infant sleeping and feeding problems but not regulation beliefs. The most important infant predictor was sleep behaviours with feeding behaviours accounting for little additional variance. An interaction between regulation beliefs and sleep behaviours was found. Mothers with high regulation beliefs were more susceptible to postnatal depressive symptoms when infant sleep behaviours were problematic. Conclusion: Mothers of young infants who expect greater control are more susceptible to depressive symptoms when their infant presents challenging sleep behaviour.

Physical activity, walking and quality of life in women with depressive symptoms

Background Physical activity (PA) has a positive association with health-related quality of life (HRQL) in the general population. The association between PA and HRQL in those with poor mental health is less clear. Purpose To examine the concurrent and prospective dose-response relationships between total physical activity (TPA) and walking only with HRQL in women aged 50-55 with depressive symptoms in 2001. Methods Participants were 1904 women born in 1946-1951 who completed mailed surveys for the Australian Longitudinal Study on Women's Health in 2001, 2004, 2007 and 2010 and who, in 2001, reported depressive symptoms. At each time point, they reported their weekly minutes of walking, moderate PA, and vigorous PA. A summary TPA score was created that accounted for differences in energy expenditure among the three PA types. Mixed models were used to examine associations between TPA and HRQL (SF-36 component and subscale scores) and between walking and HRQL, for women who reported walking as their only PA. Analyses were conducted in 2013-2014. Results Concurrently, higher levels of TPA and walking were associated with better HRQL (p<0.05). The strongest associations were found for physical functioning, vitality, and social functioning subscales. In prospective models, associations were attenuated, yet compared with women doing no TPA or walking, women doing “sufficient” TPA or walking had significantly better HRQL over time for most SF-36 scales. Conclusions This study extends previous work by demonstrating trends between both TPA and walking and HRQL in women reporting depressive symptoms.

Pathological excretion patterns of urinary proteins in miners highly exposed to dinitrotoluene

A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclinical renal damage. The study included a screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary proteins α 1-microglobulin and glutathione-S-transferase α (GST α) as biomarkers for damage of the proximal tubule and glutathione-S-transferase π (GST π) for damage of the distal tubule. The exposures were categorized semiquantitatively (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathological protein excretion patterns with the semiquantitative ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, especially those in the higher exposed groups, were confined to pathological urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tamm-Horsfall protein, a 105-kD protein marker, was noted. Data on the biomarkers α 1-microglobulin, GST α, and GST π consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients observed among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.

Women with self-reported lower-limb lymphedema after treatment for gynecological cancers: Are they more likely to self-report psychosocial symptoms and less likely to use services?

Background: Due to improved screening and treatment for gynaecological cancers survivorship has increased. Use of supportive care services after treatment is important to improve quality of life. Objective: To assess self-reported lower-limb lymphoedema (LLL), depression, anxiety, quality of life, unmet supportive care needs, and service use among gynaecological cancer survivors. Methods: In 2010 a population-based cross-sectional mail survey was conducted (n=160 gynaecological cancer survivors 5 to 30 month post-diagnosis (53% response rate)). Results: Overall, 30% of women self-reported LLL, 21% and 24% depression or anxiety, respectively. Women with LLL were more likely to also report symptoms of depression or anxiety, and with these symptoms had higher unmet supportive care needs. Services needed but not used by 10-15% of women with LLL, anxiety or depression respectively were lymphoedema specialist, pain specialist and physiotherapist, or psychiatrists, psychologists and pain specialists. Limitations: Small sample size, self-report data, limited generalisation to other countries, underrepresentation of older women (age >70) and women from non-Caucasian backgrounds. Conclusions: Women with LLL or high distress were less likely to use services they needed. Funding: This study was funded by Cancer Australia.

A prospective study investigating the links among classroom environment, school connectedness, and depressive symptoms in adolescents

School connectedness and classroom environment have both been strongly linked to depressive symptoms, but their interrelation is unclear. We tested whether school connectedness mediated the link between classroom environment and depressive symptoms. A sample of 504 Australian seventh- and eighth-grade students completed the Classroom Environment Scale, Psychological Sense of School Membership scale, and Children's Depression Inventory, at three time points. Together, the classroom environment and school connectedness accounted for 41% to 45% of variance in concurrent depressive symptoms, and 14% of subsequent depressive symptoms with prior symptoms accounted for. Only a partial mediation was found, with both classroom environment and school connectedness continuing to contribute uniquely to the prediction of concurrent and subsequent depressive symptoms. These findings provide additional support for the idea that school-based pathways to depressive symptoms are a complex interplay between environment and individual difference variables, necessitating individual and environmental school-based interventions.

Paternal postnatal depressive symptoms, infant sleeping and feeding behaviors, and rigid parental regulation : a correlational study

Paternal postnatal depression (PND) is now recognized as a serious and prevalent problem, associated with poorer well-being and functioning of all family members. Aspects of infant temperament, sleeping and feeding perceived by parents as problematic are associated with maternal PND, however, less is known about paternal PND. This study investigated depressive symptoms (Edinburgh postnatal depression scale (EPDS)) in 219 fathers of infants aged from 1 to 24 weeks (median 7.0 weeks). Infant predictor variables were sleeping problems, feeding problems and both mother and father reported temperament. Control variables were partner’s support, other support and life events. Rigidity of parenting beliefs regarding infant regulation was also measured as a potential moderating factor. Infant feeding difficulties were associated with paternal depressive symptoms, subsuming the variance associated with both sleep problems and temperament. This relationship was not moderated by regulation beliefs. It was concluded that infant feeding is important to fathers. Fathers of infants with feeding difficulties may not be able to fulfill their idealized construction of involved fatherhood. Role incongruence may have an etiological role in paternal PND.