Ghrelin and cancer

Ghrelin is a peptide hormone that was originally isolated from the stomach as the endogenous ligand for the growth hormone secretagogue receptor (GHSR). Ghrelin has many functions, including the regulation of appetite and gut motility, growth hormone release from the anterior pituitary and roles in the cardiovascular and immune systems. Ghrelin and its receptor are expressed in a number of cancers and cancer cell lines and may play a role in processes associated with cancer progression, including cell proliferation, apoptosis, and cell invasion and migration.

Body-site distribution of skin cancer, pre-malignant and common benign pigmented lesions excised in general practice

Background Concern about skin cancer is a common reason for people from predominantly fair-skinned populations to present to primary care doctors. Objectives To examine the frequency and body-site distribution of malignant, pre-malignant and benign pigmented skin lesions excised in primary care. Methods This prospective study conducted in Queensland, Australia, included 154 primary care doctors. For all excised or biopsied lesions, doctors recorded the patient's age and sex, body site, level of patient pressure to excise, and the clinical diagnosis. Histological confirmation was obtained through pathology laboratories. Results Of 9650 skin lesions, 57·7% were excised in males and 75·0% excised in patients ≥50years. The most common diagnoses were basal cell carcinoma (BCC) (35·1%) and squamous cell carcinoma (SCC) (19·7%). Compared with the whole body, the highest densities for SCC, BCC and actinic keratoses were observed on chronically sun-exposed areas of the body including the face in males and females, the scalp and ears in males, and the hands in females. The density of BCC was also high on intermittently or rarely exposed body sites. Females, younger patients and patients with melanocytic naevi were significantly more likely to exert moderate/high levels of pressure on the doctor to excise. Conclusions More than half the excised lesions were skin cancer, which mostly occurred on the more chronically sun-exposed areas of the body. Information on the type and body-site distribution of skin lesions can aid in the diagnosis and planned management of skin cancer and other skin lesions commonly presented in primary care.

In silico experimental modeling of cancer treatment

In silico experimental modeling of cancer involves combining findings from biological literature with computer-based models of biological systems in order to conduct investigations of hypotheses entirely in the computer laboratory. In this paper, we discuss the use of in silico modeling as a precursor to traditional clinical and laboratory research, allowing researchers to refine their experimental programs with an aim to reducing costs and increasing research efficiency. We explain the methodology of in silico experimental trials before providing an example of in silico modeling from the biomathematical literature with a view to promoting more widespread use and understanding of this research strategy.

A variant of the KLK4 gene is expressed as a cis sense-antisense chimeric transcript in prostate cancer cells

In humans, more than 30,000 chimeric transcripts originating from 23,686 genes have been identified. The mechanisms and association of chimeric transcripts arising from chromosomal rearrangements with cancer are well established, but much remains unknown regarding the biogenesis and importance of other chimeric transcripts that arise from nongenomic alterations. Recently, a SLC45A3–ELK4 chimera has been shown to be androgen-regulated, and is overexpressed in metastatic or high-grade prostate tumors relative to local prostate cancers. Here, we characterize the expression of a KLK4 cis sense–antisense chimeric transcript, and show other examples in prostate cancer. Using non-protein-coding microarray analyses, we initially identified an androgen-regulated antisense transcript within the 3′ untranslated region of the KLK4 gene in LNCaP cells. The KLK4 cis-NAT was validated by strand-specific linker-mediated RT-PCR and Northern blotting. Characterization of the KLK4 cis-NAT by 5′ and 3′ rapid amplification of cDNA ends (RACE) revealed that this transcript forms multiple fusions with the KLK4 sense transcript. Lack of KLK4 antisense promoter activity using reporter assays suggests that these transcripts are unlikely to arise from a trans-splicing mechanism. 5′ RACE and analyses of deep sequencing data from LNCaP cells treated ±androgens revealed six high-confidence sense–antisense chimeras of which three were supported by the cDNA databases. In this study, we have shown complex gene expression at the KLK4 locus that might be a hallmark of cis sense–antisense chimeric transcription.

A Bayesian approach to assess interaction between known risk factors: The risk of lung cancer from exposure to asbestos and smoking

We review the literature on the combined effect of asbestos exposure and smoking on lung cancer, and explore a Bayesian approach to assess evidence of interaction. Previous approaches have focussed on separate tests for an additive or multiplicative relation. We extend these approaches by exploring the strength of evidence for either relation using approaches which allow the data to choose between both models. We then compare the different approaches.

Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC50) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease.

Feasibility of brief psychological distress screening by a community-based telephone helpline for cancer patients and carers

Background Up to one-third of people affected by cancer experience ongoing psychological distress and would benefit from screening followed by an appropriate level of psychological intervention. This rarely occurs in routine clinical practice due to barriers such as lack of time and experience. This study investigated the feasibility of community-based telephone helpline operators screening callers affected by cancer for their level of distress using a brief screening tool (Distress Thermometer), and triaging to the appropriate level of care using a tiered model. Methods Consecutive cancer patients and carers who contacted the helpline from September-December 2006 (n = 341) were invited to participate. Routine screening and triage was conducted by helpline operators at this time. Additional socio-demographic and psychosocial adjustment data were collected by telephone interview by research staff following the initial call. Results The Distress Thermometer had good overall accuracy in detecting general psychosocial morbidity (Hospital Anxiety and Depression Scale cut-off score ≥ 15) for cancer patients (AUC = 0.73) and carers (AUC = 0.70). We found 73% of participants met the Distress Thermometer cut-off for distress caseness according to the Hospital Anxiety and Depression Scale (a score ≥ 4), and optimal sensitivity (83%, 77%) and specificity (51%, 48%) were obtained with cut-offs of ≥ 4 and ≥ 6 in the patient and carer groups respectively. Distress was significantly associated with the Hospital Anxiety and Depression Scale scores (total, as well as anxiety and depression subscales) and level of care in cancer patients, as well as with the Hospital Anxiety and Depression Scale anxiety subscale for carers. There was a trend for more highly distressed callers to be triaged to more intensive care, with patients with distress scores ≥ 4 more likely to receive extended or specialist care. Conclusions Our data suggest that it was feasible for community-based cancer helpline operators to screen callers for distress using a brief screening tool, the Distress Thermometer, and to triage callers to an appropriate level of care using a tiered model. The Distress Thermometer is a rapid and non-invasive alternative to longer psychometric instruments, and may provide part of the solution in ensuring distressed patients and carers affected by cancer are identified and supported appropriately.