Prevalent diabetes and risk of total,colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium

Background We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.Methods We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.Results A total of 667,916 individuals were included with an overall median (P25–P75) age at recruitment of 62.3 (57–67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86–1.04; I² = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08–1.26; I² = 0%) and a similar HR in women (1.13; 95% CI: 0.82–1.56; I² = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77–0.85; I² = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89–1.03; I² = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.Conclusions Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.Subject terms: Risk factors, Cancer epidemiology     

Interleukin-28B acts synergistically with cisplatin to suppress the growth of head and neck squamous cell carcinoma

Interleukin-28B (IL-28B), also referred to as interferon-λ3, belongs to the type III interferon family. Earlier studies showed that IL-28B suppresses proliferation of some tumor cells in vitro. IL-28B gene transfection ex vivo also resulted in growth retardation of tumor cells in mice, through either direct antiproliferative action or induction of antitumor immunity. However, it has not been reported whether in vivo therapeutic administration of recombinant IL-28B can inhibit the growth of a pre-established tumor. Here, we found that repetitive subcutaneous administration of recombinant mouse IL-28B significantly induced tumor-specific cytotoxic T lymphocytes and augmented natural killer cytolytic activity, leading to moderate suppression of the growth of a murine head and neck squamous cell carcinoma (HNSCC) cell line that was completely resistant to the direct antiproliferative effect of IL-28B. Moreover, co-administration of recombinant mouse IL-28B and cisplatin (CDDP) more significantly inhibited in vivo growth of the tumor that had been established in syngenic mice and induced tumor-specific cytotoxic T lymphocytes. The CDDP treatment induced the expression of major histocompatibility complex class I and Fas molecules on the surface of HNSCC cells both in vitro and in vivo; this may be the mechanism underlying the synergistic tumor suppression activity of IL-28B and CDDP. Unlike type I interferon, IL-28B did not suppress growth of bone marrow cells in culture. Therefore, IL-28B may be useful as a tool for a novel multidisciplinary therapy against cancer, significantly potentiating innate and adaptive antitumor immune responses, especially when co-administrated with CDDP, which is currently the first choice chemotherapeutic agent against various tumors including HNSCCs.     

Primary telangiectatic osteosarcoma of the cervical spine

Telangiectatic osteosarcoma (TOS) is one of the 8 subtypes of osteosarcoma that infrequently affects the spine. The radiopathological features of TOS overlap with those of more benign entities, most commonly the aneurysmal bone cyst), and therefore is a significant diagnostic challenge. It is a rare but well-described entity in the thoracolumbar and sacral spine, and to the authors' knowledge has not been previously reported in the cervical spine. The authors report the case of a 15-year-old boy who presented with a 6-month history of neck pain and torticollis. He underwent preoperative glue embolization followed by a staged subtotal C-5 spondylectomy and posterior fusion for a C-5 vertebral body lytic expansile lesion. Histopathological examination showed the lesion to be TOS. The surgery was followed by adjuvant radiation and chemotherapy with a favorable outcome at the 1-year follow-up. This report reiterates that TOS is an important differential diagnosis for aneurysmal bone cyst and giant-cell tumor of the spine, as its biological behavior and clinical outcome differ from those of these more benign lesions, which it mimics.     

Biomarkers of oxidative stress and risk of developing colorectal cancer: a cohort-nested case-control study in the European Prospective Investigation Into Cancer and Nutrition

Oxidative stress has been shown to play an important role in carcinogenesis, but prospective evidence for an association between biomarkers of oxidative stress and colorectal cancer (CRC) risk is limited. The authors investigated the association between prediagnostic serum levels of oxidative stress indicators (i.e., reactive oxygen metabolites (ROM) and ferric reducing ability of plasma (FRAP)) and CRC risk. This was examined in a nested case-control study (1,064 CRC cases, 1,064 matched controls) in the European Prospective Investigation Into Cancer and Nutrition cohort (1992-2003). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression analyses. ROM were associated with overall CRC risk (highest tertile vs. lowest: adjusted incidence rate ratio (IRR(adj)) = 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRR(adj) = 1.89, 95% CI: 1.06, 3.36) and distal (IRR(adj) = 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer (IRR(adj) = 1.69, 95% CI: 1.05, 2.72). When results were stratified by tertile of follow-up time, the association remained significant only in participants with less than 2.63 years of follow-up (IRR(adj) = 2.28, 95% CI: 1.78, 2.94; P-heterogeneity < 0.01). FRAP was not associated with CRC risk. In conclusion, prediagnostic serum ROM levels were associated with increased risk of CRC. However, this association was seen only in subjects with relatively short follow-up, suggesting that the association results from production of reactive oxygen species by preclinical tumors.     

Ecological-Level Associations Between Highly Processed Food Intakes and Plasma Phospholipid Elaidic Acid Concentrations: Results From a Cross-Sectional Study Within the European Prospective Investigation Into Cancer and Nutrition (EPIC)

Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations.     

Gene delivery to human chondrocytes by an adeno associated virus vector

OBJECTIVE: To investigate the efficiency of gene transduction to human chondrocytes using an adeno associated virus (AAV) vector. METHODS: We transduced green fluorescent protein (GFP) gene using AAV vector to primary human chondrocytes as well as human cartilage organ cultures, in which chondrocytes are surrounded by extracellular matrix. Expression of GFP gene was analyzed at various time points after transduction by fluorescence microscopy and immunohistochemistry. RESULTS: In primary chondrocytes, the percentages of GFP positive cells were 15.9% or 16.0% on Day 1 and 95.0% or 93.7% on Day 7 after gene transduction. In cartilage organ cultures, gene delivery was observed in cells located not only in the superficial layer but also in the deep layer within the cartilage tissue. Up to 45.3+/-7.4% or 46.0+/-3.9% of chondrocytes expressed GFP for at least 28 days. CONCLUSION: AAV vector could be useful for direct gene delivery to chondrocytes in situ.     

Structure of retracted tendons after staged repair following continuous traction

Purpose  

The effect of staged repair involving continuous re-lengthening of the retracted musculotendinous unit after rotator cuff tear is not known. We quantified changes in chronically retracted tendons undergoing no repair or a staged repair involving an initial re-lengthening of the musculotendinous unit by traction in a sheep model of massive rotator cuff tear.     

Intra‐articular injection of hyaluronan restores the aberrant expression of matrix metalloproteinase‐13 in osteoarthritic subchondral bone

Subchondral bone is a candidate for treatment of osteoarthritis (OA). We investigated the effects of intra‐articular injection of hyaluronan (IAI‐HA) on subchondral bone in rabbit OA model. OA was induced by anterior cruciate ligament transection, with some rabbits receiving IAI‐HA. OA was graded morphologically, and expression of mRNA was assessed by real‐time RT‐PCR. Tissue sections were stained with hyaluronan‐binding protein, and penetration of fluorescent hyaluronan was assessed. The in vitro inhibitory effect of hyaluronan on MMP‐13 was analyzed in human osteoarthritic subchondral bone osteoblasts (OA Ob) by real‐time RT‐PCR and ELISA. Binding of hyaluronan to OA Ob via CD44 was assessed by immunofluorescence cytochemistry. Expression of MMP‐13 and IL‐6 mRNA in cartilage and subchondral bone, and morphological OA grade, increased over time. IAI‐HA ameliorated the OA grade and selectively suppressed MMP‐13 mRNA in subchondral bone. IAI‐HA enhanced the hyaluronan staining of subchondral bone marrow cells and osteocyte lacunae. Fluorescence was observed in the subchondral bone marrow space. In OA Ob, hyaluronan reduced the expression and production of MMP‐13, and anti‐CD44 antibody blocked hyaluronan binding to OA Ob. These findings indicate that regulation of MMP‐13 in subchondral bone may be a critical mechanism during IAI‐HA. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:354–360, 2011