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Aims: To test if a New Zealand food–based Mediterranean diet (NZMedDiet) with behavioural intervention improves cardiometabolic health and wellbeing. Methods: A randomised controlled trial comparing 12 weeks of the NZMedDiet to usual diet in participants with increased cardiometabolic risk (metabolic syndrome severity score [MetSSS] > 0.35). The intervention group was provided with food and recipes to meet 75% of their energy requirements, supported by a behavioural intervention to improve adherence. The primary outcome measure was (MetSSS) after 12 weeks. Results: Two hundred individuals with mean (SD) age 49.9 (10.9) years of which 62% women were enrolled with their household/whānau. After 12 weeks, the mean (SD) MetSSS was 1.0 (0.7) in the control (n = 98) and 0.8 (0.5) in the intervention (n = 102) group; estimated difference (95% confidence interval [CI]) of −0.05 (−0.16 to 0.06), p = 0.35. The Mediterranean diet score (PyrMDS) was greater in the intervention group 1.6 (1.1–2.1), p < 0.001, consistent with a change to a more Mediterranean dietary pattern. Weight reduced in the NZMedDiet group compared with control (−1.9 kg [−2.0 to −0.34]), p = 0.006 and wellbeing, assessed by the SF‐36 quality of life questionnaire, and improved across all domains. For example, the physical component summary score difference (95% CI) was 4.0 (2.4–5.7), p < 0.001, and the mental component summary score difference was 3.0 (0.7–5.2), p = 0.01. Conclusion: In participants with increased cardiometabolic risk, food provision with a Mediterranean dietary pattern and a behavioural intervention did not improve metabolic risk scores but was associated with reduced weight and improved quality of life. [ABSTRACT FROM AUTHOR]

Aim: Nutrition challenges are common during childhood cancer treatment and can persist into survivorship, increasing the risk of non‐communicable diseases. Evidence‐based practice and implementation of nutrition interventions/education for childhood cancer survivors has been poorly investigated and may influence their future health. This study aimed to explore the nutrition interventions/education needs of childhood cancer survivors and the barriers and facilitators to delivering follow‐up services in New Zealand. Methods: Semi structured interviews were conducted with childhood cancer survivors and/or their families (n=22) and health professionals (n=9) from a specialist paediatric oncology centre in New Zealand. Interviews were audio‐recorded and transcribed verbatim. Transcripts were analysed inductively using thematic analysis. A multi‐level consensus coding methodology was used where each theme and associated subthemes were discussed with the study team for confirmation to ensure accurate coding and analysis. Results: Three themes emerged from the analysis: (1) the current survivorship care pathway does not provide adequate interventions/education, (2) weight and dietary changes are common challenges and (3) requirements for interventions/education in survivorship are varied. Common nutrition‐related concerns included fussy eating/limited dietary intake, poor diet quality, difficulties with tube weaning, and challenges with weight gain. Participants expressed a desire for education on healthy eating alongside information about cancer‐related nutrition issues, such as learned food aversions. A preference for clear referral pathways and multifaceted interventions tailored to individual patient needs was identified. Conclusion: The trifecta of treatment side effects, negative feeding practices and poor messaging from health professionals creates a challenging environment to optimise nutrition. A stepped care model matching the intervention intensity with the childhood cancer survivors is required. Education for healthcare professionals will improve the delivery of timely interventions/education and monitoring practices. [ABSTRACT FROM AUTHOR]

This study examined the effect of short‐term adaptation to a ketogenic diet (KD) on resting and post‐exercise immune markers. Using a randomized, repeated‐measures, crossover design, eight trained, male, endurance athletes ingested a 31‐day low carbohydrate (CHO), KD (energy intake: 4% CHO; 78% fat) or their habitual diet (HD) (energy intake: 43% CHO; 38% fat). On days 0 and 31, participants ran to exhaustion at 70% VO2max. A high‐CHO (2 g·kg−1) meal was ingested prior to the pre‐HD, post‐HD, and pre‐KD trials, with CHO (~55 g·h−1) ingested during exercise, whereas a low‐CHO (<10 g) meal was ingested prior to the post‐KD trial, with fat ingested during exercise. Blood and saliva samples were collected at pre‐exercise, exhaustion, and 1 hour post‐exhaustion. T‐cell‐related cytokine gene expression within peripheral blood mononuclear cells (PBMCs) and whole‐blood inflammatory cytokine production were determined using 24‐hour multi‐antigen‐stimulated whole‐blood cultures. Multi‐antigen‐stimulated PBMC IFN‐γ mRNA expression and the IFN‐γ/IL‐4 mRNA expression ratio were higher at exhaustion in the post‐KD compared with pre‐KD trial (P = 0.003 and P = 0.004); however, IL‐4 and IL‐10 mRNA expression were unaltered (P > 0.05). Multi‐antigen‐stimulated whole‐blood IL‐10 production was higher in the post‐KD compared with pre‐KD trial (P = 0.028), whereas IL‐1β, IL‐2, IL‐8, and IFN‐γ production was lower in the post‐HD compared with pre‐HD trial (P < 0.01). Salivary immunoglobulin A (SIgA) secretion rate was higher in the post‐KD compared with pre‐KD trial (P < 0.001). In conclusion, short‐term adaptation to a KD in endurance athletes may alter the pro‐ and anti‐inflammatory immune cell cytokine response to a multi‐antigen in vitro and SIgA secretion rate. [ABSTRACT FROM AUTHOR]

Objectives: Over 35 000 people live in residential aged care facilities (RACFs) in New Zealand. Texture‐modified diets (TMDs) are commonplace. They are associated with malnutrition. The aim of this study was to characterise TMD prevalence and practice in RACFs. Methods: Data from 35 460 residents were extracted from the interRAI™ database. Mealtime observations (including 459 residents), meal audits (IDDSI, 2018) and menu audits (Dietitians New Zealand Menu Audit Tool for RACFs 2013) were completed at 10 RACFs. Results: One‐third of residents were on TMDs. Half the residents ate full meals. Feeding assistance was more common in residents on TMDs compared to those on regular diets (P < 0.001). The majority of pureed meals met IDDSI standards; none of soft and bite‐sized meals complied. TMD carbohydrate and protein servings did not comply with standards. Conclusions: Texture‐modified diets reflect 1/3 of meals produced in RACFs. This study provides insight into TMD use in RACFs and highlights service gaps and training opportunities. [ABSTRACT FROM AUTHOR]

The objective of the review was to compare molecular and health effects of tobacco smoking using cigars, cigarillos, pipe and water pipe in relation to the effects of cigarette smoking. In this review we will focus on the upper respiratory tract. Mechanisms of interaction of tobacco smoke constituents after products other than cigarettes are similar to these associated with cigarette smoking. Carcinogenic activity was demonstrated for any type of tobacco smoking, although the risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of cigars, traditional pipe and water pipe as compared to cigarette smoking. Nevertheless, there is no way of safe tobacco smoking. [ABSTRACT FROM AUTHOR]

A systematic literature review was conducted to evaluate the role of diet and food intake in age‐related macular degeneration (AMD). Eighteen high‐quality studies were identified. Adherence to a Mediterranean diet had decreased risk of AMD progression. An Oriental diet pattern had decreased association with AMD prevalence, whereas a Western diet pattern had increased association with AMD prevalence. High consumption of vegetables rich in carotenoids and fatty fish containing omega‐3 fatty acids was beneficial for those at risk of AMD. Vegetable oils and animal fats containing omega‐6 fatty acids, and red/processed meat should be consumed minimally to reduce the risk of AMD progression. High glycaemic index diets and alcohol consumption of greater than two drinks a day had increased association with AMD. As the quality of diet and food intake had a vital role in AMD, the provision of appropriate nutritional advice to those at risk of AMD is recommended. [ABSTRACT FROM AUTHOR]

Background Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC) have a better survival than with HPV-negative oropharyngeal SCC. An 18F-fluorodeoxyglucose positron emission tomography-CT (18F-FDG-PET-CT) may also provide prognostic information. We evaluated glycolytic characteristics in HPV-negative and HPV-positive oropharyngeal SCC. Methods Forty-four patients underwent pretreatment 18F-FDG-PET-CT. Standardized uptake values (SUVs) and metabolic active tumor volumes (MATVs) were determined for primary tumors. HPV status was determined with p16 immunostaining, followed by high-risk HPV DNA detection on the positive cases. Results Twenty-seven patients were HPV-positive (61.4%). Median MATV was 2.8 mL (range = 1.6-5.1 mL) for HPV-positive and 6.0 mL (range = 4.4-18.7 mL) for HPV-negative tumors ( p < .001). SUV values are volume dependent (partial volume effect), therefore, MATV was included as covariate in multivariate analysis. In this multivariate analysis, the maximum SUV in HPV-positive tumors was 3.9 units lower than in HPV-negative tumors ( p = .01). Conclusion The 18F-FDG-PET-CT parameters are lower in HPV-positive than in HPV-negative patients. Low pretreatment SUV values in HPV-positive oropharyngeal SCC may be at least partly explained by HPV-induced tumor changes. © 2015 Wiley Periodicals, Inc. Head Neck 38: 529-535, 2016 [ABSTRACT FROM AUTHOR]

Objective: Oral squamous cell carcinoma (OSCC) may develop in young adults. In contrast to older patients, the well-known etiological factors, exposure to tobacco and alcohol, play a minor role in the carcinogenesis in this patient group. It has been suggested that an intrinsic susceptibility to environmental genotoxic exposures plays a role in the development of OSCC in these patients. The hypothesis was tested whether young OSCC patients have an increased sensitivity to induced chromosomal damage.Subjects and Methods: Fourteen OSCC patients with an average age of 32 years (range 20-42) were selected. Peripheral blood lymphocytes and skin fibroblasts of patients and 14 healthy controls were subjected to the chromosome breakage test with Mitomycin C. This test is routinely used to identify Fanconi anemia patients, who are well-known for their inherited high sensitivity to this type of DNA damage, but also for the high risk to develop OSCC. Human papilloma virus status of the carcinomas was also determined.Results: None of the 14 young patients with OSCC had an increased response in the MMC-chromosomal breakage test. All tumors tested negative for human papilloma virus.Conclusion: No evidence was obtained for the existence of a constitutional hypersensitivity to DNA chromosomal damage as a potential risk factor for OSCC in young adults. [ABSTRACT FROM AUTHOR]

Objective Little is known about the molecular carcinogenesis of oral squamous cell carcinoma ( OSCC) in young adult patients. The aim of this study was to investigate the detailed TP53 mutation and human papilloma virus ( HPV) status of OSCC in patients, younger than 45 years. Methods TP53 mutations were determined with direct sequencing on paraffin-embedded carcinoma tissue from 31 young patients and compared with two older age OSCC reference groups: one from the same institute ( N = 87) and an independent one ( N = 675). Biologically active tumour HPV was detected by p16-immunohistochemistry followed by a HPV- DNA GP5 + /6 + - PCR. Results HPV16 was present in one OSCC (3%). TP53 mutations were found in 14 (45%) OSCC: five were missense and nine resulted in a truncated protein. Six of these latter were insertions or deletions of one or more nucleotides leading to frameshift, one was at a splice site and two resulted in a stop codon. The percentage of truncating mutations (64% of all mutations) was higher than that observed in the institute's reference group (44%, P = 0.23) and in the independent reference group (24%, P = 0.002). Conclusions This study shows that TP53 mutations are common in OSCC of young adult patients; infection with biologically active HPV is rare. [ABSTRACT FROM AUTHOR]

Recent studies have reported that p16 protein overexpression qualifies as a surrogate marker identifying an oncogenic human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC). However, there is still a percentage of OPSCCs that are positive for p16 immunohistochemistry (p16 IHC) but lack HPV DNA. The objective of this study was to characterize this group at the molecular level by performing sensitive HPV DNA- and RNA-based PCR methods and genetic profiling. All patients diagnosed with an OPSCC in the period 2000-2006 in two Dutch university medical centers were included ( n = 841). The presence of HPV in a tumor sample was tested by p16 IHC followed by an HPV DNA GP5+/6+ PCR. p16 IHC scored positive in 195 samples, of which 161 were HPV DNA-positive and 34 (17%) HPV DNA-negative. In the latter group, a SPF10-LiPA25 assay, an HPV16 type-specific E7 PCR and an E6 mRNA RT-PCR were performed. Next, ten of these cases were further analyzed for loss of heterozygosity (LOH) of 15 microsatellite markers at chromosome arms 3p, 9p and 17p. Of the 34 p16-positive but PCR-negative OPSCCs, two samples tested positive by SPF10 assay, HPV16 E7 PCR and HPV16 E6 mRNA RT-PCR. Three samples tested positive by SPF10 assay but negative by the HPV16-specific assays. Nine of ten cases that were tested for LOH showed a genetic pattern comparable to that of HPV-negative tumors. This study categorizes p16-positive but HPV DNA-negative OPSCCs as HPV-negative tumors based on genetic profiling. This study highlights the importance of performing HPV testing in addition to p16 IHC for proper identification of HPV-associated OPSCCs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with HPV-negative OPSCCs. Important factors contributing to this better prognosis are relatively low numbers of local/regional recurrences (LRRs) and second primary tumors (SPTs) in patients with HPV-positive OPSCC. These low numbers may be explained in addition by the absence of a 'field cancerization' effect, which is a cause of LRRs and SPTs in patients with HPV-negative OPSCC. We aimed to detect a possible 'field effect' in patients with HPV-positive OPSCC. As HPV is involved in the early stage of carcinogenesis in OPSCCs, its presence is considered a reliable marker for the detection of such a field effect. Therefore, the presence of transcriptionally active HPV was analyzed in the mucosa surrounding HPV-positive OPSCCs. METHODS: We included 20 patients who were surgically treated for an HPV-positive OPSCC in the period 2000-2006. Of each patient, the formalin-fixed paraffin-embedded tumor sample and all available resection margins were collected. In total, 97 resection margins were investigated with an average of five resection margins per tumor. All samples were analyzed for the presence of tumor and the presence of transcriptionally active HPV by HPV16-E6-mRNA detection. RESULTS: All tumors were HPV16-E6-mRNA positive. HPV16-E6-mRNA could be detected in the resection margins that contained tumor (n = 6). All tumor-negative resection margins (n = 91) scored negative for HPV16-E6-mRNA. CONCLUSIONS: In conclusion, transcriptional active HPV could not be detected in the mucosa surrounding an HPV-positive OPSCC, which suggests the absence of field effect. This observation may explain the lower number of LRRs and SPTs in HPV-positive patients. [ABSTRACT FROM AUTHOR]

Exercise-induced oxidative stress is implicated in muscle damage and fatigue which has led athletes to embark on antioxidant supplementation regimes to negate these effects. This study investigated the intake of vitamin C (VC) (1 g), blackcurrant (BC) juice (15 mg VC, 300 mg anthocyanins) and placebo in isocaloric drink form on training progression, incremental running test and 5-km time-trial performance. Twenty-three trained female runners (age, 31±8 y; mean±SD) completed three blocks of high-intensity training for 3 wks and 3 days, separated by a washout (~3.7 wks). Changes in training and performance with each treatment were analysed with a mixed linear model, adjusting for performance at the beginning of each training block. Markers of oxidative status included protein carbonyl, malondialdehyde (in plasma and in vitro erythrocytes), ascorbic acid, uric acid and erythrocyte enzyme activity of superoxide dismutase, catalase and glutathione peroxidase were analysed. There was a likely harmful effect on mean running speed during training when taking VC (1.3%; 90% confidence limits ±1.3%). Effects of the two treatments relative to placebo on mean performance in the incremental test and time trial were unclear, but runners faster by 1 SD of peak speed demonstrated a possible improvement on peak running speed with BC juice (1.9%; ±2.5%). Following VC, certain oxidative markers were elevated: catalase at rest (23%; ±21%), protein carbonyls at rest (27%; ±38%) and superoxide dismutase post-exercise (8.3%; ±9.3%). In conclusion, athletes should be cautioned about taking VC chronically, however, BC may improve performance in the elite. [ABSTRACT FROM AUTHOR]

Background The immune system plays an important role in tumour immune surveillance. Head and neck squamous cell carcinoma patients are often immune compromised. Objective To chart the baseline levels of T-cell subpopulation frequencies in patients with cancer prior to treatment. Subjects and methods Blood samples of patients were taken at the time of diagnosis, analysed with flowcytometry and compared with blood samples of healthy donors. Results Compared to healthy donors, a significant shift from naive to effector memory T cells was observed. This effect was most prominent in stage II patients. A similar shift from naive to effector memory T cells was noted in patients with oropharynx or larynx squamous cell carcinomas. Furthermore, the percentage of effector memory and effector T cells was higher in the group of patients with human papillomavirus-positive oropharyngeal squamous cell carcinomas, compared with patients with human papillomavirus-negative tumours, suggestive of virus-induced T-cell activation. Conclusion Here, we provide a simple and easily implementable tool to document T lymphocyte subsets in the peripheral blood of head and neck cancer patients, which might be useful for prognosis and/or therapy response prediction. [ABSTRACT FROM AUTHOR]

Patients with head and neck squamous cell carcinoma (HNSCC) have a poor prognosis due to the development of locoregional recurrences, distant metastases, and second primary tumors. There is an urgent need for biomarkers that enable detection and monitoring of the disease to provide adequate therapeutic strategies. In this study, we have investigated markers in peripheral blood cells (PBC) of 28 HNSCC patients who underwent surgery by means of expression profiling. Our hypothesis is that nucleated blood cells circulate continuously, also pass the tumor, and change their expression profile in response to tumor cell factors. For comparison, we enrolled a control group of 11 patients who underwent surgery in the head and neck region for non-HNSCC reasons. A set of 2949 genes was found to be statistically different between the groups (P < 0.05, false discovery rate-corrected) and the most prominently different pathways were ELF2, ELF4, and mTOR signaling. These preliminary results are promising and warrant further studies on the definitive role of PBC gene expression as a biomarker for HNSCC detection and monitoring. [ABSTRACT FROM AUTHOR]

Background Head and neck squamous cell carcinoma (HNSCC) develops in the mucosal linings of the upper aerodigestive tract. HNSCC may develop in large preneoplastic fields, which are in most cases invisible, but can be detected microscopically and by genetic analysis. Methods Cells of mucosal tissue biopsies were cultured and genetically analyzed. Genetic changes in established preneoplastic cultures were compared to the corresponding tumor and surgical margins. Results Of 45 mucosal tissue biopsies taken from primary tumor resection specimen, 26 were successfully cultured and could be genetically analyzed. In 1 culture, genetic changes were found and an immortalized preneoplastic cell line was obtained with genetic changes that were also found in a surgical margin of the corresponding specimen. Conclusion Our data show that noninvasive fields surrounding HNSCC may consist of immortalized preneoplastic cell clones. Our preneoplastic cell line is a valuable tool to develop and test treatment strategies for precursor fields in patients with HNSCC. © 2012 Wiley Periodicals, Inc. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection has been etiologically linked to oropharyngeal squamous cell carcinoma (OPSCC). The prevalence of HPV-positive OPSCC varies between studies, ranging from 20 to 90%. This may be related to the lack of a standardized HPV detection assay as well as to the time period in which HPV prevalence is investigated, as rising incidence rates are reported over the last decades. Here, we validated our previously defined test algorithm for HPV detection in formalin-fixed paraffin-embedded (FFPE) tumor specimen consisting of p16INK4A immunostaining followed by high-risk HPV DNA detection by GP5+/6+ PCR on the positive cases (Smeets et al., Int J Cancer 2007;121:2465-72). In addition, we analyzed HPV prevalence rates in OPSCCs in the years 1990-2010. The test algorithm was validated on a consecutive series of 86 OPSCCs collected during 2008-2011, of which both fresh frozen and FFPE samples were available. We performed HPV-E6 RT-PCR on the frozen samples as gold standard and applied the algorithm to the corresponding FFPE samples. The test algorithm showed an accuracy of 98%. Using the validated algorithm, we determined the presence of an oncogenic HPV infection in 240 OPSCCs of patients diagnosed in the years 1990-2010 at our center. A significant increase in the proportion of HPV-positive samples was observed, from 5.1% in 1990 to 29.0% in 2010 ( p = 0.001). In conclusion, we confirmed the accuracy of the test algorithm for HPV detection in FFPE tumor specimen and we found a significant increase in the prevalence of HPV in OPSCC over the last two decades at our center. [ABSTRACT FROM AUTHOR]

Safety assessments of substances with regard to genotoxicity are generally based on a combination of in vitro and in vivo tests. These tests are performed according to a (tiered) test strategy whereby a positive result in vitro usually triggers further testing in vivo. A low specificity and high frequency of irrelevant positive results associated with most in vitro mammalian cell genotoxicity assays necessitates the design and validation of suitable alternatives. As such, we examined the feasibility of culturing primary hepatocytes from the pUR288 lacZ reporter mouse, and moreover, using established cultures to reliably assess genotoxic activity in vitro. Initial studies characterizing the metabolic capacity of proliferating lacZ primary hepatocytes indicated that these cells retained at least some activities important for xenobiotic metabolism: cytochrome P450 1A1 enzyme activities were markedly increased in the hepatocytes after exposure to benzo[ a]pyrene, and also UDP-glucuronosyl transferase and glutathione- S-transferase activities, both Phase II enzymes, were detected. Increasing levels of phosphorylated p53 at residue serine 389 after ultraviolet treatment indicated a properly functioning p53, one of the criteria for an effective new test system. Four genotoxic substances with different mechanisms of genotoxicity, i.e., benzo[ a]pyrene, bleomycin, etoposide, and cyclophosphamide, were tested in the lacZ rescue assay. For etoposide and cyclophosphamide, the induction of mutant colonies was rather low. Exposure to benzo[ a]pyrene and bleomycin, however, yielded a clear concentration-dependent induction of the lacZ mutant frequency. Based on our preliminary observations, proliferating lacZ primary hepatocytes are a promising new tool for the assessment of genotoxic hazard. Environ. Mol. Mutagen. 2012. © 2012Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined molecular risk factors for the local relapse (LR) in treated head and neck squamous cell carcinoma (HNSCC). Markers used for molecular grading were the number of Ki-67 positive cells, the number of 53 immunopositive cells, and loss of heterozygosity (LOH) at 17p, 9p and 3p. The study found that the presence of a genetically defined preneoplastic region, or field, is significantly associated with LR.

The article reports on a study examining the causative effect of high-risk human papillomavirus-type 16 (HPV16) E6 and E7 expression on the immortalization of normal oral keratinocytes (OKCs). In the study, the resulting phenotype with alternative ways of p53- and pRb-pathway abrogation frequently found in head and neck squamous cell carcinomas (HNSCCs) without HPV was also compared. The causative role of HPV16 E6/E7 in early squamous carcinogenesis is established in the study.

A great disappointment in head and neck cancer surgery is that 10–30% of head and neck squamous cell carcinoma (HNSCC) patients develop local recurrences despite histopathologically tumor-free surgical margins. These recurrences result from either minimal residual cancer (MRC) or preneoplastic lesions that remain behind after tumor resection. Distinguishing MRC from preneoplasic lesions is important to tailor postoperative radiotherapy more adequately. Here we investigated the suitability of quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using human Ly-6D (hLy-6D) transcripts as molecular marker to detect MRC in surgical margins. Submucosal samples of deep surgical margins were collected from 18 non-cancer control patients and 67 HNSCC patients of whom eight had tumor-positive surgical margins. The samples were analyzed with hLy-6D qRT-PCR, and the data were analyzed in relation to the clinicohistological parameters. A significant difference was shown between the group of patients with histopathological tumor-positive surgical margins and the non-cancer control group (p<0.001), and the group of patients with histopathological tumor-free surgical margins (p=0.001). This study shows a novel approach for molecular analysis of deep surgical margins in head and neck cancer surgery. The preliminary data of this approach for detection of MRC in deep margins of HNSCC patients are promising. [ABSTRACT FROM AUTHOR]

The common risk factors for oral and oropharyngeal cancer are tobacco smoking and alcohol consumption, and recently the human papillomavirus (HPV) was shown to be involved in a subgroup. HPV-positive and -negative carcinomas can be distinguished on basis of their genetic profiles. Aim of this study was to investigate patterns of chromosomal aberrations of HPV-negative oral and oropharyngeal squamous cell carcinomas (OOSCC) in order to improve stratification of patients regarding outcome. Thirty-nine OOSCCs were classified on basis of their genetic pattern determined by array comparative genomic hybridization (aCGH). Resulting groups were related to patient and tumor characteristics using the Fisher's exact test and in addition to survival with the Kaplan–Meier and log rank tests. Classification distinguished three groups, one characterized by hardly any chromosomal aberration (N=8) and another by a relatively high level (N=26), and one with a very high level (N=5) of chromosomal aberrations. This classification was significantly (p=0.003) associated with survival, with the best survival in the genetically ‘silent’ group and the worst survival in the most aberrant group. The silent profile was significantly (p<0.05) associated with wild-type TP53, an absence of alcohol consumption and a female gender. These carcinomas were negative for microsatellite instability. This classification of OOSCC was confirmed in an independent set of 89 oral carcinomas. In conclusion, the discovery of these new classes of oral and oropharyngeal cancer with unique genetic and clinical characteristics has important consequences for future basic and clinical studies. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinomas often develop in a pre-cancerous field, defined as mucosal epithelium with cancer-related genetic alterations, and which may appear as a clinically visible lesion. The test characteristics of three genetic assays that were developed to detect pre-cancerous fields were investigated and compared to histology. Methods: In total, 10 pre-cancerous fields that were not visible at clinical inspection and gave rise to malignant transformation based on an identical TP53 mutation in tumor and mucosal epithelium in the surgical margin, as well as 10 normal oral mucosa specimens were analyzed for numerical chromosomal changes with multiplex ligation-dependent probe amplification (MLPA), for loss of heterozygosity (LOH), with microsatellite PCR and for DNA index alterations with DNA image analysis. Results: No alterations were detected in normal tissue by either of the assays. Both MLPA and LOH assays detected all pre-cancerous fields. DNA cytometry identified aneuploidy in four of 10 pre-cancerous fields, while the corresponding tumors that developed in these fields were shown to be aneuploid. Conclusions: Both the MLPA and LOH assay seem suitable for screening pre-cancerous fields in subjects at high risk for oral cancer even in the absence of clinically abnormal appearing oral mucosa. Measurements of DNA index might be valuable to determine the time to progression. [ABSTRACT FROM AUTHOR]

Based on recent genetic studies, we propose a progression model for the development of oral squamous cell carcinoma. In the initial phase, a stem cell acquires a genetic alteration; subsequently a patch is formed, a clonal unit consisting of the stem cell with its daughter cells that all share the DNA alteration. The next critical step is the conversion of a patch into an expanding field as a result of additional genetic alterations. This mucosal field replaces the normal epithelium and in the oral cavity such fields have been detected with dimensions of over 7 cm in diameter. Sometimes these fields are visible as leukoplakia. Ultimately, clonal selection leads to the development of carcinoma within this contiguous field of pre-neoplastic cells. An important clinical implication of this model is that fields often remain after surgery of the primary tumor and may lead to new cancers, presently designated by clinicians as second primary tumors or local recurrences. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2004) 33: 317–22 Based on recent genetic studies, we propose a progression model for the development of oral squamous cell carcinoma. In the initial phase, a stem cell acquires a genetic alteration; subsequently a patch is formed, a clonal unit consisting of the stem cell with its daughter cells that all share the DNA alteration. The next critical step is the conversion of a patch into an expanding field as a result of additional genetic alterations. This mucosal field replaces the normal epithelium and in the oral cavity such fields have been detected with dimensions of over 7 cm in diameter. Sometimes these fields are visible as leukoplakia. Ultimately, clonal selection leads to the development of carcinoma within this contiguous field of pre-neoplastic cells. An important clinical implication of this model is that fields often remain after surgery of the primary tumor and may lead to new cancers, presently designated by clinicians as second primary tumors or local recurrences. [ABSTRACT FROM AUTHOR]

Fox A, Mountford J, Braakhuis A, Harrison LC. High avidity antibodies to fetal pig pancreas endocrine cells transfer rejection but are not normally generated to fetal pig pancreas xenografts. Xenotransplantation 2002; 9: 382–392. © Blackwell Munksgaard, 2002 Previous studies on the contribution of T cell-dependent antibody (Ab) to non-vascular xenograft rejection have yielded conflicting results, being confounded by the presence of recipient T cells and the use of different tissues and immunizing regimens to generate Ab. In the present study, the effect of adoptive transfer of Ab on fetal pig pancreas (FPP) and pig PK15 cell xenografts was examined in T cell-deficient severe combined immune deficiency (SCID) mice. T cell-dependent Abs raised by hyperimmunization with different cell types and by FPP transplantation were compared. Ab raised by hyperimmunization with pig thymocytes exhibited strong binding to pig thymocytes and PK15 cells but did not transfer FPP rejection. IgG1 and IgM, but not IgG3, Abs bound strongly to FPP exocrine and connective tissue, whereas binding to endocrine cells in vitro and in vivo was weak or absent. This pattern of Ab binding was similar to that observed after transplanting FPP into BALB/c mice. Furthermore, serum recovered from BALB/c mice 20 days after FPP transplantation bound strongly to non-endocrine but not endocrine cells and did not transfer FPP rejection. In contrast, serum from mice hyperimmunized with PK15 cells bound strongly to PK15 cells and transferred rejection of intraperitoneal PK15 cells. Furthermore, this serum contained IgG1 and IgM Abs that bound strongly, and IgG3 Abs that bound weakly, to endocrine cells in FPP, and also transferred rejection of FPP in SCID mice. These results indicate that endocrine cells express low concentrations of xenoreactive Ab epitopes and that high Ab concentrations and/or high avidity Abs are required for sufficient endocrine cell binding to cause damage and rejection... [ABSTRACT FROM AUTHOR]

Background Self-management programmes are an increasingly popular way of treating chronic diseases. Aims This study aims to determine the efficacy of the Stanford Chronic Disease Self-Management Programme ( CDSMP) in a New Zealand context by assessing course outcomes and readability of the accompanying reference guide Living a Healthy Life with Chronic Conditions, 4th Edition. Methods This is a cross-sectional pre-post study conducted in Auckland between August 2009 and September 2015, using CDSMP participants' baseline and follow-up Health Education Intervention Questionnaire ( heiQTM ) data. Readability of the guide was assessed using the Gunning Fog Index, Coleman Liau, Flesch Reading Ease, Flesch Kincaid Grade Level and Simplified Measure of Gobbledygook scores. Results Significant evidence of improvement ( P ≤ 0.001) was observed in seven of the eight domains measured by the heiQTM (Deakin University, Centre for Population Health Research, Melbourne, Vic., Australia). The greatest improvements were seen in skill and technique acquisition (mean change score 0.25, P ≤ 0.001) and self-monitoring and insight (0.18, P ≤ 0.001). There was little evidence of improvement in health service navigation (0.04, P = 0.17). Readability analyses indicate that a person needs to be reading at a minimum of U.S. 8th grade level in order to understand the text, and possibly up to 11th grade. Conclusions The CDSMP is effective for improving patient self-efficacy in the New Zealand setting. However, adaptation of the programme to support better health service navigation is warranted. The readability of the reference guide is not suitable for this setting and requires further improvement. [ABSTRACT FROM AUTHOR]