Mortality in a cohort of flat-coated retrievers in the UK

A cohort study of 174 flat-coated retrievers was undertaken to establish the importance of cancer in flat coat mortality in terms of the prevalence of neoplasia in the breed and also the relative effect of cancer on lifespan in relation to other forms of mortality. Dogs aged 2–7 years were recruited in 1996 and followed until 2007. An annual health census was used to collect the data. Two dogs were lost to follow-up and 72 dogs (42%) died from confirmed neoplasia. Twenty dogs (11.6%) died of unconfirmed tumours and 61 (35%) died from non-neoplastic conditions. The cause of death was unknown for 19 dogs. Soft tissue sarcoma (especially histiocytic sarcoma) was the predominant cancer type, affecting 32 dogs (44% of neoplasms). Six dogs died with malignant melanoma and three with lymphoma. Median age at death was 9 years for dogs with tumours (eight for sarcoma patients) and 12 years for non-neoplastic fatalities. The results confirm that soft tissue sarcoma, particularly histiocytic sarcoma, is a major cause of mortality in this breed.     

Validation of data collected in the Danish Veterinary Cancer Registry

The Danish Veterinary Cancer Registry (DVCR) was established in 2005 and prospectively collects information about neoplasms in Danish dogs and cats.
The present study evaluated the agreement between veterinary practice records and electronic submissions made to the DVCR from May 2005 through June 2008. The variables compared were gender, breed, diagnosis, date of birth, death and diagnosis, localization and biological behaviour of the neoplasms.
Agreement of 95% between DVCR and the original data were considered acceptable with regard to use of data in studies. Recorded proportions of agreement were: (1) breed: 97.4%; (2) diagnosis: 95.6%; (3) location: 95.6%; (4) biological behaviour: 93.0%; (5) gender: 92.5%; (6) date of death: 91.5%; (7) date of diagnosis: 80.1%; (8) date of birth: 76.7%.
All variables except date of death, birth, and diagnosis met the required 95% agreement limit. Data on dates of birth, death and diagnosis were considered less suitable for further studies.     

Canine mammary gland tumours; a histological continuum from benign to malignant; clinical and histopathological evidence*

This study describes the clinical and histopathological findings in dogs with mammary gland tumours, and compares the histopathological and clinical evidence consistent with progression from benign to malignant to human breast cancer epidemiology. Clinical and histopathological data on 90 female dogs with 236 tumours was included. Dogs with malignant tumours were significantly older than dogs with benign tumours (9.5 versus 8.5 years), P = 0.009. Malignant tumours were significantly larger than benign tumours (4.7 versus 2.1 cm), P = 0.0002. Sixty‐six percent had more than one tumour, and evidence of histological progression was noted with increasing tumour size. Dogs with malignant tumours were significantly more likely to develop new primary tumours than dogs with benign tumours, P = 0.015. These findings suggest that canine mammary tumours progress from benign to malignant; malignant tumours may be the end stage of a histological continuum with clinical and histopathological similarities to human breast carcinogenesis.     

大肠癌p53的表达与病理、PCNA、CEA及p53、PCNA、CEA与淋巴结转移的关系

目的：研究大肠癌p53的表达与病理、增殖细胞核抗原（PCNA）、癌胚抗原（CEA）及p53、PC-NA、CEA与淋巴结转移的关系。方法：应用链霉菌素-生物素（SP）免疫组化法，观察44例经病理确诊的大肠癌石腊标本中的p53表达、PCNA的阳性率和CEA的表达型式。结果：大肠癌p53阳性表达率为52．3％；大肠癌p53阳性表达与性别、年龄及肿瘤的部位、分化程度和湿润深度无关（P＞0．05），p53阳性表达者其淋巴结转移率较阴性者高（P＜0．05）；p53阳性表达及有淋巴结转移者其细胞增殖活性分别较p53阴性表达及无淋巴结转移者高（P＜0．05）；p53阳性表达及有淋巴结转移者其CEA表型均以胞浆型和间质型为主（P＜0．05）。结论：检测p53和PCNA表达及CEA表型对判断大肠癌的恶性程度、预测其林巴结转移趋势和预后及指导临床治疗有重要价值。     

Glycol Chitosan-Based Fluorescent Theranostic Nanoagents for Cancer Therapy

Theranostics is an integrated nanosystem that combines therapeutics with diagnostics in attempt to develop new personalized treatments with enhanced therapeutic efficacy and safety. As a promising therapeutic paradigm with cutting-edge technologies, theranostic agents are able to simultaneously deliver therapeutic drugs and diagnostic imaging agents and also monitor the response to therapy. Polymeric nanosystems have been intensively explored for biomedical applications to diagnose and treat various cancers. In recent years, glycol chitosan-based nanoagents have been developed as dual-purpose materials for simultaneous diagnosis and therapy. They have shown great potential in cancer therapies, such as chemotherapeutics and nucleic acid and photodynamic therapies. In this review, we summarize the recent progress and potential applications of glycol chitosan-based fluorescent theranostic nanoagents for cancer treatments and discuss their possible underlying mechanisms.     

Inhibitory Effect of Dihydroaustrasulfone Alcohol on the Migration of Human Non-Small Cell Lung Carcinoma A549 Cells and the Antitumor Effect on a Lewis Lung Carcinoma-Bearing Tumor Model in C57BL/6J Mice

There are many major causes of cancer death, including metastasis of cancer. Dihydroaustrasulfone alcohol, which is isolated from marine coral, has shown antioxidant activity, but has not been reported to have an anti-cancer effect. We first discovered that dihydroaustrasulfone alcohol provided a concentration-dependent inhibitory effect on the migration and motility of human non-small cell lung carcinoma (NSCLC) A549 cells by trans-well and wound healing assays. The results of a zymography assay and Western blot showed that dihydroaustrasulfone alcohol suppressed the activities and protein expression of matrix metalloproteinase (MMP)-2 and MMP-9. Further investigation revealed that dihydroaustrasulfone alcohol suppressed the phosphorylation of ERK1/2, p38, and JNK1/2. Dihydroaustrasulfone alcohol also suppressed the expression of PI3K and the phosphorylation of Akt. Furthermore, dihydroaustrasulfone alcohol markedly inhibited tumor growth in Lewis lung cancer (LLC)-bearing mice. We concluded that dihydroaustrasulfone alcohol is a new pure compound with anti-migration and anti-tumor growth activity in lung cancer and might be applied to clinical treatment in the future.     

Marine Low Molecular Weight Natural Products as Potential Cancer Preventive Compounds

Due to taxonomic positions and special living environments, marine organisms produce secondary metabolites that possess unique structures and biological activities. This review is devoted to recently isolated and/or earlier described marine compounds with potential or established cancer preventive activities, their biological sources, molecular mechanisms of their action, and their associations with human health and nutrition. The review covers literature published in 2003–2013 years and focuses on findings of the last 2 years.     

Diazaquinomycins E–G,Novel Diaza-Anthracene Analogs from a Marine-Derived Streptomyces sp.

As part of our program to identify novel secondary metabolites that target drug-resistant ovarian cancers, a screening of our aquatic-derived actinomycete fraction library against a cisplatin-resistant ovarian cancer cell line (OVCAR5) led to the isolation of novel diaza-anthracene antibiotic diazaquinomycin E (DAQE; 1), the isomeric mixture of diazaquinomycin F (DAQF; 2) and diazaquinomycin G (DAQG; 3), and known analog diazaquinomycin A (DAQA; 4). The structures of DAQF and DAQG were solved through deconvolution of X-Ray diffraction data of their corresponding co-crystal. DAQE and DAQA exhibited moderate LC₅₀ values against OVCAR5 of 9.0 and 8.8 μM, respectively. At lethal concentrations of DAQA, evidence of DNA damage was observed via induction of apoptosis through cleaved-PARP. Herein, we will discuss the isolation, structure elucidation, and biological activity of these secondary metabolites.     

Lamellarin O,a Pyrrole Alkaloid from an Australian Marine Sponge,Ianthella sp., Reverses BCRP Mediated Drug Resistance in Cancer Cells

ATP binding cassette (ABC) transporters, such as P-gp, BCRP and MRP1, can increase efflux of clinical chemotherapeutic agents and lead to multi-drug resistance (MDR) in cancer cells. While the discovery and development of clinically useful inhibitors has proved elusive to date, this molecular target nevertheless remains a promising strategy for addressing and potentially overcoming MDR. In a search for new classes of inhibitor, we used fluorescent accumulation and efflux assays supported by cell flow cytometry and MDR reversal assays, against a panel of sensitive and MDR human cancer cell lines, to evaluate the marine sponge co-metabolites 1–12 as inhibitors of P-gp, BCRP or MRP1 initiated MDR. These studies identified and characterized lamellarin O (11) as a selective inhibitor of BCRP mediated drug efflux. A structure–activity relationship analysis inclusive of the natural products 1–12 and the synthetic analogues 13–19, supported by in silico docking studies, revealed key structural requirements for the lamellarin O (11) BCRP inhibitory pharmacophore.     

Glycoproteomic profiling of serum peptides in canine lymphoma and transitional cell carcinoma

Differential expression of fucosylated glycoproteins has been correlated with malignancy and metastatic potential in various types of neoplasia. Utilizing glycoproteomics techniques, changes in fucosylated serum peptides associated with naturally occurring canine lymphoma and transitional cell carcinoma (TCC) have been evaluated. In both types of neoplasia, the majority of the fucosylated peptides that changed increased with the cancer. In one lymphoma case that was examined over the course of the disease, the same fucosylated peptides that increased during pre-chemotherapy decreased during post-chemotherapy, and then subsequently increased upon recurrence of the lymphoma. When comparing all the fucosylated peptides that increased in both types of cancer, there were only two peptides in common allowing discrimination between lymphoma and TCC based on their peptide profiles. These results emphasize the prospect of glycopeptide profiling in proteomics for use in discovering a panel of non-invasive, diagnostic or prognostic biomarkers of cancer.