Hyaluronan as "Agent Smith" in cancer extracellular matrix pathobiology: Regulatory roles in immune response, cancer progression and targeting.

Extracellular matrix (ECM) critically regulates cancer cell behavior by governing cell signaling and properties. Hyaluronan (HA) acts as a structural and functional ECM component that mediates critical properties of cancer cells in a molecular size-dependent manner. HA fragments secreted by cancer-associated fibroblasts (CAFs) reveal the correlation of HA to CAF-mediated matrix remodeling, a key step for the initiation of metastasis. The main goal of this article is to highlight the vital functions of HA in cancer cell initiation and progression as well as HA-mediated paracrine interactions among cancer and stromal cells. Furthermore, the HA implication in mediating immune responses to cancer progression is also discussed. Novel data on the role of HA in the formation of pre-metastatic niche may contribute towards the improvement of current theranostic approaches that benefit cancer management.

Exploring the relationship between calcitonin, ionized calcium, and bone turnover in cats with and without naturally occurring hypercalcemia.

Objectives: This case-control study aimed to evaluate calcitonin response in naturally occurring hypercalcemia in cats and assess the relationships between calcitonin and ionized calcium (iCa) and examine relationships between calcitonin, iCa and bone turnover. Methods: Hypercalcemic cats (persistently increased iCa concentration [>1.40 mmol/l]) were identified retrospectively via a medical database search; additional hypercalcemic and normocalcemic cats were recruited prospectively. Data regarding routine biochemical and urine testing, diagnostic imaging and additional blood testing were obtained. Serum alkaline phosphatase (ALP) activity was used as a marker of bone turnover. Serum calcitonin concentration was analyzed using a previously validated immunoradiometric assay. Hypercalcemic cats with an increased calcitonin concentration (>0.9 ng/L) were termed responders. Group comparisons were performed using a Mann-Whitney test for continuous variables and a χ2 test for categorical variables. Spearman's correlation coefficient was used to examine the relationships between calcitonin, iCa and ALP. Results: Twenty-six hypercalcemic and 25 normocalcemic cats were recruited. Only 5/26 (19.2%) of the hypercalcemic cats were identified as responders, and all were diagnosed with idiopathic hypercalcemia. There was no significant correlation between the concentrations of calcitonin and iCa (p = 0.929), calcitonin and ALP (p = 0.917) or iCa and ALP (p = 0.678) in hypercalcemic cats, however, a significant negative correlation was observed between calcitonin and ALP (p = 0.037) when normocalcemic and hypercalcemic cats with an elevated calcitonin concentration were analyzed together. Discussion: The expected increase in calcitonin concentration was present in only a small subset of hypercalcemic cats; no correlation was found between iCa and calcitonin concentration. The inverse relationship between calcitonin and ALP in cats with increased calcitonin concentrations suggests that the ability of calcitonin to correct hypercalcemia may be related to the degree of bone turnover.

Do owner-reported changes in mobility reflect measures of activity, pain and degenerative joint disease in cats?

OBJECTIVES: The aim of this blinded, nested case-control study was to compare cats with and without early owner-reported mobility changes using subjective and objective outcome measures (owner-completed questionnaires, orthopaedic examination). METHODS: A total of 57 cats with and without early owner-reported signs of impaired mobility were allocated to the case (n = 30) and control (n = 27) groups, respectively. Participating owners completed one inclusion and two pre-visit questionnaires (Feline Musculoskeletal Pain Index, VetMetrica). Cats were then visited in their own homes, where they underwent an orthopaedic examination, an assessment of their body condition score and temperament, and the placement of an accelerometer on their collar for 2 weeks. RESULTS: There was no significant difference between groups for age category, breed, sex, temperament and body condition score. Case cats scored significantly lower for the Feline Musculoskeletal Pain Index (P = 0.003) and the VetMetrica domain of Comfort (P = 0.002), but not Vitality (P = 0.009) or Emotional Wellbeing (P = 0.018). Total pain (P <0.0001), crepitus (P = 0.002) and thickening (P = 0.003) scores were higher in case cats, as was the presence of bilateral disease (P = 0.005, odds ratio 14) and the number of bilaterally affected joints (P = 0.001). CONCLUSIONS AND RELEVANCE: Both the Feline Musculoskeletal Pain Index and orthopaedic examination were able to differentiate cats with early owner-reported signs of impaired mobility from healthy cats. VetMetrica Comfort domain scores indicated a compromised quality of life for cats with early owner-reported signs of impaired mobility compared with healthy cats. Being able to recognise signs of mobility impairment earlier would allow interventions aimed at slowing disease progression, thereby improving feline health and welfare.

Associations between early neutering, obesity, outdoor access, trauma and feline degenerative joint disease.

OBJECTIVES: The aim of this case-control study was to identify early-life risk factors associated with the occurrence of owner-reported mobility changes in 6-year-old cats by examining prospective data from a longitudinal cohort study of pet cats, the Bristol Cats study. METHODS: Data on potential risk factors were obtained from seven sequential questionnaires completed between the ages of 2-4 months and 5 years. Mobility-related questions from the study questionnaire distributed at the age of 6 years were used to calculate each cat's mobility score. Cats with mobility scores of ⩾2 and 0 were allocated to the case and control groups, respectively, and the cat's status was the outcome variable. RESULTS: Of the 799 cats included for analysis, 238 (29.8%) had owner-reported mobility changes. Binomial logistic regression using backwards elimination identified four risk factors for owner-reported mobility changes at 6 years of age: entire neuter status at 6 months of age (odds ratio [OR] 1.97; 95% confidence interval [CI] 1.26-3.07), sustained trauma before 6 years of age (OR 1.85; 95% CI 1.30-2.60), outdoor access at 6 years of age (OR 1.67; 95% CI 0.96-2.90) and overweight/obese status at 6 years of age (OR 1.62; 95% CI 1.13-2.33). CONCLUSIONS AND RELEVANCE: Risk factor analysis demonstrated that obesity, outdoor access and a history of trauma may predispose cats to developing owner-reported mobility changes associated with degenerative joint disease, whereas neutering before 6 months of age appears to decrease that risk.