Fido's Cancer: Cell Signaling Problems

Cancer in dogs apparently exhibits similar problems of cell signaling as in humans; dog cancer may therefore be a useful model for studying the human variety.  Abstract:

Prostate cancer is a heterogeneous disease with high levels of clinical and gene heterogeneity, consequently offering several targets for therapy. Dogs with naturally occurring prostate cancer are useful models for molecular investigations and studying new treatment efficacy. Three genes and proteins associated with the WNT pathway (β-catenin, APC and E-cadherin) and Caveolin-1 (CAV-1) were evaluated in canine pre-neoplastic proliferative inflammatory atrophy (PIA), prostate cancer and metastatic disease. The APC gene methylation status was also investigated. As in human prostate cancer, cytoplasmic and nuclear β-catenin, which are fundamental for activating the canonical WNT pathway, were found in canine prostate cancer and metastasis. Membranous E-cadherin was also lost in these lesions, allowing cellular migration to the stroma and nuclear localization of β-catenin. In contrast to human prostate tumours, no APC downregulation or hypermethylation was found in canine prostate cancer. The CAV-1 gene and protein overexpression were found in canine prostate cancer, and as in humans, the highest levels were found in Gleason scores ≥8. In conclusion, as with human prostate cancer, β-catenin and E-cadherin in the WNT pathway, as well as Caveolin-1, are molecular drivers in canine prostate cancer. These findings provide additional evidence that dogs are useful models for studying new therapeutic targets in prostate cancer.

A Supplementation Failure

Here is a study asserting that Vitamin D and calcium supplementation did not prevent bone fractures in older patients.  Other studies of course may say different, but also keep in mind the possible link between excess calcium and prostate cancer in men.  Caveat emptor when looking at any one study in isolation. Abstract:

IMPORTANCE:

The increased social and economic burdens for osteoporosis-related fractures worldwide make the prevention of such injuries a major public health goal. Previous studies have reached mixed conclusions regarding the association between calcium, vitamin D, or combined calcium and vitamin D supplements and fracture incidence in older adults.

OBJECTIVE:

To investigate whether calcium, vitamin D, or combined calcium and vitamin D supplements are associated with a lower fracture incidence in community-dwelling older adults.

DATA SOURCES:

The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to December 24, 2016, using the keywords calcium, vitamin D, and fracture to identify systematic reviews or meta-analyses. The primary randomized clinical trials included in systematic reviews or meta-analyses were identified, and an additional search for recently published randomized trials was performed from July 16, 2012, to July 16, 2017.

STUDY SELECTION:

Randomized clinical trials comparing calcium, vitamin D, or combined calcium and vitamin D supplements with a placebo or no treatment for fracture incidence in community-dwelling adults older than 50 years.

DATA EXTRACTION AND SYNTHESIS:

Two independent reviewers performed the data extraction and assessed study quality. A meta-analysis was performed to calculate risk ratios (RRs), absolute risk differences (ARDs), and 95% CIs using random-effects models.

MAIN OUTCOMES AND MEASURES:

Hip fracture was defined as the primary outcome. Secondary outcomes were nonvertebral fracture, vertebral fracture, and total fracture.

RESULTS:

A total of 33 randomized trials involving 51 145 participants fulfilled the inclusion criteria. There was no significant association of calcium or vitamin D with risk of hip fracture compared with placebo or no treatment (calcium: RR, 1.53 [95% CI, 0.97 to 2.42]; ARD, 0.01 [95% CI, 0.00 to 0.01]; vitamin D: RR, 1.21 [95% CI, 0.99 to 1.47]; ARD, 0.00 [95% CI, -0.00 to 0.01]. There was no significant association of combined calcium and vitamin D with hip fracture compared with placebo or no treatment (RR, 1.09 [95% CI, 0.85 to 1.39]; ARD, 0.00 [95% CI, -0.00 to 0.00]). No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of nonvertebral, vertebral, or total fractures. Subgroup analyses showed that these results were generally consistent regardless of the calcium or vitamin D dose, sex, fracture history, dietary calcium intake, and baseline serum 25-hydroxyvitamin D concentration.

CONCLUSIONS AND RELEVANCE:

In this meta-analysis of randomized clinical trials, the use of supplements that included calcium, vitamin D, or both compared with placebo or no treatment was not associated with a lower risk of fractures among community-dwelling older adults. These findings do not support the routine use of these supplements in community-dwelling older people.

Exercise And Prostate Cancer

Something of interest to all of us men, as we get older - exercise as a possible therapeutic option against localized (presumably non-aggressive)  prostate cancer:

 

Prostate cancer that has not spread is sometimes treated with surgery or radiotherapy. But this can have side-effects so many men opt for active surveillance instead, which involves monitoring the disease. All the men in the PANTERA study are and will remain on active surveillance - and they will also be closely monitored as part of the study itself.

If the participants can successfully keep up their exercise regime for 12 months, the study is expected to lead to a full-scale trial to look at the potential benefits of combining active surveillance and exercise for some prostate cancer patients.

This trial - believed to be the first of its kind in the world - would aim to test whether regular exercise can help keep prostate cancer from spreading to other parts of the body and could be a viable NHS treatment.

Study leader Dr Liam Bourke, principal research fellow at Sheffield Hallam University, said: "Evidence suggests that men who are physically active after a prostate cancer diagnosis have better cancer survival than men who aren't active. It's not clear yet how this works, but it might be that exercise affects the way some genes regulate cancer cell growth and DNA repair.

"The clinical academic team in Sheffield have been working hard for eight years to develop the intervention that is being tested in this exciting study. It builds on what we already know and is the first step towards finding out whether exercise could be an effective and practical NHS treatment for localised prostate cancer. If we show it works and is feasible, it could be a real leap forward and good news for cancer patients."

Actionable:
Here is how I got in my best shape ever (and at middle age).