General Direct Anticancer Effects of Deer Growing Antler Extract in Several Tumour Cell Lines, and Immune System-Mediated Effects in Xenograft Glioblastoma.

Deer antlers are the fastest growing tissue. Because they are based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus their extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound by testing the direct effects in cells of different tumours: glioblastoma (GBM; lines U87MG and U251), colorectal (CRC; lines DLD-1, HT-29, SW480, and SW620), breast cancer (BRCA; lines MCF7, SKBR3, and PA00), and leukaemia (THP-1). DVA reduced the viability of tumours but not healthy cells (NHC; lines 293T and HaCaT). Mobility decreased at least for the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight by 66.3% and 61.4% respectively, and it also reduced spleen weight (43.8%). In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related to tumour fighting and down-regulated those related to inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system. DVA may contain a future anticancer medicine without secondary effects.

Is Satoyoshi syndrome an autoimmune disease? A systematic review.

OBJECTIVES: Satoyoshi syndrome is a rare multisystem disease of presumed autoimmune aetiology. We carried out a systematic review to evaluate the available evidence to support that autoimmune hypothesis. METHODS: We searched for Satoyoshi syndrome cases in PubMed, the Web of Science and Scopus up to January 2022, using keywords 'Satoyoshi syndrome' or 'Komuragaeri disease'. Data on symptoms, associated autoimmune diseases, presence of autoantibodies and response to treatment were collected. RESULTS: A total of 77 patients from 57 articles published between 1967 and 2021 were included; 59 patients were women. The mean age at diagnosis was 21.2 years. All cases had painful muscular spasms and alopecia. Frequent manifestations included: diarrhoea, malabsorption, growth retardation, amenorrhoea and bone deformity. Satoyoshi syndrome was associated with other autoimmune diseases: myasthenia gravis, autoimmune thyroiditis, idiopathic thrombocytopenic purpura, atopic dermatitis, bronchial and lupus erythematosus. Autoantibody determinations were performed in 39 patients, of which 27 had positive results. The most frequently detected autoantibodies were ANAs. Other less frequently found autoantibodies were: anti-acetylcholine receptor antibodies, anti-DNA antibodies, antithyroid antibodies, anti-glutamic acid decarboxylase (anti-GAD) and anti-gliadin antibodies. Pharmacological treatment was reported in 50 patients. Most of them improved with CS, immunosuppressants and immunoglobulins, or a combination of these medications. CONCLUSION: Satoyoshi syndrome is associated with other autoimmune diseases and a variety of autoantibodies. Improvement after CS or other immunosuppressant treatment was observed in 90% of cases. These data support an autoimmune aetiology for Satoyoshi syndrome. More studies including systematic determination of autoantibodies in all patients with Satoyoshi syndrome will help us advance in our understanding of this disease.

Anti-tumour activity of deer growing antlers and its potential applications in the treatment of malignant gliomas.

A recent study showed that antlers have evolved a high rate of growth due to the expression of proto-oncogenes and that they have also evolved to express several tumour suppressor genes to control the risk of cancer. This may explain why deer antler velvet (DAV) extract shows anti-tumour activity. The fast growth of antler innervation through the velvet in close association to blood vessels provides a unique environment to study the fast but non-cancerous proliferation of heterogeneous cell populations. We set out to study the anti-cancer effect of DAV in glioblastoma (GB) cell lines in comparison with temozolomide, a chemotherapeutic drug used to treat high-grade brain tumours. Here we report, for the first time, that DAV extract from the tip, but not from mid-parts of the antler, exhibits an anti-tumour effect in GB cell lines (T98G and A172) while being non-toxic in non-cancerous cell lines (HEK293 and HACAT). In T98G cells, DAV treatment showed reduced proliferation (37.5%) and colony-formation capacity (84%), inhibited migration (39%), induced changes in cell cycle progression, and promoted apoptosis. The anticancer activity of DAV extract as demonstrated by these results may provide a new therapeutic strategy for GB treatment.

Gastrointestinal manifestations in Satoyoshi syndrome: a systematic review.

BACKGROUND: Satoyoshi syndrome (SS) [OMIM 600705; ORFHA 3130] is a multisystemic disease with a probable autoimmune basis, whose main symptoms are muscle spasms, alopecia, diarrhea and skeletal alterations. Chronic diarrhea may be severe and result in malnutrition, anemia, growth retardation, cachexia, disability and even death. However, to date, no review of the digestive symptoms has been carried out. METHODS: A search was performed in MEDLINE, Scopus and Web of Science databases. Cases of SS, without language or date restrictions, were recorded. Sixty-seven cases of SS were found up until December 2019. Thirty-nine cases described gastrointestinal manifestations. RESULTS: Chronic diarrhea was the main digestive symptom (92.3%). Other symptoms such as abdominal pain (15.4%), nausea (7.7%) and vomiting (7.7%), were less frequent. The D-xylose test was positive in 10 out of 12 patients, and 9 out of 13 cases showed a flattened oral glucose tolerance test suggesting carbohydrate malabsorption. Antinuclear antibodies were detected in 8 out of 16 cases. Antibodies to stomach or duodenum tissue lysates were also detected by Western blot. Histological data revealed predominantly lymphoplasmacytic inflammatory infiltrate that can affect any section of the digestive tract. In 6 out of 10 patients, diarrhea improved with a treatment regimen that included corticosteroids. Other treatments, such as methotrexate, carbohydrate restricted diets or otilonium bromide, improved digestive symptoms in isolated patients. Improvement of symptoms up to three years of follow-up has been described. None of the three patients who died had received corticosteroids or immunosuppressants. CONCLUSION: Chronic diarrhea with malabsorption is one of the most disabling symptoms in SS. The early recognition of this disease is essential for immunosuppressive treatment and a better outcome.

Contribution of a new electrophysiologic test to Morton's neuroma diagnosis.

BACKGROUND: Morton's neuroma causes metatarsalgia due to the interdigital neuropathy. The small nerve diameter compromises their evaluation in image studies. To overcome this problem we propose a new electrophysiological test. METHODS: We conducted a prospective case-control study performing a orthodromic electroneurography using subdermal electrodes in controls and patients to assess the validity. Additionally all patients were tested with magnetic resonance. Some patients required surgery and subsequent histological evaluation. RESULTS: The new ENG procedure showed higher sensitivity and specificity. Methodological standardization was easy and the test was well tolerated by the subjects. CONCLUSIONS: Our test demonstrated remarkable diagnostic efficiency, and also was able to identify symptomatic patients undetected by magnetic resonance, which underlines the lack of correlation between the size and intensity of the lesion. This new electrophysiological method appears to be a highly sensitivity, well-tolerated, simple and low-cost for Morton's neuroma diagnosis.