Osteonecrosis of the jaw and antiresorptive agents in benign and malignant diseases: a critical review organized by ECTS

Context Antiresorptive therapy significantly reduces fracture risk in patients with benign bone disease and skeletal-related events (SREs) in patients with bone metastases. Osteonecrosis of the jaw (ONJ) is a rare, but severe condition, manifested as necrotic bone lesion(-s) of the jaws. ONJ has been linked to the use of potent antiresorptive agents, termed as Medication Related ONJ (MRONJ). Methods A working group of the European Calcified Tissue Society (ECTS) and two experts performed an updated detailed review of existing literature on MRONJ incidence, characteristics, and treatment applied in bone diseases with variable severity of skeletal insult, ranging from osteoporosis to prevention of cancer treatment-induced bone loss and SREs in cancer patients with bone metastases. We aimed to identify the differences in various aspects of MRONJ among these distinct patient categories and provide recommendations on how to mitigate the risk and optimally manage MRONJ in each one of them. Results The risk for MRONJ is much higher in patients with advanced malignancies compared to those with benign bone diseases, because of the higher doses and more frequent administration of antiresorptive agents in individuals with compromised general health, along with co-administration of other medications that predispose to MRONJ. The overall risk for MRONJ is considerably lower than the benefits in all categories of patients. Conclusions The risk for MRONJ largely depends on the underlying bone disease and the relevant antiresorptive regimen applied. Physicians and dentists should keep in mind that the benefits of antiresorptive therapy far outweigh the risk for MRONJ development.

Potential of Vitamin D Food Fortification in Prevention of Cancer Deaths—A Modeling Study

Meta-analyses of randomized controlled trials (RCTs) have estimated a 13% reduction of cancer mortality by vitamin D supplementation among older adults. We evaluated if and to what extent similar effects might be expected from vitamin D fortification of foods. We reviewed the literature on RCTs assessing the impact of vitamin D supplementation on cancer mortality, on increases of vitamin D levels by either supplementation or food fortification, and on costs of supplementation or fortification. Then, we derived expected effects on total cancer mortality and related costs and savings from potential implementation of vitamin D food fortification in Germany and compared the results to those for supplementation. In RCTs with vitamin D supplementation in average doses of 820–2000 IU per day, serum concentrations of 25-hydroxy-vitamin D increased by 15–30 nmol/L, respectively. Studies on food fortification found increases by 10–42 nmol/L, thus largely in the range of increases previously demonstrated by supplementation. Fortification is estimated to be considerably less expensive than supplementation. It might be similarly effective as supplementation in reducing cancer mortality and might even achieve such reduction at substantially larger net savings. Although vitamin D overdoses are unlikely in food fortification programs, implementation should be accompanied by a study monitoring the frequency of potentially occurring adverse effects by overdoses, such as hypercalcemia. Future studies on effectiveness of vitamin D supplementation and fortification are warranted.

Serum Beclin 1 and autophagy-related protein-5 and the risk of hepatocellular carcinoma among cirrhotic hepatitis C patients

Background The most common primary liver cancer in adults is hepatocellular carcinoma (HCC) which is commonly presented with a poor prognosis. Therefore, it is important to explore effective biomarkers and therapeutic targets for HCC patients. Autophagy is involved in the development and prevention of cancer. Mammalian Beclin-1 is needed for an autophagic vesicle in HCC. Autophagy-related protein-5 (ATG5) is an important molecule involved in cell death during autophagy. The objective is to investigate serum ATG 5 and Beclin 1 levels in HCV-induced liver cirrhosis with and without HCC. The study was conducted on 80 individuals classified into 3 groups: Group 1: 30 patients with HCV-induced liver cirrhosis without HCC. Group 2: 30 patients with HCV-induced liver cirrhosis with HCC. Group 3: 20 healthy subjects (control group). Results Serum ATG 5 was significantly lower in HCC than liver cirrhosis patients. Serum Beclin 1 was significantly higher in HCC than liver cirrhosis patients. A cutoff value of < 95.7 and > 5.3 of serum ATG5 and Beclin 1 could be suggested for diagnosis of HCC among patients with HCV-related cirrhosis. Conclusion Serum Beclin 1 and ATG 5 could be used as a novel diagnostic marker for HCC. Moreover, scoring of serum BECLIN 1, ATG 5, and cachexia might be a future promising tool to predict the risk of HCC development.

Eudragit, a Nifty Polymer for Anticancer Preparations: A Patent Review

Background: Polymers are the backbone of modern pharmaceutical formulations and drug delivery technologies. Polymers that may be natural, synthetic, or semisynthetic are used to control the release of drugs in a pre-programmed fashion. The drug delivery systems are mainly prepared to enhance the bioavailability, site-specific release, sustained release, controlled release, i.e., to modify the release of drug from dosage form may be a tablet, capsule, etc. Objective: The objective of the present study is to overview the recent patents concerning the application of eudragit in the prevention of cancer and other ailments. Eudragit polymers are polymethacrylates and may be anionic, cationic, or non-ionic polymers of methacrylic acid, dimethyl-aminoethyl methacrylates, and methacrylic acid esters in varying ratios. Eudragit is available in various grades with solubilities at different pH, thus helping the formulators design the preparation to have a well-defined release pattern. Method: In this review, patent applications of eudragit in various drug delivery systems employed to cure mainly cancer are covered. Results : Eudragit has proved its potential as a polymer to control the release of drugs as coating polymer and formation of the matrix in various delivery systems. It can increase the bioavailability of the drug by site-specific drug delivery and can reduce the side effects/toxicity associated with anticancer drugs. Conclusion: The potential of eudragit to carry the drug may unclutter novel ways for therapeutic intercessions in various tumors.

Key to Life: Physiological Role and Clinical Implications of Progesterone

The most recent studies of progesterone research provide remarkable insights into the physiological role and clinical importance of this hormone. Although the name progesterone itself means “promoting gestation”, this steroid hormone is far more than a gestational agent. Progesterone is recognized as a key physiological component of not only the menstrual cycle and pregnancy but also as an essential steroidogenic precursor of other gonadal and non-gonadal hormones such as aldosterone, cortisol, estradiol, and testosterone. Based on current findings, progesterone and novel progesterone-based drugs have many important functions, including contraception, treatment of dysfunctional uterine bleeding, immune response, and prevention of cancer. Considering the above, reproduction and life are not possible without progesterone; thus, a better understanding of this essential molecule could enable safe and effective use of this hormone in many clinical conditions.

Stingless Bee Propolis: New Insights for Anticancer Drugs

Natural products are important sources of biomolecules possessing antitumor activity and can be used as anticancer drug prototypes. The rich biodiversity of tropical and subtropical regions of the world provides considerable bioprospecting potential, including the potential of propolis produced by stingless bee species. Investigations of the potential of these products are extremely important, not only for providing a scientific basis for their use as adjuvants for existing drug therapies but also as a source of new and potent anticancer drugs. In this context, this article organizes the main studies describing the anticancer potential of propolis from different species of stingless bees with an emphasis on the chemical compounds, mechanisms of action, and cell death profiles. These mechanisms include apoptotic events; modulation of BAX, BAD, BCL2-L1 (BCL-2 like 1), and BCL-2; depolarization of the mitochondrial membrane; increased caspase-3 activity; poly (ADP-ribose) polymerase (PARP) cleavage; and cell death induction by necroptosis via receptor interacting protein kinase 1 (RIPK1) activation. Additionally, the correlation between compounds with antioxidant and anti-inflammatory potential is demonstrated that help in the prevention of cancer development. In summary, we highlight the important antitumor potential of propolis from stingless bees, but further preclinical and clinical trials are needed to explore the selectivity, efficacy, and safety of propolis.

Mediterranean Diet Food Components as Possible Adjuvant Therapies to Counteract Breast and Prostate Cancer Progression to Bone Metastasis

Bone metastasis is a serious and often lethal complication of particularly frequent carcinomas, such as breast and prostate cancers, which not only reduces survival but also worsens the patients’ quality of life. Therefore, it is important to find new and/or additional therapeutic possibilities that can counteract the colonization of bone tissue. High adherence to the Mediterranean diet (MD) is effective in the prevention of cancer and improves cancer patients’ health, thus, here, we considered its impact on bone metastasis. We highlighted some molecular events relevant for the development of a metastatic phenotype in cancer cells and the alterations of physiological bone remodeling, which occur during skeleton colonization. We then considered those natural compounds present in MD foods with a recognized role to inhibit or reverse the metastatic process both in in vivo and in vitro systems, and we reported the identified mechanisms of action. The knowledge of this bioactivity by the dietary components of the MD, together with its wide access to all people, could help not only to maintain healthy status but also to improve the quality of life of patients with bone metastases.

The role of viruses and bacteria in the development of cancer

Recently, there have been some scientific studies proving the role of viruses and bacteria in the development of cancer. Among them are eighteen types of pathogens (Helicobacter pylori, hepatitis B virus (HBV), hepatitis C virus (HCV), Opisthorchis viverrini, Clonorchis sinensis, Schistosoma haematobium, human papillomavirus (HPV), Barr (EBV) virus, Ephthia virus-human cell 1 (HTLV-1), human herpes virus type 8 (HHV-8) and human immunodeficiency virus type 1 (HIV-1), belong to group 1 carcinogens. Further study of the role of viruses and bacteria in the development of cancer is of great importance for the early prevention of cancer. Key words: cancer, viruses, bacteria