Cathepsin K inhibitor causes changes in crystallinity and crystal structure of newly-formed mandibular bone in rats

Publication date: Available online 18 August 2018

Source: British Journal of Oral and Maxillofacial Surgery

Author(s): Y. Yoshioka, E. Yamachika, M. Nakanishi, T. Ninomiya, K. Nakatsuji, Y. Kobayashi, T. Fujii, S. Iida

Abstract

Cathepsin K inhibitors are new drugs with the potential for the treatment of osteoporosis because they sustain bony remodelling better than bone resorption inhibitors such as bisphosphonates. The treatment of osteoporosis with inhibitors of bony resorption is associated with osteonecrosis of the jaw, as the deterioration in bony quality that they induce is thought to be one of its causes. The quality of bone is delineated by structural and material characteristics (which include the degree and quality of mineralisation, and depends on the content of proteoglycan and the structural integrity of the bony collagen).^1,2 Animal and clinical studies have shown that cathepsin K inhibitors improve the mineral density and structural characteristics of bone, but their effect on the rest remains unknown. We therefore hypothesised that these inhibitors will affect the material characteristics of newly-formed mandibular bone. To verify our hypothesis, we used Raman microspectroscopy to examine such bone in rats that were given a cathepsin K inhibitor, and found unusual crystallinity and an increased substitution of carbonate (CO₃²⁻) in its crystal structure.

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Monitoring of patients with metastatic melanoma treated with immune checkpoint inhibitors using PET–CT

Abstract

Immune checkpoint inhibitors (ICI) have revolutionized therapy of metastatic melanoma. The first ICI was ipilimumab, a cytotoxic T lymphocyte-associated Ag 4 (CLTA-4) inhibitor with response rates of approximately 11% and disease control of 22%. The programmed cell death 1 (PD-1) inhibitors, such as pembrolizumab and nivolumab, led to longer progression-free survival and overall survival rates with fewer side effects. Molecular imaging techniques, such as positron emission tomography–computed tomography (PET–CT) with 2-deoxy-2-(¹⁸F)fluoro-d-glucose (¹⁸F-FDG) are in use for staging and therapy monitoring of metastatic melanoma. However, classical radiological imaging criteria such as RECIST and WHO are not appropriate for the assessment of ICI response. New immune-related criteria have been defined such as iRECIST or irRC, which refer to radiological imaging modalities. Until now only a few studies report on immunotherapy response assessment based on ¹⁸F-FDG PET–CT. The classical criteria used for therapy monitoring with ¹⁸F-FDG PET, such as the EORTC criteria, are not suitable for ICI monitoring. In this focussed review, we present different criteria proposed for ICI monitoring with ¹⁸F-FDG and their limitations. One goal is to early identify non-responders to tailor immunotherapy. Another question is pseudoprogression and how to interpret the ¹⁸F-FDG images for response assessment. Finally, the definition of ¹⁸F-FDG criteria which can be used to identify progress is crucial and discussed in the review. The recent presented PET-based immune-related criteria, the so-called PERCIMT (PET Response Evaluation Criteria for IMmunoTherapy) are presented. Furthermore, new tracers are discussed.

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Top Reviewers

Publication date: September–October 2018

Source: American Journal of Otolaryngology, Volume 39, Issue 5

Author(s):

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Effectiveness of voriconazole and corneal cross-linking on Phialophora verrucosa keratitis: a case report

We report a rare case of Phialophora verrucosa fungal keratitis, which required various types of treatment according to the intractable natural history of the disease.

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Synchronous double primary hepatic cancer consisting of hepatocellular carcinoma and cholangiolocellular carcinoma: a case report

The incidence of synchronous double primary hepatic cancers is extremely low. Cholangiolocellular carcinoma is also a rare disease.

https://ift.tt/2nQ3eIU

Tuberculous sacroiliitis with secondary psoas abscess in an older patient: a case report

Tuberculosis is the leading infectious cause of death worldwide. Among native Swiss people, tuberculosis is more common in older people than in younger people. Approximately 25–30% of reported cases of tubercu...

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Recurrent hypoglycemia secondary to metformin toxicity in the absence of co-ingestions: a case report

Metformin toxicity is well known to cause lactic acidosis. Multiple cases of hypoglycemia due to isolated metformin overdose have been reported. Increased glucose consumption secondary to anaerobic metabolism ...

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