Rizzoli Orthopaedic Institute
Rizzoli Orthopaedic Institute
Chiarini F.,National Research Council Italy |
Chiarini F.,Rizzoli Orthopaedic Institute |
Evangelisti C.,National Research Council Italy |
Evangelisti C.,Rizzoli Orthopaedic Institute |
And 2 more authors.
Trends in Pharmacological Sciences | Year: 2015
Mammalian target of rapamycin (mTOR) is a Ser/Thr kinase that regulates a wide range of functions, including cell growth, proliferation, survival, autophagy, metabolism, and cytoskeletal organization. mTOR activity is dysregulated in several human disorders, including cancer. The crucial role of mTOR in cancer cell biology has stimulated interest in mTOR inhibitors, placing mTOR on the radar of the pharmaceutical industry. Several mTOR inhibitors have already undergone clinical trials for treating tumors, without great success, although mTOR inhibitors are approved for the treatment of some types of cancer, including advanced renal cell carcinoma. However, the role of mTOR inhibitors in cancer treatment continues to evolve as new compounds are continuously being disclosed. Here we review the three classes of mTOR inhibitors currently available for treating cancer patients. Moreover, we highlight efforts to identify markers of resistance and sensitivity to mTOR inhibition that could prove useful in the emerging field of personalized medicine. © 2014 Elsevier Ltd.
Goldring M.B.,New York Medical College |
Marcu K.B.,State University of New York at Stony Brook |
Marcu K.B.,Rizzoli Orthopaedic Institute
Trends in Molecular Medicine | Year: 2012
Osteoarthritis (OA) is a multifactorial disease subject to the effects of many genes and environmental factors. Alterations in the normal pattern of chondrocyte gene control in cartilage facilitate the onset and progression of OA. Stable changes in patterns of gene expression, not associated with alterations in DNA sequences, occur through epigenetic changes, including DNA methylation, histone modifications, and alterations in chromatin structure, as well as by microRNA (miRNA)-mediated mechanisms. Moreover, the ability of the host to repair damaged cartilage is reflected in alterations in gene control circuits, suggestive of an epigenetic and miRNA-dependent tug-of-war between tissue homeostasis and OA disease pathogenesis. Herein, we summarize epigenetic and miRNA-mediated mechanisms impacting on OA progression and in this context offer potential therapeutic strategies for OA treatment. © 2011 Elsevier Ltd.
Fosco M.,Rizzoli Orthopaedic Institute
European review for medical and pharmacological sciences | Year: 2012
Spine surgery frequently needs allogeneic blood transfusions to compensate for great blood loss. Autologous blood donations often are indicated to reduce homologous transfusions. In last decades interbody spinal fusion has gained popularity, being frequently performed in many spine procedures. Nevertheless, there are few studies evaluating the risk factors of additional blood transfusions in the postoperative course of degenerative spine surgery and no one concerning patients who underwent interbody fusion. In 15 consecutive months, in the same Department of Spine Surgery 40 different elective spine surgeries were performed, divided into four groups: laminectomy alone, laminectomy with an instrumented posterolateral fusion, laminectomy with an instrumented posterolateral and interbody fusion, extensive instrumented fusion. All patients surgery-related data were respectively recorded: patient age, gender, diagnosis, preoperative hemoglobin rate, autologous blood availability, number of spinal level decompressed and fused, duration of surgery, type of surgical procedure, duration of hospital stay. These data were statistically analysed to determine whether variables could determine higher risk of blood transfusion. In an univariate analysis of factors influencing the need of blood transfusion, significantly greater risk of blood transfusions was observed in the female, in case of low preoperative Hb rate, longer surgical times, multiple spinal level decompressed or fused and longer duration of hospital stay. Our linear multiple regression modeling showed that patients gender and increased number of levels decompressed and levels surgically fused were significant determinants of need of blood transfusion. The practical value of this work can be particularly appreciated by those who are used to consider blood predonation. According to our findings blood predonation should preferably be proposed to women supposed to undergo spine instrumented fusion or a more than three levels spine decompression.
Kon E.,Rizzoli Orthopaedic Institute
The journal of knee surgery | Year: 2012
Regenerative procedures aim to recreate a hyaline-like tissue, thus restoring a biologically and biomechanically valid articular surface with durable clinical results. Autologous chondrocyte implantation (ACI) has been developed two decades ago, and both the production of a hyaline-like articular surface and a satisfactory clinical outcome have been documented at medium-long follow-up. Bioengineering technology further improved this regenerative treatment approach to include matrix-assisted ACI (MACI) techniques. These procedures have been introduced in the clinical practice one decade ago, showing similar results while at the same time overcoming most of the concerns related to the first-generation ACI. The use of scaffolds to create a cartilage-like tissue in a three-dimensional culture system allows for the optimization of the procedure from both the biological and surgical point of view. However, despite thousands of treated patients and many published studies suggesting good clinical results and durability of these procedures, the properties of healthy, normal articular cartilage are still unmatched by any available substitute. Both indications and results of these substitutes are still controversial. The role of many variables that may influence the final outcome still need to be clarified to further improve the potential benefits of these biological regenerative procedures.
Cavallo C.,Rizzoli Orthopaedic Institute
Journal of biological regulators and homeostatic agents | Year: 2013
Bone marrow is one of the best characterized stem cell microenvironments that contains Mesenchymal Stem Cells (MSCs), a rare population of non-hematopoietic stromal cells. MSCs have been indicated as a new option for regenerative medicine because of their ability to differentiate into various lineages such as bone, cartilage and adipose tissue. However, isolation procedures are crucial for the functional activity of the transplanted cells. The use of concentrated bone marrow cells (BMCs) enables a cell population surrounded by its microenvironment (niche) to be implanted while avoiding all the complications related to the in vitro culture. The cells of the niche are able to regulate stem cell behavior through direct physical contact and secreting paracrine factors. The aim of this study was to characterize BMCs in vitro to evaluate their ability to differentiate toward mature cells and try to understand whether there are differences in the chondrogenic and osteogenic potential of cells from patients of different ages. Mononuclear Cells (MNCs) isolated by Ficoll were used as control. Both cell populations were grown in monolayers and differentiated with specific factors and analyzed by histological and molecular biology assays to evaluate the expression of some specific extracellular matrix molecules. The present investigations revealed the ability of BMCs to act as isolated cells. They are able to form colonies and differentiate toward chondrogenic and osteogenic lineages, the latter pathway appearing to be influenced by donor age. The results obtained by this study support the use of BMCs in clinical practice for the repair of osteochondral damage, which might be particularly useful for the one-step procedure allowing cells to be directly implanted in operating room.
Gasbarrini A.,Rizzoli Orthopaedic Institute
International journal of immunopathology and pharmacology | Year: 2011
Spine infections require a multidisciplinary approach to be treated and solved. A guide line to drive physicians in the deep complexity of such a disease is extremely helpful. SIMP suggests a flow-chart built up on clear concepts such as right and well managed antibiotic therapy, sound stability of the spine, correct and smart use of the standard and functional imaging techniques, such as f18 FDG PET/CT. In 16 months a total of 41 patients have been treated for spondylodiscitis, discitis and vertebral osteomyelitis by our team of physicians and 25 patients have been enrolled in a prospective study whose target is the assessment of the SIMP flow-chart and of every single aspect that characterize it.
Fini M.,Rizzoli Orthopaedic Institute
Frontiers in bioscience (Elite edition) | Year: 2012
The burden of osteoporosis is increasing in all societies. In comparison with other organs or apparatuses fewer studies have focused on incorrect lifestyles and bone. This article reviews clinical and experimental studies on the effects of obesity, alcohol abuse and smoking on bone. Overweight and obesity protect bone, thus reducing the fracture risk and the development of osteoporosis in older adults. However, extreme obesity (body mass index more than 40 kilogram/meter squared) seems to be a risk factor for osteoporosis. Moderate alcohol consumption may have a protective effect, whereas excessive consumption is an important risk factor. Cytokines are the main mediators of the detrimental effects of obesity and alcohol. Smoking contributes to bone loss and fracture probably by interfering with estrogens, calcium and vitamin D. Health information campaigns against these harmful lifestyles should be strengthened by using available scientific information to increase awareness about their consequences on the bone.
Moroni L.,Rizzoli Orthopaedic Institute |
Fornasari P.M.,Rizzoli Orthopaedic Institute
Journal of Cellular Physiology | Year: 2013
The continuous discovery of human mesenchymal stem cells (hMSCs) in different tissues is stirring up a tremendous interest as a cell source for regenerative medicine therapies. Historically, hMSCs have been always considered a sub-population of mononuclear cells present in the bone marrow (BM). Although BM-hMSCs are still nowadays considered as the most promising mesenchymal stem cell population to reach the clinics due to their capacity to differentiate into multiple tissues, hMSCs derived from other adult and fetal tissues have also demonstrated to possess similar differentiation capacities. Furthermore, different reports have highlighted a higher recurrence of hMSCs in some of these tissues as compared to BM. This offer a fascinating panorama for cell banking, since the creation of a stem cell factory could be envisioned where hMSCs are stocked and used for ad hoc clinical applications. In this review, we summarize the main findings and state of the art in hMSCs isolation, characterization, and differentiation from alternative tissue sources and we attempt to compare their potency for musculoskeletal regeneration. © 2012 Wiley Periodicals, Inc.
Rizzoli Orthopaedic Institute | Date: 2012-06-26
Composition including autologous mononuclear cells supported on scaffold chosen from the group including lyophilized scaffold or pre-constituted scaffold in the form of membrane or tissue, with possible addition of platelet gel, as well as use of said composition for the preparation of medicaments for surgical treatments.
News Article | February 27, 2017
SALT LAKE CITY, UT--(Marketwired - Feb 27, 2017) - Amedica Corporation ( : AMDA), an innovative biomaterial company which develops and manufactures silicon nitride as a platform for biomedical applications, announced today that Researchers from the Department of Orthopaedic Surgery of Tokyo Medical University (Shinjuku-ku, Tokyo, Japan) led by Professor Kengo Yamamoto MD PhD recently completed a five million cycle (Mc) comparative hip simulator study examining the wear behavior of an advanced highly cross-linked and vitamin E stabilized polyethylene (E1® Zimmer-Biomet, Warsaw, IN, USA) against two different types of ceramic femoral heads -- MC2®silicon nitride (Amedica Corporation, Salt Lake City, UT, USA) and BIOLOX®delta (CeramTec, Plochingen, Germany). BIOLOX®delta is currently considered the "gold standard" for ceramic femoral head materials. While the polyethylene wear loss induced by both types of ceramic heads was extremely small (< 0.60 mg/Mc), mean wear associated with MC2®silicon nitride heads was approximately 15% lower than the BIOLOX®delta components. This independent wear study was conducted in accordance with international standards at the Medical Technology Laboratory of the Rizzoli Orthopaedic Institute (Bologna, Italy) by Professor Aldo Toni MD under the supervision of Dr. Saverio Affatato PhD (Rizzoli Institute) with consultation and support from Professor Giuseppe Pezzotti PhD (Ceramic Physics Laboratory, Kyoto Institute of Technology, Sakyo-ku, Kyoto Japan). Amedica and Zimmer-Biomet (Tokyo Office) provided the femoral heads and acetabular liners; however, neither company actively sponsored the research. The testing was independently conceived by Professors Yamamoto and Pezzotti, and funded by the Department of Orthopaedic Surgery of Tokyo Medical University. This is the first reported improvement in polyethylene wear performance by a ceramic other than BIOLOX®delta; and it is part of a series of planned comparative wear tests that will culminate at 12 Mc. Further details of this interim hip simulation test will be provided in a joint publication planned for release in a scientific journal. "We are thrilled, though not surprised, at the remarkable wear properties of silicon nitride femoral heads," said Dr. B. Sonny Bal, CEO and President of Amedica Corporation. "Our previous work, already published in peer-review forums, has shown superb phase stability of silicon nitride in vivo, plus oxygen-scavenging properties that may confer long-term protection to polyethylene acetabular liners, along with bacterial resistance inherent in silicon nitride, toughness that is superior to any other biomaterial, and resistance to corrosion. The present wear data reflect the considerable scientific work that went into a thorough understanding of the surface chemistry and composition of our femoral heads, with development of engineering processes and proprietary methods that lead to a consistent, ultra-smooth articulating surface. Taken together, this favorable combination of properties, supported by scientific data, reflect material science advancements that are necessary to differentiate total hip replacements in an otherwise commoditized market, and more importantly, toward extending the longevity of hip replacements beyond the second decade of life, post-implantation. These data will contribute to our continuing work and dialogue with the FDA to get the product approved for use clinically." About Amedica Corporation Amedica is focused on the development and application of medical-grade silicon nitride ceramics. Amedica markets spinal fusion products and is developing a new generation of wear- and corrosion-resistant implant components for hip and knee arthroplasty. The Company manufactures its products in its ISO 13485 certified manufacturing facility and, through its partnership with Kyocera, the world's largest ceramic manufacturer. Amedica's spine products are FDA-cleared, CE-marked, and are currently marketed in the U.S. and select markets in Europe and South America through its distributor network and its OEM partnerships. For more information on Amedica or its silicon nitride material platform, please visit www.amedica.com. Forward-Looking Statements This press release contains statements that constitute forward-looking statements within the meaning of the Securities Act of 1933 and the Securities Exchange Act of 1934, as amended by the Private Securities Litigation Reform Act of 1995. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties. For example, there can be no assurance that we will be able to maintain our listing on any NASDAQ market. Other factors that could cause actual results to differ materially from those contemplated within this press release can also be found in Amedica's Risk Factors disclosure in its Annual Report on Form 10-K, filed with the Securities and Exchange Commission (SEC) on March 23, 2016, and in Amedica's other filings with the SEC. Forward-looking statements contained in this press release speak only as of the date of this press release. We undertake no obligation to update any forward-looking statements as a result of new information, events or circumstances or other factors arising or coming to our attention after the date hereof.