Hydroxyapatite-binding albumin nanoclusters for enhancing bone tumor chemotherapy

Breast cancer (BC) metastases to bone disrupt the balance between osteoblasts and osteoclasts, leading to excessive bone resorption. We identified a novel subpopulation of osteoblasts with tumor-inhibitory properties, called educated osteoblasts (EOs). Here we sought to examine the effect of EOs on osteoclastogenesis during tumor progression. We hypothesized that EOs affect osteoclast development in the bone-tumor niche, leading to suppressed pre-osteoclast fusion and bone resorption. Conditioned media (CM) was analyzed for protein expression of osteoclast factors receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα) via ELISA. EOs were co-cultured with pre-osteoclasts on a bone mimetic matrix to assess osteoclast resorption. Pre-osteoclasts were tri-cultured with EOs plus metastatic BC cells and assessed for tartrate-resistance acid phosphatase (TRAP)-positive, multinucleated (≥3 nuclei), mature osteoclasts. Tumor-bearing murine tibias were stained for TRAP to determine osteoclast number in-vivo. EO CM expressed reduced amounts of soluble TNFα and OPG compared to naïve osteoblast CM. Osteoclasts formed in the presence of EOs were smaller and less in number. Upon co-culture on a mimetic bone matrix, a 50% reduction in the number of TRAP-positive osteoclasts formed in the presence of EOs was observed. The tibia of mice inoculated with BC cells had less osteoclasts per bone surface in bones with increased numbers of EO cells. These data suggest EOs reduce osteoclastogenesis and bone resorption. The data imply EOs provide a protective effect against bone resorption in bone metastatic BC.

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Bifunctional scaffolds of hydroxyapatite/poly(dopamine)/carboxymethyl chitosan with osteogenesis and anti-osteosarcoma effect

Biomaterials Science ◽

10.1039/d0bm01785j ◽

2021 ◽

Author(s):

Mengyu Yao ◽

Qingxia Zou ◽

Wenwu Zou ◽

Zhenze Xie ◽

Zhihao Li ◽

...

Keyword(s):

Bone Tumor ◽

Tumor Therapy ◽

Carboxymethyl Chitosan

Bifunctional scaffolds prepared by hydroxyapatite/poly(dopamine)/carboxymethyl chitosan with good osteogenesis and anti-osteosarcoma effect is promising for bone tumor therapy.

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A Short-Course Antibiotic Prophylaxis Is Associated with Limited Antibiotic Resistance Emergence in Post-Operative Infection of Pelvic Primary Bone Tumor Resection

Antibiotics ◽

10.3390/antibiotics10070768 ◽

2021 ◽

Vol 10 (7) ◽

pp. 768

Author(s):

Yoann Varenne ◽

Stéphane Corvec ◽

Anne-Gaëlle Leroy ◽

David Boutoille ◽

Mỹ-Vân Nguyễn ◽

...

Keyword(s):

Antibiotic Prophylaxis ◽

Bone Tumor ◽

Tumor Resection ◽

Surgical Site Infections ◽

Implant Removal ◽

Pelvic Bone ◽

Resistance Pattern ◽

Cure Rate ◽

Implant Retention ◽

The Impact

Resections of primary pelvic bone tumors are frequently complicated by surgical site infections (SSIs), thereby impairing the functional prognosis of patients, especially in case of implant removal. Although prophylactic antibiotics play an essential role in preventing SSIs, there are presently no recommendations that support their appropriate use. This study aimed to assess the impact of a 24 h prophylactic protocol on the bacterial ecology, the resistance pattern, and the SSI healing rate. We hypothesized that this protocol not only limits the emergence of resistance but also results in a good cure rate with implant retention in case of SSI. A retrospective study was performed that included all patients with an SSI following a pelvic bone tumoral resection between 2005 and 2017 who received a 24 h antibiotic prophylaxis protocol. Twenty-nine patients with an SSI were included. We observed a 75.9% rate of polymicrobial infection, with a high prevalence of digestive flora microorganisms and a majority of wild-type phenotypes. We confirmed that there was no significant emergence of resistant flora. After first-line debridement, antibiotics (DA) if any implant was used, or debridement, antibiotics, and implant retention (DAIR) whenever possible, we obtained a 79.3% cure rate, with implant removal in 20% of cases. The absence of an implant was significantly associated with SSI healing. Early infection management and low resistance profiles may also have a positive effect, but this needs to be confirmed in a larger cohort. In light of this, the use of a 24 h prophylactic protocol in primary pelvic bone tumor resections is associated with a favorable infection cure rate and implant retention in case of SSI, and minimal selection of resistant microorganisms.

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Impact of Surgical Resection and Reasons for Poor Prognosis of Pelvic Osteosarcoma Based on the Bone Tumor Registry in Japan

Cancers ◽

10.3390/cancers13133320 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3320

Author(s):

Satoshi Takenaka ◽

Hironari Tamiya ◽

Toru Wakamatsu ◽

Sho Nakai ◽

Yoshinori Imura ◽

...

Keyword(s):

Surgical Treatment ◽

Propensity Score ◽

Surgical Resection ◽

Bone Tumor ◽

Poor Prognosis ◽

Propensity Score Analysis ◽

The Elderly ◽

Tumor Stage ◽

Tumor Registry ◽

Score Analysis

Pelvic osteosarcoma has a poor prognosis compared to osteosarcomas in other locations, and the reasons for this remain unknown. Surgical resection of pelvic osteosarcoma is technically demanding and often results in dysfunction and complications. In this study, we investigated the reasons underlying the poor prognosis of pelvic osteosarcoma by comparing it to femoral osteosarcoma using data from the Bone Tumor Registry in Japan. We used propensity score analysis to determine whether surgical resection of pelvic osteosarcoma improved its prognosis. We demonstrated that pelvic osteosarcoma had a poor prognosis because it occurred more often in the elderly, often had larger tumor size, and had metastasis at presentation more often in comparison to femoral osteosarcoma. These three factors were also associated with the non-surgical treatment of pelvic osteosarcoma, which also led to a poor outcome. The overall survival rate was only comparable in pelvic osteosarcoma and femoral osteosarcoma in cases treated with surgical resection. Propensity score analysis revealed that surgical treatment improved the prognosis of pelvic osteosarcoma. As such, we propose that surgical resection should be considered based on tumor stage and patient age in order to improve the prognosis of pelvic osteosarcoma.

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