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Background and Objectives : Changes in activities of daily living (ADL) and quality of life (QOL) of patients with bone metastasis who underwent surgical treatment through Bone Metastasis Cancer Boards (BMCBs), a recent multidisciplinary approach for managing bone metastases, have been reported; however, no reports exist on patients who undergo conservative treatment. In this study, we aimed to evaluate these patients' ADL and QOL and examine the factors influencing changes in these parameters. Materials and Methods : We retrospectively reviewed 200 patients with bone metastases who underwent conservative therapy through BMCBs between 2013 and 2021. A reassessment was conducted within 2-8 weeks after the initial assessment. Patients' background and changes in performance status (PS), Barthel Index (BI), EuroQol five-dimension (EQ-5D) scores, and Numerical Rating Scale (NRS) scores were initially assessed. Furthermore, we categorized patients into two groups based on improvements or deteriorations in ADL and QOL and performed comparative analyses. Results : Significant improvements in EQ-5D (0.57 ± 0.02 versus [vs.] 0.64 ± 0.02), NRS max (5.21 ± 0.24 vs. 3.56 ± 0.21), and NRS average (2.98 ± 0.18 vs. 1.85 ± 0.13) scores were observed between the initial assessment and reassessment (all p < 0.001). PS (1.84 ± 0.08 vs. 1.72 ± 0.08) and BI (83.15 ± 1.68 vs. 84.42 ± 1.73) also showed improvements ( p = 0.06, and 0.054, respectively). In addition, spinal cord paralysis (odds ratio [OR]: 3.69, p = 0.049; OR: 8.42, p < 0.001), chemotherapy (OR: 0.43, p = 0.02; OR: 0.25, p = 0.007), and NRS average scores (OR: 0.38, p = 0.02; OR: 0.14, p < 0.001) were independent factors associated with ADL and QOL. Conclusions : Patients with bone metastases who underwent conservative treatment through BMCBs exhibited an increase in QOL without a decline in ADL. The presence of spinal cord paralysis, absence of chemotherapy, and poor pain control were associated with a higher risk of deterioration in ADL and QOL.

Introduction: The introduction of tyrosine kinase inhibitors has revolutionized treatment strategies for metastatic renal cell carcinoma (RCC) and has improved survival rates. The number of patients with bone metastases from RCC requiring surgery will increase as survival rates improve. However, there is insufficient evidence to standardize the treatment of bone metastases after the introduction of targeted therapy for metastatic RCC. We aimed to determine the outcomes of palliative surgical treatment of bone metastases in the extremities of patients with metastatic RCC., Materials and Methods: We retrospectively reviewed 26 lesions from 17 patients who underwent surgery for extremity and acetabular bone metastases and were treated with targeted therapies for advanced RCC between 2008 and 2020. The median follow-up duration was 19 months (range, 4-76). We assessed the patients' activities of daily living, quality of life, and pain and analyzed their postoperative values relative to preoperative values. Postoperative overall survival (OS), local progression-free survival (LPFS), and the factors affecting them were evaluated using the Kaplan-Meier method and log-rank test., Results: The 5-year OS and LPFS rates were 39.5% and 65.6%, respectively. The factors affecting OS were sex, Katagiri score, visceral metastases, and preoperative targeted therapy, while the factors affecting LPFS were pathologic fractures and surgical technique., Conclusion: In this study, the postoperative outcomes of palliative surgery for bone metastases from metastatic RCC were good. We suggest that systemic treatment should be prioritized over local control for advanced bone metastasis in RCC and surgery before pathological fracture should be performed for local control., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Ewing sarcoma (ES) is an aggressive primary malignant bone tumor that predominantly affects children and young adults. Multimodal treatment approaches have markedly improved the survival of patients with localized ES. However, local recurrence and distant metastasis following curative therapies remain a main concern for patients with ES. Recent studies have suggested that slow‑cycling cells (SCCs) are associated with tumor progression, local recurrence and distant metastasis in various types of cancers. According to the results of these studies, it was hypothesized that SCCs may play a critical role in tumor progression, chemoresistance and local/distal recurrence in patients with ES. The present study applied a label‑retaining system using carboxyfluorescein diacetate succinimidyl ester (CFSE) to identify and isolate SCCs in ES cell lines. In addition, the properties of SCCs, including sphere formation ability, cell cycle distribution and chemoresistance, in comparison with non‑SCCs were investigated. RNA sequencing also revealed several upregulated genes in SCCs as compared with non‑SCCs; the identified genes not only inhibited cell cycle progression, but also promoted the malignant properties of SCCs. On the whole, the present study successfully identified SCCs in ES cells through a label‑retaining system using CFSE. Moreover, to the best of our knowledge, the present study is the first to describe the characteristic properties of SCCs in ES. The findings of this study, if confirmed, may prove to be useful in elucidating the underlying molecular mechanisms and identifying effective therapeutic targets for ES.

Osteolytic bone metastasis leads to skeletal‑related events, resulting in a decline in the patient activities and survival; therefore, it is important to understand the mechanism underlying bone metastasis. Recent studies have suggested that microRNAs (miRNAs or miRs) are involved in osteoclast differentiation and/or osteolytic bone metastasis; however, the roles of miRNAs have not been elucidated. In the present study, the roles of miRNAs in bone destruction caused by breast cancer metastasis were investigated in vitro and in vivo . miR‑16, miR‑133a and miR‑223 were transfected into a human breast cancer cell line, MDA‑MB‑231. The expression of osteolytic factors in conditioned medium (miR‑CM) collected from the culture of transfected cells was assessed. To evaluate the effects of miRNAs on osteoclast differentiation and activities, tartrate‑resistant acid phosphatase (TRAP) staining and bone resorptive assays were performed in osteoclasts following miR‑CM treatment. To create in vivo bone metastasis models for histological and morphometric evaluation, miRNA‑transfected MDA‑MB‑231 cells were transplanted into the proximal tibia of nude mice. Expression of osteolytic factors, including receptor activator for nuclear factor‑κB ligand (RANKL), interleukin (IL)‑1β, IL‑6, parathyroid hormone‑related protein (PTHrP), and tumor necrosis factor (TNF), was increased in miR‑16‑CM, whereas it was decreased in both miR‑133a‑CM and miR‑223‑CM. TRAP staining and bone resorptive assays revealed that osteoclast function and activities were promoted by miR‑16‑CM treatment, whereas they were suppressed by miR‑133a‑CM and miR‑223‑CM. Consistent with in vitro findings, in vivo experiments revealed that the overexpression of miR‑16 increased osteoclast activities and bone destruction in MDA‑MB‑231 cells, whereas the opposite results were observed in both miR‑133a‑ and miR‑223‑transfected MDA‑MB‑231 cells. Our results indicated that miR‑16 promoted osteoclast activities and bone destruction caused by breast cancer metastasis in the bone microenvironment, whereas miR‑133a and miR‑223 suppressed them. These miRNAs could be potential biomarkers and therapeutic targets for breast cancer bone metastasis.

Background: Few studies have addressed the impact of palliative surgery for cervical spine metastasis on patients' performance status (PS) and quality of life (QOL). We investigated the surgical outcomes of patients with cervical spine metastasis and the risk factors for a poor outcome with a focus on the PS and QOL., Methods: We prospectively analyzed patients with cervical spine metastasis who underwent palliative surgery from 2013 to 2018. The Eastern Cooperative Oncology Group PS (ECOGPS) and EuroQol 5-Dimension (EQ5D) score were assessed at study enrollment and 1, 3, and 6 months postoperatively. Neurological function was evaluated with Frankel grading. Univariate and multivariate analyses were performed to identify the risk factors for a poor surgical outcome, defined as no improvement or deterioration after improvement of the ECOGPS or EQ5D score within 3 months., Results: Forty-six patients (mean age, 67.5 ± 11.7 years) were enrolled. Twelve postoperative complications occurred in 11 (23.9%) patients. The median ECOGPS improved from PS3 at study enrolment to PS2 at 1 month and PS1 at 3 and 6 months postoperatively. The mean EQ5D score improved from 0.085 ± 0.487 at study enrolment to 0.658 ± 0.356 at 1 month and 0.753 ± 0.312 at 3 months. A poor outcome was observed in 18 (39.1%) patients. The univariate analysis showed that variables with a P value of < 0.10 were sex (male), the revised Tokuhashi score, the new Katagiri score, the level of the main lesion, and the Frankel grade at baseline. The multivariate analysis identified the level of the main lesion (cervicothoracic junction) as the significant risk factor (odds ratio, 5.00; P = 0.025)., Conclusions: Palliative surgery for cervical spine metastasis improved the PS and QOL, but a cervicothoracic junction lesion could be a risk factor for a poor outcome.

Management of bone metastasis is becoming increasingly important. Thus, local and systemic treatment options have been developed for control. Although systemic administration of anticancer agents is effective for bone metastasis, it is often stopped because of poor general conditions or side effects. Therefore, it is highly desirable to develop a more effective and safer local treatment for bone metastasis. The purpose of the current study was to investigate the antitumor effects and safety of gelatin hydrogel microspheres incorporating cisplatin (GM-CDDP), which we developed as a sustained release system without harmful substances. First, we assessed GM-CDDP for its in vitro degradability and potential for sustained release. Second, in vivo antitumor and side effects were evaluated using a murine bone metastasis model of MDA-MB-231 human breast cancer cells incorporating GFP. In vitro, initial bursts were observed within 2 h and CDDP was released gradually with gelatin hydrogel degradation, which reached 100% at 48 h. In vivo, local administration of GM-CDDP (2 mg/kg) significantly suppressed tumor growth and bone osteolysis compared with the control, and local and systemic administration of free CDDP (2 mg/kg; p < 0.05). Local administration of GM-CDDP significantly reduced loss of body weight and elevation of blood urea nitrogen compared with the systemic administration of free CDDP (p < .05). The current study suggests that local administration of GM-CDDP achieves higher antitumor effects with a potential for lesser side effects compared with local or systemic administration of free CDDP., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background: Cancer stem cells (CSCs) are considered to be responsible for tumor initiation, formation, and poor prognosis of cancer patients. However, the rarity of CSCs in clinical samples makes it difficult to elucidate characteristics of CSCs, especially in osteosarcoma (OS). The aim of this study is to verify whether it is possible to generate CSC-like cells by transducing defined factors into an OS cell line., Methods: We retrovirally transduced the Octamer-binding transcription factor 3/4 (OCT3/4), Kruppel-like factor 4 (KLF4), and SRY-box transcription factor 2 (SOX2) genes into the MG-63 human OS cell line (MG-OKS). Parental and GFP-transduced MG-63 cells were used as negative control. We assessed the properties of the generated cells in vitro and in vivo. Multiple comparisons among groups were made using a one-way analysis of variance (ANOVA) followed by post hoc testing with Tukey's procedure., Results: MG-OKS cells in vitro exhibited the significantly increased mRNA expression levels of CSC markers (CD24, CD26, and CD133), decreased cell growth, increased chemoresistance and cell migration, and enhanced sphere formation. Notably, MG-OKS cells cultured under osteogenic differentiation conditions showed strongly positive staining for both Alizarin Red S and alkaline phosphatase, indicating osteogenesis of the cells. Gene ontology analysis of microarray data revealed significant upregulation of epidermal-related genes. Tumors derived from MG-OKS cells in vivo were significantly larger than those from other cells in μCT analysis, and immunohistochemical staining showed that Ki-67, osteocalcin, and HIF-1α-positive cells were more frequently detected in the MG-OKS-derived tumors., Conclusions: In this study, we successfully generated OS CSC-like cells with significantly enhanced CSC properties following transduction of defined factors.