Efficacy and safety of sorafenib in adult metastatic osteosarcoma patients.

BACKGROUND: There are limited data on the efficacy of targeted therapy in metastatic osteosarcoma. The goal of this study was to assess the effectiveness of sorafenib in adult patients with heavily pretreated metastatic osteosarcoma. METHOD: Patients with metastatic osteosarcoma aged more than 18 years were assessed retrospectively. The patients' clinical, pathological, and therapeutic data were collected. For survival analysis, Kaplan-Meier models were used. RESULTS: The research involved 15 patients. The ratio of male and female patients was 2/1, with a median age of 25 years (range: 19-64 years). The most common primary tumor localization was the extremities (66.6%). Fourteen (93.3%) patients had previously received palliative chemotherapy and six (40%) patients had palliative radiotherapy. The median progression-free survival was found as 5.5 months (95% confidence interval, 1.3-9.7). A stable response was observed in seven (46.6%) patients and progressive disease in eight (53.4%) patients. Grade 1-2 toxicities were detected in 50% of the patients, while grade 3-4 toxicities were observed in 14.3% of the patients. CONCLUSIONS: We demonstrated real-life results of sorafenib for disease management in pretreated adult patients with metastatic osteosarcoma in the study. Sorafenib was effective for disease control and well tolerated in the patients. Sorafenib may be a treatment option for disease control after the disease progresses with chemotherapy in patients with metastatic osteosarcoma.

The tumor-stroma ratio in giant cell tumor of bone: associations with the immune microenvironment and responsiveness to denosumab treatment.

BACKGROUND: Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness. METHODS: We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness. RESULTS: Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients' LRFS and OS. CONCLUSION: The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.

LncRNAs as potential prognosis/diagnosis markers and factors driving drug resistance of osteosarcoma, a review.

Osteosarcoma is a common malignancy that often occurs in children, teenagers and young adults. Although the treatment strategy has improved, the results are still poor for most patients with metastatic or recurrent osteosarcomas. Therefore, it is necessary to identify new and effective prognostic biomarkers and therapeutic targets for diseases. Human genomes contain lncRNAs, transcripts with limited or insufficient capacity to encode proteins. They have been implicated in tumorigenesis, particularly regarding the onset, advancement, resistance to treatment, recurrence and remote dissemination of malignancies. Aberrant lncRNA expression in osteosarcomas has been reported by numerous researchers; lncRNAs have the potential to exhibit either oncogenic or tumor-suppressing behaviors and thus, to govern the advancement of this skeletal cancer. They are suspected to influence osteosarcoma cell growth, replication, invasion, migration, remote dissemination and programmed cell death. Additionally, they have been recognized as clinical markers, and may participate in the development of multidrug resistance. Therefore, the study of lncRNAs in the growth, metastasis, treatment and prognosis of osteosarcoma is very important for the active prevention and treatment of osteosarcoma. Consequently, this work reviews the functions of lncRNAs.

Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma.

Background: Osteosarcoma is the most common malignant primary bone tumor. The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy. Moreover, current treatment regimens bear a significant risk of serious side effects. Thus, there is an unmet clinical need for effective therapies with improved safety profiles. Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines. Methods: In this study, we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma. K7M2 murine osteosarcoma cells were injected, both intramuscular and intraperitoneal, into 60 BALB/c mice on day zero. Animals were then randomized to receive treatment with taurolidine 2% (800 mg/kg), taurolidine 1% (400 mg/kg), or NaCl 0.9% control for seven days by intravenous or intraperitoneal administration. Results: After 35 days, mice were euthanized, and the tumors were harvested for analysis. Eighteen mice were excluded from the analysis due to complications. Body weight was significantly lower in the 2% taurolidine intraperitoneal treatment group from day 9 to 21, consistent with elevated mortality in this group. Intraperitoneal tumor weight was significantly lower in the 1% (p = 0.003) and 2% (p = 0.006) intraperitoneal taurolidine treatment groups compared to the control. No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine. There were no significant differences in microvessel density or mitotic rate between treatment groups. Reduced body weight and elevated mortality in the 2% taurolidine intraperitoneal group suggest that the lower 1% dose is preferable. Conclusions: In conclusion, there is no evidence of antiangiogenic activity, and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited. Moreover, its toxic profile grants further evaluation. Given these observations, further research is necessary to refine the use of taurolidine in osteosarcoma treatment.

Effectiveness of immune checkpoint inhibitor therapy on bone metastases in non-small-cell lung cancer.

Background: Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival. Materials and methods: A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020. The primary endpoint was the real-world organ specific progression free survival (osPFS) of bone versus visceral metastases. Visceral metastases were categorized as adrenal, brain, liver, lung, lymph node, or other intra-abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs. Results: A total of 573 patients were included of which all patients had visceral metastases and 243 patients (42.4%) had BoMs. High PD-L1 expression was identified in 268 patients (46.8%). No significant difference in osPFS was observed between bone, liver, and intra-abdominal metastases (p=0.20 and p=0.76, respectively), with all showing shorter osPFS than other disease sites. There was no difference in the osPFS of extra-thoracic sites of disease in patients with high PD-L1 expression. There was significant discordance between visceral disease response and bone disease response to ICI (p=0.047). The presence of BoMs was an independent poor prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01). Conclusion: Metastatic bone, liver, and intra-abdominal lesions demonstrated inferior clinical responses to ICI relative to other sites of disease. Additionally, the presence of bone and liver metastases were independent poor prognostic factors for overall survival. This real-world data suggests that BoMs respond poorly to ICI and may require treatment adjuncts for disease control.

Combined Application of Cold Physical Plasma and Chemotherapeutics against Chondrosarcoma Cells.

Chondrosarcoma (CS) is a rare malignant bone sarcoma that primarily affects cartilage cells in the femur and pelvis. While most subtypes exhibit slow growth with a very good prognosis, some aggressive subtypes have a poorer overall survival. CS is known for its resistance to chemotherapy and radiotherapy, leaving surgery as the sole effective therapeutic option. Cold physical plasma (CPP) has been explored in vitro as a potential therapy, demonstrating positive anti-tumor effects on CS cells. This study investigated the synergistic effects of combining CPP with cytostatics on CS cells. The chemotherapeutic agents cisplatin, doxorubicin, and vincristine were applied to two CS cell lines (CAL-78 and SW1353). After determining their IC20 and IC50, they were combined with CPP in both cell lines to assess their impact on the cell proliferation, viability, metabolism, and apoptosis. This combined approach significantly reduced the cell proliferation and viability while increasing the apoptosis signals compared to cytostatic therapy alone. The combination of CPP and chemotherapeutic drugs shows promise in targeting chemoresistant CS cells, potentially improving the prognosis for patients in clinical settings.

Analgesic treatment for refractory cancer pain caused by gastric cancer bone metastasis: A case report and literature review.

RATIONALE: Patients with bone metastasis-associated cancer pain often experience a complex mix of pain types. Consequently, the use of multimodal combination therapy is essential. While monitoring for common adverse reactions in pain treatment, it is also crucial to be vigilant for the rare but serious serotonin syndrome. PATIENT CONCERNS: A 53-year-old female with metastatic gastric cancer was hospitalized due to severe, uncontrolled thoracic and cervical pain. During the titration of her cancer pain medication, she developed serotonin syndrome. DIAGNOSES: He was diagnosed with refractory cancer pain and serotonin syndrome. INTERVENTIONS: The complete process of cancer pain medication in a patient with gastric cancer and bone metastasis was analyzed, with a primary focus on the selection of analgesic medications, adjustment of opioid dosages, and prevention and treatment of medication-associated adverse reactions. OUTCOMES: The patient's cancer pain was well controlled, with the prompt management of adverse reactions. Furthermore, by adjusting the medication regimen, intolerable adverse reactions were prevented. LESSONS: In clinical settings, personalized analgesic regimens must be developed for patients with cancer pain to enhance patient compliance with medication, prevent the occurrence of severe adverse reactions, and improve the overall quality of life of patients with cancer. Healthcare professionals should pay increased attention to ADRs associated with opioid medications, whereas pharmacists should assist them in promptly identifying ADRs.

External Validation and Update of the Risk Prediction Model for Denosumab-Induced Hypocalcemia Developed From a Hospital-Based Administrative Database.

PURPOSE: Denosumab is used to treat patients with bone metastasis from solid tumors, but sometimes causes severe hypocalcemia, so careful clinical management is important. This study aims to externally validate our previously developed risk prediction model for denosumab-induced hypocalcemia by using data from two facilities with different characteristics in Japan and to develop an updated model with improved performance and generalizability. METHODS: In the external validation, retrospective data of Kameda General Hospital (KGH) and Miyagi Cancer Center (MCC) between June 2013 and June 2022 were used and receiver operating characteristic (ROC)-AUC was mainly evaluated. A scoring-based updated model was developed using the same data set from a hospital-based administrative database as previously employed. Selection of variables related to prediction of hypocalcemia was based on the results of external validation. RESULTS: For the external validation, data from 235 KGH patients and 224 MCC patients were collected. ROC-AUC values in the original model were 0.879 and 0.774, respectively. The updated model consisting of clinical laboratory tests (calcium, albumin, and alkaline phosphatase) afforded similar ROC-AUC values in the two facilities (KGH, 0.837; MCC, 0.856). CONCLUSION: We developed an updated risk prediction model for denosumab-induced hypocalcemia with small interfacility differences. Our results indicate the importance of using data from plural facilities with different characteristics in the external validation of generalized prediction models and may be generally relevant to the clinical application of risk prediction models. Our findings are expected to contribute to improved management of bone metastasis treatment.

Bone Pain and Survival Among Patients With Metastatic, Hormone-Sensitive Prostate Cancer: A Secondary Analysis of the SWOG-1216 Trial.

Importance: The presence of bone pain is significantly associated with worse overall survival (OS) in patients with castration-resistant prostate cancer. However, there are few data regarding bone pain and survival outcomes in the context of metastatic, hormone-sensitive prostate cancer (MHSPC). Objective: To compare survival outcomes among patients with MHSPC by presence or absence of baseline bone pain at diagnosis. Design, Setting, and Participants: This post hoc secondary analysis, conducted from September 1 to December 31, 2023, used patient-level data from SWOG-1216, a phase 3, prospective randomized clinical trial that enrolled patients with newly diagnosed MHSPC from 248 academic and community centers across the US from March 1, 2013, to July 15, 2017. All patients in the intention-to-treat population who had available bone pain status were eligible and included in this secondary analysis. Interventions: In the SWOG-1216 trial, patients were randomized (1:1) to receive either androgen deprivation therapy (ADT) with orteronel, 300 mg orally twice daily (experimental group), or ADT with bicalutamide, 50 mg orally daily (control group), until disease progression, unacceptable toxic effects, or patient withdrawal. Main Outcomes and Measures: Overall survival was the primary end point; progression-free survival (PFS) and prostate-specific antigen (PSA) response were secondary end points. Cox proportional hazards regression models were used for both univariable and multivariable analyses adjusting for age, treatment type, Gleason score, disease volume, Zubrod performance status, and PSA level. Results: Of the 1279 male study participants, 301 (23.5%) had baseline bone pain at MHSPC diagnosis and 896 (70.1%) did not. Bone pain status was unavailable in 82 patients (6.4%). The median age of the 1197 patients eligible and included in this secondary analysis was 67.6 years (IQR, 61.8-73.6 years). Compared with patients who did not experience bone pain, those with baseline bone pain were younger (median age, 66.0 [IQR, 60.1-73.4] years vs 68.2 [IQR, 62.4-73.7] years; P = .02) and had a higher incidence of high-volume disease (212 [70.4%] vs 373 [41.6%]; P < .001). After adjustment, bone pain was associated with shorter PFS and OS. At a median follow-up of 4.0 years (IQR, 2.5-5.4 years), patients with bone pain had median PFS of 1.3 years (95% CI, 1.1-1.7 years) vs 3.7 years (95% CI, 3.3-4.2 years) in patients without initial bone pain (adjusted hazard ratio [AHR], 1.46; 95% CI, 1.22-1.74; P < .001) and OS of 3.9 years (95% CI, 3.3-4.8 years) vs not reached (NR) (95% CI, 6.6 years to NR) in patients without initial bone pain (AHR, 1.66; 95% CI, 1.34-2.05; P < .001). Conclusions and Relevance: In this post hoc secondary analysis of the SWOG-1216 randomized clinical trial, patients with baseline bone pain at MHSPC diagnosis had worse survival outcomes than those without bone pain. These data suggest prioritizing these patients for enrollment in clinical trials, may aid patient counseling, and indicate that the inclusion of bone pain in prognostic models of MHSPC may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01809691.

Safety and efficacy of fruquintinib-based therapy in patients with advanced or metastatic sarcoma.

BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of fruquintinib-based therapy as a salvage therapy for patients with advanced or metastatic sarcoma, including soft tissue sarcoma (STS) and bone sarcoma. METHODS: Patients with advanced or metastatic sarcoma were divided into two groups. One group received fruquintinib monotherapy, while the other received fruquintinib combined therapy. Safety and efficacy of fruquintinib-based therapy were recorded and reviewed retrospectively, including progression-free survival (PFS), overall response rate (ORR), and adverse events (AEs). RESULTS: Between August 2021 and December 2022, 38 sarcoma patients were retrospectively included. A total of 14 patients received fruquintinib alone (including 6 STS and 8 bone sarcoma), while 24 were treated with fruquintinib combined therapy (including 2 STS and 22 bone sarcoma). The median follow-up was 10.2 months (95% CI, 6.4-11.5). For the entire population, the median PFS was 8.0 months (95% CI, 5.5-13.0). The ORR was 13.1%, while the disease control rate (DCR) was 86.8%. The univariate analysis showed that radiotherapy history (HR, 4.56; 95% CI, 1.70-12.24; p = 0.003), bone sarcoma (HR, 0.34; 95% CI, 0.14-0.87; p = 0.024), and treatment method of fruquintinib (HR, 0.36; 95% CI, 0.15-0.85; p = 0.021) were significantly associated with PFS. The multivariate analysis showed that patients without radiotherapy history were associated with a better PFS (HR, 3.71; 95% CI: 1.31-10.55; p = 0.014) than patients with radiotherapy history. Patients in combination group reported pneumothorax (8.3%), leukopenia (33.3%), thrombocytopenia (12.5%), diarrhea (4.2%), and anemia (4.2%) as the most frequent grade 3 or higher treatment-emergent AEs (TEAEs), while there was no severe TEAEs occurred in the monotherapy group. CONCLUSIONS: Fruquintinib-based therapy displayed an optimal tumor control and an acceptable safety profile in patients with advanced or metastatic sarcoma.

In Vitro Assessment of 4-Acetyl-Antroquinonol B and Erinacine A in Suppressing Breast Cancer-Induced Osteoclastogenesis.

Bone metastasis in metastatic breast cancer commonly results in osteolytic lesions due to osteoclast activity, promoting bone destruction and tumor progression. The bioactive fungal isolates, 4-acetyl-antroquinonol B (4-AAQB) and erinacine A, have diverse pharmacological and biological activities. However, their effects on breast cancer bone metastasis treatment remain unclear. Our study aimed to examine the impact of 4-AAQB or erinacine A on breast cancer metastases in bone. The effects of 4-AAQB and erinacine A on breast cancer-induced osteoclastogenesis, breast cancer migration, production of prometastatic cytokine (TGF-ß) and marker (MMP-9), as well as potential MAPK signaling transductions were assessed. The results revealed that 4-AAQB and erinacine A effectively suppressed breast cancer-induced osteoclastogenesis and migration, and reduced TGF-ß and MMP-9 production via Erk or JNK signaling transductions, specifically in breast cancer cells or in breast cancer cells-induced osteoclasts. Based on these findings, either 4-AAQB or erinacine A showed promise in preventing breast cancer metastases in bone.

Identification of a pro-protein synthesis osteosarcoma subtype for predicting prognosis and treatment.

Osteosarcoma (OS) is a heterogeneous malignant spindle cell tumor that is aggressive and has a poor prognosis. Although combining surgery and chemotherapy has significantly improved patient outcomes, the prognosis for OS patients with metastatic or recurrent OS has remained unsatisfactory. Therefore, it is imperative to gain a fresh perspective on OS development mechanisms and treatment strategies. After studying single-cell RNA sequencing (scRNA-seq) data in public databases, we identified seven OS subclonal types based on intra-tumor heterogeneity. Subsequently, we constructed a prognostic model based on pro-protein synthesis osteosarcoma (PPS-OS)-associated genes. Correlation analysis showed that the prognostic model performs extremely well in predicting OS patient prognosis. We also demonstrated that the independent risk factors for the prognosis of OS patients were tumor primary site, metastatic status, and risk score. Based on these factors, nomograms were constructed for predicting the 3- and 5-year survival rates. Afterward, the investigation of the tumor immune microenvironment (TIME) revealed the vital roles of γδ T-cell and B-cell activation. Drug sensitivity analysis and immune checkpoint analysis identified drugs that have potential application value in OS. Finally, the jumping translocation breakpoint (JTB) gene was selected for experimental validation. JTB silencing suppressed the proliferation, migration, and invasion of OS cells. Therefore, our research suggests that PPS-OS-related genes facilitate the malignant progression of OS and may be employed as prognostic indicators and therapeutic targets in OS.

MgSiO3 Fiber Membrane Scaffold with Triggered Drug Delivery for Osteosarcoma Synergetic Therapy and Bone Regeneration.

In this research, a novel MgSiO3 fiber membrane (MSFM) loaded with indocyanine green (ICG) and doxorubicin (DOX) was prepared. Because of MgSiO3's unique lamellar structure composed of a silicon-oxygen tetrahedron, magnesium ion (Mg2+) moves easily and can be further replaced with other cations. Therefore, because of the positively charged functional group of ICG, MSFM has a rather high drug loading for ICG. In addition, there is electrostatic attraction between DOX (a cationic drug) and ICG (an anionic drug). Hence, after loading ICG, more DOX can be adsorbed into MSFM because of electrostatic interaction. The ICG endows the MSFM outstanding photothermal therapy (PTT) performance, and DOX as a chemotherapeutic drug can restrain tumor growth. On the one hand, H+ exchanged with the positively charged DOX based on the MgSiO3 special lamellar structure. On the other hand, the thermal effect could break the electrostatic interaction between ICG and DOX. Based on the above two points, both tumor acidic microenvironment and photothermal effect can trigger DOX release. What's more, in vitro and in vivo antiosteosarcoma therapy evaluations displayed a superior synergetic PTT-chemotherapy anticancer treatment and excellent biocompatibility of DOX&ICG-MSFM. Finally, the MSFM was proven to greatly promote cell proliferation, differentiation, and bone regeneration performance in vitro and in vivo. Therefore, MSFM provides a creative perspective in the design of multifunctional scaffolds and shows promising applications in controlled drug delivery, antitumor performance, and osteogenesis.

Curcumin inhibits the proliferation and migration of osteosarcoma by regulating the expression of super-enhancer-associated genes. / å§œé»„ç´ é€šè¿‡è°ƒæŽ§è¶ çº§å¢žå¼ºå­ç›¸å ³åŸºå› æŠ‘åˆ¶éª¨è‚‰ç˜¤çš„å¢žæ®–å’Œè¿ç§».

OBJECTIVES: Super-enhancer-associated genes may be closely related to the progression of osteosarcoma, curcumin exhibits a certain inhibitory effect on tumors such as osteosarcoma. This study aims to investigate the effects of curcumin on osteosarcoma in vitro and in vivo, and to determine whether curcumin can inhibit the progression of osteosarcoma by suppressing the expression of super-enhancer-associated genes LIM and senescent cell antigen-like-containing domain 1 (LIMS1), secreted protein acidic and rich in cysteine (SPARC), and sterile alpha motif domain containing 4A (SAMD4A). METHODS: Human osteosarcoma cell lines (MG63 cells or U2OS cells) were treated with 5 to 50 µmol/L curcumin for 24, 48, and 72 hours, followed by the methyl thiazolyl tetrazolium (MTT) assay to detect cell viability. Cells were incubated with dimethyl sulfoxide (DMSO) or curcumin (2.5, 5.0 µmol/L) for 7 days, and a colony formation assay was used to measure in vitro cell proliferation. After treatment with DMSO or curcumin (10, 15 µmol/L), a scratch healing assay and a transwell migration assay were performed to evaluate cell migration ability. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) and Western blotting were used to detect mRNA and protein expression levels of LIMS1, SPARC, and SAMD4A in the cells. An osteosarcoma-bearing nude mouse model was established, and curcumin was administered via gavage for 14 days to assess the impact of curcumin on tumor volume and weight in vivo. Real-time RT-PCR was used to measure mRNA expression levels of LIMS1, SPARC, and SAMD4A in the cancer and adjacent tissues from 12 osteosarcoma patients. RESULTS: After treating cells with different concentrations of curcumin for 24, 48, and 72 hours, cell viability were all significantly decreased. Compared with the DMSO group, the colony formation rates in the 2.5 µmol/L and 5.0 µmol/L curcumin groups significantly declined (both P<0.01). The scratch healing assay showed that, compared with the DMSO group, the migration rates of cells in the 10 µmol/L and 15 µmol/L curcumin groups were significantly reduced. The exception was the 10 µmol/L curcumin group at 24 h, where the migration rate of U2OS cells did not show a statistically significant difference (P>0.05), while all other differences were statistically significant (P<0.01 or P<0.001). The transwell migration assay results showed that the number of migrating cells in the 10 µmol/L and 15 µmol/L curcumin groups was significantly lower than that in the DMSO group (both P<0.001). In the in vivo tumor-bearing mouse experiment, the curcumin group showed a reduction in tumor mass (P<0.01) and a significant reduction in tumor volume (P<0.001) compared with the control group. Compared with the DMSO group, the mRNA expression levels of LIMS1, SPARC, and SAMD4A in the 10 µmol/L and 15 µmol/L curcumin groups were significantly down-regulated (all P<0.05). Additionally, the protein expression level of LIMS1 in U2OS cells in the 10 µmol/L curcumin group was significantly lower than that in the DMSO group (P<0.05). Compared with adjacent tissues, the mRNA expression level of SPARC in osteosarcoma tissues was significantly increased (P<0.001), while the mRNA expression levels of LIMS1 and SAMD4A did not show statistically significant differences (both P>0.05). CONCLUSIONS: Curcumin inhibits the proliferation and migration of osteosarcoma both in vitro and in vivo, which may be associated with the inactivation of super-enhancer-associated gene LIMS1.

The Role of the Advanced Practice Provider in Bone Health Management for the Prostate Cancer Population.

Androgen deprivation therapy (ADT) is standard, first-line therapy for many aspects of prostate cancer treatment. Although ADT can be an effective treatment to inhibit androgen-fueled cell growth in prostate cancer, suppressi.

Cumulative incidence and risk factors for medication-related osteonecrosis of the jaw during long-term prostate cancer management.

Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear. We aimed to determine the cumulative incidence and risk factors of MRONJ. One hundred and seventy-nine patients with prostate cancer with bone metastases treated with BMA at our institution since 2008 were included in this study. Twenty-seven patients (15%) had MRONJ during the follow-up period (median, 19 months; interquartile range, 9-43 months). The 2-year, 5-year, and 10-year cumulative MRONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for MRONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93-11.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of MRONJ (HR 0.08, 95% CI 0.01-0.64). Furthermore, six or more bone metastases (HR 3.65, 95% CI 1.13-11.7) and diabetes mellitus (HR 5.07, 95% CI 1.68-15.2) were risk factors for stage 2 or more severe MRONJ. MRONJ should be considered during long-term BMA administration in prostate cancer patients with bone metastases.

Unveiling the therapeutic promise: exploring Lysophosphatidic Acid (LPA) signaling in malignant bone tumors for novel cancer treatments.

Malignant bone tumors, including primary bone cancer and metastatic bone tumors, are a significant clinical challenge due to their high frequency of presentation, poor prognosis and lack of effective treatments and therapies. Bone tumors are often accompanied by skeletal complications such as bone destruction and cancer-induced bone pain. However, the mechanisms involved in bone cancer progression, bone metastasis and skeletal complications remain unclear. Lysophosphatidic acid (LPA), an intercellular lipid signaling molecule that exerts a wide range of biological effects mainly through specifically binding to LPA receptors (LPARs), has been found to be present at high levels in the ascites of bone tumor patients. Numerous studies have suggested that LPA plays a role in primary malignant bone tumors, bone metastasis, and skeletal complications. In this review, we summarize the role of LPA signaling in primary bone cancer, bone metastasis and skeletal complications. Modulating LPA signaling may represent a novel avenue for future therapeutic treatments for bone cancer, potentially improving patient prognosis and quality of life.

In vitroassessment of a gallium-doped glass polyalkenoate cement: chemotherapeutic potential, cytotoxicity and osteogenic effects.

Metastatic bone lesions are often osteolytic, which causes advanced-stage cancer sufferers to experience severe pain and an increased risk of developing a pathological fracture. Gallium (Ga) ion possesses antineoplastic and anti-bone resorption properties, suggesting the potential for its local administration to impede the growth of metastatic bone lesions. This study investigated the chemotherapeutic potential, cytotoxicity, and osteogenic effects of a Ga-doped glass polyalkenoate cement (GPC) (C-TA2) compared to its non-gallium (C-TA0) counterpart. Ion release profiles revealed a biphasic pattern characterized by an initial burst followed by a gradually declining release of ions. C-TA2 continued to release Ga steadily throughout the experimentation period (7 d) and exhibited prolonged zinc (Zn) release compared to C-TA0. Interestingly, the Zn release from both GPCs appeared to cause a chemotherapeutic effect against H1092 lung cancer cellsin vitro, with the prolonged Zn release from C-TA2 extending this effect. Unfortunately, both GPCs enhanced the viability of HCC2218 breast cancer cells, suggesting that the chemotherapeutic effects of Zn could be tied to cellular differences in preferred Zn concentrations. The utilization of SAOS-2 and MC3T3 cell lines as bone cell models yielded conflicting results, with the substantial decline in MC3T3 viability closely associated with silicon (Si) release, indicating cellular variations in Si toxicity. Despite this ambiguity, both GPCs exhibited harmful effects on the osteogenesis of primary rat osteoblasts, raising concerns about excessive burst Zn release. While Ga/Zn-doped GPCs hold promise for treating metastatic bone lesions caused by lung cancers, further optimization is required to mitigate cytotoxicity on healthy bone.

Ferroptosis defense mechanisms: The future and hope for treating osteosarcoma.

Currently, challenges such as chemotherapy resistance, resulting from preoperative and postoperative chemotherapy, postoperative recurrence, and poor bone regeneration quality, are becoming increasingly prominent in osteosarcoma (OS) treatment. There is an urgent need to find more effective ways to address these issues. Ferroptosis is a novel form of iron-dependent programmed cell death, distinct from other forms of cell death. In this paper, we summarize how, through the three major defense systems of ferroptosis, not only can substances from traditional Chinese medicine, antitumor drugs, and nano-drug carriers induce ferroptosis in OS cells, but they can also be combined with immunotherapy, differentiation therapy, and other treatment modalities to significantly enhance chemotherapy sensitivity and inhibit tumor growth. Thus, ferroptosis holds great potential in treating OS, offering more choices and possibilities for future clinical interventions.

Neoadjuvant chemotherapy-induced hemoglobin decline as a prognostic factor in osteosarcoma around the knee joint: a single-center retrospective analysis of 242 patients.

PURPOSE: Anemia is relatively common in cancer patients, and is associated with poor survival in patients with various malignancies. However, how anemia would affect prognosis and response to neoadjuvant chemotherapy (NAC) in osteosarcoma (OS) is still without substantial evidence. METHODS: We retrospectively analysed 242 patients with stage II OS around the knee joint in our institute. Changed hemoglobin (Hb) levels (before and after NAC) were recorded to assess the prognostic value in DFS (disease-free survival) and tumor response to NAC. Univariate and multivariate analyses were conducted to identify prognostic factors related with outcome in OS patients. RESULTS: The mean Hb level significantly decreased after NAC (134.5 ± 15.3 g/L vs. 117.4 ± 16.3 g/L). The percentage of mild (21%), moderate (4.2%) and severe (0%) anemia patients markedly increased after NAC: 41%, 24% and 4.1% respectively. There was higher percentage of ≥ 5% Hb decline in patients with tumor necrosis rate < 90% (141 out of 161), compared with those with tumor necrosis rate ≥ 90% (59 out of 81). Further univariate and survival analysis demonstrated that Hb decline had a significant role in prediction survival in OS patients. Patients with ≥ 5% Hb decline after NAC had an inferior DFS compared with those with < 5% Hb decline. CONCLUSION: In osteosarcoma, patients with greater Hb decrease during neoadjuvant treatment were shown to have worse DFS and a poorer response to NAC than those without. Attempts to correct anemia and their effects on outcomes for osteosarcoma patients should be explored in future studies.