Relapsed primary extraskeletal osteosarcoma of liver:A case report and review of literature

BACKGROUND Extraskeletal osteosarcoma(ESOS)is a highly malignant osteosarcoma that occurs in extraskeletal tissues.It often affects the soft tissues of the limbs.ESOS is classified as primary or secondary.Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient,which is very rare.CASE SUMMARY Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient.The patient had a giant cystic-solid mass in the right hepatic lobe that was evident on ultrasound and computed tomography.Postoperative pathology and immunohistochemistry of the mass,which was surgically removed,suggested fibroblastic osteosarcoma.Hepatic osteosarcoma reoccurred 48 d after surgery,resulting in significant compression and narrowing of the hepatic segment of the inferior vena cava.Consequently,the patient underwent stent implantation in the inferior vena cava and transcatheter arterial chemoembolization.Unfortunately,the patient died of multiple organ failure postoperatively.CONCLUSION ESOS is a rare mesenchymal tumor with a short course and a high likelihood of metastasis and recurrence.The combination of surgical resection and chemotherapy may be the best treatment.

Alterations in Serum Lipids and Lipoproteins Induced by Neoadjuvant Chemotherapy in Patients with Osteosarcoma around the Knee Joint:A Retrospective Analysis

Objective To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy.Methods After retrospectively screening the data of 742 patients between January 2007 and July 2020,50 patients aged 13 to 39 years with Enneking stage II disease were included in the study.Serum lipid levels,including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),lipoprotein-α[Lp(a)],and apolipoprotein A1,B,and E(ApoA1,ApoB,and ApoE),and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy.Results The mean levels of TC,TG,and ApoB were significantly increased following neoadjuvant chemotherapy(16%,38%,and 20%,respectively,vs.pretreatment values;P<0.01).The mean levels of LDL-C and ApoE were also 19%and 16%higher,respectively(P<0.05).No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy.An increase in Lp(a)was strongly correlated with the Ki-67 index(R=0.31,P=0.023).Moreover,a trend toward longer disease-free survival(DFS)was observed in patients with decreased TG and increased LDL-C following chemotherapy,although this difference was not statistically significant(P=0.23 and P=0.24,respectively).Conclusion Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma.There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy.The scale of increase in serum Lp(a)might have a potential prognostic role in osteosarcoma.Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.

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.

Influence of neoadjuvant chemotherapy on proliferation, apoptosis and multi-drug resistance in osteosarcoma cells

Objective: To study the influence of neoadjuvant chemotherapy on the expression of cyclin D1, Bcl-2, PCNA and P- gp in osteosarcoma cells and the relationship between the expression and tumor cell necrosis rate (TCNR) after chemotherapy. Methods: By using immunohistochemistry, the expression of cyclin D1, Bcl-2, PCNA and P-gp was detected in 23 cases of osteosarcoma and TCNR were calculated. Results: The pre-chemotherapy positive expression rate of cyclin D1, Bcl-2, PCNA and P-gp was 73.9%, 69.6%, 91.3% and 21.7%, respectively, and that post-chemotherapy positive expression rate was 52.1%, 34.8%, 43.5% and 56.5%, respectively. The positive expression rate of Bcl-2 and PCNA after chemotherapy was much lower than that before chemotherapy (P=0.039, 0.034). After chemotherapy, the expression rate of P-gp was higher (P=0.021) and the expression of cyclin D1 had no statistically significant difference (P=0.180) comparing with that before chemotherapy. No correla- tion existed between the expression of cyclin D1, Bcl-2, PCNA, P-gp and TCNR before chemotherapy (P=0.155, 0.371, 1.000 and 0.640). There was a negative correlation between the expression of Bcl-2, PCNA, P-gp and TCNR (P=0.009, 0.012 and 0.015), but no relationship existed between the cyclin D1 and TCNR (P=0.100) after chemotherapy. Conclusion: Chemotherapy could inhibit proliferation and induce apoptosis of osteosarcoma cells. At the same time, due to the overexpression of the P-gp, the drug resistance of the osteosarcoma cells was increased. The detection of cyclin D1, Bcl-2, PCNA and P-gp in osteosarcoma samples before chemotherapy might not be used to predict the curative effect of the chemotherapy.

Role of Neo-Adjuvant Chemotherapy in the Treatment of Osteosarcoma

Osteosarcoma is a tumour characterized by the production of osteoid by malignant cells. The incidence is approximately 1 to 3 million/year. The incidence is slightly higher in males. Onset can occur at any age;however, primary high grade osteosarcoma usually occurs in the second decade of life. Historically patients with osteosarcoma were treated with immediate wide or radical amputation. Despite the treatment, 80% patients with apparently isolated disease died of distant metastases. In recent years the number of patients with osteosarcoma of the limb treated by amputation + chemotherapy has increased. In our study, we divided the patients into two groups. One group (A) was treated with amputation + adjuvant chemotherapy. The other group (B) was treated with neo-adjuvant chemotherapy + amputation followed by adjuvant-chemotherapy. In our study, the margin negativity in post surgical specimen was significantly higher (P-value 0.0007) for the group treated with neo-adjuvant chemotherapy. Local recurrence in the group treated without neoadjuvant chemotherapy was significantly more (P-value 0.0005).The systemic recurrence at the end of 6 months was higher the group treated without neoadjuvant chemotherapy (P-value 0.0169).However systemic recurrence between 6 months -1 year and 1 year - 2 years were not significant(P-values 0.1501 and 0.4902). From the above figures it may be concluded that treatment with neo-adjuvant chemotherapy + amputation + adjuvant chemotherapy had definite advantages over upfront amputation + adjuvant chemotherapy.)

Comprehensive Analysis of Key mRNAs and lncRNAs in Osteosarcoma Response to Preoperative Chemotherapy with Prognostic Values

Objective:Osteosarcoma is one of the most common types of bone sarcoma with a poor prognosis.However,identifying the predictive factors that contribute to the response to neoadjuvant chemotherapy remains a significant challenge.Methods:A public data series(GSE87437)was downloaded to identify differentially expressed genes(DEGs)and differentially expressed lncRNAs(DElncRNAs)between osteosarcoma patients that do and do not respond to preoperative chemotherapy.Subsequently,functional analysis of the transcriptome expression profile,regulatory networks of DEGs and DElncRNAs,competing endogenous RNAs(ceRNA)and protein-protein interaction networks were performed.Furthermore,the function,pathway,and survival analysis of hub genes was performed and drug and disease relationship prediction of DElncRNA was carried out.Results:A total of 626 DEGs,26 DElncRNAs,and 18 hub genes were identified.However,only one gene and two lncRNAs were found to be suitable as candidate gene and lncRNAs respectively.Conclusion:The DEGs,hub genes,candidate gene,and candidate lncRNAs screened out in this context were considered as potential biomarkers for the response to neoadjuvant chemotherapy of osteosarcoma.

The “predictive molecule targeted chemotherapy” for relapsed ovarian cancer—a pilot study

Objective: How to choose chemotherapy regimen is a often-encountered and formidable problem in the setting of relapsed ovarian cancer. So far, it was usually according to the clinical trials and doctors’ experience and the response rate was very low. In the present study, we proposed a new treatment strategy–the “predictive molecule targeted chemotherapy, PMTC” to choose supposedly sensitive protocols and void supposedly resistant protocols based on the specific predictive molecule expression of individual tumor tissue. Methods: Retrospectively analysis of 16 cases of relapsed ovarian cancer patients from January 2002 to December 2003, as the experience-directed chemotherapy group (control group), to calculate the response rate. Prospectively recruit 9 cases of relapsed ovarian cancer patients after January 2004, whose chemotherapy drug choice was based on the expression of 6 predictive molecules (p53, et al) by means of immunohistochemistry, as the PMTC group, to calculate the response rate. χ2 test was used for the statistical analysis. Results: The response rate of control group was 26%, including 31% for second line and 14% for third line respectively. The response rate of PMTC group was 78%, in which 5 cases of early relapse all responded. The difference was significant (P=0.011). Conclusions: PMTC is a new effective method to treat the relapsed ovarian cancer.

Perspectives of the Role of Chemotherapy in the Management of Osteosarcoma

Background: Multimodality management of osteosarcoma has significantly improved the 5-year-survival rate for localized disease over the past 40 years: from 5% - 10% (in historical controls) to 65% - 75% and 20% - 30% in metastatic disease. These results were achieved with doxorubicin, cisplatin, high-dose methotrexate and ifosfamide (or cyclophosphamide). In the absence of new and effective agents the results have remained stationary for at least the past 30 years. No standard second line therapy exists for patients who relapse. In these circumstances surgery when feasible, constitutes the main therapeutic option. Questions/Purposes: To understand the present approach to therapy and determine the possibilities for improvement a review of the chemotherapeutic agents currently deployed in the treatment of Osteosarcoma was undertaken. Methods: The review focused on the results achieved with the evolution of therapy following the discovery of effective chemotherapeutic agents. Results: There was an improvement in survival during the first decade following the introduction of effective chemotherapy and limb salvage replaced amputation in the majority of patients. Attempts to rescue pulmonary metastases patients with surgical intervention were also enhanced but produced only minor improvement in survival. An international collaborative study, EURAMOS has been launched to investigate the utility of neoadjuvant chemotherapeutic agents in improving survival based upon their efficacy in the treatment of the primary tumor. Conclusions: New agents and or new strategies are urgently required to improve the outcome in Osteosarcoma.

Neoadjuvant chemotherapy for osteosarcoma of the extremity: Outcome of the Chinese 1st protocol in a single institute

Objective： The aim of this study was to determine stand protocol for patients with extremity osteosarcoma by case following up after neoadjuvant chemotherapy and limb salvage operation. Methods： Between January 2000 and January 2007, 121 patients with extremity osteosarcoma were eligible for this analysis. After being graded according to Enneking classification, all patients were preoperative chemotherapy （methotrexate, cisplatin, doxorubicin, and ifosfamide. Some patients with liB tumors received extra interventional embolism）. And postoperatively, the same protocols were employed, but poor responders （tumor necrosis 〈 95%） received more treatment cycles than good responders and took some new medicine in place of the former one. Most of patients underwent limb salvage operation （99/121）, and the Musculoskeletal Tumor Society Score （MSTS） was used to evaluate the recovery of their limb functions. Results： The followed up last for average 37.3 months （range： 16-101 months）. Most patients （76/121） survived, and the overall survival （OS） was 62.8%. Forty-seven of the 121 patients underwent osteoarticular allografts, among which 12 cases of disunion between the host bone and graft bone, 4 cases of allograft absorption and 3 local recurrences appeared. The mean MSTS score was 22.6 ± 4.13, with an excellent limb function in 17 patients, good in 19 patients, fair in 6 patients and poor in 7 patients. The overall excellent and good function outcome was obtained in 76.6% of the patients. Fifty-two of 121 patients underwent custom-made or modular tumor endoprosthesis replacememt, among which 1 case of aseptic loosening, 1 case of peri-prosthesis infection and 4 local recurrences appeared. The mean MSTS was 24.32 ＋ 3.85, with an excellent limb function in 28 patients, good in 16 patients, fair in 5 patients and poor in 3 patients. The overall excellent and good function outcome was obtained in 84.6% of the patients. Conclusion： Neoadjuvant chemotherapy and limb salvage surgery are effective methods to treat osteosarcoma at present, although some patients still dying from postoperative metastases. Therefore, early diagnosis individualized treatment and exploring for new and effective therapeutic strategy should be the key to an ideal treatment for osteosarcoma.

A chemotherapy-driven increase in Mcl-1 mediates the effect of miR-375 on cisplatin resistance in osteosarcoma cells

Osteosarcoma(OS)is one of the most difficult cancers to treat due to its resistance to chemotherapy.The essential role played by Mel-l in promoting chemoresistance has been observed in a variety of cancers,including OS,while the underlying mechanism remains unclear.We investigated the expression of Mcl-1 in 42 paired OS specimens obtained before and after adjuvant chemotherapy,and its correlation with clinicopathological characteristics.Loss and gain of function studies were performed to analyze the effects of Mcl-1 modulations on the chemosensitivity,and the mechanism involved in the deregulation of Mcl-1 in OS cells.

Haploidentical hematopoietic stem-cell transplantation for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy

Objective To investigate the therapeutic effects of haploidentical hematopoietic stem - cell transplantation ( Haplo - PBSCT) for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy. Methods Eighty - nine cases of AML in first relapse after complete remission by standard DA

Enrichment of osteosarcoma stem cells by chemotherapy

Osteosarcoma is the most common primary malignant bone cancer in children and adolescents.Emerging evidence has suggested that the capability of a tumor to grow is driven by a small subset of cells within a tumor,termed cancer stem cells(CSCs).Although several methods have been explored to identify or enrich CSCs in osteosarcoma,these methods sometimes seem impractical,and chemotherapy enrichment for CSCs in osteosarcoma is rarely investigated.In the present study,we found that short exposure to chemotherapy could change the morphology of osteosarcoma cells and increase sarcosphere formation in vitro,as well as increase tumor formation in vivo.Furthermore,methotrexate(MTX)-resistant U2OS/MTX300 osteosarcoma cells were larger in size and grew much more tightly than parental U2OS cells.More importantly,U2OS/MTX300 cells possessed a higher potential to generate sarcospheres in serum-free conditions compared to parental U2OS cells.Also,U2OS/MTX300 cells exhibited the side population(SP)phenotype and expressed CSC surface markers CD117 and Stro-1.Notably,U2OS/MTX300 cells showed a substantially higher tumorigenicity in nude mice relative to U2OS cells.Therefore,we conclude that chemotherapy enrichment is a feasible and practical way to enrich osteosarcoma stem cells.

New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma:a retrospective study

Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.Methods: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen(cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis(methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Diferences were evaluated using a two?tailed test, and P < 0.05 was considered signiicant.Results: At a median follow?up of 46 months, 25(4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3?year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R?CHOP group(P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much beneit in terms of preventing CNS relapse. Bone involvement [hazard ratio(HR) = 4.21, 95% conidence interval(CI) 1.38–12.77], renal involvement(HR = 3.85, 95% CI 1.05–14.19), alkaline phosphatase(ALP) >110 U/L(HR = 3.59, 95% CI 1.25–10.34), serum albumin(ALB) <35 g/L(HR = 3.63, 95% CI 1.25–10.51), treatment with rituxi?mab(HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days(HR = 0.22, 95% CI 0.06–0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement(HR = 4.44, 95% CI 1.08–18.35), bone marrow involvement(HR = 11.70, 95% CI 2.24–60.99), and renal involvement(HR = 10.83, 95% CI 2.27–51.65) were independent risk factors for CNS relapse in the R?CHOP set.Conclusions: In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemo?therapy prophylaxis alone was not suicient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R?CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.

Cyclophosphamide and Etoposide as a Salvage Treatment in Metastatic Osteosarcoma Patients

Background and Objective: Osteosarcoma is a rare bone cancer with approximately 30% - 35% of patients who will relapse either systemically or locally, with the lung being the commonest site of relapse. The objective of this trial was to evaluate the efficacy of cyclophosphamide and etoposide, in treatment of metastatic osteosarcoma patients progressed after one or more chemotherapy lines, with the progression free survival and treatment response as the primary endpoints, while the secondary endpoints were overall survival and treatment toxicity. Patients and Methods: Twenty seven metastatic osteosarcoma patients were enrolled into this trial and received cyclophosphamide and etoposide chemotherapy. Cyclophosphamide was given at a dose of 500 mg/m2 per day, I.V for 5 days and etoposide (100 mg/m2 per day I.V for 5 days). Response was assessed after 3 cycles according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Chemotherapy Toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: The median overall survival time and progression-free survival were 12 months and 8 months, respectively. Four patients (14.8%) achieved partial response;14 patients (51.9%) had stationary disease (SD);and 9 (33.3%) expressed tumor progression. Hematologic toxicity was the main toxicity. None of the patients had G4 or life threatening toxicities. Conclusion: The combination of cyclophosphamide and etoposide represents an efficient and tolerable treatment option for patients with metastatic osteosarcoma.

Comparison between preadolescent and adolescent patients with high-grade osteosarcoma in China

Objective:The aim of this study was to assess the differences in clinical appearance and prognosis of osteosarcoma between preadolescent and adolescent in Chinese patients and investigate whether age at diagnosis is a prognostic indicator.Methods:Between May 2002 and May 2009,ninety-six children with high-grade osteosarcoma treated at our institute were stratified according to the age of 10.There were 19 preadolescents(≤ 10 years) and 77 adolescents(10 years < age ≤ 19 years),and their medical records were reviewed and compared using Fisher exact tests.Overall survival and disease-free survival was estimated by Kaplan-Meier methods and compared using log-rank tests.The prognostic significance of the various factors on survival was examined by Cox regression analysis.Results:There were no significant differences in terms of Karnofsky Performance Status(KPS) score,Enneking stage,tumor location,histologic type,pathologic fracture,tumor necrosis rate,tumor size,relapse and frequencies of adjuvant chemotherapy between the two groups.A high proportion of preadolescent patients was treated with amputation(78.9% vs.44.2%;P = 0.01).The 5-year survival of the preadolescent and adolescent groups was(38 ± 14)% and(33 ± 10)%,and the 2-year disease free survival for each group was(45 ± 12)% and(44.4 ± 6.3)%,respectively.Our study showed that age did not have any statistical significance for survival(P = 0.803).Univariate analysis indicated that KPS score;frequencies of adjuvant chemotherapy,tumor size and relapse were significantly related to overall survival.Multivariate Cox regression analysis revealed that both frequencies of adjuvant chemotherapy and relapse were independently prognostic factors for survival.Conclusion:Clinical characteristics and survival between the preadolescents and adolescents with osteosarcoma in China were compatible.So we suggested that there did not need to treat preadolescents patients by alternative and/or aggressive therapies compared with adolescent patients.

Association between HER-2 Over-Expression and Prognosis in Human Osteosarcoma:a Meta-Analysis

OBJECTIVE Various studies examining the relationship be-tween HER-2 over-expression and the response to chemotherapy and clinical outcome in patients with osteosarcoma have yielded inconclusive results.The purpose of the current study was to evaluate the relation of HER-2 status with the response to chemo-therapy and clinical outcome in osteosarcoma.METHODS We conducted a meta-analysis of 6 studies that evaluated the correlation between HER-2 status and histologic response to chemotherapy and 2-year survival.Data were syn-thesized in summary receiver operating characteristic curves and with summary likelihood ratios(LRs) and relative risk.RESULTS The quantitative synthesis showed that HER-2 status is not a prognostic factor for the response to chemotherapy.The positive LR was 1.27(95% conf idence interval,0.91～1.77),and the negative LR was 0.68(95% confidence interval,0.38～1.22).There was no significant between-study heterogeneity.HER2-positive status tended to be associated with a worse 2-year survival,but the overall results were not formally statistically signif icant.CONCLUSION HER-2 status is not associated with the histo-logic response to chemotherapy in patients with osteosarcoma,whereas HER-2 positive patients may be associated with decreased survival.

Anti-osteosarcoma trimodal synergistic therapy using NiFe-LDH and MXene nanocomposite for enhanced biocompatibility and efficacy

Osteosarcoma is usually resistant to immunotherapy and,thus primarily relies on surgical resection and high-dosage chemotherapy.Unfortunately,less invasive or toxic therapies such as photothermal therapy(PTT)and chemodynamic therapy(CDT)generally failed to show satisfactory outcomes.Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma.Herein,a simple nanocomposite that synergistically combines CDT,PTT,and chemotherapy for osteosarcoma treatment was fabricated.In this composite,small 2D Ni Fe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil(5-FU)with high loading capacity.The nanospheres were then adsorbed onto larger 2D Ti3C2MXene monolayers and finally shielded by bovine serum albumin(BSA)to form 5-FU@Ni Fe-LDH/Ti3C2/BSA nanoplatforms(5NiTiB).Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy,Ni Fe-LDH driven chemodynamic effects,and MXene-based photothermal killing collectively exhibited a synergistic“all-in-one”anti-tumor effect.5NiTiB improved tumor suppression rate from<5%by 5-FU alone to~80.1%.This nanotherapeutic platform achieved higher therapeutic efficacy with a lower agent dose,thereby minimizing side effects.Moreover,the composite is simple to produce,enabling the fine-tuning of dosages to suit different requirements.Thus,the platform is versatile and efficient,with potential for further development.

Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcoma

Osteosarcoma(OS)is one of the most common malignant tumors in children and young adults.As chemotherapy and other therapies are limited by low therapeutic efficiency,severe side effects and single therapeutic function,it is of high value to develop innovative therapies for precise and efficient treatment of OS.Herein,natural photo-synthetic microalgae(C.vulgaris,CV)were utilized as carriers for the chemotherapeutic agent doxorubicin(DOX)to create a multifunctional therapeutic platform(CV@DOX)for the photo-modulation of the tumor microenvi-ronment(TME)and synergistic chemo-photodynamic therapy of osteosarcoma.CV@DOX exhibited rapid drug release behavior in the acidic TME,improving the efficiency of chemotherapy against tumors and reducing side effects on other normal tissues.Under 650 nm laser irradiation,CV@DOX demonstrated the ability to effectively generate oxygen to alleviate tumor hypoxia and utilize the photosensitizing properties of chlorophyll in CV to produce an increased amount of reactive oxygen species(ROS),thereby enhancing photodynamic therapy(PDT).CV@DOX-mediated synergistic chemo-photodynamic therapy demonstrated efficacy in halting tumor progression in an orthotopic osteosarcoma mouse model by promoting tumor cell apoptosis,inhibiting tumor proliferation and angiogenesis.Moreover,chlorophyll-assisted fluorescence imaging enabled monitoring of the distribution of CV@DOX in osteosarcoma after administration.Finally,CV@DOX did not cause significant hematological and tissue toxicity,and prevented DOX-induced cardiotoxicity,showing good in vivo biocompatibility.Overall,this work presents a novel TME-responsive and TME-modulating platform for imaging-guided multimodal osteosar-coma treatment.

Targeting the mammalian target of rapamycin pathway in osteosarcoma using combinative chemotherapy

Osteosarcoma is the most common primary malignant ＇bone sarcoma, and occurs predominantly in childrenand young adults. The overall survival of patients with osteosarcoma remains low at approximately 60%.1 The prognosis of osteosarcoma patients is highly associated with response to chemotherapy. Although multiple chemotherapy regimens have improved the outcome of patients with osteosarcoma, resistance to current regimens has been reported in more than 30% of patients,2 highlighting the need for novel, targeted therapies.

Is There a Reliable Method to Predict the Limb Length Discrepancy after Chemotherapy and Limb Salvage Surgery in Children with Osteosarcoma？

Background： For a child with osteosarcoma, prediction of the limb length discrepancy at maturity is important when planning for limb salvage surgery. The purpose of this study was to provide a reliable prediction method. Methods： A retrospective review of Chinese children receiving chemotherapy for osteosarcoma before skeletal maturity was conducted. Standing full-length radiographs of the lower extremity were used for length measurements. Length-for-age curves were constructed using the LMS method. The lower limb multiplier for a specific age and gender was calculated using the formula M =Lm/L, where M was the gender- and age-specific multiplier, Lm was the bone length at maturity, and L was the age-specific bone length. Prematurity and postmaturity radiographs were used to assess the accuracy of the prediction methods. Results： A total of 513 radiographs of 131 boys and 314 radiographs of 86 girls were used to calculate the coefficients of the multiplier. The multipliers of 8-, 9-, 10-, 11-, 12-, 13-, 14-, 15-, 16-, 17-, and 18-year-old boys after chemotherapy for osteosarcoma were 1.394, 1.306, 1.231, 1.170, 1.119, 1.071, 1.032, 1.010, 1.004, 1.001, and 1.000, respectively; while for girls at the same ages, the multipliers were 1.311, 1.221, 1.146, 1.092, 1.049, 1.021, 1.006, 1.001, 1.000, 1.000, and 1.000, respectively. Prematurity and postmaturity femoral and tibial lengths of 21 patients were used to assess the prediction accuracy. The mean prediction error was 0 cm, 0.8 cm, and 1.6 cm fbr the multiplier method using our coefficients, Paley＇s coefficients, and Anderson＇s method, respectively. Conclusions： Our coefficients for the multiplier method are reliable in predicting lower limb length growth of Chinese children with osteosarcoma.