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At least 19 recordsLinked to original sources
PubMed2026

NFS1 activates PI3K/AKT/mTOR signaling to upregulate GPX4 expression and enhance ferroptosis resistance in osteosarcoma.

Osteosarcoma continues to exhibit poor survival outcomes due to chemoresistance and metastasis, with metabolic reprogramming and ferroptosis resistance being key features of tumor heterogeneity, yet their upstream regulators remain poorly defined. NFS1, a cysteine desulfurase essential for iron-sulfur cluster biogenesis, protects multiple cancers from ferroptosis, but its role in osteosarcoma is unknown. In this study, we performed a transcriptomic meta-analysis and found that NFS1 expression was significantly upregulated in osteosarcoma tissues, with further elevation in metastatic lesions, and high NFS1 expression correlated with poor overall survival. Genome‑wide CRISPR screening data revealed a marked NFS1 dependency in osteosarcoma cell lines. Functionally, NFS1 promoted cell proliferation, migration, and invasion, whereas its knockdown suppressed these phenotypes. Using single‑cell RNA sequencing data from 27 osteosarcoma specimens, we applied a multi‑algorithm glycolytic scoring framework and observed NFS1 enrichment in highly glycolytic malignant cells, along with an association with PI3K/AKT/mTOR pathway activation. Mechanistically, NFS1 selectively enhanced PI3K, AKT, and mTOR phosphorylation without altering total protein levels, and upregulated GPX4, a central ferroptosis suppressor, leading to elevated ferroptosis resistance scores in NFS1‑high malignant cells. Collectively, these findings identify a previously unrecognized NFS1-PI3K/AKT/mTOR-GPX4 regulatory axis in osteosarcoma, linking metabolic reprogramming to ferroptosis resistance, and suggest that NFS1 functions as an oncogenic driver, as well as a promising prognostic biomarker and therapeutic target in osteosarcoma.

Humans↗
PubMed1977

Virus-induced animal model of osteosarcoma in the rat: Morphologic and biochemical studies.

Osteosarcomas were produced by the intratibial inoculation of New Zealand black rats with Moloney sarcoma virus (MSV) at 1 day and 4 days of age. Radiographic evidence of osteosarcoma development was first demonstrated at 10 to 15 days postinoculation in both groups. Subsequent radiographic and light and electron microscopic evaluation of tumor-bearing rats demonstrated that osteosarcomas in rats inoculated at Day 4 of age were more osteoproliferative osteosarcomas than those in rats inoculated on Day 1. Rats inoculated at 4 days of age lived longer, had more slowly growing osteosarcomas, and developed a consistent tumor-associated cachexia compared to tumor-bearing rats inoculated at Day 1. Both groups of rats had a 93% metastasis rate involving either sublumbar lymph nodes, lungs, or both. Tumor-bearing rats inoculated at 4 days of age had consistent elevations in both urinary hydroxyproline excretion (HOP/CR) and serum alkaline phosphatase levels, and in serum calcium levels at some time points. The high tumor incidence after a short latent period and the morphologic and biochemical similarities between the MSV-induced murine osteosarcoma and the osteosarcoma in human beings makes this discrete tumor and a valuable animal model for the evaluation of new therapeutic regimens.

Animals↗
PubMed2026

Kaposi Sarcoma-Associated Herpesvirus Is Not Detected in Osteosarcoma From KSHV-Endemic African Countries and the Non-Endemic United States Populations.

Osteosarcoma is an aggressive primary malignant bone tumor of poorly defined etiology that predominantly affects adolescents and young adults. A viral cause has long been proposed, and a recent study from Xinjiang, China, reported frequent detection of Kaposi sarcoma-associated herpesvirus (KSHV) in Uyghur osteosarcoma cases, suggesting a possible association in this KSHV-endemic population. Whether this association extends to broader populations remains unknown. Our study investigated the presence of KSHV in osteosarcoma specimens from KSHV-endemic African countries (Cameroon, Kenya, South Africa, Zambia) and the non-endemic United States. A total of 356 formalin-fixed paraffin-embedded and fresh-frozen specimens were retrieved or prospectively collected. In 77 selected high-quality specimens, KSHV infection was assessed by immunohistochemistry for LANA1 and by qPCR targeting 5 viral open reading frames (ORF25, ORF26, ORF37, ORF65, and ORF73). LANA1 expression was undetectable in all tumors. Using qPCR, 75/77 specimens were negative for all targets, 1/77 excluded due to insufficient remaining DNA quantity to perform the assay, and 1/77 positive across all five targets. Additionally, we studied the KSHV seroprevalence in a separate cohort comprised of 49 sera obtained from individuals with osteosarcoma from Zambia (n = 39) and the United States (n = 10). We measured by ELISA the presence of specific antibodies against four KSHV antigens: K8.1, KCP, VCA, and LANA1. KSHV seropositivity was detected in 15/39 individuals from Zambia and none from the United States. In the absence of compelling evidence, our findings could not support an association between KSHV infection and osteosarcoma in our study population.

Humans↗
PubMed1975

A laboratory model for the study of the immunobiology of osteosarcoma.

Inoculation of Moloney sarcoma virus into the marrow cavity of the tibia of newborn Wistar-Lewis rats resulted in the appearance of an initially localized osteosarcoma in 97.7% of these animals. At least 77.9% of the rats developed lung metastases and died, usually within 6 weeks of inoculation. The remaining 22.1% showed regression of disease after initial growth of the tumor. Tumor cells were maintained in tissue culture and used as target cells for a visual and isotopic (3H-thymidine or 125IUdR) microcytotoxicity assay. Cell-mediated immunity could be measured by these methods throughout the course of the illness in animals with progressive disease as well as in those whose tumors eventually regressed. The presence of serum factors capable of modifying the level of CMI was documented. This Moloney-sarcoma-virus-induced rat osteosarcoma and human osteosarcoma thus appear to have several basic pathologic and immunologic similarities. The model may be useful for studying the effects of a variety of treatment protocols upon the clinical course and immune response to osteosarcoma.

Animals↗
PubMed2026

Efficacy and safety of microwave ablation for the treatment of pulmonary osteosarcoma oligometastases.

PURPOSE: Evaluate efficacy and safety of microwave ablation (MWA) for pulmonary osteosarcoma oligometastases. METHODS: Twenty-two patients (median age, 16 years [range, 9-41 years]; 15 male) with pulmonary osteosarcoma oligometastases who underwent MWA from January 2018 to December 2023 were included, with 27 MWA sessions for 36 lung metastases. Technical success and complications were evaluated in all 22 patients, while efficacy and survival were evaluated in 19 patients with 24 MWA sessions in treatment of 32 tumors. Technical success was assessed for each tumor. Local tumor control, progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Complications were classified using Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Technical success was achieved in all 36 tumors (100.0%). Local tumor progression occurred in five of 32 tumors (15.6%). The estimated local tumor control rates at 12, 24 and 36 months were 96.9%, 86.1% and 81.5%, respectively. No significant difference in local control was found between tumors ≤ 10 mm and > 10 mm (p = .470). Twelve of 19 patients (63.2%) developed new lung metastases outside the ablation area, including one with concurrent newly developed bone metastases and one with recurrence of primary osteosarcoma. The median PFS was 21.5 months. The estimated OS rates at 12, 24 and 60 months were 100.0%, 94.4% and 94.4%, respectively. Major complications occurred in five of 27 sessions (18.5%). CONCLUSIONS: MWA preliminarily demonstrates a high technical success rate, notable local tumor control, promising overall survival and acceptable safety for pulmonary osteosarcoma oligometastases.

Adolescent↗
PubMedDate not supplied

The use of naturally occurring cancer in domestic animals for research into human cancer: general considerations and a review of canine skeletal osteosarcoma.

For many years, research into human cancer has concentrated on human patients and on artificially induced neoplasms in inbred murine hosts. Cancer, however, affects a great variety of mammals, particularly those that have been domesticated. Suchf naturally occurring neoplasms are common in dogs, cats, cattle, horses, etc., and offer fertile ground for studies relating to epidemiologyf, etiology, immunobiology, and therapy. Canine osteosarcoma is described in detail. The clinicopathologic features of this canine tumor closely approximate that of human osteosarcoma and thus make canine osteosarcoma an invaluable comparative model. Canine osteosarcoma and other naturally occurring tumors lie intermediate between the mouse models and human cancer. The use of these veterinary models in the future fabric of cancer research will broaden its base and will influence our conceptual approach to research and clinical options.

Age Factors↗
PubMed1977

Aneurysmal bone cyst and telangiectatic osteosarcoma. A histopathological and morphometric study.

In a series of 105 cases of aneurysmal bone cyst, 18 showed an unusually high level of mitotic activity and/or increased nuclear pleomorphism which complicated the differential diagnosis with respect to telangiectatic osteosarcoma. An attempt was made to use semi-automatized morphometric and histophotometric techniques to establish objective morphological differences between these unusual cases of aneurysmal bone cyst and 16 cases of telangiectatic osteosarcoma. Three cases (two of aneurysmal bone cyst and one of telangiectatic osteosarcoma) proved unsuitable for analysis. In 24 of the remaining 31 cases (77%) a computerized discriminant analysis permitted correct discreimination with a high degree of certainty on the basis of quantitative nuclear characteristics determined in paraffin sections. In the other 7 cases the diagnosis was less certain (3), doubtful (2) or erroneous (2). The relevant nuclear characteristics were (in ascending sequence of discrimination): the largest nuclear surface area, the mitotic index, and the percentage of nuclear sections exceeding an arbitrarily chosen limit of 60 micron2. The criterion of nuclear size for discrimination between these benign and malignant lesions could be applied for two reasons: firstly, because a group of extremely large nuclei occur in malignant cases, and secondly, because the average nuclear size is larger in malignant than in benign lesions. The extremely large nuclei occur as only a small percentage of the total nuclear population. The other variables investigated, i.e., cellularity and nuclear contour ratio, did not contribute greatly to the differentiation. In 11 cases, the average nuclear Feulgen extinction was estimated as an additional variable.

Adolescent↗
PubMed1978

Ultrastructural cytology of human osteosarcoma cells.

The cytology of 6 osteosarcomas was examined by electron microscopy. In keeping with the varied pattern of osteosarcomas seen by light microscopy several types of tumor cells could be differentiated: osteoblast-like, fibroblast-like, chondroblast-like, osteoclast-like and histiocyte-like cells. Moreover, atypical malignant mesenchymal cells and vascular spaces were present. The individual cytoplasmic organelles are not considered to be specific to particular types of cell as seen from the discussion of the significance of rough endoplasmic reticulum, microfilaments and lysosomes. Only examination of the composite pattern of subcellular organelles allows the differentiation of certain cell types. All tumor cells visible in osteosarcomas are considered as modifications of a transformed common progenitor cell. Because of the variegated cytological picture a multipotent mesenchymal cell rather than an osteoblastic cell is assumed to be the ancestor cell.

Adolescent↗
PubMed2026

Flavones in osteosarcoma: Molecular mechanisms, antitumor activity, and translational challenges.

Osteosarcoma remains the most common primary malignant bone tumor, and survival has improved little over recent decades because of metastasis and therapeutic resistance. Flavones exhibit diverse anti-osteosarcoma activities by suppressing proliferation, inducing apoptosis, ferroptosis and autophagy, inhibiting metastasis, and modulating oncogenic signaling pathways, including PI3K-Akt, Wnt-β-catenin, STAT3, MAPK, and NF-κB. This review summarizes the cell-line-specific molecular mechanisms of representative flavones, critically evaluates current experimental limitations, and discusses strategies to improve clinical translation through nanotechnology-based delivery and combination therapy. Although clinical evidence remains lacking, flavones represent promising adjunctive candidates for overcoming chemoresistance and improving osteosarcoma treatment.

apoptosis and metastasis↗
PubMed1975

Pathology of osteosarcoma.

Osteosarcoma of bone is a tumor composed of malignant cells that produce osteoid. Some tumors show predominant chondroid or fibromatoid ground substance. All, however, are highly malignant and about 80 per cent produce death with metastases. The roentgenogram affords important evidence for the correct diagnosis of many of them. Differential diagnosis should include consideration of those sarcomas with many benign giant cells and the group of "telangiectatic" osteosarcomas that may contain only small diagnostic areas. Malignant fibrous histiocytoma is now considered as a possible diagnosis for some malignant bone tumors, but the exact criteria for the diagnosis of this condition are still somewhat obscure. Newer modalities of adjunctive treatment, such as resection of pulmonary metastases, chemotherapy, and immunotherapy, give promise of improving the prognosis for osteosarcoma.

Adult↗
PubMed1975

Electron microscopic observations of 20 human osteosarcomas.

Twenty primary osteosarcomas of bone and two osteosarcomas metastatic to the lung were examined by electron microscopy. The tumor cells, whether from an area exhibiting chondroid, osteoid or collagenous matrix, showed common abnormalities in configuration and fine structure. The cells tended to be spindle-shaped with centralized nuclei. The nucleus was enlarged, irregular in shape, and frequently lobulated. The choromatin was dense and arranged around the periphery of the nucleus. There was a large prominent, irregularly shaped nucleolus. Smooth membranes were sparse to absent. The rough endoplasmic reticulum was abundant, disorderly, and tended to be markedly dilated in mature cells. The mitochondria were numerous, variable in size and configuration, and were intimately surrounded by rough endoplasmic reticulum. The collagenous matrix was disorganized with the fibers and bundles randomly oriented and arranged. No structures definitely identifiable as virus-particles were seen. However, microstructures resembling unenveloped nucleocapsids of paramyxo- or related viruses were noted. All fine structure abnormalities could be associated with an increased metabolic rate and/or with abnormal protein and enzyme synthesis. No definitive diagnostic features were found. The fine structure of cell cultures derived from the osteosarcomas in this study was similar to that of the fresh tissue. No virus-like particles were seen in any of these cell lines.

Bone Matrix↗
PubMed1978

Ultrastructural study of tumor cell differentiation in osteosarcoma of jaw bones.

Tw osteosarcomas of jaw bones have been studied by electron microscopy. The objectives were to examine the specific cell types in relation to functions and ultrastructural features, and to examine matrices produced by tumor cells. The osteosarcoma cells were subdivided into four cell types: anaplastic, chondroblastic, osteoblastic, and osteocytic--giant cells were not considered in the present investigation. Compared to normal bone cells, no specific sign of malignancy was found. However, tumor cells seem to lose functional abilities, i.e. a modification of matrix. Consequently, tumor matrix has altered organic and inorganic components with impairment of collagen maturation and matrix mineralization. The alteration in both processes may be related to a diminished production of proteoglycans. The cytogenic hypothesis of a tumor stem cell may be supported by the identification of anaplastic osteosarcoma cells resembling immature reticulum cells. One may speculate on transformation of this cell type as a genetically predetermined osteoprogenitor cell of malignant potential.

Adult↗
PubMed1979

[Immunologic studies concerned with high dose radiotherapy for osteosarcoma (author's transl)].

The 5-year cumulative survival rate was measured in 28 cases of osteosarcoma treated with high dose radiation since 1969 is 48.8% in our clinic. It can be said that high dose radiotherapy has a significant survival effect compared to early amputation therapy for the patient with osteosarcoma. The difference of the prognosis between both therapies may be related to immunological reactions. In order to obtain further information on this possibility, experimental studies on mice suffering from tumors have been performed. Results revealed that spleen cell migration inhibition reaction, as a specific immunity, became negative and anti-tumor properties were eliminated as a results of the amputation of the limb bearing the tumor. Also, when BCG as well as irradiated tumor cells were administered to tumor-afflicted mice, an improved rate of survival among the mice was observed. As a result of the study of patients with osteosarcoma that has been treated with high dose radiation related to changes in their immunity, it was disclosed that there was a marked tendency to diminution in peripheral blood lymphocytes or T cells in cases with poorer prognoses. In cases of long survival, both showed high values. Lymphoblastgenesis by PHA and PWM showed higher values in cases with better prognoses than in those with poor prognoses. Furthermore, in many of the cases in which the tuberculin skin reaction became negative, a short survival period was noted.

Adolescent↗
PubMed1979

Purification and biochemical characterization of a virus-specific reverse transcriptase from human osteosarcoma tissue.

A RNA-dependent DNA polymerase (RTase) was purified from human osteosarcoma tissue by successive column chromatography of the microsomal fraction on DEAE-cellulose (DE-23 and DE-52) and phosphocellulose. The purified enzyme has a molecular weight of about 68,000, a pH optimum of 8.1, a Mg2+ optimum of 0.8 mM, Mn2+ optimum of 1.0 mM and a KCl optimum of 60 mM. The enzyme transcribes (rA)n . (dT)12, (rC)n . (dG)12-18 and (2-O-methyl C)n . (dG)18, but is unable to transcribe (dA)n . (dT)10. The enzyme has no catalytic activity in the presence of oligodeoxynucleotide initiators alone, indicating the absence of terminal deoxynucleotidyl transferase. The purified enzyme is able to transcribe the heteropolymeric regions of a 70S RNA from R(Mu)LV. The presented data support the presence of a RNA-dependent DNA polymerase in human osteosarcoma tissue with biochemical properties, resembling those of C-type RNA tumor viruses.

Adolescent↗
PubMed1975

The etiology of osteosarcoma. A review of current considerations.

Various agents have caused osteosarcoma in several experimental animal systems. These agents or initiators may be classified as chemicals, radiation, viruses, and miscellaneous. Zinc beryllium silicate with beryllium oxide in rabbits and FBJ virus in mice are two such initiating agents. The relevance of these animal experiments to the human situation is not known, but recent reports regarding a transmissible agent obtained from human osteosarcoma tissue suggest that a virus may be implicated. There is a theoretic indication that the various etiologic agents, including viruses, may affect the DNA of normal cells in such a way that further evolution and differentiation through several cell divisions may result in the clinical appearance of cancer.

Animals↗
PubMed1979

Computed tomography in the evaluation of osteosarcoma: experience with 25 cases.

Experience with computed tomography (CT) in 25 patients with histologically proven osteosarcoma is presented. CT was as accurate as conventional radiographic methods in determining the presence of a lesion, but it was definitely superior in defining the extent of disease, particularly intramedullary extension and soft tissue extraosseous tumor component. CT was capable of demonstrating skip metastases in one patient. CT plays a key role in the preoperative evaluation of osteosarcoma patients, particularly when less than radical surgery is planned as primary treatment and when postoperative recurrence is suspected. CT is also useful in assessing the response to therapy in nonsurgical cases. The technique involved in the performance of this examination is discussed.

Bone Neoplasms↗
PubMed1978

Difference in the induction of osteosarcoma in rabbit bone with single administration of three kinds of chemical carcinogens.

A single intramedullary administration of each dose (15 approximately 20 mg) of 4-nitroquinoline 1-oxide, 3-methylcholanthrene, or 7,12-dimethylbenz[alpha]anthracene was applied to the mandible, diaphysis, or distal metaphysis of the femur of rabbits. The highest incidence in production of osteosarcoma was obtained from the group in which 4-nitroquinoline 1-oxide was applied to the distal metaphysis (75%, including one case of chondrosarcoma). Tumors hardly appeared in any of the groups when given 3-methylcholanthrene or 7,12-dimethylbenz[alpha]anthracene. Histologically, three kinds of entities were recognized from the quantitative difference of the reactive tissues which appeared around carcinogens. It is estimated that the condition of entity III induces the highest incidence of osteosarcoma if chemical carcinogens are given into the bone marrow of experimental animals.

4-Nitroquinoline-1-oxide↗