Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

International patterns of childhood cancer incidence are well documented but equivalent information relating to adolescence is scarce. This article synthesizes international data on cancer in adolescents from population based cancer registries. Total incidence ranged from 95 to 255 per million person years in the series studied. The highest rates were in Australia and among Jews in Israel and the lowest in India and Japan. Lymphomas were the most frequent cancers in western industrialised countries of the northern hemisphere and in the Middle East, and occurred in substantial numbers in all other regions. Hodgkin lymphoma outnumbered non-Hodgkin in western industrialised countries but was relatively rare in most developing countries and in Japan. Leukaemias were the most frequent diagnostic group in India, East Asia and Latin America. Melanoma was the commonest cancer of adolescents in Australia and New Zealand and moderately frequent in many other predominantly white populations but rarely seen elsewhere. Kaposi sarcoma was the most frequent cancer in both sub-Saharan African series studied. The highest rates for nasopharyngeal carcinoma were in Algeria and Hong Kong and for liver carcinoma in Hong Kong and sub-Saharan Africa. Testicular germ cell tumours were relatively frequent in predominantly white populations. Central nervous system tumours and thyroid carcinoma were most often registered in countries with higher standard of living. Osteosarcoma was moderately frequent almost everywhere. Characteristic embryonal tumours of childhood and the most common carcinomas of adulthood were rarely seen. Only osteosarcoma, ovarian germ cell tumours and, in some populations, nasopharyngeal carcinoma have their highest incidence at age 15-19 years. Total cancer incidence was higher in adolescent males than females, but there was often a female excess in melanoma and thyroid carcinoma, and Hodgkin lymphoma was at least as frequent among females as males in several countries with relatively high incidence. More complete delineation of worldwide patterns of cancer in adolescence would be facilitated by availability of more data classified in a standard way to take account of morphology.
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PMID:International patterns of cancer incidence in adolescents. 1732 31

Osteosarcoma derives from primitive bone-forming mesenchymal cells and is the most common primary bone malignancy. The incidence rates and 95% confidence intervals of osteosarcoma for all races and both sexes are 4.0 (3.5-4.6) for the range 0-14 years and 5.0 (4.6-5.6) for the range 0-19 years per year per million persons. Among childhood cancers, osteosarcoma occurs eighth in general incidence and in the following order: leukemia (30%), brain and other nervous system cancers (22.3%), neuroblastoma (7.3%), Wilms tumor (5.6%), Non-Hodgkin lymphoma (4.5%), rhabdomyosarcoma (3.1%), retinoblastoma (2.8%), osteosarcoma (2.4%), and Ewing sarcoma (1.4%). The incidence rates of childhood and adolescent osteosarcoma with 95% confidence intervals areas follows: Blacks, 6.8/year/million; Hispanics, 6.5/year/million; and Caucasians, 4.6/year/million. Osteosarcoma has a bimodal age distribution, having the first peak during adolescence and the second peak in older adulthood. The first peak is in the 10-14-year-old age group, coinciding with the pubertal growth spurt. This suggests a close relationship between the adolescent growth spurt and osteosarcoma. The second osteosarcoma peak is in adults older than 65 years of age; it is more likely to represent a second malignancy, frequently related to Paget's disease. The incidence of osteosarcoma has always been considered to be higher in males than in females, occurring at a rate of 5.4 per million persons per year in males vs. 4.0 per million in females, with a higher incidence in blacks (6.8 per million persons per year) and Hispanics (6.5 per million), than in whites (4.6 per million). Osteosarcoma commonly occurs in the long bones of the extremities near the metaphyseal growth plates. The most common sites are the femur (42%, with 75% of tumors in the distal femur), the tibia (19%, with 80% of tumors in the proximal tibia), and the humerus (10%, with 90% of tumors in the proximal humerus). Other likely locations are the skull or jaw (8%) and the pelvis (8%). Cancer deaths due to bone and joint malignant neoplasms represent 8.9% of all childhood and adolescent cancer deaths. Death rates for osteosarcoma have been declining by about 1.3% per year. The overall 5-year survival rate for osteosarcoma is 68%, without significant gender difference. The age of the patient is correlated with the survival, with the poorest survival among older patients. Complete surgical excision is important to ensure an optimum outcome. Tumor staging, presence of metastases, local recurrence, chemotherapy regimen, anatomic location, size of the tumor, and percentage of tumor cells destroyed after neoadjuvant chemotherapy have effects on the outcome.
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PMID:The epidemiology of osteosarcoma. 2021 83

Osteosarcoma is the most common type of solid bone cancer and the second leading cause of cancer-related death in pediatric patients. Many patients are not cured by the current osteosarcoma therapy consisting of combination chemotherapy along with surgery and thus new treatments are urgently needed. In the last decade, cancer stem cells have been identified in many tumors such as leukemia, brain, breast, head and neck, colon, skin, pancreatic, and prostate cancers and these cells are proposed to play major roles in drug resistance, tumor recurrence, and metastasis. Recent studies have shown evidence that osteosarcoma also possesses cancer stem cells. This review summarizes the current knowledge about the osteosarcoma cancer stem cell including the methods used for its isolation, its properties, and its potential as a new target for osteosarcoma treatment.
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PMID:Targeting the osteosarcoma cancer stem cell. 2097 39

Osteosarcoma is the most frequent, nonhematopoietic, primary malignant tumor of bone. Histopathologically, osteosarcoma is characterized by complex mixtures of different cell types with bone formation. The role of environmental factors in the formation of such a complicated tissue structure as osteosarcoma remains to be elucidated. Here, a newly established murine osteosarcoma model was used to clarify the roles of environmental factors such as fibroblast growth factor-2 (Fgf2) or leukemia-inhibitory factor (Lif) in the maintenance of osteosarcoma cells in an immature state. These factors were highly expressed in tumor environmental stromal cells, rather than in osteosarcoma cells, and they potently suppressed osteogenic differentiation of osteosarcoma cells in vitro and in vivo. Further investigation revealed that the hyperactivation of extracellular signal-regulated kinase (Erk)1/2 induced by these factors affected in the process of osteosarcoma differentiation. In addition, Fgf2 enhanced both proliferation and migratory activity of osteosarcoma cells and modulated the sensitivity of cells to an anticancer drug. The results of the present study suggest that the histology of osteosarcoma tumors which consist of immature tumor cells and pathologic bone formations could be generated dependent on the distribution of such environmental factors. The combined blockade of the signaling pathways of several growth factors, including Fgf2, might be useful in controlling the aggressiveness of osteosarcoma.
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PMID:Fibroblast growth factor-2 is an important factor that maintains cellular immaturity and contributes to aggressiveness of osteosarcoma. 2222 19

Osteosarcoma is the most common primary osseous malignancy excluding malignant neoplasms of marrow origin (myeloma, lymphoma and leukemia) and accounts for approximately 20% of bone cancers. It predominantly affects patients younger than 20 years and mainly occurs in the long bones of the extremities, the most common being the metaphyseal area around the knee. These are classified as primary (central or surface) and secondary osteosarcomas arising in preexisting conditions. The conventional plain radiograph is the best for probable diagnosis as it describes features like sun burst appearance, Codman's triangle, new bone formation in soft tissues along with permeative pattern of destruction of the bone and other characteristics for specific subtypes of osteosarcomas. X-ray chest can detect metastasis in the lungs, but computerized tomography (CT) scan of the thorax is more helpful. Magnetic resonance imaging (MRI) of the lesion delineates its extent into the soft tissues, the medullary canal, the joint, skip lesions and the proximity of the tumor to the neurovascular structures. Tc99 bone scan detects the osseous metastases. Positron Emission Tomography (PET) is used for metastatic workup and/or local recurrence after resection. The role of biochemical markers like alkaline phosphatase and lactate dehydrogenase is pertinent for prognosis and treatment response. The biopsy confirms the diagnosis and reveals the grade of the tumor. Enneking system for staging malignant musculoskeletal tumors and American Joint Committee on Cancer (AJCC) staging systems are most commonly used for extremity sarcomas.
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PMID:Classification, imaging, biopsy and staging of osteosarcoma. 2493 27

Conventional high-grade osteosarcoma is the most common primary bone sarcoma, with relatively high incidence in young people. In this study we found that expression of Aven correlates inversely with metastasis-free survival in osteosarcoma patients and is increased in metastases compared to primary tumours. Aven is an adaptor protein that has been implicated in anti-apoptotic signalling and serves as an oncoprotein in acute lymphoblastic leukaemia. In osteosarcoma cells, silencing Aven triggered G2 cell-cycle arrest; Chk1 protein levels were attenuated and ATR-Chk1 DNA damage response signalling in response to chemotherapy was abolished in Aven-depleted osteosarcoma cells, while ATM, Chk2 and p53 activation remained intact. Osteosarcoma is notoriously difficult to treat with standard chemotherapy, and we examined whether pharmacological inhibition of the Aven-controlled ATR-Chk1 response could sensitize osteosarcoma cells to genotoxic compounds. Indeed, pharmacological inhibitors targeting Chk1/Chk2 or those selective for Chk1 synergized with standard chemotherapy in 2D cultures. Likewise, in 3D extracellular matrix-embedded cultures, Chk1 inhibition led to effective sensitization to chemotherapy. Together, these findings implicate Aven in ATR-Chk1 signalling and point towards Chk1 inhibition as a strategy to sensitize human osteosarcomas to chemotherapy.
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PMID:Aven-mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in conventional osteosarcoma. 2575 65

Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults. miR-145 is a microRNA highly expressed in vascularized tissues and has been widely studied in cancers. In this study, we explored the expression and function of miR-145 in OS. We found that miR-145 was consistently under-expressed in OS tissues and cell lines as compared to normal bone tissues and osteoblast cells. Ectopic expression of miR-145 in OS cells inhibited their proliferation and migration and induced apoptosis. miR-145 targets a putative microRNA regulatory element (MRE) in the 3'-UTR of friend leukemia virus integration 1 gene (FLI-1), and its abundance was inversely related to FLI-1 expression in OS tissues and cell lines. miR-145 decreased expression FLI-1 protein and mRNA, but mutation of the miR-145 MRE sequence in the FLI-1 3'-UTR abolished the activity of miR-145 in a reporter assay. Restored expression of FLI-1 diminished miR-145-mediated suppression of tumor progression. These results suggest that miR-145 acts as a tumor suppressor by directly reducing expression of FLI-1, and that the miR-145/FLI-1 pathway is important for tumor progression in OS.
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PMID:miR-145 promotes osteosarcoma growth by reducing expression of the transcription factor friend leukemia virus integration 1. 2730 58

Osteosarcoma is a rare disease diagnosed as malignant bone tumor. It is generally refractory to chemotherapy, which contributes to its poor prognosis. The reversal of chemoresistance is a major clinical challenge to improve the prognostic outcome of osteosarcoma patients. We developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301 (telomelysin) and assessed its synergistic effects with chemotherapeutic agents (cisplatin and doxorubicin) using human osteosarcoma cell lines and a xenograft tumor model. The molecular mechanism underlying the chemosensitizing effect of OBP-301 was evaluated in aspects of apoptosis induction. OBP-301 inhibits anti-apoptotic myeloid cell leukemia 1 (MCL1) expression, which in turn leads to chemosensitization in human osteosarcoma cells. The siRNA-mediated knockdown of MCL1 expression sensitized human osteosarcoma cells to common chemotherapeutic agents. We also found that upregulation of microRNA-29 targeting MCL1 via virally induced transcriptional factor E2F-1 activation was critical for the enhancement of chemotherapy-induced apoptosis in osteosarcoma cells. Telomerase-specific oncolytic adenovirus synergistically suppressed the viability of human osteosarcoma cells in combination with chemotherapeutic agents. The combination treatment also significantly inhibited tumor growth, as compared to monotherapy, in an osteosarcoma xenograft tumor model. Our data suggest that replicative virus-mediated tumor-specific MCL1 ablation may be a promising strategy to attenuate chemoresistance in osteosarcoma patients.
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PMID:Ablation of MCL1 expression by virally induced microRNA-29 reverses chemoresistance in human osteosarcomas. 2735 24

Cardiac mass can be described as an abnormal structure within or directly contiguous to the heart. Tumors and thrombi are the most common types of cardiac masses. Intracardiac thrombi have been encountered in various clinical settings and can result in severe morbidity and mortality due to embolic events. Cardiac neoplasms are extremely rare, and are usually metastatic tumors. The major primary malignancies associated with cardiac metastases include cancers of the lung, breast, stomach, and liver, and lymphoma, leukemia, and melanoma. Osteosarcoma (OS) is the most common type of bone malignancy, and is almost always highly malignant. A previous study demonstrated that OS very rarely metastasizes to the heart. Presently reported is an unusual case of OS with intracaval, right atrial, and right ventricular extension that was misdiagnosed as venous thrombus.
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PMID:Massive pulmonary embolism and a cardiac mass: Thrombus or metastasis? 2777 70

Osteosarcoma is an aggressive malignant bone tumor that causes bone destruction. Although tumor-specific replicating oncolytic adenovirus OBP-301 induces an antitumor effect in an osteosarcoma tumor, it cannot prevent bone destruction. Zoledronic acid (ZOL) is a clinically available agent that inhibits bone destruction. In this study, we investigated the potential of combination therapy with OBP-301 and ZOL against osteosarcomas with bone destruction. The antitumor activity of OBP-301 and ZOL in monotherapy or combination therapy was assessed using three human osteosarcoma cell lines (143B, MNNG/HOS, SaOS-2). The cytotoxic effect of OBP-301 and/or ZOL was measured by assay of cell apoptosis. The effect of OBP-301 and ZOL on osteoclast activation was investigated. The potential of combination therapy against tumor growth and bone destruction was analyzed using an orthotopic 143B osteosarcoma xenograft tumor model. OBP-301 and ZOL decreased the viability of human osteosarcoma cells. Combination therapy with OBP-301 and ZOL displayed a synergistic antitumor effect, in which OBP-301 promoted apoptosis through suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1). Combination therapy significantly inhibited tumor-mediated osteoclast activation, tumor growth and bone destruction compared to monotherapy. These results suggest that combination therapy of OBP-301 and ZOL suppresses osteosarcoma progression via suppression of MCL1 and osteoclast activation.
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PMID:Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction. 2868 48


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