Cancer Osteogenic sarcoma

Methotrexate Inhibits DHFR inhibits TS inhibits de novo purine nucleotide synthesis Breast cancer, head and neck cancer, osteogenic sarcoma, primary central nervous system lymphoma, non-Hodgkin s lymphoma, bladder cancer, chorioca rcinoma Mucositis, diarrhea, myelosuppression with neutropenia and thrombocytopenia... 

Human Toxicity Inhalation, ingestion or body exposure may result in lung cancer, osteogenic sarcoma, osteitis, blood dyscrasias, skin injury. 

Acute lymphocytic leukemia choriocarcinoma breast, head, neck, and lung cancer osteogenic sarcoma bladder cancer Mesothehoma, lung cancer... 

MTX is part of curative therapeutic schedules for acute lymphoblastic leukemias (ALL), Burkitt s lymphoma, and choriocarcinoma. It was also used in adjuvant therapy of breast cancer. High dose MTX with leucovorin rescue can induce about 30% remissions in patients with metastatic osteogenic sarcoma. MTX is one of the few antineoplastic drugs that can be safely administered intrathecally for the treatment of meningeal metastases and leukemic infiltrations (routine prophylaxis in ALL). In addition, MTX can be used as an immunosuppressive agent for the treatment of severe rheumatoid arthritis and psoriasis. 

Interferon does not only inhibit vims replicahon, it also has mulhple effects on cell metabolism and slows down the growth and mulhplicahon of treated cells. This is probably responsible for its widely reported anhtumour effect Encouraging results have been reported from clinical trials of interferon against several human tumours such as osteogenic sarcoma, myeloma, lymphoma and breast cancer. 

This is an unusual drug in that it contains a metal atom, platinum (Pt) in this case. Cisplatin reacts with DNA to cross-link bases, disrupting normal DNA structure and function. This agent has found broad use in cancer chemotherapy, including efficacy in tumors of the testis, ovary, bladder, head and neck, thyroid, cervix, and endometrium. It is also active against neuroblastoma and osteogenic sarcoma. 

The radiation from radium can cause cancer in the lung, osteogenic sarcoma, blood dyscrasias and injury to skin. Inhalation, ingestion, skin contact or body exposure to radium and aU its salts must be avoided. 

Doxorubicin is one of the most effective agents used in the treatment of carcinomas of the breast, ovary, endometrium, bladder, and thyroid and in oat cell cancer of the lung. It is included in several combination regimens for diffuse lymphomas and Hodgkin s disease. Doxorubicin can be used as an alternative to daunorubicin in acute leukemias and is useful in Ewing s sarcoma, osteogenic sarcoma, soft-tissue sarcomas, and neuroblastoma. Some activity has been reported in non-oat cell lung cancer, multiple myeloma, and adenocarcinomas of the stomach, prostate, and testis. 

Recent work has centered upon use of interferon as a therapeutic agent in humans and animals. In humans, local application of monkey interferon is effective in reducing the seventy of vaccinia virus skin infections. Recent results with herpes keratitis and chronic hepatitis are promising. Interferon appears to be active against oncogenic viruses in the treatment of such cancers as osteogenic sarcoma, and at present it is only the limited availability of interferon that pie vents more extensive testing. 

Some of the radium dial painters ingested amounts of radium sufficient to cause death within a few years of their employment. Martland (1931) described the cases of 18 dial painters who died of cancer at ages 20 to 54 years old. Causes of death were listed as anemia, necrosis of the jaw, and osteogenic sarcoma. The typical period of exposure was about two years. 

Intermediate-Duration Exposure. There are no data on intermediate-duration exposure of humans to radium via the inhalation, oral, or dermal routes. There are no data on animals exposed via inhalation or the dermal route. The only information located was a very limited 20-day oral study in rats that resulted in osteogenic sarcomas. The data were not sufficient to calculate an MRL by any route. The available toxicokinetic data show that radium can be absorbed and retained after inhalation or oral exposure, although quantitative data are lacking. It would be useful to have information on the effects of intermediate-duration exposure to radium via inhalation, oral, and dermal routes in order to help assess the potential health effects of exposure to radium in the vicinity of hazardous waste sites and other settings, and to evaluate the possibility of long-range effects such as cancer that may emerge years later. 

Martland H. 1931. The occurrence of malignancy in radioactive persons A general review of data gathered in the study of the radium dial painters, with special reference to the occurrence of osteogenic sarcoma and the inter-relationship of certain blood diseases. Am J Cancer 15 2435-2515. 

Primary chemotherapy (prior to local surgery) is now extensively used in patients with osteogenic sarcoma and has facilitated limb-sparing procedures. Primary chemotherapy is also being evaluated in breast cancer to "downstage" patients prior to surgery. 

Osteogenic sarcoma Cancer associated with bone structures. 

OEHHA Office of Environmental Health Hazard Assessment OSHA Occnpational Safety and Health Administration Osteogenic sarcoma Cancer associated with bone structures Oxidation Chemical addition of oxygen to break down pollutants or organic waste, for example, destruction of chemical substances such as cyanides, phenols, and organic sulfur compounds in sewage by bacterial and chemical means Oxidative stress Process whereby the metabolic balance of a cell is disrupted by exposure to environmental substances, resulting in accumulation of free radicals, which can damage the cell... 

Smith MA, Ungerleider RS, Horowitz ME, Simon R. Influence of doxorubicin dose intensity on response and outcome for patients with osteogenic sarcoma and Ewing s sarcoma. J Natl Cancer Inst 1991 83 1460-70. 

Using the Bodansky (B18, 52) procedure with 8-glycerophosphate as substrate, Woodard (W8) was unable to obtain such elevations. She determined the serum acid phosphatase activities in 83 females and 342 males, or a total of 425 patients with miscellaneous diseases. Of these, 61 had various types of infectious or metabolic disorders, including 11 cases of inflammatory disease of bone and 12 cases of hepatic cirrhosis. The remainder had some type of neoplastic disease and about one-third had metastases to bone from cancer of various primary sites. There were 15 cases of osteogenic sarcoma and 32 cases of osteitis deformans. All these cases, whether their serum alkaline phosphatase activities were elevated or not, had serum acid phosphatase values that were essentially within the normal range, 0.06-0.89 Bodansky unit for females and 0.11-0.88 unit for males. In contrast to the Gutman method (GIO, G14), there-... 

Epirubicin EU and osteogenic sarcomas, pediatric malignancies, and adult solid tumors (particularly lung and breast cancers) Breast, ovarian, gastric, and... 

Although beryllium produces cancer in more than one animal species (lung cancer in rats and monkeys osteogenic sarcoma in rabbits), it does not appear to be teratogenic. 

Folate analogues, such as methotrexate (Figure 27-3), are folate antagonists. They block production of FH2 and FH4 by dihydrofolate reductase and lead to diminished purine biosynthesis (inhibition of reactions 3 and 9 in Figure 27-8). Methotrexate also affects metabolism of amino acids and pyrimidine (inhibition of thymidylate synthesis) and inhibits DNA, RNA, and protein synthesis. It is effective in the treatment of breast cancer, cancer of the head and neck, choriocarcinoma, osteogenic sarcoma, and acute forms of leukemia. High doses of methotrexate can be tolerated provided that the patient also receives folinic... 

Thorpe, W. P., Reilly, J. J., and Rosenberg, S. A., Prognostic significance of alkaline phosphatase measurements in patients with osteogenic sarcoma receiving chemotherapy. Cancer 43, 2178-2181 (1979). 

Srivastava A, Euchs B, Zhang K, et al. High WTl expression is associated with very poor survival of patients with osteogenic sarcoma metastasis. Clin Cancer Res. 2006 12 4237-4243. 

Argyris BF, Reif AE. 1981. Lack of suppressor cell activity in the spleens of mice with radiation-induced osteogenic sarcomas. Cancer Res 41 839-844. 

One of the early applications of this leucovorin rescue technique was osteogenic sarcoma. It has since been successfully applied to acute leukemia, non-Hodgkin s lymphoma, and lung cancer. 

The classic antifolate methotrexate MTX continues to be an important component of the chemotherapeutic armamentarium for a variety of cancers including pediatric ALL, osteogenic sarcoma, lymphoma, and breast cancer. Raltitrexed, another anti-folate, is used throughout much of the world outside of the United States for advanced colorectal cancer. Finally, Peme-trexed was approved in 2004 for the treatment of pleural mesothelioma and shortly thereafter as a second line treatment for nonsmall cell lung cancer. These drugs mimic the natural folate molecule and in so doing utilize the membrane-bound reduced folate carrier (RFC) protein system to gain entry into the cell. 

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