Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0279530 (bone cancer)
 1,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recent development of rodent models of bone cancer pain has started to provide the basis for demonstrating the particular neurochemical and behavioral entity of cancer pain. Behaviourally, both spontaneous pain and hyperalgesia related to mechanical, but not thermal, noxious stimuli have been described in cancer-bearing animals. We have carried out a histological and behavioural study focused on the reactivity to noxious heat in C3H/HeJ mice receiving an intratibial injection of 10(5) NCTC 2472 cells. These cells, able to induce an osteosarcoma, break through bone into soft tissues 2 weeks after cell inoculation, producing a macroscopical increase of the limb size from the fourth week. Thermal reactivity is diminished during the first 2 weeks after cell implantation, this hypoalgesia being reversed by the administration of naloxone (10 mg/kg). In contrast, during the fourth and fifth weeks after NCTC 2472 cell implantation, an increased nociceptive heat reactivity, instead of hypoalgesia, was obtained. This thermal hyperalgesia was prevented by the systemic administration of morphine (15 mg/kg). Throughout the whole period studied, mice showed signs of spontaneous pain behaviour that reached its maximum 3 weeks after inoculation. In conclusion, we show that the presence of thermal heat hyperalgesia is preceded by an initial opioid-mediated hypoalgesic state, in this murine model of bone cancer pain.
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PMID:Initial thermal heat hypoalgesia and delayed hyperalgesia in a murine model of bone cancer pain. 1267 70

Studies of occupational exposures have been a fruitful area of research for identifying carcinogens. Some of the early observations, such as increased risk of breast cancer among nuns and bone cancer among radium dial workers, were made among women. Recent research on cancer among women has shown increased risks of cancer in many industries and occupations. Estimates that 1% of cancer among women is attributable to occupation are based on research conducted mainly in the 1970s among men in developed countries. These studies do not reflect the dramatic changes in the participation of women in the workplace or the patterns of employment of women in developing countries. The proportion of women in the paid workforce, the amounts and types of unpaid labor, the distribution of women by economy sector, the scale of the workplaces, the allowable exposure levels in the workplace, and implementation of controls have changed over time and vary internationally. Occupational cancer researchers need to expand their focus on women, increase activities in developing countries, include newly created industries, use sophisticated exposure assessment methods, and, where appropriate, incorporate molecular epidemiologic techniques to discover new occupational carcinogens and to identify where better control measures are needed.
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PMID:Occupational cancer among women: where have we been and where are we going? 1463 33

Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The North American pediatric cooperative groups have performed a series of clinical treatment trials in this disease over the past several decades, and biology studies of tumor tissue have been an important study component. A meeting was held in Bethesda, Maryland on November 29-30, 2001, sponsored by the NIH Office of Rare Diseases, the Children's Oncology Group, and the National Cancer Institute-Cancer Therapy Evaluation Program with the general objectives: (a) to review the current state of knowledge regarding OS biology; (b) to identify, prioritize, and support the development of biology studies of potential clinical relevance in OS; and (c) to discuss the available tissue resources and the appropriate methods for analysis of OS samples for the conduct of biology studies. This report summarizes the information presented and discussed by the meeting participants.
Clin Cancer Res 2003 Nov 15
PMID:Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary. 1465 23

Radiotherapy is the cornerstone of palliative treatment for primary bone cancer in animals and metastatic bone cancer in humans. However, the mechanism(s) responsible for pain relief after irradiation is unknown. To identify the mechanism through which radiation treatment decreases bone cancer pain, the effect of radiation on mice with painful bone cancer was studied. Analysis of the effects of a 20-Gy treatment on localized sites of painful bone cancers was performed through assessments of animal behavior, radiographs and histological analysis. The findings indicated that radiation treatment reduced bone pain and supported reduced cancer burden and reduced osteolysis as mechanisms through which radiation reduces bone cancer pain.
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PMID:Radiation treatment decreases bone cancer pain, osteolysis and tumor size. 1473 Oct 66

Although bone cancer pain can be severe and is relatively common, as it frequently arises from metastases from breast, prostate, and lung tumours, very little is known about the basic mechanisms that generate and maintain this chronic pain. To begin to define the mechanisms that give rise to bone cancer pain, we have developed mouse and rat models using the intramedullary injection and containment of tumour cells into the femur. These tumour cells induced bone remodelling as well as ongoing and movement evoked pain behaviours similar to that found in patients with bone cancer pain. In addition there is a significant reorganization of the spinal cord that received sensory input from the cancerous bone and this reorganization generated a neurochemical signature of bone cancer pain that is both dramatic and significantly different from that observed in mouse and rat models of chronic neuropathic or inflammatory pain. These models have provided insight into the mechanisms that drive cancer pain and have begun to allow the development of mechanism-based therapies. Together these advances should reduce tumour-induced pain and suffering and significantly improve the quality of life of cancer patients.
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PMID:Mechanisms that generate and maintain bone cancer pain. 1528 53

Rubitecan [Orathecin, 9-nitrocamptothecin, 9NC, RFS 2000] is a topoisomerase I inhibitor extracted from the bark and leaves of the Camptotheca acuminata tree, which is native to China. Rubitecan is an oral compound being developed for the treatment of pancreatic cancer and other solid tumours by SuperGen. One of the major benefits of rubitecan is that it can be administered in an outpatient setting, so patients can be treated in their homes. Rubitecan was isolated by the Stehlin Foundation in the US. SuperGen is currently awaiting regulatory approval in the US and the EU for rubitecan in the treatment of pancreatic cancer. At the BIO-2004 conference, SuperGen announced it is seeking a partner for rubitecan for territories outside the US. SuperGen acquired exclusive worldwide rights to rubitecan from the Stehlin Foundation in 1997 except in Mexico, Canada, Spain, Japan, the UK, France, Italy and Germany. SuperGen has also received approval from the US FDA to use its own manufactured rubitecan in clinical trials. SuperGen and the Stehlin Foundation have an 8-year research agreement that secures global rights to other camptothecins and additional anticancer compounds for the former. In December 1999, SuperGen and Abbott signed a worldwide sales and marketing agreement for rubitecan. Under the terms of the agreement, Abbott had exclusive distribution and promotion rights for rubitecan outside the US, and co-promotion rights with SuperGen within the US. In return, Abbott made an initial equity investment in SuperGen. SuperGen and Abbott Laboratories ended their collaboration agreement in February 2002 by mutual consent with SuperGen stating that the dissolution of the agreement was based on commercial motivation rather than anything to do with rubitecan's safety or efficacy. Abbott no longer has rights or obligations to purchase shares of SuperGen stock or an option to purchase up to 49% of the company. For its part, SuperGen will no longer receive milestone payments worth up to $US57 million. SuperGen has formed a clinical and business alliance with US Oncology (created by the merger between American Oncology Resources and Physician Reliance Network in the US), and will collaborate on clinical trials of rubitecan. SuperGen believes that this relationship will increase the patient population available for trials and enable it to market the drug directly to Oncologists. SuperGen and Capital Research and Management Company have completed a $US16.6 million private placement transaction that will enable future funding for the rubitecan programme as well as other oncology programmes. In July 2004, SuperGen's European subsidiary, EuroGen Pharmaceuticals, submitted a Marketing Authorisation Application for rubitecan in the treatment of pancreatic cancer. The application will be reviewed under the EMEA Centralised Procedure. In June 2003, the EMEA granted SuperGen orphan drug status for rubitecan for the treatment of pancreatic cancer. The US FDA has also granted orphan drug status for rubitecan in the treatment of pancreatic cancer and fast-track status for rubitecan for the treatment of locally advanced or metastatic pancreatic cancer that is resistant or refractory to chemotherapy. SuperGen has conducted three phase III pivotal trials in patients with pancreatic cancer. A phase III randomised trial in chemotherapy-naive patients was conducted at 132 centres throughout the US. The trial enrolled approximately 994 patients who were randomised to receive rubitecan or gemcitabine. Enrollment was completed in October 2001. Another phase III trial has compared rubitecan with the most appropriate chemotherapy in chemotherapy-resistant patients. Enrollment of over 400 patients at 200 medical centres across the US was completed in June 2001. Results from the trial were presented at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO-2003) [Chicago, US; 31 May - 3 June 2003], after they had been compiled, analysed and submitted to the FDA. The results of the study showed that rubitecan could not help all chemotherapy-resistant patients, but could increase survival in those that do respond. The other phase III pivotal trial was conducted in patients with pancreatic cancer who had failed treatment with gemcitabine. This trial completed enrollment in October 2001, and had enrolled approximately 448 patients. SuperGen is conducting phase II trials of rubitecan in patients with solid tumours in the UK, Italy, France, Germany, the Netherlands and Denmark. Each trial will enroll 100-150 patients with various tumour types, including colorectal, lung, breast, gastric, prostate, cervical and head and neck cancers. Phase I/II trials are underway to investigate rubitecan as a radiosensitiser in patients with lung cancer, and phase II trials in patients with breast cancer are also being conducted. A phase II study in ovarian cancer patients is also being conducted. Results from an ongoing phase II study in cancer patients have shown that rubitecan was effective against chordomas, a rare type of bone cancer. Phase II studies are also underway in haematological malignancies including myelodysplastic syndrome (preleukaemia) and chronic myelomonocytic leukaemia. In February 2000, SuperGen announced that its IND submission for rubitecan had been approved by the Therapeutics Products Programme of Canada. The company stated that it intended to begin clinical trials in Canada in the near future. In February 2004, SuperGen announced an offering of shares of its common stock to finance the commercialisation of rubitecan capsules. In July 2003, SuperGen was granted a US patent covering combination therapies with chemotherapeutic anthracycline agents and structural modifications that may one day lead to next-generation rubitecan compounds. In December 2002, SuperGen was granted US patent No. 6,482,830, covering its polymorphic formulations of rubitecan. The patent also covers a class of polymorphs that are similar to the one at the centre of rubitecan. In addition, SuperGen was also issued US patent No. 6,485,514 in December 2002, covering the local delivery of rubitecan via stents and/or catheters to sites of proliferating cells. Stent- or catheter-delivered rubitecan may be beneficial in certain types of cardiac procedures, such as ablation or angioplasty, as well as for direct injection into a certain number of solid tumours. SuperGen is also developing an inhaled, liposomal formulation of rubitecan. It acquired the worldwide rights to this formulation from the Clayton Foundation in December 1999. Inhaled rubitecan is in clinical trials in the US for the treatment of lung cancer and pulmonary metastatic cancer.
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PMID:Rubitecan: 9-NC, 9-Nitro-20(S)-camptothecin, 9-nitro-camptothecin, 9-nitrocamptothecin, RFS 2000, RFS2000. 1535 30

Data from beagle experiments and radium dial painters were used to derive two-mutation carcinogenesis models for bone cancer induced by the bone-seeking radionuclides radium, strontium and plutonium. For all data, the model fits indicate that at low doses both mutation rates depend linearly and equally strongly on dose rate. For the high-LET alpha-particle emitters, a cell killing term reduces the second mutation rate at high dose rates. In all cases, the combined effect of both mutation rates is a linear-quadratic dose-effect relationship for cancer at low doses. This behavior may lead to experimental data that could be mistaken as showing a threshold below which no cancers are induced. Derived parameters such as toxicity ratios and tumor growth times compare well with values reported in the literature. Furthermore, results for plutonium indicate that rapid burial of the nuclide in the growing bones of juvenile beagles leads to a significant reduction of its toxicity, as was suggested previously. The results for radium in beagles compare well with those for humans and suggest that the models derived for strontium and plutonium in beagles may be translated to humans. The significant model parameters for the accurate animal data could then also be used to fit human epidemiological data.
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PMID:Two-mutation models for bone cancer due to radium, strontium and plutonium. 1629 90

Cancer-induced bone diseases are common and can have a devastating impact at the end of life. One of the most difficult sequelae of cancer is metastases to the skeleton, an event that results in bone destruction and bone cancer pain. Bone cancer pain is usually progressive as the disease advances, and is particularly difficult to treat. Recently, experimental models of bone cancer pain have been developed and have provided seminal insight in understanding the pathophysiology of bone cancer pain. Animal models of bone cancer provided the finding that bone destruction (osteolysis) is associated with pain, and it has been determined that cancer-induced osteolysis is mediated by osteoclasts. Having established that RANK ligand contributed to cancer-induced osteoclastogenesis, it was determined that disruption of the RANKL-RANK axis with OPG inhibited tumor-induced osteoclastogenesis and decreased bone cancer pain.
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PMID:Bone cancer pain and the role of RANKL/OPG. 1561 97

The potential targeting of therapeutic bisphosphonate conjugates to bone metastatic lesions was evaluated in vivo in mice. A bisphosphonate conjugate with 5-fluorouracil was synthesized as a potential chemotherapy agent, and a bisphosphonate conjugate with diethylenetriaminepentaacetic acid (DTPA) was prepared as a potential carrier of cytotoxic radionuclides. The compounds are hypothesized to be able to deliver either high doses of radiation or a high concentration of chemotherapy agents at sites of increased osteoclastic activity in patients with bony metastases while exhibiting minimal toxicity to normal tissues. Tissue distribution studies with the 99mTc-labeled bisphosphonate conjugates with DTPA and 5-fluorouracil showed rapid blood clearance and excretion of unbound activity, clearance from most tissues, and substantial retention of the bisphosphonates in bone. For the DTPA conjugate, activity in the bone represents 13.6% of the total injected dose at 8 hours following injection, representing 54.3% of the total whole-body activity at this time period. Under the same conditions, the 5-fluorouracil conjugate showed a 17.1% bone uptake at 60.2% of the whole-body activity. This normal bone uptake predicts that high concentrations of conjugates are expected to be achieved at sites of bone metastatic disease. Chemotherapy and radiotherapy studies with these compounds in animal models of metastatic bone cancer are underway.
Cancer Biother Radiopharm 2004 Oct
PMID:Preclinical investigations of drug and radionuclide conjugates of bisphosphonates for the treatment of metastatic bone cancer. 1565 Apr 56

Pain often discloses the existence of bone tumors in children. The complex physiopathology of pain in malignant bone tumors remains largely unknown and is currently investigated. Cancer-related bone pain is independent from the type and the location of the tumor, and from the number and size of the malignant lesions. It does not necessarily increase with tumor growth. Pain, which is the most common early symptom of bone cancer, may also be present at every step of the disease. It may arise from postsurgery injury, side effects of chemo- or radiotherapy, tumor evolution, secondary sequels of treatments, phantom pain. Tumor eradication using cancer therapeutic strategies is the major etiological treatment option for bone cancer pain. Symptom control requires multidisciplinary medical management with drugs effective against bone lysis, analgesics, drugs with anti-neuropathic activity, as well as non-pharmacological techniques and psycho-social management. This psycho-social management must be tailored to the specific needs of teenagers who are particularly prone to this pathological manifestation. Measures to prevent the occurrence of residual chronic pain must be implemented, whereas children and their family should be clearly informed of the risks and of analgesic options available.
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PMID:[Cancer-related bone pain in children]. 1569 47


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