Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fotemustine was investigated in 17 patients with progressive hepatic metastases from colorectal carcinoma to define the maximally tolerated dose for a daily hepatic intra-arterial infusion (HAI) schedule. Haematotoxicity was delayed, dose-dependent and related to pretreatment, with thrombo- and leucocytopenia being dose-limiting. Local side-effects at the liver were mild. Infection (WHO grade III) occurred in 1 patient due to neutropenia. Other side-effects, particularly renal, pulmonal, neurological or cardiac toxicity, mucositis and diarrhoea, hair loss or allergic reactions did not occur. Pharmacokinetic analysis indicated a short plasma half-life (t1/2 = 25.8 +/- 11.5 min) and a high body clearance (CL = 2193 +/- 870 ml/min) with large inter- and intra-individual variations. Of 15 evaluable patients, one complete and three partial responses were observed (ORR = 27%; CI95% [4.5-49.5%]). All tumour remissions appeared at higher dose levels in previously untreated patients. Considering the absence of mucosal side-effects, such as mucositis/diarrhoea and of hepatic toxicity, this agent was well tolerated. The recommended intra-arterial dose for consecutive phase II trials is 125 mg/m2/day1-3.
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PMID:Phase I pharmacological study of intra-arterially infused fotemustine for colorectal liver metastases. 962 43

Interleukin 2 (IL-2) administered at low doses for prolonged periods can markedly expand the number of CD56(+) natural killer (NK) cells in patients with metastatic cancer. The cytotoxic capacity of NK cells obtained from patients receiving IL-2 in vivo can be dramatically augmented by additional exposure to IL-2 in vitro. These observations formed the basis of a clinical trial in which patients with metastatic cancer were treated with low-dose continuous daily infusions of IL-2 to increase the number of their NK cells in conjunction with intermittent boluses of additional IL-2 to stimulate this expanded pool of cytotoxic cells. Twenty-three patients were registered to receive IL-2 at 4.5 x 10(5) units/m2/day for 8 weeks by continuous i.v. infusion. After 4 weeks of "priming" with low-dose continuous infusion IL-2, cohorts of three to five patients received 5 weekly 2-h boluses of IL-2 at doses ranging from 2.5 x 10(5) units/m2 to 1.0 x 10(6) units/m2. Low-dose continuous infusion IL-2 was usually well tolerated; 2-h bolus infusions of IL-2 were often associated with high fevers and constitutional symptoms that resolved after several hours. Low-dose continuous infusion IL-2 resulted in the progressive expansion of circulating CD56(+)CD3(-) NK cells. In contrast, each bolus infusion of IL-2 resulted in an immediate dramatic decrease in both the number of NK cells and activated T lymphocytes with recovery noted within 24 h. Bolus doses of IL-2 as low as 2.5 x 10(5) units/m2 were capable of producing these effects. Cytolytic activity against NK-sensitive and -resistant targets correlated with the presence of circulating activated NK cells. Our results demonstrate that NK cells expanded by low-dose continuous infusions of IL-2 can be further activated in vivo by exposure to very low doses of IL-2 as a 2-h i.v. bolus. This capacity to manipulate human NK cells in vivo through varying the dose and schedule of IL-2 administration may help in defining the therapeutic potential of these cytotoxic effectors in the treatment of both neoplastic and infectious diseases.
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PMID:Expansion and manipulation of natural killer cells in patients with metastatic cancer by low-dose continuous infusion and intermittent bolus administration of interleukin 2. 981 95

Imaging of the spine and spinal cord has traditionally been accomplished with plain radiography, myelography, and CT. Recently, MR imaging has become the technique of choice in the assessment of lesions of the spine and spinal cord. MR imaging provides accurate localization of intramedullary, intradural extramedullary, and extradural tumors. Ependymomas and low-grade astrocytomas are the most common intramedullary tumors. MR imaging findings are distinguishable by the delineation and size of the lesion, and the signal intensity on T2-weighted images. Other less common tumors include malignant astrocytomas, hemangioblastomas, and intramedullary metastasis. Numerous foci of high-velocity signal loss are seen in the hemangioblastomas. Metastasis, meningiomas, and schwannomas are the most common intradural extramedullary tumors. Meningiomas are characterized by dural enhancement on postcontrast T1-weighted images. Schwannomas and neurofibromas often erode bony structures and appear to be dumbbell-shaped. Epidural metastasis accounts for the majority of extradural tumors. Primary malignant extradural tumors include lymphomas, chordomas, and so on. The most common primary benign extradural tumor is hemangioma, which often appears to be hyperintense on both T1-weighted and T2-weighted images. Intramedullary non-neoplastic lesions include demyelinating, vascular, and infectious diseases. Diffuse, peripheral, or speckled contrast enhancement, and lack of contrast enhancement may suggest non-neoplastic lesions.
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PMID:[Imaging of tumors of the spine and spinal cord]. 1086 Mar 80

The most frequent orthopedic emergency in oncology patients is fracture. Stabilization of the entire fractured bone restores function and relieves pain. The site, quality, and extent of the lesion can identify impending fractures that should be stabilized. New methods of pelvic stabilization effectively bypass periacetabular bone deficiency. Spinal cord decompression is important to maintain neurologic function. Advances in segmental fixation of the spine have improved the outcome over what was achieved by radiation alone. Infection is common in neutropenic patients, and should be treated aggressively with antibiotics and drainage of abscesses of the musculoskeletal system. Extravasation of doxorubicin requires prompt local debridement to limit the extent of necrosis propagation. These treatments can effectively improve the quality of life of patients with metastatic cancer. They should be included as "best supportive care" for patients with more than 1 month to live.
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PMID:Orthopedic emergencies in cancer patients. 1086 18

Improvement in the high mortality from Staphylococcus aureus septicemia must address the individualized treatment (surgery and/or prolonged antibiotic treatment) of metastatic complications. The aim of this study was to evaluate the results of a comprehensive diagnostic monitoring for metastatic complications in S. aureus septicemia. 68 consecutive patients with S. aureus septicemia were prospectively followed. The performance rate and results of chest X-ray, echocardiography, bone scintigraphy and leukocyte scintigraphy are described. Metastatic complications were found in 53% of the 68 patients, endocarditis in 26%. Positive findings resulted in surgical intervention in 23 patients. The total mortality defined as all deaths within 12 weeks was 24%; 81% of the deceased were > or = 60 years of age. Non-endocarditis patients with peripheral septic metastases had good prognosis. An active monitoring for metastatic complications in S. aureus septicemia is a necessary prerequisite for optimizing treatment and to improve survival rate.
Infection
PMID:Metastatic complications of Staphylococcus aureus septicemia. To seek is to find. 1087 35

Thyroid imaging approach is based on the preliminary clinical evaluation. Lesions that are smaller than 2 cm should be assessed with US, which is capable of discriminating masses as small as 2 mm and distinguishing solid from cystic nodules. US-guided FNAB provides tissue for cytologic examination of thyroid nodules. CT and MR imaging are indicated for larger tumors (greater than 3 cm diameter) that extend outside the gland to adjoining structures, including the mediastinum, and retropharyngeal region. Metastatic lymph nodes in the neck and invasion of the aerodigestive tract are also in the realm of CT and MR imaging. Thyroid nodules are categorized on scintigraphy as hot or cold nodules. Hot nodules are rarely malignant, whereas cold nodules have an incidence of 10% to 20% of malignancy. Calcifications (amorphous, globular, nodular, and linear) occur in adenomas and carcinomas and have no differential diagnostic features except for psammomatous calcifications, which are a pathognomonic finding in papillary carcinomas and a small percentage of medullary carcinomas. Papillary carcinoma is the most common malignant tumor (80%) followed by follicular (20% to 25%); medullary (5%); undifferentiated; anaplastic carcinomas (< 5%); lymphoma (5%); and metastases. Lymph node metastases are common in papillary carcinoma, 50% at presentation, and less common in follicular carcinomas. The metastatic nodes in papillary carcinoma may enhance markedly (hypervascular); show increased signal intensity on T1-weighted images (increased thyroglobulin content or hemorrhage); and reveal punctate calcifications. Localized invasion of the larynx, trachea, and esophagus occurs predominantly in papillary and follicular carcinomas; the incidence is less than 5%. Ectopic thyroid tissue may be encountered in the tongue (foramen cecum); along the midline between posterior tongue and isthmus of thyroid gland; lateral neck; mediastinum; and oral cavity. Goiter and malignant tumors, notably papillary carcinoma, may develop in ectopic thyroid tissue. Carcinomas may also arise in thyroglossal duct cysts, which develop from duct remnants between the foramen cecum and thyroid isthmus. Infectious disease of the thyroid gland is not common and the CT and MR imaging findings are similar as described under neck infection. Other types of inflammatory disorders including Hashimoto's thyroiditis, granulomatous thyroiditis, and Riedel's struma display no specific imaging features. Imaging studies may, however, be indicated to confirm a suspected clinical diagnosis and assess compromise of the airway (Riedel's struma). HPT is a clinical diagnosis in which hypercalcemia is the most important finding. Parathyroid hyperplasia, adenoma, and carcinoma represent underlying lesions. To relieve the patient's symptoms surgical extirpation is indicated. The surgical success rate without imaging is 95%. The indications for imaging studies vary but it is generally agreed that reoperation after a previous failed surgical attempt and suspicion of an ectopic parathyroid adenoma should be investigated by imaging. These consist of US, nuclear medicine studies, CT and MR imaging. US and technetium sestamibi scanning have the highest accuracy rate for localizing an adenomatous gland at and near the thyroid gland. Ectopic adenomas, particularly if they are located in the mediastinum, are preferrably investigated with CT and MR imaging with gadolinium and fat suppression. Carcinomas and parathyroid cysts are optimally evaluated by CT and MR imaging. On MR imaging adenomas are low in signal intensity on T1-weighted images, high in signal intensity on T2-weighted images, and enhance post introduction of gadolinium.
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PMID:The thyroid and parathyroid glands. CT and MR imaging and correlation with pathology and clinical findings. 1105 72

The sacrum is a structure that is imaged by both general and subspecialty radiologists. A wide variety of disease processes can involve the sacrum either focally or as part of a systemic process. Plain radiographs, although limited in evaluation of the sacrum, should be carefully examined when abnormalities of the sacrum are suspected. Cross-sectional imaging, particularly computed tomography and magnetic resonance (MR) imaging, plays a crucial role in identification, localization, and characterization of sacral lesions. Congenital lesions of the sacrum, including sacral agenesis and meningocele, are optimally imaged with MR. The most common sacral neoplasm is metastatic disease. Primary neoplasms of the sacrum, which include giant cell tumor, chordoma, and teratoma, are infrequent. Infection of the sacrum or sacroiliac joint is most often due to contiguous spread from a suppurative focus. A wide variety of arthritic disorders such as ankylosing spondylitis and osteoarthritis can involve the sacroiliac joints as part of a localized or systemic process. Sacral fractures related to acute trauma or repetitive stress are difficult to diagnose and treat. Knowledge of these abnormalities and familiarity with the imaging of these processes will allow radiologists of all subspecialties to contribute to the diagnosis and management of sacral disorders.
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PMID:The sacrum: pathologic spectrum, multimodality imaging, and subspecialty approach. 1115 46

A massive prosthesis and medial gastrocnemius muscle transfer were used to reconstruct the knee after extracapsular en bloc excision for bone sarcoma. Magnetic resonance images showed intraarticular involvement. This technique was used in nine patients, six men and three women aged 18 to 51 years, with primary malignant bone tumors of the knee. Extraarticular resection of the knee, including the patella, was done in every case. A knee prosthesis was implanted, and the extensor mechanism was reconstructed by transfer of the medial gastrocnemius muscle and pes anserinus tendons. All resections had negative margins. There were no local recurrences, but metastases occurred in two patients. Infection was the only major complication and was seen in two patients. The mean postoperative Musculoskeletal Tumor Society score was 61% (range, 36%-100%). The mean postoperative range of flexion was 62 degrees (range, 30 degrees-90 degrees), and the mean extensor lag was 12 degrees (range, 0 degrees-40 degrees). Three patients required a crutch to walk. The functional outcome was poor in the two patients whose proximal tibia was removed with the joint, suggesting that arthrodesis may be best in this situation. In properly selected patients, prosthesis and muscle flap reconstruction provides acceptable function and a good cosmetic result.
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PMID:Knee reconstruction with prosthesis and muscle flap after total arthrectomy. 1124 67

Expression of Fas (CD95, APO-1), a cell surface receptor capable of inducing ligand-mediated apoptosis, is involved in tissue homeostasis and elimination of targeted cells by natural killer and T cells. Corruption of this pathway, such as reduced Fas expression, can allow tumor cells to escape elimination and promote metastatic potential. In this study, the status of Fas expression has been examined in the parental SAOS human osteosarcoma cells that do not metastasize and in selected variants that cause lung metastases in 16 weeks (LM2) or 8 weeks (LM6) after i.v. injection into nude mice. Fas expression correlated with the metastatic potentials of the three cell lines. Northern and fluorescence-activated cell-sorting analyses indicated that LM6 cells expressed Fas at a lower level than seen in the parental cells. Infection of the LM6 cells with an adenoviral vector containing the murine interleukin (IL)-12 gene (AD:mIL-12) or treatment with recombinant murine IL-12 resulted in a dose-dependent up-regulation of FAS: The up-regulation of Fas by IL-12 was also demonstrated in human etoposide-resistant MDA-MB-231 breast cancer cells. [(3)H]Thymidine growth inhibition studies indicated that the cell surface Fas induced after IL-12 exposure was functional and able to mediate cell death on cross-linking with anti-FAS: We also demonstrate that this effect is independent of IFN-gamma. Whereas these cell lines are sensitive to IFN-gamma, incubation with IFN-gamma does not increase susceptibility to Fas-mediated cell death, nor do these cells produce IFN-gamma with or without IL-12 treatment. We hypothesize that expression of Fas may play a role in the elimination of metastatic tumor cells in the lung, an organ in which Fas ligand is expressed. The antitumor activity of IL-12 may be secondary in part to its ability to up-regulate Fas expression on tumor cells, which subsequently increases immune-mediated destruction of osteosarcoma cells.
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PMID:Interleukin (IL)-12 and IL-12 gene transfer up-regulate Fas expression in human osteosarcoma and breast cancer cells. 1135 27

PRUNE, the human homologue of the Drosophila gene, is located in 1q21.3, a region highly amplified in human sarcomas, malignant tumours of mesenchymal origin. Prune protein interacts with the metastasis suppressor nm23-H1, but shows impaired affinity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggested that prune may act as a negative regulator of nm23-H1 activity. We found amplification of PRUNE in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant fibrous histiocytomas (MFH) as well as in the less malignant liposarcomas. PRUNE amplification was generally accompanied by high mRNA and moderate to high protein levels. The sarcoma samples expressed nm23-H1 mostly at low or moderate levels, whereas mRNA and protein levels were moderate to high in breast carcinomas. For the more aggressive sarcoma subtypes, 9/13 patients with PRUNE amplification developed metastases. A similar situation was observed in all breast carcinomas with amplification of PRUNE. Infection of NIH3T3 cells with a PRUNE recombinant retrovirus increased cell proliferation. Possibly, amplification and overexpression of PRUNE has the same effect in the tumours. We suggest that amplification and overexpression of PRUNE could be a mechanism for inhibition of nm23-H1 activity that affect the development or progression of these tumours.
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PMID:Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas-a possible mechanism for altering the nm23-H1 activity. 1168 67


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