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)

Improvements in surgery and radiotherapy techniques have led to only a modest increase in the 5-year survival rate for patients with head and neck cancer. This is because the pattern of clinical disease is changing, such that locoregional recurrence now accounts for fewer treatment failures, but more patients develop a second primary cancer or distant metastatic disease. In this study, we have used the p53 phage plaque assay, immunocytochemistry, and mutational analysis to assess the contribution of minimal residual cancer and genetic aberrations in clinically normal upper aerodigestive tract mucosa to treatment failure. Eighteen consecutive patients with oral tumors, with conventional clear margins, have been followed for a minimum of 36 months. Molecular assessment identified tumor-positive surgical margins for 6 of 11 assessable patients and additional tumor-positive lymph nodes for three cases. Disseminated malignant cells were detected in the hematopoietic cell compartment for six cases, and one patient had molecular evidence of field cancerization. Locoregional recurrence developed in five patients with tumors harboring a p53 gene mutation; four of these were associated with tumor-positive surgical margins, and one was associated with molecular evidence of field cancerization. Radiotherapy to the primary site did not prevent development of local recurrence when the residual tumor harbored a p53 gene mutation. Three of six cases with a tumor-positive bone marrow aspirate developed distant metastases. These findings reveal that molecular and immunocytochemical detection of minimal residual cancer and field cancerization can help identify patients who may develop locoregional or distant recurrence and justify further studies to evaluate the contribution of these remaining malignant cells to treatment failure.
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PMID:Detection of minimal residual cancer to investigate why oral tumors recur despite seemingly adequate treatment. 1091 16

Primary surgical cytoreduction followed by chemotherapy usually is the preferred management of advanced (stage III or IV) ovarian cancer. The presence of residual disease after surgery is one of the most important adverse prognostic factors for survival. Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management of bulky ovarian cancer, with the goal of improving surgical quality. Since 1989, we have been treating advanced epithelial ovarian cancer with neoadjuvant chemotherapy instead of primary cytoreductive surgery in approximately half of the patients with stage III-IV disease. Selection of neoadjuvant chemotherapy was based on disease-related characteristics (eg, metastatic tumor load, stage of disease, performance status). Since 1993, open laparoscopy also has been used to aid in evaluating operability. A retrospective analysis of 338 patients was conducted to compare outcomes during 1989 to 1998, when neoadjuvant chemotherapy was used, with those observed during 1980 to 1988, when all patients underwent primary cytoreductive surgery. Crude 3-year survival rates were higher and postoperative mortality rates were lower during the second time period compared with the first. Overall, the results suggest that neoadjuvant chemotherapy results in survival rates in selected patients with advanced ovarian cancer that are comparable with those associated with primary cytoreductive surgery. Patients with stage IV disease, total metastatic tumor load greater than 1,000 g, uncountable plaque-shaped peritoneal metastases, and/or a poor performance status are probably the best candidates for this alternative approach. A prospective randomized study of neoadjuvant chemotherapy and primary cytoreductive surgery is ongoing.
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PMID:Neoadjuvant chemotherapy versus primary debulking surgery in advanced ovarian cancer. 1095 24

Breast carcinoma is the most common primary tumor producing intraocular metastasis. Metastases to the iris and ciliary body are relatively rare. The authors report a case of a 61-year-old lady, operated for carcinoma of the left breast 3 years back, who presented with symptoms and signs of acute narrow-angle glaucoma in the right eye. A diffuse whitish plaque-like mass in the upper nasal quadrant of the iris with an episcleral nodule on the limbus in the corresponding area and all the signs of acute narrow-angle glaucoma were present in the right eye. Intraocular pressure was controlled medically. Fine-needle aspiration cytology from the episcleral nodule showed malignant cells. Histopathology of the excised nodule showed metastatic poorly differentiated carcinoma, and the cellular pattern was similar to the carcinoma of the breast. There was no other metastasis anywhere in the body. Fine-needle aspiration cytology from an external lesion of the eye is a less invasive and easier procedure than paracentesis to diagnose the metastatic nature of the lesions. The rare features in our case are the clinical presentation as acute glaucoma and the ocular structures being the first and only site of metastasis.
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PMID:Anterior uveal and episcleral metastases from carcinoma of the breast. 1096 54

The host-immune response against adenoviruses forms a major obstacle for their use as gene therapy vectors for treatment of genetic defects. None the less, they are the preferred vectors for in vivo gene transfer in experimental gene therapy protocols for cancer. In this article we demonstrate the antitumor efficacy of adenovirus-mediated transfer of human interleukin-2 cDNA in the rat-CC531 model for hepatic metastases of colorectal cancer: intratumoral administration of 10 plaque-forming units of the hlL-2-expressing adenoviral vector, AdCAIL-2, resulted in a cessation of tumor growth in 80% of the injected tumors. In control groups receiving AdCnull, a vector with the same viral backbone, but lacking transgene expression, none of the tumors responded. However, intratumoral treatment with this vector significantly enhanced tumor regression induced by systemic IL-2 protein treatment, which was used as a positive control. In addition we show, by performing delayed-type of hypersensitivity assays, that AdCnull when injected intratumorally enhances recognition of tumor antigens by T lymphocytes to the same extent as intratumoral treatment with the IL-2-expressing vector. The replication-deficient adenoviruses appear to have a therapeutic advantage in cytokine-mediated immunotherapy: even adenovirus vectors that do not express a transgene, show adjuvant activity and stimulate an antitumor immune response.
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PMID:Recombinant adenoviral vectors have adjuvant activity and stimulate T cell responses against tumor cells. 1098 68

A prospective study with a new tumour-seeking agent, 99Tcm-glutathione (GSH), was performed on 17 patients with choroidal melanoma. Planar and SPECT images using 99Tcm-GSH clearly demonstrated melanotic melanoma but failed to show amelonotic melanomas. Following confirmation of our results by concurrent ultrasonography and magnetic resonance imaging or computed tomography, patients were managed by either 125I plaque brachytherapy, diode laser transpupillary thermotherapy or enucleation depending on the site and location. In combination with other diagnostic tests, 99Tcm-GSH scintigraphy may play a role in the detection of uveal melanoma and its possible distant metastases.
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PMID:Scintigraphic imaging of uveal melanoma with 99Tcm-glutathione. 1125 7

Prostate cancer has a high propensity to metastasize to bone, which often resists hormone, radiation, and chemotherapies. Because of the reciprocal nature of the prostate cancer and bone stroma interaction, we designed a cotargeting strategy using a conditional replication-competent adenovirus to target the growth of tumor cells and their associated osteoblasts. The recombinant Ad-OC-E1a was constructed using a noncollagenous bone matrix protein osteocalcin (OC) promoter to drive the viral early E1a gene with restricted replication in cells that express OC transcriptional activity. Unlike Ad-PSE-E1a, Ad-OC-E1a was highly efficient in inhibiting the growth of PSA-producing (LNCaP, C4-2, and ARCaP) and nonproducing (PC-3 and DU145) human prostate cancer cell lines. This virus was also found to effectively inhibit the growth of human osteoblasts and human prostate stromal cells in vitro. Athymic mice bearing s.c. androgen receptor-negative and PSA-negative PC-3 xenografts responded to a single intratumoral administration of 2 x 10(9) plaque-forming unit(s) of Ad-OC-E1a. In SCID/bg mice, intraosseous growth of androgen receptor-positive and PSA-producing C4-2 xenografts responded markedly to i.v. administrations of a single dose of Ad-OC-E1a. One hundred percent of the treated mice responded to this systemic Ad-OC-E1a therapy with a decline of serum PSA to an undetectable level, and 80% of the mice with PSA rebound responded to the second dose of systemic Ad-OC-E1a. Forty percent of the mice were found to be cured by systemic Ad-OC-E1a without subsequent PSA rebound or tumor cells found in the skeleton. This cotargeting strategy shows a broader spectrum and appears to be more effective than systemic Ad-PSE-E1a in preclinical models of human prostate cancer skeletal metastasis.
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PMID:A conditional replication-competent adenoviral vector, Ad-OC-E1a, to cotarget prostate cancer and bone stroma in an experimental model of androgen-independent prostate cancer bone metastasis. 1150 44

Experimental data show accumulation of superparamagnetic iron oxide (SPIO) particles in atherosclerotic plaques. SPIO uptake occurred in plaques, suggesting an increased endothelial permeability and macrophage infiltrates as signs of inflammatory plaque activity. We incidentally observed SPIO uptake in aortic and arterial wall segments in patients who had originally received the magnetic resonance (MR) contrast agent for staging lymph node metastases. Twenty patients (19 male, 1 female; mean age, 64; range, 41-78 years) with bladder or prostate cancer underwent MR imaging (MRI) using a T2*-weighted high-resolution gradient-echo sequence prior to and 24-36 hours after intravenous injection of 2.6 mg of Fe/kg of SPIO (Sinerem). The aorta, both common external and internal iliac, as well as both superficial femoral arteries, were retrospectively analyzed for atherosclerotic wall changes. One patient was excluded. A positive finding was defined as an area of pronounced signal loss on postcontrast images clearly confined to the arterial wall, which was absent in the precontrast examination or increased in size. Such a finding was observed in one to three arteries in 7 of the 19 patients. The pronounced signal loss in the wall of the aorta and pelvic arteries seen in part of an elderly patient population after intravenous SPIO administration strongly suggests that this contrast agent accumulates in human atherosclerotic plaques.
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PMID:Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic iron oxide particles. 1159 58

An 81-year-old woman developed a necrotic plaque and a surrounding purple-red, irregularly shaped macule on her scalp. The diagnosis of angiosarcoma was confirmed histologically. A wide surgical excision was made followed by a split-thickness skin graft from her right buttock. Nine months later, she noticed a dark purple-red lesion on the donor site which grew rapidly into a large mass. Histological examination revealed irregular clefts and vascular channels lined by atypical endothelial cells. Lung metastasis and pneumothorax were also noted. The secondary tumor appeared to represent Koebner phenomenon in a patient with angiosarcoma of the scalp.
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PMID:Koebner phenomenon on skin graft donor site in cutaneous angiosarcoma. 1170 15

Atypical fibrous histiocytoma is an uncommon, poorly documented variant of cutaneous fibrous histiocytoma. We studied 59 cases of atypical fibrous histiocytoma to better characterize the clinicopathologic spectrum. There were 33 males and 26 females (median age 38 years; range 5-79 years) with solitary lesions arising on lower (25 cases) and upper (17 cases) extremities, trunk (6 cases), head and neck (4 cases), and vulva (1 case); anatomic location was not stated in six cases. Lesions measured 0.4-8 cm in diameter (median 1.5 cm) and clinically were nodules (40 cases), polypoid tumors (18 cases), or a slightly elevated plaque (1 case). Histologically, the lesions were primarily dermal with superficial involvement of the subcutis in one third of the cases. Salient features included a proliferation of pleomorphic, plump, spindle, and/or polyhedral cells with mainly large, hyperchromatic, irregular, or bizarre nuclei, set in a background of classic features of fibrous histiocytoma, including spindle cell areas showing a storiform pattern and entrapped thickened, hyaline collagen bundles, especially at the periphery. Multinucleated giant cells, often with bizarre nuclei and foamy, sometimes hemosiderin-rich, cytoplasm were also variably present. The degree of pleomorphism varied from only focal and minimal (14 cases) or moderate (24 cases) to marked (21 cases). Mitotic activity was observed in 55 lesions, and the number of mitotic figures ranged from 1 to 15 per 10 high power fields. Atypical mitoses were noted in 20 lesions. Furthermore, some cases of atypical fibrous histiocytoma displayed other worrisome features less often observed in ordinary FH, including unusually large size (diameter >2 cm, 8 cases), involvement of the superficial subcutis (19 cases), and geographic necrosis (7 cases). Immunohistochemical studies performed in 42 cases showed only focal smooth muscle actin (10 cases) and CD34 (4 cases) positivity, whereas CD68, S-100 protein, desmin, pan-keratin, and epithelial membrane antigen were negative. Clinical follow-up data available in 21 patients (mean duration of follow-up 50.6 months, median 43 months) revealed local recurrences in three patients (one repeated); two patients developed distant metastases, one of whom died after 96 months. These two cases were not histologically distinct from the group as a whole. We conclude that atypical fibrous histiocytoma has a broader clinicopathologic spectrum than previously realized. Lesions with floridly atypical features represent potential pitfalls for overinterpretation as pleomorphic sarcoma, which would appear to be inappropriate in most cases. Provided that atypical fibrous histiocytoma is treated by complete excision, a benign outcome is to be expected in most cases. However, similar to the cellular and aneurysmal variants of fibrous histiocytoma, atypical fibrous histiocytoma shows a higher tendency to recur locally than ordinary fibrous histiocytoma and may rarely metastasize.
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PMID:Atypical fibrous histiocytoma of the skin: clinicopathologic analysis of 59 cases with evidence of infrequent metastasis. 1175 67

Cancer may affect the eye and orbit as a direct result of metastatic neoplastic infiltration, compression, or circulating antibodies involving paraneoplastic retinal degeneration. A metastatic tumor to the uvea is the most common form of an intraocular metastatic process. The choroid is the most common site for uveal metastasis; metastases to the ciliary body, iris, retina, optic disk, and vitreous are rare. Approximately one-third of patients have no history of primary cancer at the time of ocular diagnosis. Breast and lung carcinomas for women and lung and gastrointestinal carcinomas for men most commonly metastasize to the eye and orbit. The short-term prognosis for vision is usually good after an individualized therapeutic approach (chemotherapy, hormonal therapy, external beam radiotherapy, or plaque radiotherapy), but the systemic prognosis is poor. The visual paraneoplastic syndromes encompass several distinct clinical and pathological entities including carcinoma-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), and bilateral diffuse melanocytic uveal proliferation (BDUMP). The CAR syndrome affects photoreceptors, MAR is thought to affect bipolar cell function, and BDUMP targets the uveal tract. Identification of circulating antibodies against retinal proteins (recovering, 23-kDa retinal protein; 46-kDa and 60-kDa retinal proteins) serves to recognize the paraneoplastic nature of the patient's symptoms, which frequently develop before the cancer is diagnosed. Anecdotal therapeutic responses are described after systemic steroids, immunoglobulin injection, and plasmapheresis. Recognition of their visual symptoms and ocular findings should alert the ophthalmologist to the possibility of cancer and systemic evaluation should be pursued.
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PMID:[Ocular manifestations of cancer]. 1194 Dec 43


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