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)

Merkel cell carcinoma (MCC) is a malignant cutaneous neuroendocrine tumor which may be difficult to diagnose. It mostly occurs in old patients and the commonest sites are the skin of the head and neck and the extremities. MCC appears as a solitary violaceous dome-shaped nodule or indurated plaque. Histopathologic diagnosis may be difficult and three main patterns have been described. With immunohistochemistry studies, MCC express both epithelial (cytokeratins, EMA) and neuroendocrine (NSE, chromogranin, ...) markers. The tumor develops an aggressive course not unlike an aggressive melanoma. Local recurrence and regional lymph node metastases occur in 40 to 75% of cases. Long-term prognosis is unfavorable (3-year survival rate is 55%). Wide surgical excision associated with radiotherapy is the treatment of choice, regional lymph node metastases should be treated by lymph node excision and radiotherapy; chemotherapy should be used in systemic disease.
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PMID:[Merkel cell carcinoma]. 992 75

The management of uveal metastasis is focused on both the patient's systemic condition and the ocular condition. If there is evidence of systemic metastatic disease, then treatment of the nonocular and ocular metastatic tumors consists of chemotherapy, hormone therapy, immunotherapy, multiple-site radiotherapy, or observation. If there is no evidence of systemic involvement, then whole-eye treatment with chemotherapy, hormone therapy, immunotherapy, radiotherapy, or, rarely, enucleation is considered. For solitary uveal metastases, plaque radiotherapy is offered, and if the tumor is small, laser photocoagulation, resection, or thermotherapy can be used. Inactive uveal metastases are managed by periodic observation, but active uveal metastases often produce visual loss, secondary glaucoma, and pain, therefore, treatment is usually indicated. Radiotherapy is quite effective for control of most uveal metastasis. The technique of external beam radiotherapy is most often used and is delivered over a 3- to 4-week period in an outpatient setting. For those patients who fail chemotherapy, hormone therapy, immunotherapy, or external beam radiotherapy or those patients with a solitary uveal metastasis, plaque radiotherapy is an alternative method. Plaque radiotherapy is focal radiotherapy delivered to the eye in an inpatient setting over a relatively short period of approximately 3 days. Plaque radiotherapy provides satisfactory tumor control, even in eyes that fail other treatments. Side effects from plaque radiotherapy are comparable to those from external beam radiotherapy. Importantly, the plaque treatment requires less of a time commitment for these patients with a limited life expectancy.
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PMID:Plaque radiotherapy for the management of uveal metastasis. 1018 97

Soft tissue tumors of the penis are uncommon. We report here the clinicopathologic features of a penile epithelioid sarcoma (ES), review the literature concerning this unusual location and focalize our attention on its differentiation. The 34-year-old patient was admitted for abrupt urinary retention due to the growth of a firm and painful plaque on the left side of the shaft, three years previously clinically diagnosed as Peyronie's disease. Magnetic nuclear resonance revealed an infiltrating lesion of both corpora cavernosa. Histology of bioptic fragments showed a nodular malignant spindle and epithelioid cell tumor with focal necrosis and relatively high mitotic rate. Based on the immunohistochemical data (cytokeratin+, vimentin+, EMA+, CD34+, and S100-), the diagnosis of ES was strongly considered. Penectomy was undertaken and the diagnosis confirmed by both light and ultrastructural microscopy. The 22 month follow-up was free of recurrences and metastases. Although not dissimilar from the 10 previously described ES of the penis in terms of natural history and histology, the tumor reported here showed myogenic features as revealed by both immunohistochemistry (immunoreactivity for muscle specific actin) and ultrastructure (intercellular junctions, discontinuous basal lamina, pinocytotic vesicles and thin filaments with intercalated dense bodies). Although previously observed in ES of other sites, this feature has never been established in ES of the penis.
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PMID:Epithelioid sarcoma of the penis. Clinicopathologic study of a tumor with myogenic features and review of the literature concerning this unusual location. 1039 86

Uveal melanoma is the most common primary intraocular malignant tumour, although it is a rare condition. Between January 1993 and December 1997 a total of 120 patients were referred from Scotland to the Ocular Oncology Service at St. Paul's Eye Unit in Liverpool. Of these, 98 had uveal melanoma, which was treated with primary enucleation (24), or by conservative methods, consisting of plaque radiotherapy (30), proton beam radiotherapy (19), trans-scleral local resection (19), or endoresection (6). After conservative treatment, 92% of eyes were retained, with 65% of eyes maintaining the same level of vision as at presentation or better. The main complications were retinal detachment (8), death from metastatic disease (7) and local tumour recurrence (4). This study gives an overview of the treatment of uveal melanoma and demonstrates that most patients with uveal melanoma can be treated conservatively, with the large majority retaining the eye and good vision.
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PMID:Auditing outcomes after treatment of Scottish patients with uveal melanoma in Liverpool. 1045 50

Seven immunocompetent, revaccinated patients with surgically incurable cutaneous melanoma underwent treatment of dermal and/or subcutaneous metastases with twice-weekly intratumoral injections of escalating doses (10(4)-2 x 10(7) plaque-forming units (PFU)/lesion; 10(4)-8 x 10(7) PFU/session) of a vaccinia/GM-CSF recombinant virus for 6 weeks. Patients with stable or responding disease were maintained on treatment until tumor resolution or progression. Systemic toxicity was infrequent, dose-related, and limited to mild flu-like symptoms that resolved within 24 hours. Local inflammation, at times with pustule formation, was consistently seen with doses of > or =10(7) PFU/lesion. Chronically treated lesions showed a dense infiltration, with CD4+ and CD8+ lymphocytes, histiocytes, and eosinophils. All seven patients developed an antivaccinia humoral immune response 14-21 days following revaccination. Despite the presence of these antivaccinia antibodies, the reporter gene was expressed, as judged by the development of anti-beta-galactosidase antibodies in all patients. Passenger cytokine gene function was evidenced by the presence of virally encoded GM-CSF mRNA at injection sites both early (weeks 1 and 5) and late (week 31) in the course of treatment. Eosinophilia at treatment sites indicated that physiologically significant levels of functional cytokine were generated. However, there were no changes in the total number of peripheral white blood cells or in the numbers or percentages of polymorphonuclear leukocytes, monocytes, or eosinophils. GM-CSF was not detected in the sera. The two patients with the largest tumor burdens failed to respond even at treatment sites. Three patients had mixed responses, with regression of treated and untreated dermal metastases and progression of disease elsewhere. One patient had a partial response, with regression of injected and uninjected regional dermal metastases. Residual melanoma was excised, rendering the patient disease free. One patient with only dermal metastases confined to the scalp achieved a complete remission. Sequential administration of escalating doses of a GM-CSF recombinant vaccinia virus is safe, effective at maintaining passenger gene function, and can induce tumor regression.
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PMID:Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma. 1050 51

A well-recognized but rare presentation of scalp metastasis is alopecia neoplastica, which occurs as a single or multiple areas of cicatricial alopecia. Alopecia neoplastica is usually a presentation of metastasis from breast cancer, and other primary sites are extremely rare. We report a 36-year-old woman with alopecia neoplastica due to metastasis from gastric carcinoma. She also had pelvic metastases. An asymptomatic erythematous alopecic plaque had developed 10 months before presentation and biopsy was consistent with scalp metastasis. Total abdominal hysterectomy and salphingo-oophorectomy was performed and chemotherapy was proposed.
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PMID:Alopecia neoplastica in a patient with gastric carcinoma. 1060 65

We hypothesize that adenovirus (Ad) vector-mediated delivery of the human interleukin-2 (IL-2) cDNA (AdIL2) or the murine IL-12 cDNA heterodimer (AdIL12) would produce high concentrations of cytokines in the local hepatic milieu to induce host responses sufficient to inhibit the growth of experimental colon carcinoma-derived hepatic metastases. Ad vectors administered intravenously, which is a route known to deliver >90% of the vector to the hepatic parenchyma, achieved significant levels of each cytokine locally, with minimal levels in the sera. To examine the therapeutic effect, the AdIL2 and AdIL12 vectors were evaluated in a hepatic metastasis model that was established by injecting 3 x 10(4) cells from the poorly immunogenic syngeneic C26 colon carcinoma cell line into the right lobe of the livers of BALB/c mice. Animals received AdIL2, AdIL12, or control virus (10(8) plaque-forming units each) intravenously for 2 days after tumor implantation, and tumor growth was compared with naive controls. The AdNull control tumors measured 116 +/- 25 mm2 at 2 weeks. The control virus showed no significant antitumor effect. In marked contrast, both AdIL2 and AdIL12 vectors that were delivered regionally had significant antitumor effects, with AdIL2-treated animals having an average tumor size of 16 +/- 8 mm2; AdIL12-treated tumors measured 6 +/- 6 mm2 (P < .01, both compared with control). Both the AdIL2 and AdIL12 vectors provided a significant survival advantage by log-rank analysis (P < .01), but only AdIL12 translated into an increase in mean survival from 27 (naive control) to 37 days. To evaluate whether these antitumor effects were T-cell-mediated, splenocytes from AdIL2-treated, AdIL12-treated, and naive control groups were stimulated in vitro with gamma-irradiated C26 tumor cells for 5 days and tested for C26 tumor cell cytolysis by an in vitro cytotoxicity assay. Splenocytes from both AdIL2- and AdIL12-treated animals showed a dose-dependent, T-cell-mediated, specific cytolysis of CT26 cells. AdIL12 and to a lesser extent AdIL2 induced natural killer cell activity, as determined by a dose-dependent increase in lysis of the natural killer-specific target cell YAC-1. Overall, these data suggest that regional Ad-mediated delivery of IL-2 and IL-12 cDNAs may be useful for local tumor control and may warrant further investigation as a potentially useful adjuvant for the treatment of hepatic micrometastasis.
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PMID:Regional treatment of hepatic micrometastasis by adenovirus vector-mediated delivery of interleukin-2 and interleukin-12 cDNAs to the hepatic parenchyma. 1060 45

Retinoblastoma is the most common primary intraocular tumour in children, with an incidence of 1 in 15,000 live births. Treatment strategies for retinoblastoma have gradually evolved over the past few decades. There has been a trend away from enucleation (removal of the eye) and external beam radiation therapy toward focal 'conservative' treatments. Every effort has been made to save the child's life with preservation of eye and sight, if possible. Primary enucleation continues to be the commonly used method of treatment for retinoblastoma. It is employed in situations where eyes contain large tumours, long standing retinal detachments, neovascular glaucoma and suspicion of optic nerve invasion or extrascleral extension. Most of these eyes either have or are expected to have no useful vision. Radiation therapy continues to be an effective treatment option for retinoblastoma. However, external beam radiotherapy has unfortunately been associated with secondary non-ocular cancers in the field of radiation (primarily in children carrying the RB-1 germline mutation). Ophthalmic plaque brachytherapy has a more focal and shielded radiation field, and may carry less risk. Unfortunately, its applicability is limited to small to medium-sized retinoblastomas in accessible locations. Cryotherapy and transpupillary thermotherapy (TTT) have been used to provide control of selected small tumours. TTT is an advanced laser system adapted to the indirect ophthalmoscope which provides flexible nonsurgical treatment for small retinoblastomas. Recent research in the treatment of retinoblastoma has concentrated on methods of combining chemotherapy with other local treatment modalities (TTT, radiotherapy, cryotherapy). This approach combines the principle of chemotherapeutic debulking in paediatric oncology with conservative focal therapies in ophthalmology. Termed chemoreduction, intravenous or subconjunctival chemotherapy is used to debulk the initial tumour volume and allow for local treatment with TTT, cryotherapy and plaque radiotherapy. Cyclosporin has been added to the chemotherapy regimen in several centres. Other clinical settings where chemotherapy is considered are situations where the histopathology suggests a high risk for metastatic disease and where there is extraocular extension. There is no consensus that chemotherapy is needed when choroidal invasion is observed on histopathology. However, in patients where the retinoblastoma is noted beyond the cut end of the optic nerve or if there is disruption of the sclera with microscopic invasion of the orbital tissue, treatment has been helpful. Systemic and intrathecal chemotherapy with local and cranial radiotherapy has improved the survival of these patients. Most recently, the use of new chemotherapy modalities with haematopoietic stem cell rescue or local radiotherapy has increased the survival of patients with distant metastasis. Nevertheless, the prognosis of patients with central nervous system involvement is still poor.
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PMID:Chemotherapy for retinoblastoma: a current topic. 1065 86

A recombinant vaccinia virus encoding human prostate-specific antigen (rV-PSA) was administered as three consecutive monthly doses to 33 men with rising PSA levels after radical prostatectomy, radiation therapy, both, or metastatic disease at presentation. Dose levels were 2.65 x 10(6), 2.65 x 10(7), and 2.65 x 10(8) plaque forming units. Ten patients who received the highest dose also received 250 microg/m2 granulocyte-macrophage colony-stimulating factor (GM-CSF) as an immunostimulatory adjunct. No patient experienced any virus-related effects beyond grade I cutaneous toxicity. Pustule formation and/or erythema occurred after the first dose in all 27 men who received > or =2.65 x 10(7) plaque forming units. GM-CSF administration was associated with fevers and myalgias of grade 2 or lower in 9 of 10 patients. PSA levels in 14 of 33 men treated with rV-PSA with or without GM-CSF were stable for at least 6 months after primary immunization. Nine patients remained stable for 11-25 months; six of these remain progression free with stable PSA levels. Immunological studies demonstrated a specific T-cell response to PSA-3, a 9-mer peptide derived from PSA. rV-PSA is safe and can elicit clinical and immune responses, and certain patients remain without evidence of clinical progression for up to 21 months or longer.
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PMID:A phase I trial of a recombinant vaccinia virus expressing prostate-specific antigen in advanced prostate cancer. 1081 80

Patients with advanced stages of head and neck cancer frequently develop locoregional recurrence as well as distant metastases. These data indicate that traditional diagnostic methods such as histopathology and radiology are not sensitive enough to detect the small numbers of tumor cells which are left behind, defined as minimal residual disease (MRD). Sensitive diagnostic assays based on molecular markers appear to be powerful tools to improve the staging of these patients. At the DNA level, tumor-specific p53 mutations seem to have great potential for the detection of "occult" tumor cells at surgical margins and lymph nodes. At the RNA level HNSCC associated antigens like the E48 antigen, allow the detection of rare HNSCC cells in blood and bone marrow and, it is hoped, also in lymph nodes and lymph node aspirates. However, the molecular assays which are used to detect MRD are subject to certain (technical) problems which affect their sensitivity and specificity. In this paper we will present examples of molecular assays such as the plaque assay using p53 mutations and the E48 RT-PCR, and show their use for MRD detection in cervical lymph nodes. In addition, we will discuss the problems and pitfalls associated with these sensitive techniques.
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PMID:Molecular diagnosis of head and neck cancer. 1085 64


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