Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A panel of 60 human tumor cell lines is currently being used in the U.S. National Cancer Institute's in vitro anticancer drug screen. The panel is organized into 7 subpanels; 6 leukemia/lymphoma lines comprise one subpanel, and 54 other lines are organized into subpanels representing solid tumors of the central nervous system (CNS), colon, lung, ovaries, kidneys and melanomas. In the present study, the leukemia and lymphoma cell lines were analyzed by flow cytometry for appropriate CD antigens; all but 1 line showed patterns of expression consistent with their reported derivations. The solid tumor lines were characterized individually using morphological and immunocytochemical techniques to determine their relative degrees of representativity for the subpanels within which they are currently grouped. Histological, histochemical and ultrastructural examinations were performed on cell lines grown under identical conventional culture conditions and as xenografts in nude mice. Immunocytochemistry using panels of antibodies raised against 6 types of intermediate filaments, 7 adenocarcinoma-associated antigens, 7 melanoma/neuro-ectodermal-associated antigens, 3 neuroendocrine-associated antigens, 9 urinary tract associated antigens, and 4 markers of muscle differentiation was done on cells grown in monolayer culture. Central nervous system (CNS) cell lines lacked expression of glial fibrillary acidic protein, but all had other features consistent with derivation from glioblastoma. Lines derived from adenocarcinomas of the colon, lung and ovary, for the most part, expressed adenocarcinoma-associated antigens and showed histological and/or ultrastructural evidence of gland formation and other adenomatous features. Most of these lines were poorly differentiated. Lines derived from large-cell and squamous-cell cancers also showed some characteristics consistent with their reported origins, except for one line which showed immunocytochemical and morphologic characteristics consistent with rhabdomyosarcoma. The 2 lines derived from small cell lung cancer (SCLC) lacked neurosecretory granules and 3 other SCLC markers but showed morphologic features consistent with SCLC. Most melanoma cell lines strongly expressed melanoma-associated antigens and were morphologically similar to human melanoma. Five lines produced premelanosomes, melanosomes or melanin. Most of the renal cancer cell lines showed morphologic or immunocytochemical features consistent with renal clear cell carcinoma. Collectively, these morphological and immunocytochemical analyses provide information concerning tissue of origin, tumor type, degree of differentiation and other biologic features essential to the use of these lines in a disease-oriented in vitro antitumor drug screen and to the interpretation of data derived therefrom.
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PMID:Morphological and immunocytochemical characteristics of human tumor cell lines for use in a disease-oriented anticancer drug screen. 150 99

The cyclopropylpyrroloindole analogues are DNA minor-groove binders containing a cyclopropyl group, which mediates N3-adenine covalent adduct formation in a sequence-selective fashion. Carzelesin (U-80244) is a cyclopropylpyrroloindole prodrug containing a relatively nonreactive chloromethyl precursor to the cyclopropyl function. Activation of carzelesin requires two steps, (a) hydrolysis of a phenylurethane substituent to form U-76073, followed by (b) ring closure to form the cyclopropyl-containing DNA-reactive U-76074. The formation of the DNA-reactive U-76074, via U-76073, from carzelesin was shown to proceed very slowly in phosphate-buffered saline (t1/2 greater than 24 h) but to occur rapidly in plasma from mouse, rat, dog, and human (initial t1/2 values ranging from 18 min for mouse to 52 min for rat) and in cell culture medium (t1/2 approximately 40 min). Although carzelesin was less potent in terms of in vitro cytotoxicity and in vivo optimal dosage and showed low affinity for binding to DNA, it was therapeutically more efficacious against mouse L1210 leukemia than was U-76074 or adozelesin (U-73975), another cyclopropylpyrroloindole analogue which is currently in phase I clinical trials. Carzelesin also proved to be more efficacious than U-76074 or adozelesin against mouse pancreatic ductal 02 adenocarcinoma, a system reported to be resistant to every agent tested. Carzelesin was highly effective against this tumor and produced 97% tumor growth inhibition. In addition, i.v. administered carzelesin showed significant activity (National Cancer Institute criteria) against i.v. or s.c. implanted Lewis lung carcinoma, i.p. or s.c. implanted B16 melanoma, s.c. implanted colon 38 carcinoma, and five s.c. implanted human tumor xenografts, including clear cell Caki-1 carcinoma, colon CX-1 adenocarcinoma, lung LX-1 tumor, ovarian 2780 carcinoma, and prostatic DU-145 carcinoma. Carzelesin treatment produced 100% complete remissions (no palpable tumor mass at the termination of the experiment) in mice bearing early-stage human ovarian 2780. Pharmacologically, carzelesin proved to be relatively schedule and route independent and was highly active against i.p. implanted L1210 leukemia, regardless of whether the analogue was given i.v., i.p., s.c., or p.o. These results, collectively, suggest that carzelesin is absorbed and distributed well. Both carzelesin and adozelesin caused marked tumor shrinkage in mice bearing human lung LX-1 or advanced-stage human ovarian 2780 carcinoma; however, tumor regrowth occurred shortly after the treatment with adozelesin was stopped. Little or no apparent tumor regrowth occurred after treatment with carzelesin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytotoxicity and antitumor activity of carzelesin, a prodrug cyclopropylpyrroloindole analogue. 151 47

59 (80%) of 74 patients with vulvar cancer treated at the University Department of Obstetrics and Gynecology in Ljubljana in the period 1973-85 underwent radical vulvectomy with bilateral inguinofemoral lymphadenectomy, and 15 (20%) patients single vulvectomy because of advanced age and poor general condition. Histologically there were 69 cases of squamous cell carcinoma, 1 adenocarcinoma, 3 malignant melanoma and 1 rhabdomyosarcoma. 52% of the patients were classified as Stage I, 41% Stage II and 7% Stage III. Positive inguinofemoral nodes were observed in 24% (6.5% in Stage I, 35% in Stage II and 80% in Stage III). The total 5 year survival rate was 70% (83% in Stage I, 61% in Stage II and 20% in Stage III). The 5 year survival rate in the patients with negative nodes was 80%, and in cases with positive nodes only 50% in spite of postoperative irradiation. None of the 3 patients with melanoma survived 2 years nor did the patient with rhabdomyosarcoma. There was no case of primary mortality. Nowadays the cure rate for vulvar cancer is higher especially owing to the improvement of operability. The problem of lymphatic and distant metastases still remains unresolved.
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PMID:Surgical treatment of vulvar cancer. 151 82

A 51 year old man with biopsy proven pulmonary sarcoidosis and skin test positive for tuberculosis presented with features of an amelanotic flat choroidal mass suggestive of choroiditis. The mass enlarged despite corticosteroids and anti-tuberculous medications. A thorough systemic evaluation for possible primary tumor metastatic to the choroid was negative. Further clinical evaluation and magnetic resonance imaging suggested a diffuse primary choroidal malignant melanoma with optic nerve invasion. The eye was enucleated and the mass proved histopathologically to be a mucin secreting adenocarcinoma of unknown origin despite a repeat systemic work-up. The patient died three months after the onset of symptoms and three weeks after enucleation with diffuse metastases from an unknown primary cancer. Magnetic resonance imaging (MRI) is usually helpful in the differentiation of uveal melanoma from uveal metastasis. In this case, however, it suggested the diagnosis of a diffuse choroidal melanoma. The reason for the atypical MRI findings will be discussed.
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PMID:Unusual MRI findings in metastatic carcinoma to the choroid and optic nerve: a case report. 153 48

Urethral cancer is the only genitourinary neoplasm with a predilection for women, the ratio being 4:1. The histologic type depends on the cells of origin. Squamous-cell carcinoma predominates, with adenocarcinoma and transitional-cell carcinoma being less common and undifferentiated carcinoma, malignant melanoma, mixed tumors, clear-cell carcinoma, and cloacogenic carcinoma accounting for the remaining lesions. The authors describe the various options for the management of low-stage and high-stage cancers and of cancers arising in urethral diverticula.
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PMID:Surgical treatment of female urethral carcinoma. 157 27

In this retrospective study, 81 patients operated by craniotomy for a brain metastasis are reviewed. Mean age is 56.3 years and most of the patients are male (71.6%). Clinically, 79% of the patients present a focal semiology, most frequently with neuropsychologic disturbances (43%); epilepsy is found in 31% of the cases. Symptoms related to intracranial hypertension (vomiting and headache) are present in 43% of the patients. On C.T.-scan, there is a solitary metastasis in 89% and the most common intracranial location is the frontal lobe (33.3%). The most frequent primary neoplasms are: bronchial adenocarcinoma in 19%, squamous carcinoma of the lung in 11%, melanoma in 12% and unknown origin in 18%. The surgical removal (as judged by the surgeon) is total in 70%, subtotal in 19% and partial in 11%. Standard operative mortality (30 days after craniotomy) is 7.4%. The postoperative course (till the patients leave our department) is excellent in 58% (complete neurologic recovery), steady in 20% (stability of symptoms and neurologic examination) and bad in 22%, with worsening of the neurological deficits. Most of the patients (84% of the patients who survive more than 30 days after the craniotomy) had postoperative whole brain radiotherapy with a hypofractionned schedule (total doses of 15 to 40 Gy with fractions of 200 to 650 cGy). Ten patients had surgery alone. Mean survival is 10.2 months with a follow-up of 12 months to 10 years. Ten patients survived over 18 months and one is still alive almost 4 years after his craniotomy. In this study, the survival is not modified by the primary lesion's histology.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cerebral metastases. A study of a surgical series of 81 cases]. 160 35

Therapeutic studies were conducted with L-histidinol, in combination with cyclophosphamide, bischloroethylnitrosourea, 5-fluorouracil, phenylalanine mustard, or cis-platinum(II)diammine dichloride, in several transplantable tumors in mice. These tumor types included murine L1210 P388 leukemias, M5076 sarcoma, mammary 16/C adenocarcinoma, human LOX melanoma, and colon HT-29 adenocarcinoma. Therapeutic benefits of adding L-histidinol to a regimen, compared to the regimen alone, were marginal. Pharmacokinetic studies indicated a rapid clearance of L-histidinol following a bolus dose (250 mg/kg i.p.), peak plasma concentration of 200 micrograms/ml (1.4 mM), and beta phase t1/2 of 12.6 min. Maximum tolerable plasma steady state concentrations with a 24-h infusion (2000 mg/kg/24 h) were no greater than 25 micrograms/ml (0.18 mM).
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PMID:L-histidinol: preclinical therapeutic studies in combination with antitumor agents and pharmacokinetic studies in mice. 161 31

Human monoclonal IgM antibodies reactive with cancer-associated antigens may not have the optimal imaging capability due to their large size. Fragmentation of human IgM is less than straight-forward due to the loss of immunoreactivity. From the human monoclonal IgM antibody COU-1 we have prepared monomeric and half-monomeric fragments, which retain the ability to bind to colon cancer cells in vitro. The pharmacokinetics and tumour localization were evaluated in nude mice bearing human colon adenocarcinoma and human melanoma grafts. Faster clearance from the circulation was seen for the smaller half-monomeric fragment with a half-life (rapid phase/slow phase) of 2 h/16 h compared with the intact antibody, 4 h/25 h, and the monomeric fragment, 3 h/27 h. Intact COU-1 as well as the fragments accumulated in the colon tumour graft. Higher amounts of radioactivity were found in the colon tumour as compared to normal organs for intact COU-1 at days 4 and 6, for the monomeric fragment at day 4, and for the half-monomeric fragment at day 2 after injection. This investigation demonstrates the favourable biodistribution of the half monomeric COU-1 fragment. The fast clearance of this fragment resulted in a tumour-to-muscle ratio as high as 22 on day 2 after injection. Also, only this fragment gave a positive tumour-to-blood ratio. Normal IgM and its fragments were used as controls. Radioimmunoscintigraphy demonstrated the colon tumour discriminatory properties of each of the three iodine-labelled antibody preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumour localization and pharmacokinetics of iodine-125 human monoclonal IgM antibody (COU-1) and its monomeric and half-monomeric fragments analysed in nude mice grafted with human tumour. 161 32

The influence of various normal and malignant human cells on the level of collagen synthesis by human fibroblasts was tested in coculture. As revealed by immunoperoxidase staining, in cocultures with breast adenocarcinoma cells (MCF7, SA52, T47D) fibroblasts synthesized collagen while tumor cells did not. Fibroblasts displayed increased collagen production without change in the overall protein synthesis. Several other types of cells derived from normal human tissues (keratinocytes, normal mammary cells) or from fibrosarcoma, melanoma, cervical carcinoma, choriocarcinoma, or other breast adenocarcinoma (SW613, MDA, BT20) did not affect collagen synthesis of fibroblasts. Although to a lesser extent, this stimulating effect was reproduced by using the conditioned medium (CM) of the active cells but not with CM of the other cell types. A slight stimulation was also obtained when tumoral MCF7 cells and fibroblasts shared the same medium but were physically separated, suggesting that close contact was required for optimal stimulation of collagen synthesis. The collagen synthesis stimulating activity was not related to a modification of fibroblast proliferation rate. The production of collagen types I, III, and VI and fibronectin were increased in cocultures of fibroblasts with MCF7 cells. The increased synthesis of collagen types I and III and fibronectin was paralleled by similar changes in the steady-state level of their mRNAs. On the contrary, the increased production of collagen type VI appeared regulated at a post-transcriptional level.
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PMID:Modulation of collagen and fibronectin synthesis in fibroblasts by normal and malignant cells. 161 29

Fine-needle aspiration biopsy (FNAB) specimens obtained from nine consecutive iris lesions were examined. The lesions included primary malignant melanoma (four cases), metastatic melanoma, metastatic adenocarcinoma, leukemic infiltrate, lymphocytic infiltrate, and epithelial ingrowth. Subsequent histopathologic correlation was performed in all cases. Patient treatment influenced by the results of the FNABs included enucleation (three cases), clinical observation (two cases), external beam irradiation (two cases), resection, and radioactive plaque application. No complications occurred from the FNABs. Fine-needle aspiration biopsy of the iris can be performed with local anesthesia at the slit lamp as an outpatient procedure. In general, FNAB is a safe, effective method of obtaining diagnostic material from primary neoplastic, secondary neoplastic, and degenerative processes involving the iris. Limitations of the procedure include discrepancies in interpretation of the cytologic study and inadequate specimen.
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PMID:Fine-needle aspiration biopsy of the iris. 163 83


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