Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With radioactive compounds of high specific activity, the binding of carcinogens to DNA can be measured with doses that are ineffective in long-term studies. The binding of tritiated benzo(a)pyrene to liver DNA of adult male rats has been determined 50 hr after a single i.p. injection of doses between 40 microgram/kg and 4 mg/kg. The dose-response relationship is linear up to 1 mg/kg, shows a step towards 2 mg/kg, and gives a shallow linear slope above that value. The observed binding ranges from 1.7 to 180 nmoles benzo(a)pyrene per mole DNA phosphate. The nonlinearity could be due to an induction of metabolizing enzymes. The microsomal aryl hydrocarbon hydroxylase activity increases significantly 24 hr after a single dose of 4 mg/kg and 48 hr after doses of 2 and 4 mg/kg, but no induction is found with 1 mg/kg. The binding from an equimolar dose is 35 times lower than the one found on mouse skin DNA and 300 times lower than that of N,N-dimethylnitrosamine in rat liver. A good correlation exists to the respective tumor formation in long-term studies.
Cancer Res 1978 Mar
PMID:Nonlinear dose-response relationship for the binding of the carcinogen benzo(a)pyrene to rat liver DNA in vivo. 62 63

A 59-year-old woman had thick plaques of leukoplakia on the tongue bilaterally. The condition was initially diagnosed by biopsy as a white-sponge nevus. A second biopsy of a suspicious area on the right side showed squamous-cell carcinoma two years later. It is speculated that prednisone therapy for steroid-dependent intrinsic asthma may have caused a loss of "immunologic surveillance," which permitted development of malignancy in a previously benign condition.
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PMID:Oral squamous-cell carcinoma within a white-sponge nevus. 65

Melanoma specific protein is immunologically related to altered naevus cell cytoplasm. It is excreted by patients with malignant melanoma but in no other malignancy. The protein has been detected in patients with actively developing halo naevi but not when repigmentation is taking place. It also occurs in patients with very active vitiligo but in no other pigment condition we have studied. It is suggested that the protein is a marker of active destruction of naevus cells by immune mechanisms and that the release of toxic materials during this immune reaction may be responsible for the production of the halo phenomenon and for the areas of vitiligo that may be seen elsewhere on the skin.
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PMID:Melanoma specific protein: occurrence in the urine of patients with halo naevus and vitiligo. 67 52

Ultrastructural examination of the intraepidermal component of superficial spreading melanomas (SSM) and benign melanocytic lesions was undertaken to determine the diagnostic value of electron microscopy in clinically "borderline" melanoma problems. Seventeen SSMs and ten benign melanocytic nevi and lentigenes which clinically resembled melanoma were studied. Melanocytes of the intraepidermal component of the SSMs showed a greater tendency for abnormal melanosome formation than did melanocytes of the benign simulants. However, the abnormalities were variable and were not limited to the SSMs. Our observations suggest that qualitative ultrastructural evaluation cannot be reliably used differentiating SSMs from benign melanocytic lesions.
Cancer 1978 Aug
PMID:Ultrastructural study of superficial spreading melanoma and benign simulants. 67 52

Forty-five immunocompetent patients with solid tumors were immunized with BCG, PPD, and tumor cells. The methods were practical, but the morbidity was significant, including painful draining ulcerations at vaccine sites, possible enhancement of tumor growth in three patients, and the discovery at autopsy of systemic tuberculosis in one patient. Various facets of cellular immunity were altered, namely: 1) a majority of the patients developed enhanced cutaneous reactions to the microbial skin-test antigens (particularly tuberculin) and tumor cells; 2) nine patients developed the equivalent of delayed hypersensitivity reactions or flares at all previous PPD and BCG inoculation sites following subsequent injection of these agents, which supports the concept of immunologic memory for these target antigens; 3) lesions resembling those of "spontaneous" regressed moles (halo-nevi) were observed at previous vaccine sites in 20 patients and generalized depigmentation occurred in three patients; 4) foreign body giant cells in tumor metastasis remote from BCG-PPD-tumor vaccine sites may indicate a cross-reactivity of microbial and tumor antigens; and 5) intralesional inoculation of the nonspecific agents (BCG, PPD, Varidase, and Mumps) resulted in dense mononuclear cell infiltration and complete regression of most of the injected lesions. Destruction of single or multiple lesions by local injections of antigens did not provide either significant regression of uninjected lesions or clinical benefit.
Cancer 1976 Jul
PMID:Feasibility study of active immunotherapy in patients with solid tumors. 77 50

N-alkanes from C12 to C28 were tested for their cocarcinogenic or promoting activities to evaluate a correlation of their biologic activity with their effects on transport properties of phospholipid micelles. On this basis, we had predicted that the C18 and C20 homologues would be more active than the better known dodecane. The C12, C16, C18, and C20 n-alkanes, at various dilutions from 6 to 40% by volume in decahydronaphthalene (Decalin), were tested for their relative activity in a cocarcinogenic relationship to benzo[a]pyrene. At a 20% alkane concentration level, the solutions containing octadecane and eicosane induced tumors most rapidly. A 40% dodecane concentration was required to produce this level of cocarcinogenic activity. The activity of octadecane paralleled its physical effects on transport kinetics closely in the 6-40% (by volume) concentration. The C18, C20, and C28 n-alkanes and the C30 olefin squalene at dilutions from 10 to 40% in Decalin (by volume) were tested for their relative promoting activity after a single application of 7,12-dimethylbenz[a]anthracene in benzene. At comparable mole fractions in Decalin, the three n-alkanes had essentially the same promoting activity; squalene, at 20%, showed only borderline activity. Thus the high biologic activity of the C18, C20, and C28 n-alkanes correlated well with their physical effects on the structure of phospholipid micelles (chain-chain interactions of the alkanes with the acyl chains of the lipid). This correlation was interpreted as a strong indication that the liquid crystalline region of the phospholipid assembly (adjacent to the aqueous interface) in the membranes of latent (initiated) cancer cells was the site of action of hydrocarbon cocarcinogens. Application of a modified physical model to pristane, a branched-chain C19 alkane from coal and Colorado shale, indicated higher cocarcinogenic activity than that of n-C18H38. Applied to purified samples of docosane and tetracosane, activity comparable to that of octadecane was indicated.
J Natl Cancer Inst 1976 Feb
PMID:Correlation of cocarcinogenic activity among n-alkanes with their physical effects on phospholipid micelles. 81 59

Seventy albino guinea pigs were used in the experiment to investigate the influence of 9,10-dimethyl-1,2-benzanthracene on amelanotic melanocytes. A field 5 sq cm was marked on the flank of each animal. Hairs from these fields were clipped twice a week and painted for 20 consecutive weeks with 0.3 ml of 1% 9,10-dimethyl-1,2-benzanthracene in acetone. During the 1-year observation period, pigmented sports appeared in 40 animals. Biopsies were taken under local anesthesia, and sections were prepared for light and electron microscopic observations. Melanin formation of unknown mechanism took place in the epidermal melanocytes and in the melanocytes from the outer root sheath. These melanocytes also formed junctional and compound nevi; serial sections revealed various stages of pigmented nevi development. Schwann cells did not participate in the formation of nevi. Evidence is presented that 9,10-dimethyl-1,2-benzanthracene can convert amelanotic melanocytes into melanin-producing cells in the albino guinea pig skin. In addition, this system produces an animal model for the development of junctional and compound nevi.
Cancer Res 1976 Aug
PMID:Junctional and compound pigmented nevi induced by 9, 10-dimethyl-1,2-benzanthracene in skin of albino guinea pigs. 81 33

Aggregates of cells resembling those of cutaneous nevi have been found in the capsules of lymph nodes. Although seemingly rare, this extraordinary lesion could conceivably occur often enough to be more than a pathological curiosity, and should be differentiated from metastatic tumor. Slides from every axillary lymph node dissection for female mammary carcinoma in the years 1964 and 1974 at Memorial Hospital were reviewed, as were slides from 100 consecutive lymph node dissections performed during 1974 in patients with malignant melanoma. Nevus cell aggregates (NCA) were associated with three of 17,504 lymph nodes (0.017%) obtained from 909 mastectomies, or 0.33% of the cases. Among the 100 lymph node dissections for malignant melanoma, NCA were found associated with three of the 2,607 lymph nodes examined (0.12%), or 3.0% of the cases studied. Since NCA occur in association with lymph nodes more often than previously thought, the possibility that they may be a potential source of malignant melanoma in patients without a demonstrable cutaneous or mucosal primary is discussed.
Cancer 1977 Jan
PMID:Nevus cell aggregates associated with lymph nodes: estimated frequency and clinical significance. 83 30

Two cases of desmoplastic malignant melanoma are described, bringing the total reported to nine. The first developed in a lentigo maligna melanoma and contains the seed of its local recurrence in the primary lesion. The second developed in a clinically apparent congenital nevus and unites the histologic features of the desmoplastic variant with the epithelioid and spindle cell histology of its primary, side by side in a local recurrence. Both primaries were clinically recognized pigmented lesions while the desmoplastic recurrences were amelanotic. Other clinico-pathologic characteristics of DMM as previously described, are confirmed. Light microscopic evidence is presented supporting the view that the desmoplastic reaction is a rare manifestation elicited by a highly invasive spindle cell component of malignant melanoma.
Cancer 1977 Jan
PMID:Desmoplastic malignant melanoma: a report on two additional cases. 83 43

Mechanism of transport of the alkylating agent [14C]melphalan was investigated in L5178Y lymphoblasts in vitro. A time course of melphalan uptake was approximately linear for 5 to 10 min and thereafter entered a plateau region. Evidence that unidirectional influx of melphalan is carrier mediated was that uptake obeyed simple Michaelis-Menten kinetics, that it demonstrated chemical specificity, and that the cell/medium distribution ratio of drug decreased with increasing extracellular drug concentration. The kinetic parameters for melphalan transport consisted of a Km (mean +/- S.E.) of 1.53 +/- 0.18 X 10(-4) M and a transport capacity (Vmax) of 3.48 +/- 0.31 X 10(-17) mole/min/cell. Findings suggesting that transport was at least in part energy dependent and not simply a passive process were that drug uptake was temperature sensitive and sodium dependent. Analysis of cell sap constituents indicated the presence of intact drug within the cell. The percentage of radioactivity (mean +/- S.D.) found in the cell sap fraction was 95.8 +/- 2.2% of total cell activity, and 92.6 +/- 4.1% of this was trichloroacetic acid soluble. Thin-layer chromatography of the cell sap fraction and medium each revealed that the majority of radioactivity migrated as a single peak with an RF value identical with that obtained for free drug. The alkylating potential of intact drug complicated interpretation of the finding of apparent uphill transport against a concentration gradient. This observation, together with the relatively low cell-medium ratio (mean +/- S.D.) of 3.07 +/- 1.07, favors the concept that melphalan transport occurs by a facilitated diffusion process, although an active transport system has not been entirely excluded. The relative insensitivity of melphalan uptake to a wide range of metabolic inhibitors also suggests that transport is by a facilitated diffusion mechanism rather than an active process. Other alkylating agents and several amino acids including the L and D isomers of phenylalanine did not inhibit melphalan transport; thus a native substrate was not identified for the melphalan carrier and transport was by a mechanism separate from that of other alkylating agents.
Cancer Res 1977 Mar
PMID:Evidence for carrier-mediated transport of melphalan by L5178Y lymphoblasts in vitro. 83 75


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