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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three heteroarotinoids containing a nitrogen atom in the first ring and a C-O linking group between the two aryl rings were synthesized and evaluated for RAR and RXR retinoid receptor transactivation, tumor cell growth inhibition, and transglutaminase (TGase) induction. Ethyl 4-(N,4,4-trimethyl-1,2,3,4-tetrahydroquinolinyl)benzoate (1) contained an N-CH(3) group and activated all retinoid receptors except for RARgamma. Inceasing the hydrophobicity around the rings with analogues ethyl 4-(N,4,4,7-tetramethyl-1,2,3, 4-tetrahydroquinolin-6-oyloxy)benzoate (2) [7-methyl group added] and ethyl 4-(4,4-dimethyl-N-isopropyl-1,2,3, 4-tetrahydroquinolin-6-oyloxy)benzoate (3) [NCH(CH(3))(2) group at C-4] increased the potency and specificity for RARalpha, RARbeta, and RXRalpha, compared to 1, but had little effect on RXRbeta and RXRgamma activation. Although 1 and 3 were unable to activate RARgamma, 2 did activate this receptor with efficacy and high potency equal to that of 9-cis-retinoic acid (9-c-RA). All three heteroarotinoids exhibited 5-8-fold greater specificities for RARbeta over RARalpha. In addition, esters 1-3 inhibited the growth of two cell lines each derived from cervix, vulvar, ovarian, and head/neck tumors with similar efficiencies to that of 9-c-RA through a mechanism independent of apoptosis. The vulvar cell lines were the most sensitive, and the ovarian lines were the least sensitive. Ester 2 was similar to 1 and 3 except that 2 was a much more potent growth inhibitor of the two vulvar cell lines, which is consistent with strong RARgamma activation by 2 (but not by 1 and 3) and the high levels of RARgamma expression in skin. All three heteroarotinoids induced production of TGase, a marker of retinoid activity in human erythroleukemic cells. Esters 2 and 3 were the more potent TGase activators than 1, in agreement with the stronger activation of the RAR receptors by 2 and 3. The biological activities of these agents, and the RARgamma potency of 2 in particular, demonstrate the promise of these compounds as pharmaceutics for cancer and skin disorders.
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PMID:Synthesis, structure-activity relationships, and RARgamma-ligand interactions of nitrogen heteroarotinoids. 1047 91

Short chain fatty acids (SCFAs) are the end products of anaerobic bacteria break down of carbohydrates in the large bowel. This process, namely fermentation, is an important function of the large bowel; SCFAs, mainly acetate, propionate and butyrate account for approximately 80% of the colonic anion concentration and are produced in nearly constant molar ratio 60:25:15. Among their various properties, SCFAs are readily absorbed by intestinal mucosa, are relatively high in caloric content, are metabolized by colonocytes and epatocytes, stimulate sodium and water absorption in the colon and are trophic to the intestinal mucosa. While the fermentative production of SCFAs has been acknowledged as a principal mechanism of intestinal digestion in ruminants, the interest in the effects of SCFAs production on the human organism has been raising in the last ten years. SCFAs are of major importance in understanding the physiological function of dietary fibers and their possible role in intestinal neoplasia. SCFAs production and absorption are closely related to the nourishment of colonic mucosa, its production from dietary carbohydrates is a mechanism whereby considerable amounts of calories can be produced in short-bowel patients with remaining colonic function and kept on an appropriate dietary regimen. SCFAs enemas or oral probiotics are a new and promising treatment for ulcerative colitis. The effects have been attributed to the oxidation of SCFAs in the colonocytes and to the ability of butyrate to induce enzymes (i.e. transglutaminase) promoting mucosal restitution. Evidence is mounting regarding the effects of butyrate on various cell functions the significance of which needs further considerations. Up until now, attention has been related especially to cancer prophylaxis and treatment. This article briefly reviews the role of SCFAs, particularly butyrate, in intestinal mucosal growth and potential clinical applications in inflammatory and neoplastic processes of the large bowel.
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PMID:Short-chain fatty acid in the human colon. Relation to inflammatory bowel diseases and colon cancer. 1073 23

The clinicopathologic and immunohistochemical features of three metastasizing fibrous histiocytomas of the skin are presented. The first patient had a 1.3-cm nodule in the right thigh, with right inguinal lymph node metastases 19 years later. The second patient, who had a 3-cm nodule excised from his left thigh and inguinal lymph node metastasis after 4 months, had a favorable outcome 14 years after local radiotherapy and chemotherapy. The third had a 2-cm nodule in his neck, which recurred 16 months later. Four months later, cervical lymph node metastases were found. The patient was alive and well 26 months after initial surgery. All three primary skin tumors involved the dermis and subcutis, appeared well-delineated but nonencapsulated, were associated with some degree of epidermal hyperplasia, and showed features of aneurysmal/atypical or cellular fibrous histiocytoma. The number of mitoses ranged from 6 to 11 per 10 high-power fields. Recurrences and metastases showed morphologic features similar to primary lesions. Tumor cells were positive, at least focally, for CD 68, Ki-M1p, and Factor XIIIa, and occasionally for smooth muscle actin. Desmin, CD 34, S-100 protein, and cytokeratin stainings were negative. Primary neoplasms, recurrences, and metastases showed a Mib-1 labeling index of 10% or less. Cellular, aneurysmal, and atypical (pseudosarcomatous) fibrous histiocytomas of the skin can metastasize, yet they often show a protracted clinical course. Risk factors for metastatic dissemination include large size, high cellularity, aneurysmal changes, marked cellular pleomorphism, high mitotic activity, tumor necrosis, and repeated local recurrences.
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PMID:Metastasizing fibrous histiocytoma of the skin: a clinicopathologic and immunohistochemical analysis of three cases. 1135 67

Calcifying fibrous pseudotumor is an uncommon lesion characterized by hyalinized collagen, psammomatous or dystrophic calcifications, and a predominantly lymphoplasmacytic infiltrate. Although the pathogenesis is unclear, a possible relationship with other inflammatory "pseudotumors" has been proposed. We describe the pathology of two right neck calcifying fibrous pseudotumors present in a five-week-old female infant. The masses had many of the pathologic features of calcifying fibrous pseudotumor. The presence of a florid, mixed infiltrate, and the occurrence of more than one lesion in the same patient, favor the proposal that calcifying fibrous pseudotumor may be a sclerosing end stage of inflammatory myofibroblastic tumor. However, the presence of a previously undescribed participation of Factor XIIIa-positive cells suggests that the tumor may be of dermal dendrocyte origin.
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PMID:Calcifying fibrous pseudotumor involving the neck of a five-week-old infant. Presence of factor XIIIa in the lesional cells. 1092 31

This report describes a composite (or "collision") of a dendritic cell neoplasm and small lymphocytic lymphoma. It represents the seventh example of dendritic cell neoplasia occurring in the setting of low-grade B-cell malignancy and the third example of a composite tumor, in which both neoplasms were present within the same lymph node. The small lymphocytic lymphoma component exhibited a typical CD20+, CD5+, and CD23+ immunophenotype. The dendritic cell neoplasm exhibited reactivity with CNA-42, but nonreactivity for CD21, CD35, smooth muscle actin, desmin, and epithelial membrane antigen (EMA). Equivocal cytoplasmic staining was seen for S100p, CD68, and Factor XIIIa. Ultrastructurally, the dendritic cell neoplasm exhibited desmosomes, rough endoplasmic reticulum, cytoplasmic intermediate filaments, and intercellular collagen. Because the immunophenotype and ultrastructure did not correspond to one of the five recognizable dendritic cell subtypes, the neoplasm was designated dendritic cell neoplasm, not otherwise specified (NOS). Polymerase chain reaction (PCR) analysis for immunoglobulin heavy chain gene rearrangements performed on individual components of the composite tumor demonstrated rearrangement within the small lymphocytic lymphoma component, but none in the dendritic cell component. The lack of an immunoglobulin heavy chain gene rearrangement within the dendritic cell component argues against a transformational event and supports the concept that these separate neoplasms represent a true "collision" or composite lesion.
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PMID:Composite dendritic cell neoplasm (NOS) and small lymphocytic lymphoma. 1112 25

Cell invasion requires cooperation between adhesion receptors and matrix metalloproteinases (MMPs). Membrane type (MT)-MMPs have been thought to be primarily involved in the breakdown of the extracellular matrix. Our report presents evidence that MT-MMPs in addition to the breakdown of the extracellular matrix may be engaged in proteolysis of adhesion receptors on tumor cell surfaces. Overexpression of MT1-MMP by glioma and fibrosarcoma cells led to proteolytic degradation of cell surface tissue transglutaminase (tTG) at the leading edge of motile cancer cells. In agreement, structurally related MT1-MMP, MT2-MMP, and MT3-MMP but not evolutionary distant MT4-MMP efficiently degraded purified tTG in vitro. Because cell surface tTG represents a ubiquitously expressed, potent integrin-binding adhesion coreceptor involved in the binding of cells to fibronectin (Fn), the proteolytic degradation of tTG by MT1-MMP specifically suppressed cell adhesion and migration on Fn. Reciprocally, Fn in vitro and in cultured cells protected its surface receptor, tTG, from proteolysis by MT1-MMP, thereby supporting cell adhesion and locomotion. In contrast, the proteolytic degradation of tTG stimulated migration of cells on collagen matrices. Together, our observations suggest both an important coreceptor role for cell surface tTG and a novel regulatory function of membrane-anchored MMPs in cancer cell adhesion and locomotion. Proteolysis of adhesion proteins colocalized with MT-MMPs at discrete regions on the surface of migrating tumor cells might be controlled by composition of the surrounding ECM.
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PMID:Matrix-dependent proteolysis of surface transglutaminase by membrane-type metalloproteinase regulates cancer cell adhesion and locomotion. 1127 23

Cancer-related fibrin deposition and fibrinolysis were investigated by two-dimensional gel electrophoresis of human solid tumor and effusion specimen in addition to plasma samples. Fibrinogen gamma-chain dimer indicating fibrin deposition and plasmin-generated fibrinogen beta-chain fragments were identified in various solid tumor types by amino acid sequencing, mass spectrometry analysis and Western blotting. In tumor-associated effusions, these techniques allowed to observe plasmin-generated fragments of fibrinogen alpha, beta and gamma-chains in addition to elevated levels of acute-phase proteins. Similar observations were made in case of inflammation-associated effusions. No fibrin degradation product was observed in plasma samples, however, high amounts of fibrinogen gamma-chain dimer crosslinked by transglutaminase were detected in plasma from tumor patients, but not in plasma from controls and patients suffering acute infections and/or inflammations. This finding demonstrated that high transglutaminase activity may be associated with cancer. The presented data indicate that the amount of crosslinked fibrinogen gamma-chain dimer in plasma may correlate with tumor-associated fibrin deposition. The tumor-biological relevance of this potential marker protein is discussed.
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PMID:Elevated plasma levels of crosslinked fibrinogen gamma-chain dimer indicate cancer-related fibrin deposition and fibrinolysis. 1130 21

Calcifying fibrous pseudotumor (CFP), a recently described lesion, is characterized by a predominantly lymphoplasmacytic infiltrate with abundant hyalinized collagen and psammomatous or dystrophic calcifications. The cause and pathogenesis are unclear, but it has been postulated that CFP may represent a sclerosing end stage of inflammatory myofibroblastic tumor (IMT). We compared the histological and immunohistochemical profiles of seven cases diagnosed as CFP and seven as IMT. Histologically, the CFP demonstrated varying degrees of calcifications in addition to fibroblastic proliferation admixed with inflammatory cells composed of lymphocytes, eosinophils, and mast cells. The IMTs rarely contain calcifications and had a myofibroblastic proliferation varying from hyalinized acellular collagen to florid fibroblastic proliferations simulating sarcoma. The inflammatory component was composed primarily of plasma cells and lymphocytes, sometimes arranged as lymphoid aggregates with germinal centers. All CFP cases were diffusely positive for factor XIIIa and negative for smooth muscle actin, muscle-specific actin, and CD34. All IMTs demonstrated diffuse positivity for actin, variable positivity for CD34, and focal positivity for Factor XIIIa. This study demonstrates certain distinct histologic, immunohistochemical, and electron microscopic features between IMTs and CFPs.
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PMID:Calcifying fibrous pseudotumor versus inflammatory myofibroblastic tumor: a histological and immunohistochemical comparison. 1150 38

We have shown previously that administration of acyclic retinoid to cirrhotic patients who had undergone curative treatment of preceding hepatocellular carcinoma (HCC) induced the disappearance of serum lectin-reactive alpha-fetoprotein (AFP-L3) and subsequently reduced the incidence of second liver cancers. AFP-L3 is a tumor marker that indicates the presence of occult tumors below the detection limit by diagnostic images. Therefore, we have proposed a new concept of 'clonal deletion' therapy with acyclic retinoid for the cancer chemoprevention against HCC. Such eradication of AFP-L3-producing latent malignant (or premalignant) cells from the liver suggested a new strategy to prevent HCC, which may be involved in the same category as cancer chemotherapy. In the present series of studies, we explored the molecular mechanism of 'clonal deletion' and found a novel mechanism of apoptosis induction by the retinoid. We have demonstrated a modification of a retinoid receptor, RXRalpha, by mitogen-activated protein (MAP) kinase-dependent phosphorylation, resulting in the loss of transactivating activity. This may lead HCC cells to be resistant to natural retinoic acid. However, acyclic retinoid restored the function of phosphorylated RXRalpha and induced its downstream pro-apoptotic genes including tissue transglutaminase, an enzyme that is implicated in apoptosis. Tissue transglutaminase-dependent apoptosis in HCC cells was independent of the activation of caspases. This novel mechanism of retinoid-induced apoptosis may give a clue to understand the molecular mechanism of clonal deletion.
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PMID:Apoptosis induction by acyclic retinoid: a molecular basis of 'clonal deletion' therapy for hepatocellular carcinoma. 1157 27

Thirty-four cases of fibrous histiocytoma (dermatofibroma) arising on the face are reported. These neoplasms occurred frequently in females (24 female, 10 male) and showed a broad age range (12 to 85 years; mean: 43.6 years, median: 41 years). The neoplasms originated on the forehead (nine cases), the cheek (eight cases), the eyebrow (four cases), the temporal region (three cases), the nose (two cases), and the ear (one case); in seven cases the location face was given only. Five of 27 cases with follow-up information (median: 5 years) recurred locally; in one case four recurrences were excised within 8 years. The majority of cases extended into the subcutis and deep soft tissue including striated muscle (50% of cases). Histologically, only the minority of cases was composed entirely of histiocytoid and spindle-shaped tumor cells arranged in a storiform growth pattern. In many cases cellular fascicles and bundles of spindle-shaped tumor cells were noted in addition to classical morphological features of fibrous histiocytoma. A moderate mitotic rate (mean: 2.97 mitoses in 10 HPFs) was observed, and in few cases increased atypia was evident. Frank tumor necrosis and/or vascular invasion were not identified. Immunohistochemical studies revealed Factor XIIIa positivity in 13 out of 17, focal CD68 positivity in 6 out of 10, and alpha-smooth muscle actin positivity in 16 out of 19 cases tested. These lesions should be distinguished from dermatofibrosarcoma protuberans, including its fibrosarcomatous variant, leiomyosarcoma, and low-grade myofibroblastic sarcoma. Cases of fibrous histiocytoma of the face have to be excised with wider margins in comparison with examples of classical fibrous histiocytoma occurring on the extremities because of diffuse infiltration, involvement of deeper structures, and an increased rate of local recurrences.
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PMID:Benign fibrous histiocytoma (dermatofibroma) of the face: clinicopathologic and immunohistochemical study of 34 cases associated with an aggressive clinical course. 1180 74


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