Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report immunomorphologic observations on a pleomorphic hyalinizing angiectatic tumor of soft parts (PHAT), a rare tumor recently described by Smith, Fisher, and Weiss. A 2 cm skin-covered, grossly lobulated, firm, yellow-tan, focally hemorrhagic tumor was excised from the dorsum of a 59-year-old woman's right foot. It infiltrated dermis and subcutis and entrapped skin adnexae. The tumor microscopically resembled both a pleomorphic malignant fibrous histiocytoma and a neurilemoma with fascicular spindle cell pattern, pleomorphic tumor giant cells, and focal congeries of ectatic, fibrinous, and slightly hyalinized vessels. Tumour cells produced abundant reticulin but collagenous sclerosis was minimal. Mast cells were numerous. Pleomorphic cells, some phagocytic, had intranuclear vacuolar inclusions and many cells had large pale cytoplasmic globular inclusions. Most tumor cells expressed vimentin and CD34, including pleomorphic cells. Factor XIIIa stained focally 20-40% of the spindle cells. S-100 and cytokeratin were negative and actin and desmin stained only vessel myopericytes. The Ki 67 index was 3% with mostly large CD34+ cells and a few smaller FXIIIa+ cells in the cycling fraction. We conclude that PHAT is a fibrohistiocytic tumor probably derived from proliferating microvascular CD34+ dendritic cells and FXIIIa+ dendrophage cell subsets. Possible interactions between these cell types deserve further study in PHAT and other fibrohistiocytic tumors.
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PMID:Pleomorphic hyalinizing angiectatic tumor of soft parts: immunohistochemical case study shows cellular composition by CD34+ fibroblasts and factor XIIIa+ dendrophages. 924 66

The list of entities comprising a proliferation of CD34 (+) spindle cells continues to grow. Described, herein, is a patient who had an indolent eruption of scattered papules composed of CD34 (+) spindle cells, beginning in adolescence. An 18-year-old female patient presented with asymptomatic, tan/brown papules over the neck, chest, and proximal extremities. They appeared 6 years previously and had slowly increased in number. Biopsy from the neck showed a proliferation of plump spindle cells, associated with delicate collagen, in the upper reticular dermis. No atypia nor mitotic figures were present. The spindle cells were negative for S-100, muscle actins, and Factor XIIIa, but stained intensely with CD34. This unusual mesenchymal proliferation of CD34 (+) apparent dermal dendrocytes did not have the storiform pattern, short fascicles, nor mitotic figures of DFSP. The completely negative muscle markers helped to exclude dermatomyofibroma, and no morphological evidence of vasoformative differentiation was seen. The clinical picture militated against solitary fibrous tumor. These eruptive tumors are benign and thought to represent a distinctive fibroma produced by proliferated CD34 (+) stromal cells.
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PMID:CD34-positive eruptive fibromas. 952 2

Fifty samples of lung tissue from patients with non-small cell lung cancer were analyzed for the expression and localization of biomarkers related to squamous differentiation and programmed cell death. These markers include tissue transglutaminase (tTG), keratinocyte transglutaminase (kTG), involucrin, loricrin, and Bcl-2. We found that all of these markers are overexpressed in tumors as compared with histologically normal lung epithelium, where expression is minimal. Expression of the oncoprotein, Bcl-2, increased starting in squamous metaplasia and remained elevated in all lesions, including frank carcinoma. In contrast, expression of the other markers was elevated in the histologically abnormal noninvasive lesions but was decreased somewhat in invasive malignancy. In addition, we found that tTG, kTG, and Bcl-2, when expressed, were detected in mutually exclusive areas. These findings suggest that (1) these markers may prove useful, with more extensive testing and clinical correlation, in predicting risk for the development of lung cancer; and (2) pulmonary carcinogenesis may result from the failure of differentiation and programmed cell death mechanisms in the presence of oncogene overexpression rather than through oncogene/tumor suppressor gene abnormalities alone.
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PMID:Differentiation and programmed cell death-related intermediate biomarkers for the development of non-small cell lung cancer: a pilot study. 974 13

Tumor cell adhesion and migration to laminin are important events during invasion and metastatic spread. Galectin-3, a multifunctional member of the galectin family, binds specifically the poly-N-acetyllactosamine residues of laminin and has been implicated in tumor invasion and metastasis. Galectin-3 is multimerized by transglutaminase, an enzyme that catalyzes cross-linking between glutamine and other aminoacid residues. In this study, we examined the consequences of transglutaminase-mediated galectin-3 oligomerization on the interactions between cancer cells and laminin. We first demonstrated that human galectin-3 is cross-linked by guinea pig liver transglutaminase, forms oligomers, and incorporates the marker 5-(biotinamido) pentylamine. Expression of transglutaminase activity in the A375 and A2058 human melanoma cell extracts was revealed by its ability to induce galectin-3 oligomerization and 5-(biotinamido) pentylamine incorporation. Transglutaminase-treated galectin-3 did not affect adhesion or migration of the melanoma cells to laminin but consistently induced a significant increase of the percentage of cell spreading compared to the control (23.5 +/- 2.3%, vs. 10.6 +/- 1.9% at 180 min, p < 0.05), or to untreated galectin-3 or transglutaminase alone. Our study is the first demonstration that human galectin-3 is oligomerized by transglutaminase with, as a consequence, a specific effect of melanoma cell spreading on laminin. This phenomenon could be of significance in the modulation of cancer cell interactions with laminin during tumor invasion and metastasis.
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PMID:Transglutaminase-mediated oligomerization of galectin-3 modulates human melanoma cell interactions with laminin. 979 24

Diffuse tenosynovial giant cell tumor (DGCT) could present as a large intra-articular mass (pigmented villonodular synovitis, or PVNS) or as an extraarticular mass, which might be confused with a sarcoma, particularly when growth is destructive and giant cells are few. Prompted by a DGCT in which a subpopulation of cells was desmin positive and in which an erroneous diagnosis of myosarcoma was made, we analyzed the frequency of desmin, myogenin, MyoD1, and muscle-specific actin immunoreactivity in 45 well-characterized GCTs. We also analyzed a subset of these cases with antibodies to smooth muscle actin, as well as macrophage, follicular dendritic cell, extrafollicular dendritic cell, and dermal dendrocyte-associated antigens. Sections from 45 cases of formalin-fixed GCTs (22 DGCTs, 13 cases of PVNS, and 10 localized GCTs) were immunostained for desmin, myogenin, MyoD1, and muscle-specific actin. The eight cases that showed the largest number of desmin-positive cells were immunostained for smooth muscle actin, CD45, CD68, CD21, CD35, cytokeratin 8, and Factor XIIIa. Desmin-positive cells were seen in 20 (43%) of 45 cases: 10 (43%) of 22 DGCTs, 5 (38%) of 13 cases of PVNS, and 5 (50%) of 10 localized GCTs. In contrast, none were positive for any of the other muscle-associated proteins. In almost all of the cases, the desmin-positive cells were large and dendriform, with long processes that interdigitated between adjacent round cells. Desmin immunoreactivity was found in almost 50% of all GCTs, in the absence of positivity for other muscle markers. Desmin immunoreactivity in GCT seemed to be confined to a variably sized subpopulation of large dendritic cells whose exact identity remains uncertain.
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PMID:Tenosynovial giant cell tumors: evidence for a desmin-positive dendritic cell subpopulation. 979 19

Recent evidence suggests that cholesterol sulfate may be an important second messenger involved in signaling epidermal differentiation in skin. The activity of cholesterol sulfotransferase (Ch-ST) is increased during squamous differentiation of keratinocytes and is believed to be a marker enzyme for terminal differentiation. The primary objective of this study was to examine changes in levels of cholesterol sulfate (CS) and activity of its biosynthetic enzyme, Ch-ST, during multistage carcinogenesis in mouse skin. Using SENCAR mice, we determined the activity of Ch-ST in normal epidermis, in tumor promoter-treated epidermis, in epidermis during wound healing, and in mouse skin tumors generated by initiation-promotion regimens. A single topical application of tumor promoters led to significantly elevated levels of Ch-ST activity and of CS. Epidermal Ch-ST activity was also elevated during wound healing. Dramatic increases in CS levels and in the activity of Ch-ST were found in nearly all of the papillomas and squamous cell carcinomas examined. The increased levels of CS and activity of Ch-ST in tumor promoter-treated epidermis were accompanied by increased transglutaminase-I activity. In contrast, transglutaminase I activity was not elevated in primary papillomas or squamous cell carcinomas. Finally, Ch-ST activity was significantly elevated in the epidermis of newborn HK1.ras transgenic mice, whereas transglutaminase I activity did not correlate with Ch-ST activity in these mice. These results demonstrate that diverse tumor-promoting stimuli all produce elevated CS levels and Ch-ST activity and that CS levels and Ch-ST activity were constitutively elevated in both papillomas and squamous cell carcinomas. The data also suggest a mechanism for upregulation of Ch-ST in skin tumors involving activation/upregulation of Ha-ras.
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PMID:Alterations in cholesterol sulfate and its biosynthetic enzyme during multistage carcinogenesis in mouse skin. 985 4

The expression of cholesterol sulfate (CS) is known to increase during squamous differentiation of keratinocytes and to activate the epsilon, eta, and zeta forms of protein kinase C as a signal transduction molecule for the subsequent expression of transglutaminase-1 (TG-1) and cytokeratins. To gain further insight into the regulation of cellular differentiation and tumorigenesis by CS, we examined the concentration and the potential for synthesis of CS in seven and four surgical specimens from human ovarian and uterine cervical cancer patients, respectively, and eight cell lines established from human uterine cervical cancer patients and compared them for the rate of expression of cytokeratin. CS was present in all of the uterine cervical cancer tissue specimens but only in the mucinous type of cystadenocarcinoma among ovarian cancer tissue specimens, and cytokeratin was highly expressed in the tissues with a high concentration of CS, which were classified as well-differentiated on the basis of morphological examination. Similarly, cells derived from a keratinizing type of well-differentiated cervical carcinoma demonstrated strong potential for synthesis of CS, stained positive with anti-cytokeratin antibody, and exhibited a higher specific activity of TG-1, whereas the cells without CS did not stain positive with anti-cytokeratin antibody and exhibited a lower specific activity of TG-1. These findings indicate that CS is coexpressed with TG-1 and cytokeratin in the well-differentiated types of squamous cell cancers as a tumor marker.
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PMID:Coexpression of cholesterol sulfate and cytokeratin as tumor markers in well-differentiated squamous cell carcinoma of the human uterine cervix. 986 10

Our previous results and data in the literature have suggested a potential role for phospholipase D (PLD) in the regulation of epidermal keratinocyte growth and differentiation. Therefore, we investigated the effect of agents reported to modulate keratinocyte growth and differentiation on PLD activation. The purported protein kinase C (PKC) 'inhibitor', staurosporine (Stsp), has been reported to activate PKC in keratinocytes, eliciting many of the same effects as active tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). Stsp also induces a programmed pattern of differentiation similar to that seen in keratinocytes in vivo; TPA, on the other hand, appears to preferentially elicit markers consistent with late (granular) differentiation. In contrast, bradykinin is reported to stimulate keratinocyte proliferation. We found that these three agents had different effects on PLD activation in primary mouse epidermal keratinocytes. TPA increased PLD activity acutely and in a sustained fashion. In contrast, Stsp did not acutely activate PLD and inhibited acute TPA-induced activation of PLD. However, treatment of keratinocytes with Stsp for longer time periods (3-5 h) induced sustained PLD activation and this long-term effect was additive with that of TPA. Bradykinin activated PLD acutely but transiently. Both TPA and Stsp increased transglutaminase activity, a marker of late differentiation, whereas bradykinin had little or no effect on either cell proliferation or transglutaminase activity. These results suggest that a sustained activation of PLD is associated with the induction of keratinocyte differentiation. We hypothesize that PLD activity mediates late keratinocyte differentiation through generation of diacylglycerol and activation of specific PKC isoforms. Furthermore, we propose that the profound and immediate TPA-induced stimulation of PLD activity 'drives' the keratinocytes to late differentiation steps. However, the less efficacious (and more gradual) sustained activation of PLD by Stsp may allow a patterned differentiation more like that observed in skin.
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PMID:Sustained phospholipase D activation is associated with keratinocyte differentiation. 1022 83

Inactivation of antineoplastics is a serious problem in cancer therapy, and prevention of the inactivation is a surpassing strategy for enhancement of their therapeutic effects. BOF-A2, which contains both EM-FU, a masked form of 5-fluorouracil (5-FU), and CNDP, an inhibitor of 5-FU degradation, was developed with this aim. We compared the antitumor effects of BOF-A2 and 5-FU in human squamous cell carcinoma cells transplanted to nu/nu mice. Each drug (0.9-7.0 mg/kg of 5-FU and 3.8-30 mg/kg of BOF-A2) was orally administered every day to 5 mice in each dosage group for 4 weeks. Although the maximal tumor growth inhibition by 5-FU (3.5 mg/kg per day) was about 50% of the control value, 15 mg/kg per day of BOF-A2, which is equimolar to 3.5 mg/kg per day of 5-FU, almost completely inhibited the tumor growth. The flow-cytometric analysis revealed that BOF-A2 (15 mg/kg per day) induced more prominent S-phase-accumulation (63 +/- 6%) of tumor cells than did 3.5 mg/kg per day of 5-FU (43 +/- 18%), and immunohistochemical stainings indicated that the decrease of proliferating cell nuclear antigen expression was more prominent in tumor cells in the BOF-A2-treated mice than in the 5-FU-treated mice. Correspondingly, the DNA synthesis was markedly suppressed in tumor cells obtained from BOF-A2-treated mice. Compared with 5-FU, BOF-A2 more strongly induced apoptosis; apoptotic cells detected by nick-end labeling techniques were about 20% of the tumor cells in 5-FU (3.5 mg/kg per day)-treated mice, and nearly 50% in BOF-A2 (15 mg/kg per day)-administered mice. The expressions of involucrin, cytokeratin 10 and protein kinase C eta, which are associated with squamous cell differentiation, were not increased by BOF-A2 or 5-FU, although the expression of transglutaminase was slightly augmented by both drugs. These results indicate that compared with 5-FU, BOF-A2 more strongly suppresses the growth of squamous cell carcinoma by inhibiting DNA synthesis and inducing apoptosis but not cell differentiation.
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PMID:The inhibitory action of BOF-A2, a 5-fluorouracil derivative, on squamous cell carcinoma. 1037 90

The induction of apoptosis in T cells is one of several mechanisms by which tumors escape immune recognition. We have investigated whether tumors induce apoptosis in dendritic cells (DC) by co-culture of murine or human DC with different tumor cell lines for 4-48 h. Analysis of DC morphological features, JAM assay, TUNEL, caspase-3-like and transglutaminase activity, Annexin V binding, and DNA fragmentation assays revealed a time- and dose-dependent induction of apoptosis in DC by tumor-derived factors. This finding is both effector and target specific. The mechanism of tumor-induced DC apoptosis involved regulation of Bcl-2 and Bax expression. Double staining of both murine and human tumor tissues confirmed that tumor-associated DC undergo apoptotic death in vivo. DC isolated from tumor tissue showed significantly higher levels of apoptosis as determined by TUNEL assay when compared with DC isolated from spleen. These findings demonstrate that tumors induce apoptosis in DC and suggest a new mechanism of tumor escape from immune recognition. DC protection from apoptosis will lead to improvement of DC-based immunotherapies for cancer and other immune diseases.
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PMID:Tumor's other immune targets: dendritic cells. 1044 78


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