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 tested 20 human carcinoma samples for the production of transforming growth factor beta (TGFbeta) in vitro. Tumour cell suspensions without obvious contamination with non-malignant cells were kept in culture conditions for 16 h and their supernatants were added to CCL-64 cells. The proliferation of these cells is inhibited by TGFbeta. According to this assay, the supernatants contained both active and latent TGFbeta. In addition, the supernatants were found to suppress the spontaneous cytotoxic function and activation of T-cell-enriched lymphocyte populations. A specific monoclonal antibody (mAb) counteracted these effects and therefore we concluded that they were mediated to a large extent by TGFbeta. In line with the results obtained with the supernatants, activation of lymphocytes could also be inhibited by tumour cells and their inhibitory effect was weaker in the presence of the TGFbeta-specific mAb. It is important to note that, when TGFbeta-specific mAb was added to autologous mixed lymphocyte/tumour cell cultures, lymphocyte activation occurred more often. These results thus substantiate the assumption that production of TGFbeta may help the survival of potentially immunogenic tumour cells in immunocompetent patients.
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PMID:Human ex vivo carcinoma cells produce transforming growth factor beta and thereby can inhibit lymphocyte functions in vitro. 906 2

The paracrine influence of prostatic stroma on the proliferation of prostatic epithelial cells was investigated. Using a double-layer soft agar assay it was demonstrated that stromal cells from the human prostate inhibit the anchorage-independent growth of the prostatic tumor epithelial cell lines PC-3 and LNCaP. Anchorage-dependent growth was inhibited too as was shown in the semi-automated colorimetric MTT test performed on multiwell plates. Antiproliferative activity was mediated by a diffusible factor in the stromal cell conditioned medium and was found to be produced specifically by prostatic stromal cells. Although the putative inhibiting factor shared some properties with transforming growth factor beta (TGF-beta) evidence is presented that the factor is different from this well-known inhibitor of epithelial cell growth. Absence of TGF-beta activity was shown by the lack of inhibitory response of the TGF-beta-sensitive mink lung cell line CCL-64 to prostate stromal cell conditioned medium and to concentrated partially purified preparations of the inhibitor. Furthermore, neutralizing antibodies against TGF-beta 1 or TGF-beta 2 did not cause a decline in the level of PC-3 growth inhibition caused by partially purified inhibitor. It is concluded that the prostate stroma-derived factor may be a novel growth inhibitor different from any of the currently described inhibiting factors.
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PMID:Stromal inhibition of epithelial cell growth in the prostate; overview of an experimental study. 914 94

In this study, 18 BUF rats with 7316 A liver cancer burden were divided into three groups. Groups A underwent simple laparotomy, group B had 70% hepatectomy, and group C with laparotomy plus TGF-beta . Splenic adhesive cells and serum of postoperative day 5 in both group A and B were added into mixed lymphocellular culture and CCL-64 cell culture, TGF-beta was also added into MLC and 7613 A liver cancer culture. It was found that in group B and C the growth rate of tumor cells was greatly accelerated (P < 0.01); whereas MLC and CCL-64 cell proliferation was inhibited by the serum and splenic adhesive cells from group B (P < 0.05). TGF-beta also significantly inhibited MLC through it had no effect on 7316 A liver cancer cells. The authors came to the conclusion that there was the activity of TGF-beta in the serum of the rats with partial hepatectomy which inhibits the proliferation of host immune cells.
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PMID:[A study of mechanism by which tumor growth was induced by partial hepatectomy]. 959 Jul 61

Primary lymphoma of the stomach (PLS) is an uncommon neoplasm, accounting for up to 8 per cent of all malignant neoformations with this particular localization. Its development is linked to the so-called mucosa associated lymphoid tissue (MALT), wherefrom its denomination--MALT lymphoma--is derived. In the stomach, under ordinary conditions, it is nonexistent, and in most of the cases it is acquired through infection with H. pylori. In a prevailing percentage of PLS it is a matter of B-cell lymphoma with low-degree malignancy. T-cell lymphomas occur sporadically, as well as primary Hodgkin's lymphoma which is exceptionally rare. Histologically the B-cell lymphoma reiterates the structural pattern of Peyer's plaque prototype, involving also a number of non-neoplastic components. The most distinguishing cells are reminiscent of centrocytes (centrocyte-like cells--CCL)--a term adopted for all MALT-lymphoma cases. They vary considerably in terms of cytological appearance, and may even bear resemblance to Hodgkin's and Sternberg's cells. Signet-ring lymphomas, known in several variants, are also by no means ruled out. Immunohistochemical typing presupposes a definitive diagnosis being made. In case of immunosuppression (transplantation, HIV-infection) the risk of B-cell lymphomas development augment, and what is more, most of them associated with Epstein-Barr viruses characterized by a substantially more aggressive course and poor prognosis.
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PMID:[Primary lymphoma of the stomach]. 973 58

Shortening of telomeres along with an up-regulation of telomerase is implicated in the immortality of tumor cells. Targeting either telomeres or telomerase with specific compounds has been proposed as an anticancer strategy. Because telomerase activity and telomeres are found in normal cells, telomere or telomerase targeting agents could induce side effects in normal tissues. We evaluated the effects of telomere and telomerase interactive agents in human tumor and normal cell lines to try to determine the potential side effects those agents might induce in patients. Toxicity of the G-quadruplex interactive porphyrins (TMPyP4, TMPyP2) and azidothymidine (AZT) were tested using a cell-counting technique against normal human cell lines (CRL-2115 and CRL-2120, fibroblasts; NHEK-Ad, adult keratinocytes; CCL-241, small intestinal cells; NCM 460, colonic mucosal epithelial cells) and human tumor cell lines (MDA-MB 231 and Hs 578T, breast cancer; SK-N-FI, neuroblastoma; HeLa, cervix cancer; MIA PaCa-2, pancreatic cancer; HT-29 and HCT-116, colon cancer; DU 145, prostatic cancer cell line). Telomerase activity of these cell lines was measured by a non-PCR-based conventional assay. The effects of TMPgammaP2, TMPyP4, and AZT were also evaluated against normal human bone marrow specimens, using a granulocyte-macrophage colony-forming assay (CFU-GM). AZT showed very low cytotoxic effects against normal and tumor cell lines, with the IC50 values above 200 microM. The IC50 values for TMPyP2 and TMPyP4 in normal human cell lines were in the range of 2.9-48.3 microM and 1.7-15.5 microM, respectively, whereas in tumor cell lines the IC50 values were 11.4-53 microM and 9.0-28.2 microM, respectively. Within the tissue types, keratinocytes were more sensitive to TMPyP4 than fibroblasts, and small intestinal cells were more sensitive than colonic mucosal epithelial cells. The IC50 for TMPyP2 and TMPyP4 in the normal marrow colony-forming assays were 19.3 +/- 5.1 microM and 47.9 +/-1.0 microM, respectively. In conclusion, the in vitro cytotoxicity of the telomere interactive agent TMPyP4 is comparable in human tumor and normal cell lines, which indicates that TMPyP4 could have effects on normal tissues.
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PMID:Effect of telomere and telomerase interactive agents on human tumor and normal cell lines. 1074 25

Potent photosensitizer Hypericin (HY), is a lipid soluble perylquinone derivative of the genus Hypericum and has a strong photodynamic effect on tumors and viruses. However, the mechanisms of tumor cell death induced by this compound is still unclear. Furthermore, there are no reports on mechanisms in cell apoptosis induced by perylquinones in human nasopharyngeal carcinoma (NPC) and other mucosal cells. We studied the photodynamic effects of HY compound in poorly differentiated (CNE2) and moderately differentiated (TW0-1) human NPC cells as well as human mucosal colon (CCL-220.1) and bladder (SD) cells. Using these cell lines we investigated few hall marks of apoptotic commitments in a drug and light dose dependent manner. Tumor cells photoactivated with HY showed cell size shrinkage and an increase in the sub-diploid DNA content. A loss of membrane phospholipid asymmetry associated with apoptosis was induced in all tumor cell lines as evidenced by the externalization of phosphatidylserine. Under apoptotic conditions, Western blot analysis of poly (ADP-ribose) polymerase, a caspase substrate, showed the classical cleavage pattern (116-85 kDa) associated with apoptosis in PDT-treated cell lysates. In addition, 85 kDa cleaved product was blocked by using tetrapeptide caspase inhibitors such as DEVD-CHO or z-VAD-fmk. These results demonstrate that tumor cell death induced by photoactivated HY is mediated by caspase proteases. This study also identifies that CNE2, CCL-220.1 (colon) and SD (bladder) cell lines are more sensitive than TW0-1 cell line to PDT using perylquinone HY.
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PMID:Induction of apoptosis by Hypericin through activation of caspase-3 in human carcinoma cells. 1160 21

BRCA2 is a tumor suppressor gene associated with familial predisposition to breast and ovarian cancer. BRCA2 has been implicated in response to DNA damage, cell cycle control and transcription. However, the mechanisms by which the BRCA2 protein suppresses tumor cell growth are largely unknown. To begin to understand the contribution of BRCA2 protein to tumorigenesis, we evaluated the specificity of 4 anti-BRCA2 antibodies directed against several different epitopes using immunoblotting techniques. The two monoclonal antibodies (3E6 and 5F6) detected a specific 384-kDa protein in human breast cancer cell lines (MCF7 and MDA-MB 231) and in a human colon carcinoma cell line (CCL 221). The two polyclonal antibodies (9433 and 9434) recognized the 384-kDa BRCA2 protein respectively in MCF7 and in CCL 221 cells, but both BRCA2 polyclonal antibodies also cross-reacted with smaller proteins.
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PMID:Characterization of anti-BRCA2 antibodies in cell lines by Western blot analysis. 1160 67

We systematically investigated the impact of the relative maturation levels of dendritic cells (DCs) on their cell surface phenotype, expression of cytokines and chemokines/chemokine receptors (by DNA array and RNase protection analyses), biological activities, and abilities to induce tumor immunity. Mature DCs expressed significantly heightened levels of their antigen-presenting machinery (e.g., CD54, CD80, CD86) and numerous cytokines and chemokines/chemokine receptors (i.e., Flt-3L, G-CSF, IL-1alpha and -1beta, IL-6, IL-12, CCL-2, -3, -4, -5, -17, and -22, MIP-2, and CCR7) and were significantly better at inducing effector T cell responses in vitro. Furthermore, mice vaccinated with tumor peptide-pulsed mature DCs better survived challenge with a weakly immunogenic tumor (8 of 8 survivors) than did mice vaccinated with less mature (3 of 8 survived) or immature (0 of 8 survivors) DCs. Nevertheless, intermediate-maturity DCs expressed substantial levels of Flt-3L, IGF-1, IL-1alpha and -1beta, IL-6, CCL-2, -3, -4, -9/10, -17, and -22, MIP-2, osteopontin, CCR-1, -2, -5, and -7, and CXCR-4. Taken together, our data clearly underscore the critical nature of employing DCs of full maturity for DC-based antitumor vaccination strategies.
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PMID:DNA array and biological characterization of the impact of the maturation status of mouse dendritic cells on their phenotype and antitumor vaccination efficacy. 1190 30

Nasopharyngeal carcinoma (NPC) is a malignant disease of the head/neck region with a 5-year survival level of approximately 65%. To explore the novel therapeutic strategies in the management of this disease, the potential effects of photodynamic therapy (PDT) in NPC cells were investigated. PDT, a new mode of treatment, is based on the combined use of light-absorbing compounds and light irradiation. Two human NPC cells such as, poorly differentiated (NPC/CNE2) and moderately differentiated (NPC/TW0-1) and other types of tumor cells like colon (CCL-220.1) and bladder (SD) undergo rapid apoptosis when treated with PDT sensitized with hypericin (HY). It has been shown that this compound has a strong photodynamic effect on tumors and viruses. However, the initiating events of PDT sensitized HY-induced apoptosis are not identified completely. In this study, we sought to determine whether Fas/FasL upregulation and involvement of mitochondrial events are an early event in HY-treated PDT induced apoptosis. Loss of mitochondrial transmembrane potential, release of cytochrome c, involvement of caspases 8 and 3 and the status caspase-3 specific substrate PARP, were evaluated in PDT treated tumor cells. Photosensitization of HY enhanced both CD95/CD95L expression and induced CD95-signaling dependent cell death in all tumor cell lines studied. CD95/CD95L expression appeared within 2 h following light irradiation and appeared to be a principal event in PDT induced apoptosis. Furthermore, these results indicate that release of mitochondrial cytochrome c into the cytoplasm within 2-3 h post PDT is a secondary event following the activation of initiator caspase-8 preceding Apaf-1, caspase-9 and caspase-3 activation, cleavage of PARP and DNA fragmentation.
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PMID:Hypericin induced death receptor-mediated apoptosis in photoactivated tumor cells. 1201 77

The development of new-generation photosensitizers to improve photodynamic therapy (PDT) and photodynamic diagnosis (PDD) is an area of extensive research. One such compound that has been studied in our group is Hypericin (HY). To study the mechanism of action we have investigated uptake, intracellular localization, cell phototoxicity and morphological changes especially to ultrastructures following photodynamic treatment in poorly (CNE2) and moderately (TW0-1) differentiated human nasopharyngeal carcinoma (NPC) cells and also other tumor cells such as colon (CCL-220.1) and bladder (SD) cells in vitro. Following irradiation, phototoxicity was determined by crystal fast violet assay and apoptosis was assessed using annexin-V assay. Using spectrofluorimetry and confocal laser scanning microscopy (CLSM) we have determined cellular fluorescence localization and uptake of HY. Co-labeling with HY and fluorescent dyes specific for cell organelles revealed an intracellular localization of HY predominantly in mitochondria and lysosomes. Since many photosensitizing agents in current clinical use have mitochondrial targets, HY may be a valuable addition to current protocols. In addition, our results also indicate that leakage of lysosomal protease into cytosolic compartment might be involved in the induction of apoptosis. Electron microscopy revealed damage to plasma membrane with high drug dose (>5 microM); indicating a mechanism related to necrosis, whereas sub-lethal lower doses (<2.5 microM) resulted in induction of apoptosis indicated by typical ultrastructural signs of apoptosis. Our results based on mitochondrial and lysosomal localization support the idea that PDT can contribute to elimination of malignant cells by the induction of apoptosis, and can be of physiological significance.
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PMID:Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells. 1216 96


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