Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD40 is a receptor at the surface of B lymphocytes with important functions in the immune response. CD40 has also been found on a variety of carcinoma and melanoma cell lines where it has been suggested to serve as a possible receptor for mitogenic signals. We studied the expression and distribution of CD40 in paraffin sections of 71 uniformly treated malignant melanomas (MMs) with a long clinical follow-up using well known monoclonal antibodies. For comparison, 71 benign nevi were also studied. Common acquired nevi occasionally expressed CD40 in nests or single cells at the dermo-epidermal junction; no immunoreactivity was observed in the dermal part of acquired nevi, and all Spitz' nevi were entirely negative. One-third of large congenital nevi expressed CD40 in small clusters of heavily pigmented, epithelioid cells, corresponding to so-called proliferative nodules. In 41 of 71 MMs, CD40 was expressed in single or clustered neoplastic melanocytes; 9 cases showed CD40 expression only in the radial growth phase, and in 32 cases, the vertical growth phase showed CD40 expression. The same staining pattern was obtained with other anti-CD40 monoclonal antibodies, directed to different epitopes of the CD40 molecule. In 29 of 32 MMs showing CD40 in the vertical growth phase, expression of the CD40 ligand (CD40L) was studied; in 13 of these 29, CD40L was found in the same tumor areas that expressed CD40. Analysis of 28 metastases from 24 MM patients showed in the majority of cases a similar, scattered or nodular staining pattern as observed in the primary tumor. Patients expressing CD40 in the vertical growth phase of their MM did not differ significantly from CD40-negative patients with respect to any of the known prognostic parameters but showed a significantly shorter tumor-free survival. Patients with CD40+ CD40L+ MM tended to have a shorter tumor-free survival than those lacking CD40L. We conclude that CD40 represents a novel prognostic parameter in primary cutaneous MM. The co-localization of CD40 and CD40L suggests an autocrine growth loop in the vertical growth phase of MM.
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PMID:CD40 is a prognostic marker in primary cutaneous malignant melanoma. 895 30

CD40 binding produces multifaceted growth signals in normal and malignant B cells, whereas its physiological role is less well characterized in epithelial cancers. We examined the growth outcome of CD40 ligation in human breast cancer cells, using CD40+ (T47D and BT-20) and CD40-negative (MCF-7, ZR-75-1) cell lines as defined by flow cytometric analysis, immunohistochemistry, and reverse transcription-PCR. Treatment with the soluble recombinant CD40 ligand (CD40L) molecules gp39 or CD40L-trimer significantly reduced [3H]thymidine uptake in BT-20 and T47D cells by up to 40%, but did not affect the growth of CD40-negative MCF-7 or ZR-75-1 cells. Similarly, significant growth inhibition was observed after co-incubation with CD40L-transfected murine L cells (55.0 +/- 8.9%, P < 0.001) that express membrane CD40L constitutively, or with paraformaldehyde-fixed, CD3+ CD40L+ PBLs from three different HLA-mismatched donors (39.7 +/- 3.7%, P < 0.01). Untransfected L cells and non-CD40L-expressing lymphocytes did not produce significant growth inhibition. The in vivo antitumorigenic effects of CD40L were examined using a s.c. severe combined immunodeficient-hu xenograft model. Pretreatment with two different soluble recombinant CD40L constructs (CD40L and gp39) produced similar xenograft growth-inhibitory effects [67 +/- 24% (n = 4), and 65 +/- 14% (n = 8) inhibition, respectively], which were reversed by co-treatment with the CD40L-neutralizing antibody LL48. In vitro analysis indicated that CD40L-induced growth inhibition was accompanied by apoptotic events including cell shrinkage, rounding, and detachment from the adherent T47D culture monolayer. Thirty-one and 27% of gp39-treated T47D and BT-20 cells underwent apoptosis, respectively, as compared with 56 and 65% from the same cell lines after treatment with the Fas agonistic antibody CH-11. An up-regulation of the proapoptotic protein Bax in T47D and BT-20 cells was observed, which indicated that this Bcl-2 family member may contribute to this growth-inhibitory effect. To explore the clinical relevance of CD40L-CD40 interaction, retrospective immunohistochemical analysis was carried to characterize in situ CD40- and CD40L-expression in breast cancer patient biopsies. All of the infiltrating ductal (5 of 5 cases tested) and lobular (4 of 4 cases) breast carcinomas, carcinomas in situ (6 of 6 cases), and mucinous carcinoma tested (1 case) expressed CD40. Varying proportions of tumor cells also expressed CD40L in the majority of infiltrating ductal (3 of 5 cases) and lobular (3 of 4 cases) carcinomas, and carcinomas in situ (4 of 6 cases), as determined by immunohistochemistry and validated by RT-PCR detection of the CD40L message in only CD40L positive-staining cases. Tumor infiltrating mononuclear cells from infiltrating carcinomas and carcinomas in situ expressed CD40 (10 of 10 cases), but less commonly CD40L (1 case of infiltrating lobular carcinoma, 2 cases of carcinoma in situ). Our findings indicate that the CD40 signaling pathway is active in human breast carcinoma cells. However, tumor-infiltrating lymphocytes from primary tumor tissues may be limited in their capacity to directly modulate tumor growth through the CD40L-CD40 loop.
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PMID:Growth-inhibitory effects of CD40 ligand (CD154) and its endogenous expression in human breast cancer. 1129 66

CD40, a member of the tumor necrosis factor receptor superfamily, is widely expressed on various cell types. Some studies show that CD40 expression is related to several carcinomas, where its function remains largely unknown. This study investigated the expression of CD40 on colon cancer, and evaluated the effect of recombinant soluble human CD40L (rshCD40L) on colon cell lines. CD40 expression on the primary colon cancer samples was detected by immunohistochemistry. The expression of CD40 on colon cell lines was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry. To examine the effects of rshCD40L, the growth-inhibitory activity of rshCD40L on colon cancer cell was examined by MTT assay and the proportion of apoptotic tumor cells was examined in the TUNEL assay. Results showed that CD40 is expressed in human colon primary tumor. Expression of CD40 was elevated in 3 out of 4 colon cell lines examined by RT-PCR and flow cytometry. CD40 expression could be induced by interferon-gamma (IFN-gamma). CD40 ligand, rshCD40L, significantly inhibited the proliferation of the CD40(+) colon cancer cell lines. The inhibition could also be enhanced by IFN-gamma in HCT116 and SW48 cell lines. In addition, rshCD40L induced apoptosis of the CD40(+) colon cancer cell lines. Theses results suggest that CD40 present in colon cancer, and rshCD40L may be of clinical use to inhibit human colon cancer growth.
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PMID:Expression of CD40 and growth-inhibitory activity of CD40 ligand in colon cancer ex vivo. 1860 31

The presence of CD40 on carcinoma cells is an important factor for the generation of tumor-specific responses induced by CD40 ligation. In an N-methyl-N-nitrosourea (MNU)-induced autochthonous mammary tumor model, we analyzed the immune features of primary tumor cells. Here, CD40 was frequently detected on the primary tumor cultures and selectively expressed on the malignant mammary tissue in vivo. On the other hand, every mammary tumor cell culture had a heterogeneous and reduced expression of proinflammatory TNFalpha, IL-1beta, IL-6 and CXCL1 cytokines compared to normal mammary epithelial cells. Low-efficiency transfection of CD40 ligand (CD40L) gene enhanced the expression of proinflammatory cytokines in the tumor cells and strengthened allogeneic immune reactions and costimulatory activity which may help overwhelming suppressive features of the tumor.
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PMID:Primary tumor cells obtained from MNU-induced mammary carcinomas show immune heterogeneity which can be modulated by low-efficiency transfection of CD40L gene. 1910 41