Purpose: Chlamydia psittaci (Cp) has been associated to ocular adnexal lymphomas (OAL) with variable geographic distribution. Herein, we used multiple Chlamydia detection tools to identify Cp elementary bodies^containing cell and to assess Cp prevalence in both nodal and extranodal lymphomas. Experimental Design: TETR-PCR, immunohistochemistry, immunofluorescence, electron microscopy, and laser-capture microdissection were done in 35 OALs to define their effect in Chlamydia detection and, moreover, to identify the Cp cellular carrier. Cp prevalence was screened byTETR-PCR in 205 extraorbital lymphomas and 135 nonneoplastic controls. Results: Twenty-six (74%) OALs were associated with Cp infection: immunohistochemistry, immunofluorescence, and laser-capture microdissection-assisted PCR showed that monocytes/ macrophages were the Cp carriers; electron microscopy showed the presence of intact Cp elementary bodies into these cells. Immunohistochemistry andTETR-PCR showed a 70% concordance rate (P = 0.001). Cp DNA was equally prevalent in non-OAL, nodal, and extranodal lymphomas: among the latter, it was more common in diffuse large B-cell lymphomas of the skin (P = 0.03) and Waldeyer's ring.Conclusions: This multiparametric approach shows, for the first time, that monocytes/macrophages are the carriers of Cp, Cp seems preferentially associated with lymphomas arising in organs primarily exposed to antigens. The clinical implications of these findings deserve to be prospectively investigated.
Gap‐junction‐mediated intercellular communication (GJIC) is required for completion of embryonic development, tissue homeostasis, and regulation of cell proliferation and death. Although, as emphasized in several reports, defects or disruption of GJIC may be important in carcinogenesis, the potential role of GJIC in the onset and progression of human prostate cancer remains ill‐defined. The gap junction channel‐forming connexins (Cx) comprise a multigene family of highly conserved proteins that are differentially expressed in a tissue‐ and development‐specific manner; changes in connexin expression are also commonly seen during cellular differentiation. However, when multiple connexins are concurrently expressed, gap junction channels may consist of more than one connexin species. This is important, because only certain pairings give rise to functional channels. In our studies, we investigated GJIC in a panel of both nontumorigenic (RWPE‐1) and malignant (RWPE‐2, LNCaP, DU‐145) human prostate epithelial cells, compared to a normal rat liver epithelial F344 (WB‐1) cell line, as it was found to be junctionally proficient. In addition, expression and regulation of Cx43 and Cx32 were also inspected using western blot analysis. The ability of hormones, antihormones, and the antihypertensive drug forskolin to restore GJIC in nontumorigenic and malignant human prostate epithelial cells was examined by the scrape‐loading/dye transfer (SL/DT) or fluorescence recovery after photobleaching (FRAP) methods using an Ultima laser cytometer. Results from both assays showed that neither nontumorigenic nor malignant prostate cells have functional GJIC. However, both estrone (E1) and forskolin (FK) induced a significant increase (4.4‐ and 2.8‐fold, respectively) in cell‐cell communication only in the RWPE‐1 cells. Interestingly, the use of Matrigel, a solubilized basement membrane, as substrate for cell attachment and growth resulted in the rescue of GJIC activity in RWPE‐1 cells, as revealed by the SL/DT method. Furthermore, E1 induced a twofold increase in connexin 43 (Cx43), whereas forskolin caused a 50% reduction in Cx32 expression in RWPE‐1 cells. These data suggest that agents that increase Cx43:Cx32 ratio may restore GJIC in junctionally deficient cells, providing a basis for the development of new strategies for the prevention and treatment of human prostate cancer.
In the present work, we have inspected expression of estrogen receptors (ER) and their regulation by the phorbol diester 12-O-tetradecanoylphorbol 13-acetate (TPA) in a leukemic cell line, the THP-1 cells, using multiple experimental approaches. Firstly, ligand binding assay (LBA) revealed that control (unstimulated) THP-1 cells express type I (high affinity, limited capacity) ER in the nuclear fraction only, whilst treatment of cells with TPA resulted in the appearance of type I ER in the soluble fraction as well, with the 50 ng/ml dose and the 48 h incubation time being the most effective experimental condition. A concomitant increase of type II ER was also seen in both soluble and nuclear cell fractions. Unstimulated THP-1 cells were found to be ER negative by immunocytochemistry; conversely, cells exposed to 50 ng/ml TPA for 48 h stained positively for ER, with the majority of cells having a strong nuclear staining. Scrutiny of ER mRNA expression using reverse transcriptase-polymerase chain reaction showed the presence of a wild type ER transcript in both control and TPA-treated THP-1 cells, though levels of ER mRNA were found to be comparatively higher in the latter. This combined evidence would imply that the TPA-induced differentiation of THP-1 cells is accompanied by the rise of high affinity (type I) ER, suggesting that estrogens may play a role in the regulation of macrophage activity during the inflammatory and/or the immune response.
In recent years there has been a continuingly increasing interest in novel research subjects, as yet poorly explored, either because they relate to aspects previously thought to be marginal with respect to classical fields of investigation, or because they require both specialized competence and intense cross-talk by researchers from disparate areas. The potential interaction between immunity and cancer has generated a remarkable number of studies, including those related to the newly explored immune-neuro-endocrine system. In this paper, we review a few autoimmune diseases as examples of a mutual relationship between immune diseases and malignancies. We also review our previous studies on patients with rheumatoid arthritis (RA). In particular, aiming to define the hormone-responsive or -sensitive status of synovial tissues and cells, we have inspected different endocrine end-points, including (1) high- and low-affinity sites of androgen and estrogen binding; (2) the activity of key enzymes of steroid metabolism; and (3) the hormonal profile of synovial fluids as an indication of local endocrine milieu. Overall, our data provide convincing evidence for synovial macrophage-like cells and a subset of T lymphocytes to be considered as target cells for gonadal steroids. This provides a basis for developing new strategies for alternative treatments of RA and possibly unveils novel perspectives in both research and the clinic for other autoimmune diseases as well. In addition, the association of autoimmunity and cancer may disclose promising new avenues of research linking steroid hormones, the immune system, and malignant transformation.
In this retrospective study we assessed the expression of the HER2/neu oncogene product in a series of 574 consecutive breast cancer cases, all recruited at the Maurizio Ascoli Cancer Center of Civico Hospital, in Palermo, between January 1998 and June 2003. The HER2/neu expression was evaluated using immunohistochemistry and scored from 0 to +3 as per FDA recommendations. The HER2/neu expression levels were related to the clinical-pathological features of the disease, including tumor size, nodal and menopausal status, estrogen and progesterone receptors, and hormonal or chemotherapeutic treatment. In 108 patients with a follow-up period of 3 years or more, the HER2/neu expression was also related to their survival characteristics. A significant correlation (P = 0.011) between HER2/neu +3 and estrogen receptor-negative cases was observed in the 487 M0 patients. In addition, HER2/neu +3 cases were associated with a positive nodal status (57.4%), although this association was not quite significant (P = 0.06). More importantly, follow-up data revealed that, in the 91 M0 patients with an average follow-up period of 37 months, the percentage of HER2/neu +3 patients who relapsed was remarkably greater (54.8%) than that observed for the HER2/neu +1/0 cases when combined (34.2%). Furthermore, the disease-free interval (DFI) was 47 months in the HER2/neu +1/0 group, while it dropped to 45 months in c-HER2/neu +3 cases. Although the limited number of cases does not allow us to draw any definitive conclusions, our data suggest that high expression levels of HER2/neu +3 are associated with an early relapse and a shorter disease-free interval in M0 breast cancer patients.
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