Non-neoplastic Cells (non-neoplastic + cell)

Distribution by Scientific Domains

Selected Abstracts

Reduction of intracellular pH inhibits constitutive expression of Cyclooxygenase-2 in human colon cancer cells

Daniela Pirkebner
Cyclooxygenase-2 (COX-2) over-expression is critically involved in tumor formation. Intracellular pH (pHi) has been shown to be alkaline in cancer cells, and to be an important trigger for cell proliferation. This study therefore analyzed the relationship between pHi and COX-2 expression. HRT-18 and Caco-2 cells cultured in medium with bicarbonate maintained a pHi of ,7.6, which is higher than that of non-neoplastic cells. Cells grown in bicarbonate-free medium with a pH at 6.8 showed a reduction in pHi to approximately 7.0. Importantly, reduction of pHi resulted in a complete inhibition of COX-2 mRNA and protein expression. When cells were grown in bicarbonate-supplemented medium at pH 6.8, pHi maintained at ,7.6 and COX-2 expression was not inhibited. Additionally, analysis utilizing protein synthesis inhibitor cycloheximide demonstrated that pHi mediated inhibition of COX-2 mRNA expression requires de novo protein synthesis of regulatory protein(s). These data strongly suggest that an alkaline pHi is an important trigger for constitutive COX-2 expression. Defining pHi -mediated mechanisms that govern the constitutive COX-2 expression may help in developing new strategies to block COX-2 over-expression in cancer cells. J. Cell. Physiol. 198: 295,301, 2004© 2003 Wiley-Liss, Inc. [source]

Cancer, chitosan nanoparticles and catalytic nucleic acids

Mei Lin Tan
Abstract Objectives The aim of this review was to examine gene therapy involving DNAzyme and siRNA encapsulation into chitosan nanoparticles, discussing the current and future status of this drug delivery system in enhancing drug delivery and cancer therapy. Key findings Cancer is a disease state in which the cells in our body undergo mutations at the genetic level and are transformed, acquiring the ability to replicate limitlessly. Conventional cancer treatment involves the use of surgery and cytotoxic chemotherapy and/or radiotherapy, which have the potential of harming normal, otherwise healthy, non-neoplastic cells. Newer forms of therapy such as immunotherapy and gene therapy have shown initial promise, but still require better ways to limit exposure to cancerous lesions in the body. As a result drug delivery systems have been developed in attempts to deliver therapeutics specifically to the target lesion site. One recent drug delivery system has revolved around the use of chitosan nanoparticle technology, where therapeutics are encapsulated into nanoparticles and targeted to tumours. Summary Though few, attempts at encapsulating therapeutics such as deoxyribozymes and small or short interfering RNA have been optimistic and encouraging. [source]

Photo-induced cytomorphologic changes in an advanced cancer phase I clinical trial

Luis A. Santana-Blank MD
Abstract Background and Objectives The aim of this study was to investigate whether the application of an Infrared Pulsed Laser Device (IPLD) photo-induced significant cytomorphologic changes during the monitoring of advanced cancer patients participating in a phase I clinical trial. Materials and Methods Patients were irradiated with an IPLD (904 nm pulsed at 3 MHz) under a one-dose, one-schedule, and one-procedure design. Total daily dose consisted of a Radiant Exposure of 4.5,×,105 J/m2. Thirty-one tissue samples from eleven patients with progressive solid neoplastic diseases (TNM IV, UICC) were obtained at three intervals: Time 0 (15,90 days pre-treatment, n,=,11); Time I (2,5 months post-treatment; n,=,11); Time II (6,12 months post-treatment, n,=,09). Three blinded pathologists evaluated samples; scores were determined by consensus. Data were evaluated by using the Wilcoxon matched-pairs signed-rank test and Spearman rank correlation coefficient. The level of statistical significance was ,,=,0.05. Results Increased apoptosis (Time I, P,<,0.003; Time II, P,<,0.007), necrosis (Time I, NS; Time II, P,<,0.01), cytoplasmic vacuoles (Time I, P,<,0.03; Time II, P,<,0.02), and nuclear vacuoles (Time I, NS; Time II, P,<,0.01), reduced cell size (Time I, P,<,0.007; Time II, P,<,0.01) and intercellular adhesion (Time I, P,<,0.01; Time II, P,<,0.02) were present in neoplastic cells after IPLD treatment. No apparent changes were noted in non-neoplastic cells. The Spearman rank correlation coefficient between apoptosis, necrosis, nuclear vacuoles, cytoplasmatic vacuoles, intercellular adhesion, and cell size was positive and highly significant (P,<,0.006). Conclusions Although further research is necessary, our preliminary results support the novel possibility that the IPLD photo-induces chaotic dynamics that modulate complex physiologically reparative bioeffects. Lasers Surg. Med. 30:18,25, 2002. © 2002 Wiley-Liss, Inc. [source]

Chromogenic in situ hybridization analysis of HER-2/neu status in breast carcinoma: Application in screening of patients for trastuzumab (Herceptin®) therapy

Hiroyuki Kumamoto
Evaluation of HER-2/neu status is important in the management of patients with breast carcinoma, especially in determining the possible application of trastuzumab, a humanized anti-HER-2/neu monoclonal antibody. Chromogenic in situ hybridization (CISH) detection of the HER-2/neu oncogene is a newly developed in situ hybridization method that utilizes a robust and unique-sequence DNA probe labeled with digoxygenin, and sequential incubations with antidigoxygenin fluorescein, antifluorescein peroxidase, and diaminobenzidine. In this study, we examined 20 archival specimens of human breast carcinoma using CISH, and we correlated findings with immunohistochemical findings for HER-2/neu. HER-2/neu immunohistochemistry was carried out with HercepTestTM, a standardized immunohistochemical examination system for HER-2/neu overexpression in surgical pathology specimens. CISH analysis could be done in 18 out of 20 cases examined. Gene copy signals for HER-2/neu were recognized as intranuclear brown dots in both neoplastic and non-neoplastic cells. Seven carcinomas showed an increased number or size of signals and were interpreted as being positive for HER-2/neu amplification. Eight cases were positive with the HercepTestTM. Seven out of eight carcinoma cases found to overexpress immunoreactive HER-2/neu also demonstrated HER-2/neu gene amplification following CISH analysis. There was a significant correlation between immunohistochemical and CISH analyses (P< 0.001). We found that CISH was a specific, sensitive and easily applicable method for the detection of HER-2/neu gene amplification, which may be used together with immunohistochemical examination for the evaluation of patients with breast carcinoma. [source]

Differentiating germinal center-derived lymphomas through their cellular microenvironment,

Antonino Carbone
Recent studies on normal and malignant B-cells have provided evidence that the germinal center (GC) of lymphoid follicles exerts a role in B-cell physiology and malignancy. GC-derived lymphomas include both B-cell and T-cell lymphomas. Remarkably, tumor cells of GC-derived lymphomas proliferate in close association with cellular environment that retains key features of normal GC cellular microenvironment. Neoplastic follicles in follicular lymphoma contain, in addition to follicular dendritic cells (FDC) other non-neoplastic cells including macrophages and GC T-cells. In addition to aggregates of FDCs, the background infiltrate of nodular lymphocyte predominant Hodgkin lymphoma includes small B-cells, T-cells, and histiocytes. Typically, most of the lymphocyte predominant (LP) cells are ringed by CD3+/CD4+ T-cells expressing CD57, PD1, BCL6, and MUM1/IRF4. By contrast, Reed,Sternberg cells of classic Hodgkin lymphoma (cHL) are surrounded by CD3+/CD4+ T-cells expressing CD40L. Unlike cHL and other peripheral T-cell lymphomas, the AITL microenvironment characteristically contain a prominent proliferation of high endothelial venules and FDC. Thus, these findings shed new light on the characterization of GC-derived lymphomas and may help in the differential diagnosis and acknowledge several novel pathogenetic mechanisms on these lymphomas. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source]