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Abstract: Breast cancer develops in an adipose rich environment of normal adipocytes that are known to aid in tumor progression through an unknown method of lipid transfer from normal cells to tumor cells. Much research is built around lipid analysis of breast tumor and adjacent normal tissues to identify variations in the lipidome to gain an understanding of the role lipids play in progressing cancer. Ideally, single-cell analysis methods coupled to mass spectrometry that retain spatial information are best suited for this endeavor. However, many single-cell analysis methods are not capable of subcellular analysis of intact lipids while maintaining spatial information. One-Cell analysis is a true single-cell technique with the precision to extract single organelles from intact tissues while not interfering or disrupting adjacent cells. This method is used to extract and analyze single organelles from individual cells using nanomanipulation coupled to nanoelectrospray ionization mass spectrometry. Presented here is a demonstration of the analysis of single lipid bodies from two different sets of breast tumor and normal adjacent tissues to elucidate the fatty acid composition of triglycerides using One-Cell analysis coupled to tandem mass spectrometry. As a result, thirteen fatty acid species unique to the tumor tissues were identified, five in one set of tissues and eight in the other set. Download Full Article |
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Abstract: We report on two patients, successfully treated by the combination therapy of gemcitabine and 24-h intravenous infusion of cisplatin, who were initially diagnosed with node-positive advanced urothelial cancer. Each patient had a very good clinical response and underwent curative radical surgery after gemcitabine/cisplatin chemotherapy. A microscopically detailed examination of surgically obtained specimens showed the complete disappearance of malignant cells in the two cases. As a pilot study, we have used the regimen of gemcitabine plus 24-h continuous infusion of cisplatin, instead of bolus injection, for the treatment of 20 patients with node-positive or metastatic urothelial cancer. The clinical response rate in this regimen was 75% (complete response 7/20; 35%, partial response 8/20; 40%). The median overall survival was 665 days. As for the adverse effects, the incidences of severe neutropenia and thrombocytopenia (grade 3-4) were 20% and 15%, which might be less toxic than conventional gemcitabine plus cisplatin therapy. The 24-h infusion of cisplatin combined with gemcitabine can be highly recommended as neoadjuvant chemotherapy for locally advanced urothelial cancer. Keywords: Urothelial carcinoma, cisplatin, gemcitabine, pathological complete response.Download Full Article |
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Abstract: We previously showed that in low- as well as in high-grade astrocytomas IL-8 overexpression is triggered by prostaglandin E2 (PGE2) through the upregulation of the transcription factors CCAAT/enhancer-binding protein-β (C/EBP-β) and C/EBP homologous protein (CHOP). Here we investigated the signal transduction pathways and the molecular mechanisms underlying the PGE2-dependent IL-8 gene expression in astrocytomas. Low- and high-grade PGE2-treated astrocytoma cells were transfected with wild-type and mutated IL-8 promoter constructs in the presence of various signal transduction pathway inhibitors, and cotransfected with transcription factor overexpressing plasmids or small-interfering RNAs. p38MAPK, C/EBP-β, and CHOP phosphorylation was analyzed by Western blotting. Electrophoretic mobility shift assay and chromatin immunoprecipitation evaluated the in vitro and in vivo binding of CHOP and C/EBP-β to IL-8 promoter. The results obtained allowed us to find out the signaling pathways triggered by PGE2 and responsible for the activation of the transcription factors involved in the overproduction of IL-8 by astrocytoma. Therefore, it can be argued that the inhibition of the PGE2 downstream pathways may represent a novel therapeutic approach for the treatment of patients with astrocytoma. Keywords: Astrocytoma, IL-8, PGE2, p38MAPK.Download Full Article |
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Abstract: Background: Peritoneal carcinomatosis and multi-organ metastases might be prognostic factors in patients with advanced colorectal cancer and inoperable metastases at diagnosis. Methods: A retrospective study was performed to examine the relationship between patient clinical characteristics and prognosis in patients with colorectal cancer and indication for first-line systemic chemotherapy. Results: One hundred and twelve patients were accrued. According to univariate analysis, peritoneal carcinomatosis, lack of primary tumour resection and multi-organ metastases were associated with poor overall survival. According to multivariate analysis, patients with peritoneal carcinomatosis and patients with multi-organ metastases had a shorter overall survival (12 vs 27.0 months, p<0.001 and 14,6 vs 27 months, p=0.007, respectively). Conclusions: Our results indicate that presence of peritoneal carcinomatosis and multi-organ metastases are independent predictors of poor outcome for patients with colorectal cancer undergoing first line treatment with standard chemotherapy. Keywords: Colorectal cancer, prognostic factors, peritoneal carcinomatosis, first line chemotherapy, multi-organ metastases.Download Full Article |
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Abstract: The pH monitoring of the tumor microenvironment in vivo seems to be in fact complicated and technically quite challenging nowadays. Also the strategy of measuring urine pH of a little amount is not fully solved. Thus, the aim of our study was to monitor pH of urine samples (< 0.1 ml) and of tumor microenvironment of anesthetized rats in a minimal invasive way. The small urine volumes of rats or mice make pH measurements difficult, as standard pH electrodes usually need a minimal volume of several milliliters to function. The manual micromanipulator together with a needle-type housed pH microsensor offers a simple and effective way to do so. Our results show that pH of urine and tumor microenvironment was lower in tumor bearing rats compared to healthy subjects. The unique technology of pH microsensors could be a promising way to monitor the pH in many experimental designs and clinical praxis. Keywords: pH, tumor microenvironment, urine, monitoring, in vivo, rats.Download Full Article |