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Molecular Factors (molecular + factor)
Selected AbstractsCutaneous head and neck squamous cell carcinoma metastatic to parotid and cervical lymph nodesHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2007FRANZCR, Michael J. Veness MMed (Clin Epi) Abstract Nonmelanoma skin cancers occur at an epidemic rate in Australia and are increasing in incidence worldwide. In most patients, local treatment is curative. However, a subset of patients will be diagnosed with a high-risk cutaneous squamous cell carcinoma (SCC) and are defined as patients at increased risk of developing metastases to regional lymph nodes. Patients with high-risk SCC may be identified based on primary lesion and patient factors. Most cutaneous SCC arises on the sun-exposed head and neck. The parotid and upper cervical nodes are common sites for the development of metastases arising from ear, anterior scalp, temple/forehead, or scalp SCC. The mortality and morbidity associated with high-risk cutaneous SCC is usually a consequence of uncontrolled metastatic nodal disease and, to a lesser extent, distant metastases. Patients with operable nodal disease have traditionally been recommended for surgery. The efficacy of adjuvant radiotherapy has previously been questioned based on weak evidence in the early literature. Recent evidence from larger studies has, however, strengthened the case for adjuvant radiotherapy as a means to improve locoregional control and survival. Despite this, many patients still experience relapse and die. Research aimed at improving outcome such as a randomized trial incorporating the addition of chemotherapy to adjuvant radiotherapy is currently in progress in Australia and New Zealand. Ongoing research also includes the development of a proposed new staging system and investigating the role of molecular factors such as the epidermal growth factor receptor. © 2007 Wiley Periodicals, Inc. Head Neck, 2007 [source] Gene signatures of pulmonary metastases of renal cell carcinoma reflect the disease-free interval and the number of metastases per patientINTERNATIONAL JOURNAL OF CANCER, Issue 2 2009Daniela Wuttig Abstract Our understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis are largely unknown. Herein, transcriptome-wide expression profiles of a unique cohort of 20 laser-resected pulmonary metastases (Mets) of 18 patients with clear-cell renal cell carcinoma (RCC) were analyzed to identify expression patterns associated with two important prognostic factors in RCC: the disease-free interval (DFI) after nephrectomy and the number of Mets per patient. Differentially expressed genes were identified by comparing early (DFI , 9 months) and late (DFI , 5 years) Mets, and Mets derived from patients with few (,8) and multiple (,16) Mets. Early and late Mets could be separated by the expression of genes involved in metastasis-associated processes, such as angiogenesis, cell migration and adhesion (e.g., PECAM1, KDR). Samples from patients with multiple Mets showed an elevated expression of genes associated with cell division and cell cycle (e.g., PBK, BIRC5, PTTG1) which indicates that a high number of Mets might result from an increased growth potential. Minimal sets of genes for the prediction of the DFI and the number of Mets per patient were identified. Microarray results were confirmed by quantitative PCR by including nine further pulmonary Mets of RCC. In summary, we showed that subgroups of Mets are distinguishable based on their expression profiles, which reflect the DFI and the number of Mets of a patient. To what extent the identified molecular factors contribute to the development of these characteristics of metastatic spread needs to be analyzed in further studies. © 2009 UICC [source] Molecular markers and therapeutic targets in ductal carcinoma in situMICROSCOPY RESEARCH AND TECHNIQUE, Issue 1 2002Gary P. Boland Abstract Ductal carcinoma in situ (DCIS) of the breast is a premalignant condition which accounts for approximately 20% of all new breast cancers and up to 40% of neoplastic lesions detected by mammographic screening. Since recurrence is common after DCIS treated with breast conservation surgery, there is a need to determine molecular factors that predict recurrence. In parallel with this and with the finding that oestrogen receptor (ER) positive breast cancer can be prevented with anti-oestrogens, there have been recent advances in the understanding of the molecular biology of DCIS. Receptor coexpression in DCIS has been determined largely by immunohistochemistry. Animal models have provided evidence for the signalling pathways involved in the regulation and dysregulation of proliferation and apoptosis in both normal breast and in situ cancer. ER-negative DCIS has been shown to be hormone-independent. Blockade of the pathways involved in cell proliferation in ER-negative DCIS is possible and will be necessary to prevent ER-negative breast cancers if the goal of breast cancer chemoprevention is to be realistically achieved. Microsc. Res. Tech. 59:3,11, 2002. © 2002 Wiley-Liss, Inc. [source] Proteomics analysis of hypothalamic response to energy restriction in dairy cowsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 19 2007Björn Kuhla Abstract The hypothalamus is the central regulatory unit that balances a number of body functions including metabolic rate, hunger, and satiety signals. Hypothalamic neurons monitor and respond to alterations of circulating nutrients and hormones that reflect the peripheral energy status. These extracellular signals are integrated within the cell at the ATP:AMP ratio and at the level of ROS, triggering gene expression associated with glucose and lipid metabolism. In order to identify new molecular factors potentially associated with the control of energy homeostasis, metabolic adaptation, and regulation of feed intake, hypothalami from ad libitum fed and energy restricted cows were characterized using 2-DE and MALDI-TOF-MS. Among 189 different protein spots identified, nine proteins were found to be differentially expressed between groups. Beside the 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase, stress-induced phosphoprotein-1, heat shock protein 70,kDa-protein-5, dihydropyrimidinase-related protein-2, [Cu-Zn]-superoxide dismutase, ubiquitin carboxy-terminal hydrolase-L1, and inorganic pyrophosphatase were found to be up-regulated, whereas glyceraldehyde 3-phosphate dehydrogenase and aconitase-2 were down-regulated in the restricted group. In conclusion, differentially expressed proteins are related to energy and nucleotide metabolism and cellular stress under conditions of dietary energy deficiency. These proteins may be new candidate molecules that are potentially involved in signaling for maintaining energy homeostasis. [source] Detailed understanding of enhanced specific antibody productivity in NS0 myeloma cellsBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2009Soo Hean Gary Khoo Abstract The understanding of how cellular productivity is modulated in cell lines is of significant importance in the biopharmaceutical industry. Often, single molecular mechanisms fail to fully explain how specific antibody productivity is enhanced during proliferation arrest. Previously, we reported that certain physiological changes occur when proliferation is arrested by p21CIP1 over expression. In this work, we correlate physiological and molecular factors to enhance antibody productivity. Using biomass, cell volume and total cellular protein content as a basis for determining specific productivity, it was found that total cellular protein correlated best with cellular productivity. This meant that there was no preferential increase in antibody production relative to cellular proteins in arrested cultures. However, molecular analysis of mRNA transcription and stability indicated that both processes were altered in arrested cultures resulting in up to threefold increased heavy chain mRNA levels. While flow cytometric analysis revealed that arrested cells had elevated translational capacity for both heavy and light chains, the heavy to light chain polypeptide ratio was 10,50% higher than in the control. This resulted in a lower extracellular accumulation of light chains and a better utilization of cellular resources for the formation of complete antibodies. Active transcriptional regulation of heavy and light chain mRNA and the modulation of translational activities play a vital role in the modulation of overall antibody productivity of these cells. The combined effect of heavy chain mRNA enhancement and the increased cellular assembly capacity was determined to effectively increase specific productivity. Biotechnol. Bioeng. 2009;102: 188,199. © 2008 Wiley Periodicals, Inc. [source] Molecular markers and mortality in prostate cancerBJU INTERNATIONAL, Issue 6 2007John Concato OBJECTIVE To evaluate prognosis in prostate cancer by assessing the independent effect of selected molecular factors (e.g. markers of cell-cycle regulation), in addition to the effect of traditional clinical factors (e.g. anatomical stage, histological grade), in predicting long-term mortality among men newly diagnosed with prostate cancer. PATIENTS AND METHODS In a community-based population of 64 545 USA veterans aged ,,50 years and receiving ambulatory care during 1989,90 at nine Veterans Affairs (VA) medical centres in New England, 1274 had incident prostate cancer during 1991,95. We obtained the medical records and diagnostic tissue for these men, and then extracted demographic data and clinical information, and conducted immunohistochemical assays of molecular markers in biopsy tissue, as potential prognostic factors. In this interim analysis, data on 250 patients were analysed; the main outcome was overall mortality to 31 December 2003, providing 8,13 years of follow-up. RESULTS In 228 (91%) patients with available medical record and laboratory data, the median age was 72 years and the median prostate-specific antigen level was 10.4 ng/mL. In adjusted (multivariate) analyses that included traditional prognostic factors, bcl-2 staining (hazard ratio 2.14, 95% confidence interval 1.27,3.58, P = 0.004) and high microvessel density (1.76, 1.19,2.60; P = 0.005) had an independent effect on the outcome. CONCLUSIONS Bcl-2 and microvessel density are independent predictors of subsequent death among men with prostate cancer and might have a clinical role in assisting in deciding on treatment. [source] Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinomaCANCER, Issue 1 2003Hung-Wei Pan M.S. Abstract BACKGROUND Intrahepatic metastasis via portal vein spread is an important feature and a crucial unfavorable prognostic factor of hepatocellular carcinoma (HCC). To identify the molecular factors for tumor progression, the authors used differential display (DD) to analyze aberrant gene expression in HCC. The goal of the current study was to elucidate the clinicopathologic and prognostic significance of osteopontin (OPN) in HCC progression. METHODS OPN mRNA levels, which were increased preferentially in HCC in a DD assay and verified with Northern blotting, were measured in 240 surgically removed, unifocal, primary HCCs using the reverse transcription,polymerase chain reaction at the exponential phase. OPN mRNA expression was correlated with clinicopathologic features, particularly portal vein invasion, early tumor recurrence, and prognosis. RESULTS Osteopontin mRNA was overexpressed in 133 tumors (55%). The OPN overexpression was associated closely with ,-fetoprotein elevation (P = 0.001), p53 mutation (P = 0.021), larger tumors (P = 0.002), high-grade HCC (P < 0.001), late-stage HCC (P < 0.001), early tumor recurrence and/or metastasis (P = 0.003), and a lower 10-year survival rate (P = 0.00013). Multivariate analysis revealed that tumor stage and early tumor recurrence were crucial prognostic factors. In early-stage HCC, which has no vascular invasion and a lower early tumor recurrence than late-stage HCC, OPN mRNA overexpression predicted a higher early recurrence rate (P = 0.003). CONCLUSIONS OPN mRNA overexpression was correlated closely with high-grade, late-stage, and early tumor recurrence, which lead to poorer prognosis. Osteopontin overexpression might serve as an unfavorable prognostic factor and a useful marker for predicting early recurrence in early-stage HCC. Cancer 2003;98:119,27. © 2003 American Cancer Society. DOI 10.1002/cncr.11487 [source] Diabetic macular oedema: physical, physiological and molecular factors contribute to this pathological processACTA OPHTHALMOLOGICA, Issue 3 2010Rita Ehrlich Abstract. Diabetic macular oedema (DMO) is an important cause of vision loss in patients with diabetes mellitus. The underlying mechanisms of DMO, on both macrocellular and microcellular levels, are discussed in this review. The pathophysiology of DMO can be described as a process whereby hyperglycaemia leads to overlapping and inter-related pathways that play a role not only in the initial vascular events, but also in the continued tissue insult that leads to chronic DMO. On a macrocellular level, DMO is believed to be in part caused by alterations in hydrostatic pressure, oxygen tension, oncotic pressure and shear stress. Three key components of the microvascular pathways include angiogenic factor expression, inflammation and oxidative stress. These molecular mediators, acting in conjunction with macrocellular factors, which are all stimulated in part by the hyperglycaemia and hypoxia, can have a direct endothelial effect leading to hyperpermeability, disruption of vascular endothelial cell junctions, and leukostasis. The interactions, signalling events and feedback loops between the various molecules are complicated and are not completely understood. However, by attempting to understand the pathways involved in DMO, we can help guide new treatment options targeted towards specific factors or mediators. [source] | ||||||||||