Impact of proteolytic enzymes in colorectal cancer development and progression.

Tumor invasion and metastasis is a highly complicated, multi-step phenomenon. In the complex event of tumor progression, tumor cells interact with basement membrane and extracellular matrix components. Proteolytic enzymes (proteinases) are involved in the degradation of extracellular matrix, but also in cancer invasion and metastasis. The four categories of proteinases (cysteine-, serine-, aspartic-, and metalloproteinases) are named and classified according to the essential catalytic component in their active site. We and others have shown that proteolytic enzymes play a major role not only in colorectal cancer (CRC) invasion and metastasis, but also in malignant transformation of precancerous lesions into cancer. Tissue and serum-plasma antigen concentrations of proteinases might be of great value in identifying patients with poor prognosis in CRC. Our results, in concordance with others indicate the potential tumor marker impact of proteinases for the early diagnosis of CRC. In addition, proteinases may also serve as potential target molecules for therapeutic agents

Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis

AIM: To investigate the role of glutathione S-transferase (GST) and matrix meta lloproteinase-9 (MMP-9) expressions in the development and progression of reflux esophagitis-Barrett's meta plasia-dysplasia-adenocarcinoma sequence in the esophagus. METHODS: GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohistochemistry including patients with reflux esophagitis (n = 7), Barrett's metaplasia (n = 14), Barrett and esophagitis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant. RESULTS: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett's metaplasia and the other groups. No major changes were observed between Barrett, esophagitis, and Barrett and concomitant esophagitis. Barrett and concomitant dysplasia, and adenocardnoma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r 0.82). CONCLUSION: Decreased GST and increased expression of MMP-9 in Barrett's meta plasia-clysplasiaadenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dysplasia compared to non-clysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett's esophagus might be useful to identify patients at higher risk for progression to cancer. (c) 2007 The WJG Press. All rights reserved

Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer

The underpinnings of STAT3 hyperphosphorylation resulting in enhanced signaling and cancer progression are incompletely understood. Loss-of-function mutations of enzymes that dephosphorylate STAT3, such as receptor protein tyrosine phosphatases, which are encoded by the PTPR gene family, represent a plausible mechanism of STAT3 hyperactivation. We analyzed whole exome sequencing (n = 374) and reverse-phase protein array data (n = 212) from head and neck squamous cell carcinomas (HNSCCs). PTPR mutations are most common and are associated with significantly increased phospho-STAT3 expression in HNSCC tumors. Expression of receptor-like protein tyrosine phosphatase T (PTPRT) mutant proteins induces STAT3 phosphorylation and cell survival, consistent with a “driver” phenotype. Computational modeling reveals functional consequences of PTPRT mutations on phospho-tyrosine–substrate interactions. A high mutation rate (30%) of PTPRs was found in HNSCC and 14 other solid tumors, suggesting that PTPR alterations, in particular PTPRT mutations, may define a subset of patients where STAT3 pathway inhibitors hold particular promise as effective therapeutic agents.Fil: Lui, Vivian Wai Yan. University of Pittsburgh; Estados UnidosFil: Peyser, Noah D.. University of Pittsburgh; Estados UnidosFil: Ng, Patrick Kwok-Shing. University Of Texas Md Anderson Cancer Center;Fil: Hritz, Jozef. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados Unidos. Masaryk University; República ChecaFil: Zeng, Yan. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Lu, Yiling. University Of Texas Md Anderson Cancer Center;Fil: Li, Hua. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Wang, Lin. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Gilbert, Breean R.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: General, Ignacio. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Bahar, Ivet. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Ju, Zhenlin. University Of Texas Md Anderson Cancer Center;Fil: Wang, Zhenghe. Case Western Reserve University; Estados UnidosFil: Pendleton, Kelsey P.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Xiao, Xiao. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Du, Yu. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Vries, John K.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Hammerman, Peter S.. Harvard Medical School; Estados UnidosFil: Garraway, Levi A.. Harvard Medical School; Estados UnidosFil: Mills, Gordon B.. University Of Texas Md Anderson Cancer Center;Fil: Johnson, Daniel E.. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Grandis, Jennifer R.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados Unido

Measuring Surface Tension of Secondary Atmospheric Aerosols using Atomic Force Microscopy

Accurate measurements of particle surface tension are required for models concerning atmospheric aerosol nucleation and activation. However, it is difficult to collect sufficiently large volumes of atmospheric aerosol for use in typical instruments that measure surface tension, such as goniometers or Wilhelmy plates. In this work, a method that measures the surface tension of collected liquid nanoparticles using atomic force microscopy is presented. A film of particles is collected via impaction and probed using nanoneedle tips with the atomic force microscope (AFM). This micro-Wilhelmy method allows for direct measurements of surface tension of small amounts of sample. The micro-Wilhelmy method was verified using liquids whose surface tensions were known. Particles of oxidized ¿-pinene were then produced, collected, and analyzed using this method. Preliminary results show that oxidized ¿-pinene particles formed in dry conditions have a surface tension similar to that of pure ¿-pinene, and particles formed in wet conditions have a surface tension that is significantly higher

Using Shuttle Radar Topography to map ancient water channels in Mesopotamia

The Shuttle Radar Topography Mission (SRTM) is currently producing a digital elevation model of most of the world's surface. Here the authors assess its value in mapping and sequencing the network of water channels that provided the arterial system for Mesopotamia before the petrol engine

Gyermekkori pancreatitis. A Magyar Hasnyalmirigy Munkacsoport bizonyitekon alapulo kezelesi iranyelvei.

Pediatric pancreatitis is a rare disease with variable etiology. In the past 10-15 years the incidence of pediatric pancreatitis has been increased. The management of pediatric pancreatitis requires up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidences. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. In 8 topics (diagnosis; etiology; prognosis; imaging; therapy; biliary tract management; complications; chronic pancreatitis) 50 relevant clinical questions were defined. (Evidence was classified according to the UpToDate(R) grading system. The draft of the guidelines was presented and discussed at the consensus meeting on September 12, 2014. All clinical questions were accepted with total (more than 95%) agreement. The present Hungarian Pancreatic Study Group guideline is the first evidence based pediatric pancreatitis guideline in Hungary. This guideline provides very important and helpful data for tuition of pediatric pancreatitis in everyday practice and establishing proper finance and, therefore, the authors believe that these guidelines will widely serve as a basic reference in Hungary. Orv. Hetil., 2015, 156(8), 308-325

To Travel or to Compete: Motivations of Masters Swimmers

The underlying motivations behind participating in a sports event such as a swim meet are complex and varied especially for adult participants. These motivations may be related to the thrill of competition or excitement at traveling to a new pool or aquatic facility. Investigations of motivations behind participation can enable meet directors and aquatic facility managers to create more memorable experiences that boost participation and encourage repeat visitors who produce social and economic benefits for the aquatic facility and event. We measured motivations of Masters swimmers using the Participant Motivation Questionnaire (PMQ) modified for swimmers and the Travel Career Ladder (TCL) at the 2006 US Masters Swimming Short Course Championships. Descriptive and multivariate statistics revealed that Masters swimmers participated primarily for competitive reasons with travel only as a secondary motivator. Participating to be with other members of their team was revealed as another important motivation

To Travel or to Compete? Motivations of Masters Swimmers

The underlying motivations behind participating in sports event such as a swim meet are complex and varied especially for adult participants. These motivations may be related to the thrill of the competition, or the excitement of traveling to a new pool or aquatic facility. Investigation of motivations behind participation can enable aquatic facility managers to create memorable experiences that boost participation and encourage repeat visitors that have social and economic benefits for the aquatic facility and event. We motivations of Masters swimmers using the Participant Motivation Questionnaire (PMQ) modified for swimmers and the Travel Career Ladder (TCL) at the 2006 USMS Short Course Championships. Descriptive and multivariate statistics revealed that Masters swimmers participated primarily for competitive reasons with travel only as a secondary motivator. Participating to be with other members of their team was revealed as another important motivation

Achieving Wellness through Tourism: Comparing International and U.S. Travelers

Health and wellness tourism has become an increasingly popular trend in recent years as many resorts and destinations now offer wellness activities and amenities. This study sought to investigate what might be significant predictors of achieving a high perceived wellness as a result of travel. The results revealed that for international travelers internal motivations of action related activities, the need to be with others, the size of their travel party and education were significant predictors. For domestic travelers, only their perceived physical wellness was a predictor or their overall wellness state. Future research could explore relationships between the domestic and international traveler