bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression pattern of four membrane‐type matrix metalloproteinases in the normal and diseased mouse mammary gland
Authors: Szabova Ludmila , Yamada Susan S. , Birkedal‐Hansen Henning , Holmbeck Kenn 
Published: May 2005

AbstractBoth mammary gland development and mammary carcinogenesis involve extensive remodeling of the mammary gland extracellular matrix. The expression of four membrane‐type matrix metalloproteinases (MT‐MMPs) with matrix remodeling potential in development and tumorigenesis was evaluated by in‐situ hybridization on mouse mammary gland sections. MT1‐MMP and MT3‐MMP were found in the mammary stroma mainly around epithelial structures in both developing and mature mammary gland. In contrast, MT2‐MMP was found exclusively in the mammary epithelium. Lactating gland expressed none of the examined MT‐MMPs. Mammary gland tumors expressed MT1‐MMP, MT2‐MMP, and MT3‐MMP while MT4‐MMP was not expressed in any developmental or cancerous stage analyzed here. Our results suggest that MT1‐MMP, MT2‐MMP, and MT3‐MMP may be involved in remodeling of both the normal and diseased mammary gland either directly or indirectly by activation of other MMPs. Published 2005 Wiley‐Liss, Inc.
Trying to compose the puzzle with all the pieces: Epidermal growth factor receptor tyrosine kinase inhibitors in non‐small cell lung cancer
Authors: Di Maio Massimo , Gridelli Cesare , Normanno Nicola , Perrone Francesco , Ciardiello Fortunato 
Published: May 2005

AbstractSmall molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown promising activity in patients with non‐small cell lung cancer (NSCLC). Gefitinib has been the first of these drugs to be licensed for third‐line treatment of advanced NSCLC patients. More recently, erlotinib has been shown to be more effective than placebo in increasing overall survival (OAS) and has been approved for NSCLC patients after failure of chemotherapy. However, a large body of clinical and experimental evidence suggests that the benefit from these drugs is limited to a subgroup of patients. The availability of clinical or molecular criteria for predicting sensitivity to EGFR‐TKIs is the most relevant issue for their correct use and for planning future research. Determination of EGFR expression is not sufficient to predict sensitivity to EGFR‐TKIs. However, several clinical features (female gender, adenocarcinoma/bronchioloalveolar histotype, never‐smoking status, Oriental Asian origin) are associated with major clinical responses. The identification of somatic mutations in the tyrosine kinase domain of the EGFR gene represents the most important molecular marker of sensitivity to EGFR‐TKIs. These “activating” mutations can be found in a high proportion of gefitinib‐ or erlotinib‐responding patients. However, clinical effectiveness might not be limited to patients carrying EGFR mutations, in which the objective response is probably the detectable effect of apoptosis induction in cancer cells. In fact, clinical efficacy with gefitinib or erlotinib is also observed in another subgroup of patients, in which a tumor growth delay, determined by a block in cancer cell proliferation, could induce a prolonged and clinically relevant disease stabilization. © 2005 Wiley‐Liss, Inc.
Induction of TGF‐β1 in the trabecular meshwork under cyclic mechanical stress
Authors: Liton P.B. , Liu X. , Challa P. , Epstein D.L. , Gonzalez P. 
Published: May 2005

AbstractThe pathophysiological mechanisms involved in the failure of the trabecular meshwork (TM) to maintain normal levels of aqueous outflow in glaucoma are not yet understood. Aberrant activation of the transforming growth factor beta‐1 (TGF‐β1) pathway has been implicated in several degenerative diseases. We investigated the possibility that chronic cyclic mechanical stress that affects the TM might result in increased production of TGF‐β1. Primary cultures of TM cells subjected to cyclic mechanical stress (5% stretching, 1 cycle/sec) demonstrate a significant increase in total and biologically active secreted TGF‐β1 that was associated with activation of the TGF‐β1 promoter, measured using a recombinant adenovirus expressing the secreted reporter gene secreted alkaline phosphatase protein (SEAP) under the TGF‐β1 gene promoter (AdTGFβ1‐SEAP). Associated changes in the transcription of MMP‐2, TIMP‐2, and CTGF were assessed by semiquantitative PCR. Immunohistochemical analysis of TGF‐β1 in organ culture of human eyes revealed a generalized accumulation of this protein in the extracellular matrix (ECM) of the TM, while expression of the TGF‐β1 promoter, analyzed using the LacZ reporter gene, was localized in some specific cells within the outflow pathway. Induction of the TGF‐β1 promoter in organ culture was demonstrated using a novel model for cyclic mechanical stress in human perfused anterior segments infected with AdTGFβ1‐SEAP. Given the relevant physiological and pathophysiological roles of TGF‐β1, its induction after cyclic mechanical stress in the TM supports the hypothesis that this cytokine might play a significant role in the physiology of the TM, and contribute to the pathological changes of this tissue in certain forms of glaucoma. © 2005 Wiley‐Liss, Inc.
Properties of Mg2+‐dependent cation channels in human leukemia K562 cells
Authors: Semenova Svetlana B. , Fomina Alla F. , Vassilieva Irina O. , Negulyaev Yuri A. 
Published: May 2005

AbstractThe endogenous Mg2+‐inhibited cation (MIC) current was recently described in different cells of hematopoietic lineage and was implicated in the regulation of Mg2+ homeostasis. Here we present a single channel study of endogenously expressed Mg2+‐dependent cation channels in the human myeloid leukemia K562 cells. Inwardly directed unitary currents were activated in cell‐attached experiments in the absence of Ca2+ and Mg2+ in the pipette solution. The current–voltage (I–V) relationships displayed strong inward rectification and yielded a single channel slope conductance of ∼30 pS at negative potentials. The I–V relationships were not altered by patch excision into divalent‐free solution. Channel open probability (Po) and mean closed time constant (τC) were strongly voltage‐dependent, indicating that gating mechanisms may underlie current inward rectification. Millimolar concentrations of Ca2+ or Mg2+ applied to the cytoplasmic side of the membrane produced slow irreversible inhibition of channel activity. The Mg2+‐dependent cation channels described in this study differ from the MIC channels described in human T‐cells, Jurkat, and rat basophilic leukemia (RBL) cells in their I–V relationships, kinetic parameters and dependence on intracellular divalent cations. Our results suggested that endogenously expressed Mg2+‐dependent cation channels in K562 cells and the MIC channels in other hematopoietic cells might be formed by different channel proteins. © 2005 Wiley‐Liss, Inc.
Meeting report on the 12th International Congress of Histochemistry and Cytochemistry (ICHC)
Authors: De Falco Maria , De Luca Antonio 
Published: May 2005

AbstractThe International Congress of Histochemistry and Cytochemistry (ICHC) promoted in San Diego La Jolla (CA, USA), the 12th meeting where researchers of all over the world presented their work and the most innovative methods in histochemical disciplines. A summary of the last meeting is reported. © 2005 Wiley‐Liss, Inc.
LIGHT regulates CD86 expression on dendritic cells through NF‐κB, but not JNK/AP‐1 signal transduction pathway
Authors: Zou Gang‐Ming , Hu Wen‐Yang 
Published: May 2005

AbstractThe members of the tumor necrosis factor (TNF) family play pivotal roles in the regulation of the immune system. LIGHT is a type II transmembrane protein belonging to the TNF family that was originally identified as a weak inducer of apoptosis. This cytokine has been extensively studied for its role in T cell regulation. Recently, we identified its role in inducing maturation of dendritic cells, such as LIGHT upregulated CD86 expression on dendritic cells in our previous report. However, the signal transduction pathway on this regulation remains unknown. In this study, we found that LIGHT activated NF‐κB, p44/42 MAPK, but not JNK. LIGHT upregulates CD86 expression on DCs through activation of NF‐κB, but not p44/42 signal pathway, because inhibition of NF‐κB activity by its inhibitor could blunt the effect of LIGHT in up‐regulation of CD86 expression, but neither inhibitor of p44/42 MAPK nor JNK inhibitor has this effect. Thus we demonstrate that LIGHT regulates CD86 expression through NF‐κB signal transduction pathway but neither p44/42 MAPK nor JNK/AP‐1 signaling pathway. We conclude that NF‐κB signal plays a key role in LIGHT‐mediated upregulation of CD86 expression. © 2005 Wiley‐Liss, Inc.
Negative regulation of melanogenesis by phospholipase D1 through mTOR/p70 S6 kinase 1 signaling in mouse B16 melanoma cells
Authors: Ohguchi Kenji , Banno Yoshiko , Nakagawa Yoshihito , Akao Yukihiro , Nozawa Yoshinori 
Published: May 2005

AbstractMelanogenesis is a principal parameter of differentiation in melanocytes and melanoma cells. Our recent study has demonstrated that phospholipase D1 (PLD1) regulates the melanogenic signaling through modulating the expression of tyrosinase, the rate‐limiting step enzyme in the melanin biosynthesis. The current study was designed to gain more insight into the involvement of PLD1 in the regulation of melanogenesis. To investigate the role of PLD1, we examined the effect of knockdown of endogenous PLD1 by small interference RNA (siRNA) on melanogenesis in B16 melanoma cells. It was shown that the melanin synthesis was induced in PLD1‐knockdowned cells, and also that the level of melanin synthesis was well correlated with increases in expression level of tyrosinase and its related proteins (Tyrp1 and Dct). Furthermore, the reduction of expression levels of PLD1 by siRNA transfection was accompanied by diminution of ribosomal S6 kinase 1 (S6K1) phosphorylation. The activity of mammalian target of rapamycin (mTOR) is essential for phosphorylation of S6K1 and the treatment malanoma cells with rapamycin, a potent inhibitor of mTOR effectively induced melanogenesis. The results obtained here provide possible evidence that PLD1 exerts a negative regulatory role in the melanogenic process through mTOR/S6K1 signaling. © 2005 Wiley‐Liss, Inc.
Gastric cancer: New genetic developments
Authors: Lynch Henry T. , Grady William , Suriano Gianpaolo , Huntsman David 
Published: May 2005

AbstractGastric cancer's (GC) incidence shows large geographic differences worldwide with the lowest rates occurring in most Western industrialized countries including the United States and the United Kingdom; in contrast, relatively high rates of GC occur in Japan, Korea, China, and South America, particularly Chile. The Laurén classification system classifies GC under two major histopathological variants: 1) an intestinal type and 2) a diffuse type. The intestinal type is more common in the general population, more likely to be sporadic and related to environmental factors such as diet, particularly salted fish and meat as well as smoked foods, cigarette smoking, and alcohol use. It exhibits components of glandular, solid, or intestinal architecture, as well as tubular structures. On the other hand, the diffuse type is more likely to have a primary genetic etiology, a subset of which, known as hereditary diffuse gastric cancer (HDGC), is due to the E‐cadherin (CDH1) germline mutation. The diffuse type pathology is characterized by poorly cohesive clusters of cells which infiltrate the gastric wall, leading to its widespread thickening and rigidity of the gastric wall, known as linitis plastica. Helicobacter pylori infection is associated with risk for both the intestinal and diffuse varieties of gastric cancer. Germline truncating mutations of the CDH1 gene, which codes for the E‐cadherin protein, were initially identified in three Maori families from New Zealand that were predisposed to diffuse GC. Since then, similar mutations have been described in more than 40 additional HDGC families of diverse ethnic backgrounds. It is noteworthy that two‐thirds of HDGC families reported to date have proved negative for the CDH1 germline mutation. A number of candidate genes have been identified through analysis of the molecular biology of E‐cadherin. Patients with evidence of the CDH1 germline mutation in the context of a family history of HDGC must be considered as candidates for prophylactic gastrectomy, given the extreme difficulty in its early diagnosis and its exceedingly poor prognosis when there is regional or distant spread. Specifically, the E‐cadherin cytoplasmic tail interacts with catenins, assembling the cell‐adhesion complex involved with E‐cadherin mediated cell:cell adhesion. β‐catenin and γ‐catenin compete for the same binding site on the E‐cadherin cytoplasmic tail, directly linking the adhesion complex to the cytoskeleton through α‐catenin. β‐catenin gene (CTNNB1) mutations have been described predominantly in intestinal‐type gastric cancers and CTNNB1 gene amplification and overexpression have recently been described in a mixed‐type gastric cancer. This paper reviews the genetics of both intestinal and diffuse types of gastric carcinoma, their differential diagnosis, molecular genetics, pathology, and, when known, their mode of genetic transmission within families. J. Surg. Oncol. 2005;90:114–133. © 2005 Wiley‐Liss, Inc.
New strategies for the prevention of gastric cancer: Helicobacter pylori and genetic susceptibility
Authors: Correa Pelayo 
Published: May 2005

AbstractRecently acquired knowledge points to the potential of markedly improved strategies for the prevention of gastric cancer. The International Agency for Cancer Research has reached the conclusion that infection with Helicobacter pylori (H. pylori) is carcinogenic to humans (Group I) 1. The bacterium displays marked genetic heterogeneity. Virulence related genes, especially cag A and vac A s1 m1 are associated with an increased cancer risk. Genetic susceptibility, especially polymorphisms of the cytokine genes may increase cancer risk. Highly susceptible individuals infected with high virulence bacterial genotypes have a markedly increased gastric cancer risk. They should be targeted for endoscopic monitoring to detect advanced precancerous lesions. The state of the art is briefly reviewed and the needed research identified. J. Surg. Oncol. 2005;90:134–138. © 2005 Wiley‐Liss, Inc.
Recent advances in sentinel node navigation for gastric cancer: A paradigm shift of surgical management
Authors: Kitagawa Yuko , Fujii Hirofumi , Kumai Koichiro , Kubota Tetsuro , Otani Yoshihide , Saikawa Yoshiro , Yoshida Masashi , Kubo Atsushi , Kitajima Masaki 
Published: May 2005

AbstractThe sentinel node (SN) is defined as the first draining node from the primary lesion and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. In the past 5 years, the validity of SN concept for gastric cancer has been demonstrated by a number of single institutional studies. Using a dual tracer method as the optimal procedure, the radio‐guided method allows us to confirm the complete harvest of SNs by gamma probing, while the dye procedure enables us to perform real time observation of the lymphatic vessels. From previous reports, clinically staged T1N0 gastric cancer seems to be a good entity on which to try to change the therapeutic approach based on SN biopsy. At present, two large scale prospective multicenter trials are on‐going in Japan. To overcome some remaining issues, such as limited sensitivity of intra‐operative diagnosis of metastasis, and technical difficulty in laparoscopic SN detection, further technical and instrumental developments will be required. During this transitional phase, focused lymph node dissection targeted to sentinel lymphatic basins and modified resection of the stomach is an acceptable approach. Although there are several remaining issues, SN navigation should provide a paradigm shift for the surgical management of early gastric cancer in near future. J. Surg. Oncol. 2005;90:147–151. © 2005 Wiley‐Liss, Inc.
Status of extended lymph node dissection: Locoregional control is the only way to survive gastric cancer
Authors: Hartgrink Henk H. , van de Velde Cornelis J.H. 
Published: May 2005

AbstractThere are many factors that are of influence on gastric cancer treatment. The only way to survive is complete locoregional control. More extended dissections should lead to better outcome, but increased morbidity and mortality probably offset its long‐term effect in survival in randomised studies. In this article the factors of influence on outcome of gastric cancer treatment such as the extent of lymph node dissection, splenectomy, pancreatectomy, age, volume and additional treatments are discussed. A literature review of these factors in relation to the latest results of the Dutch Gastric Cancer Trials are presented. If morbidity and mortality can be reduced there might be an advantage of extended lymph node dissection. Splenectomy and pancreatectomy should be performed only in case of direct in growth from the tumour into these organs. Centralisation of gastric cancer treatment should be achieved in order to improve results and to facilitate research. By refining selection criteria in the treatment of gastric cancer further improvements are to be expected. J. Surg. Oncol. 2005;90:153–165. © 2005 Wiley‐Liss, Inc.
Role of post‐operative chemoradiation in resected gastric cancer
Authors: Macdonald John S. 
Published: May 2005

AbstractThe curative management of gastric adenocarcinoma depends upon complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are at least 70%–80%. There is continued debate over whether more extensive lymph node dissection (D2) improves survival when compared to less extensive operations. Until recently, attempts at preventing recurrence have employed adjuvant chemotherapy and have been ineffective. A large U.S. Intergroup study (INT‐0116) demonstrated that combined chemoradiation following complete gastric resection improves median time to relapse (30 vs. 19 months, P < 0.0001) and overall survival (35 vs. 28 months, P = 0.01). The improvements in disease‐free and overall survival resulting from post‐operative chemoradiation have defined a new standard of care. An update of the results of INT‐0116 analysis performed in 2004 with 7 years median follow‐up, not only confirms the benefits from post‐operative chemoradiation but also shows that chemoradiation does not produce significant long‐term toxicity. The recent publication of the first large adequately powered III neoadjuvant chemotherapy trial suggested this technique might downstage tumors and increase resectability. Future advances in the therapy of resectable gastric cancer may come from studies of pre‐operative neoadjuvant chemoradiation and the application of targeted therapies such as growth receptor antagonists and antiangiogenesis agents. J. Surg. Oncol. 2005;90:166–170. © 2005 Wiley‐Liss, Inc.
Minimally invasive treatment for gastric cancer: Approaches and selection process
Authors: Noh Sung Hoon , Hyung Woo Jin , Cheong Jae‐Ho 
Published: May 2005

AbstractMinimally invasive treatment of gastric cancer has emerged as a result of the technical advances, better understanding of gastric physiology, and more knowledge of the biologic behavior of gastric cancer. This treatment results in improved quality of life embodied by smaller incisions, reduced length of hospital stay, and a faster return to productive life. However, minimally invasive treatment for gastric cancer must take into consideration the potential effects of these techniques on tumor dissemination at the time of the treatment procedure, as well as the rates of recurrence and overall survival. Several technical treatment approaches to gastric cancer have now become possible, utilizing endoscopy, laparoscopy, or an open method. Endoscopic mucosal resection (EMR), limited resection, and laparoscopic surgical resection are the currently practiced modalities as the minimally invasive treatment. Lymph node dissection with the minimally invasive techniques is a barrier to its wide application. Although it is not commonly performed in Western countries, the use of minimally invasive treatment for gastric cancer is growing, especially in Korea and Japan. Minimally invasive treatment for early gastric cancer (EGC) has already been shown to be safe and effective in many retrospective series though no prospective randomized studies comparing it to open resection have been performed. Therefore, routine implementation of these procedures must await confirmatory outcomes generated by well‐done randomized prospective clinical trials. J. Surg. Oncol. 2005;90:188–193. © 2005 Wiley‐Liss, Inc.
Gastric GI stromal tumors (GISTs): The role of surgery in the era of targeted therapy
Authors: Heinrich Michael C. , Corless Christopher L. 
Published: May 2005

AbstractGastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm arising in the stomach. These tumors were previously classified as smooth muscle tumors, but in recent years it has become clear that they are clinically, pathologically, and molecularly distinct from other tumors and are much more common than previously appreciated. Historically, patients with primary localized or advanced GIST have been managed surgically, as there was no proven role of other treatment modalities such as radiation or chemotherapy. However, the field of GIST was revolutionized with the 1998 discovery that the vast majority of these tumors have oncogenic gain‐of‐function mutations of the KIT receptor tyrosine kinase. Follow‐up studies have confirmed that KIT is both a useful diagnostic marker and an excellent therapeutic target. Imatinib, an inhibitor of KIT kinase activity, is now the standard front‐line therapy for patients with advanced GIST. In this review, we discuss pathological and molecular features of gastric GISTs and review the historic and current roles of surgery in the treatment of patients with primary or metastatic GIST. The importance of a multi‐disciplinary approach using both surgery and imatinib therapy is emphasized. J. Surg. Oncol. 2005;90:195–207. © 2005 Wiley‐Liss, Inc.