New perspectives on the molecular basis of hereditary bone tumours.

Bone development is a highly regulated process sensitive to a wide variety of hormones, inflammatory mediators and growth factors. One of the most common hereditary skeletal dysplasias, hereditary multiple exostoses (HME), is an autosomal dominant disorder characterized by skeletal malformations that manifest as bony, benign tumours near the end of long bones. HME is usually caused by defects in either one of two genes, EXT1 and EXT2, which encode enzymes that catalyse the biosynthesis of heparan sulphate, an important component of the extracellular matrix. Thus, HME-linked bone tumours, like many other skeletal dysplasias, probably result from disruptions in cell surface architecture. However, despite the recent success in unravelling functions for several members of the EXT gene family, significant challenges remain before this knowledge can be used to develop new approaches for the diagnosis and treatment of disease.     

Microenvironmental influences in melanoma progression

An often overlooked facet of tumor biology research is the involvement of the surrounding tumor microenvironment. Increasing evidence is being presented to support a major role for stromal components in all stages of tumorigenesis including initiation, progression, and metastasis. Melanoma serves as a model for studying cellular and stromal interactions within the tumor microenvironment due to the array of cell types localized to these lesions. Here, we discuss the both the molecular mechanisms, as well as the extracellular and contextual input that contribute to melanoma progression. Special emphasis is given to the assorted cell types and their interactions with the extracellular matrix and adjacent cells. Melanoma progression also initiates development of intralesional hypoxic regions; the relative significance of hypoxia in disease is also addressed. Lastly, a number of laboratories are currently developing innovative strategies to study melanoma within a microenvironmental platform. These promising model systems and their potential for closing current gaps in knowledge of disease are reviewed. The development of such models holds translational value that cannot be achieved with most current systems.     

Nuclear envelope influences on cell-cycle progression

The nuclear envelope is a complex double membrane system that serves as a dynamic interface between the nuclear and cytoplasmic compartments. Among its many roles is to provide an anchor for gene regulatory proteins on its nucleoplasmic surface and for the cytoskeleton on its cytoplasmic surface. Both sets of anchors are proteins called NETs (nuclear envelope transmembrane proteins), embedded respectively in the inner or outer nuclear membranes. Several lines of evidence indicate that the nuclear envelope contributes to cell-cycle regulation. These contributions come from both inner and outer nuclear membrane NETs and appear to operate through several distinct mechanisms ranging from sequestration of gene-regulatory proteins to activating kinase cascades.     

New determinates of disease progression and outcome in metastatic ovarian carcinoma

Ovarian cancer is the most lethal gynecologic malignancy. This is attributed to frequent presentation at late stage, when the tumor has metastasized, as well as to development of chemotherapy resistance along tumor progression. Patients with advanced-stage ovarian carcinoma have widespread intraperitoneal metastases, including the formation of malignant serous effusions within the peritoneal cavity. Pleural effusions constitute the most frequent site of distant metastasis (FIGO stage IV disease). Unlike the majority of solid tumors, particularly at the primary site, cancer cells in effusions are not amenable to surgical removal, and failure in their eradication is one of the main causes of treatment failure. Our research in recent years has demonstrated that a large number of cancer-associated molecules are differentially expressed in effusions compared to primary carcinomas and solid metastases. We have additionally observed that expression of several of these molecules differs between primary diagnosis (pre-chemotherapy) and disease recurrence (post-chemotherapy) specimens, and that they are significantly associated with response to chemotherapy and patient survival. These observations are thought to be related to disease progression, as well as to the unique microenvironment of effusions, and may have impact on the selection of targeted therapy in this cancer. This review discusses our recent observations with respect to the biology of ovarian carcinoma cells in effusions, and focuses on the clinical role of tumor-associated molecules at this anatomic site.     

Targeting key steps in metastatic tumour progression

The key determinants of tumour progression and discriminators of benign and malignant lesions include neoangiogenesis (the induction of a new blood supply) and the capacity of malignant cells to invade and metastasise. It is now recognized that these processes can be co-ordinately regulated by the activity of specific genes -- often distinct from those involved in early oncogenesis -- and involve common signalling pathways. Cell motility and chemotaxis (the ability to respond to gradients of chemoattractants) are implicated in both tumour-cell invasion and response of activated endothelial cells to angiogenic cytokines, and provide interesting and novel points for therapeutic intervention.     

New perspectives on chrononutrition

Chrononutrition proposes that nutrients or meal timing per se could affect the circadian clock system, and that the desynchronization of biological rhythms could negatively influence timing and food choices. Research in this area has suggested that mealtime, energy distribution throughout the day, nocturnal eating and food ingestion frequency may influence nutrient metabolism, being associated with metabolic and nutritional diseases. Given the growing amount of evidence linking the circadian clock system to metabolic and nutritional health, circadian organization seems to be clinically important in the understanding of diseases such as obesity and, maybe, in the nutritional treatment of them. Thus, chrononutrition emerges as an important tool to enhance the metabolic and nutritional health of particular population groups (e.g. shift workers) and in the treatment of diseases such as obesity. For this reason, the area needs to be further explored.     

Clinical hematological progression of hereditary lymphosarcoma in rabbits.

Considerable diversity exists in the clinical progression data for lymphosarcoma both between and within species. Thirty-four rabbits with hereditary lymphosarcoma were used to define the clinical progression of this condition under controlled genetic conditions. Changes in the erythropoietic cells of the rabbit hemogram in cases of hereditary lymphosarcoma (ha/ha) follow a fairly well defined clinical course of about one-and-one-half months duration. Data are presented showing that these changes are subsequent to schanges in the granulocytic cells of the leukocyte series both peripherally and in the bone marrow.     

New perspectives on protozoa

The interest of the British research community in protozoa has in the past emphasized the parasitic organisms-especially those causing diseases of economic importance in Africa. The last 20 years have witnessed dramatic changes in protozoology, and the purpose of this meeting was to indicate the nature and significance of these changes.
Three areas were discussed. The first was our present understanding of protozoan diversity and the evolution of protozoa (by David Patterson), the second (by Bland Finlay) presented some novel and ecological important symbiotic relationships between protozoa and other microorganisms), and finally Graham Coombs discussed the problems still being posed by parasitic protozoa and the application of new technologies to those problems.     

Emerging roles for LPP in metastatic cancer progression

LIM domain containing proteins are important regulators of diverse cellular processes, and play pivotal roles in regulating the actin cytoskeleton. Lipoma Preferred Partner (LPP) is a member of the zyxin family of LIM proteins that has long been characterized as a promoter of mesenchymal/fibroblast cell migration. More recently, LPP has emerged as a critical inducer of tumor cell migration, invasion and metastasis. LPP is thought to contribute to these malignant phenotypes by virtue of its ability to shuttle into the nucleus, localize to adhesions and, most recently, to promote invadopodia formation. In this review, we will examine the mechanisms through which LPP regulates the functions of adhesions and invadopodia, and discuss potential roles of LPP in mediating cellular responses to mechanical cues within these mechanosensory structures.     

Blood pressure follows the kidney: Perinatal influences on hereditary hypertension

Epidemiological and experimental data strongly suggest that cardiovascular diseases can originate from an aberrant environment during fetal development, a phenomenon referred to as perinatal programming. This review will focus on the role of the kidneys in determining blood pressure, and how (re)programming the renal development can persistently ameliorate hereditary hypertension. By combining physiologic and genomic studies we have discovered some candidate pathways suited for (re)programming the development of hypertension. This sets the stage for mechanistic analysis in future studies.Key words: perinatal development, spontaneously hypertensive rat, citrulline, nitric oxide, hypertension     

Recent progression and future perspectives in cotton genomic breeding

Upland cotton is an important global cash crop for its long seed fibers and high edible oil and protein content.Progress in cotton genomics promotes the advancement of cotton genetics,evolutionary studies,functional genetics,and breeding,and has ushered cotton research and breeding into a new era.Here,we summarize high-impact genomics studies for cotton from the last 10 years.The diploid Gossypium arboreum and allotetraploid Gossypium hirsutum are the main focus of most genetic and genomic studi...     

New perspectives on integrin-dependent adhesions

Integrins are heterodimeric transmembrane receptors that connect the extracellular matrix environment to the actin cytoskeleton via adaptor molecules through assembly of a range of adhesion structures. Recent advances in biochemical, imaging and biophysical methods have enabled a deeper understanding of integrin signalling and their associated regulatory processes. The identification of the consensus integrin-based ‘adhesomes’ within the last 5 years has defined common core components of adhesion complexes and associated partners. These approaches have also uncovered unexpected adhesion protein behaviour and molecules recruited to adhesion sites that have expanded our understanding of the molecular and physical control of integrin signalling.     

New perspectives on glutamine synthetase in grasses

Members of the glutamine synthetase (GS) gene family have now been characterized in many crop species such as wheat, rice, and maize. Studies have shown that cytosolic GS isoforms are involved in nitrogen remobilization during leaf senescence and emphasized a role in seed production particularly in small grain crop species. Data from the sequencing of genomes for model crops and expressed sequence tag (EST) libraries from non-model species have strengthened the idea that the cytosolic GS genes are organized in three functionally and phylogenetically conserved subfamilies. Using a bioinformatic approach, the considerable publicly available information on high throughput gene expression was mined to search for genes having patterns of expression similar to GS. Interesting new hypotheses have emerged from searching for co-expressed genes across multiple unfiltered experimental data sets in rice. This approach should inform new experimental designs and studies to explore the regulation of the GS gene family further. It is expected that understanding the regulation of GS under varied climatic conditions will emerge as an important new area considering the results from recent studies that have shown nitrogen assimilation to be critical to plant acclimation to high CO(2) concentrations.     

New perspectives on socioeconomic inequalities in health

In all countries with available data, risks of disease and premature death tend to be systematically higher for those with lower levels of education and income. During the 1990s, substantial progress has been made in understanding the mechanisms and factors involved in generating these variations in health. What has emerged from recent research efforts is a rather complex picture of how individuals in the lower socioeconomic strata are exposed over their lifetime to a wide variety of unfavorable and interacting material, cultural, and psychological conditions, and how these exposures lead to ill-health-either directly, or indirectly through unhealthy behaviors or psychosocial stress. This research has opened a number of new perspectives which we review here: life-course perspectives (dealing with the clustering of advantage and disadvantage over an individual's lifetime), biological perspectives (dealing with the biological mechanisms that bring socioeconomic disadvantage under the skin), macrosocial perspectives (dealing with the effect of the wider social, economic, and political environment), and policy perspectives (dealing with the implications of research findings for the development of effective strategies to reduce inequalities in health).