Sialidase and malignancy: a minireview

Aberrant sialylation in cancer cells is thought to be a characteristic feature associated with malignant properties including invasiveness and metastatic potential. Sialidase which catalyzes the removal of sialic acid residues from glycoproteins and glycolipids, has been suggested to play important roles in many biological processes through regulation of cellular sialic acid contents. The altered expression of sialidase observed in cancer would, therefore, suggest its involvement in the malignant process. In mammalian cells, three types of sialidase cloned and characterized to date were found to behave in different manners during carcinogenesis. Recent progress in molecular cloning of these sialidases has facilitated elucidation of the molecular mechanisms and significance of these alterations. Herein we briefly describe our own studies on sialidase changes associated with malignant transformation and summarize the topic from both a retrospective and a prospective viewpoint. Sialidases are indeed closely related to malignancy and are thus potential targets for cancer diagnosis and therapy.     

Apoptotic markers for tumor recurrence: a minireview

The control of apoptotic mechanisms is integral to many aspects of tumor biology and appears to be involved in the process of recurrence. Apoptosis serves as an essential mechanism to prevent the proliferation of cells with a higher mutation rate, thus tempering malignant transformation. Most antineoplastic therapies function by triggering apoptosis in sensitive cells. Resistance to treatment may result from specific inhibition of apoptotic signaling. Chemotherapy or radiation may increase the mutation rate and hasten tumor evolution in cancer cells that are resistant to apoptosis. Summarizing the current evidence regarding the usefulness of various apoptotic markers for predicting tumor recurrence, the most extensively studied appear to be bcl-2 and p53, as well as the apoptotic rate itself, with promising prognostic potential in several neoplasias. Investigative results, however, mostly refer to multiple single-center retrospective studies, awaiting validation by large prospective clinical trials. Despite initial optimism, it becomes apparent that the measurement of one or more gene products is inadequate to directly predict a phenomenon as complex as the clinical outcome. One of the challenges that is only beginning to be addressed is the combined assessment of traditional prognostic parameters and molecular biomarkers by creating models or equations to predict the likelihood of recurrence. Such screening of patients may help define prognostic categories and influence treatment decisions.     

Stress and immunity: minireview

Stress, a state of threatened homeostasis, may be induced by various physical or psychological factors (stressors), including antigenic stimulation. Stressful experiences may affect both physical/psychological well being and immune functioning of humans and animals; the ongoing immune reaction may affect other physiological functions and psychological comfort. The molecular basis of these effects involves a network of multidirectional signalling and feedback regulations of neuroendocrine- and immunocyte-derived mediators. The consecutive stages of the multistep immune reactions might be either inhibited or enhanced owing to the previous and/or parallel stress experiences, depending on the kind of stressor and the animal species, strain, gender, or age. Therefore, the final results of stress-induced alteration of immune reactions are difficult to predict. The effect of a particular stressor on immune functions varies according to the previous stress experience of the individual (e.g. social confrontation, sterile saline injection) while various stressors may act in the same or in opposite ways on the same immune parameter. In general, the efficacy of immune response depends on the neuroendocrine environment on which it is superimposed. Conversely, neural and endocrine responses depend on the concurrent immune events upon which they are superimposed. It seems that the consequences of stress on the immune functioning are generally adaptive in the short run but can be damaging when stress is chronic.     

Reovirus-induced apoptosis: A minireview

Reoviruses infect a variety of mammalian hosts and serve as an important experimental system for studying the mechanisms of virus-induced injury. Reovirus infection induces apoptosis in cultured cells in vitro and in target tissues in vivo, including the heart and central nervous system (CNS). In epithelial cells, reovirus-induced apoptosis involves the release of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) from infected cells and the activation of TRAIL-associated death receptors (DRs) DR4 and DR5. DR activation is followed by activation of caspase 8, cleavage of Bid, and the subsequent release of pro-apoptotic mitochondrial factors. By contrast, in neurons, reovirus-induced apoptosis involves a wider array of DRs, including TNFR and Fas, and the mitochondria appear to play a less critical role. These results show that reoviruses induce apoptotic pathways in a cell and tissue specific manner. In vivo there is an excellent correlation between the location of viral infection, the presence of tissue injury and apoptosis, indicating that apoptosis is a critical mechanism by which disease is triggered in the host. These studies suggest that inhibition of apoptosis may provide a novel strategy for limiting virus-induced tissue damage following infection.     

Cell death in the rat thymus: a minireview

During the last decades, the literature has clearly established the fundamental role of the thymus in the development of an effective immune system. During thymocyte development and maturation, potentially autoreactive thymocytes are eliminated by a process known as apoptosis or programmed cell death responsible for the negative selection occurring within the thymus. This process is in sharp contrast to other types of cell death referred to as necrosis. Actually, three different types of cell death have been recently observed morphologically in the rat thymus, i.e. necrosis, apoptosis and clustered cell death. Moreover, among the numerous factors influencing thymocyte cell death, particular attention has been paid to hormones, chemicals, biological compounds and physical agents that may influence the type and/or the extent of cell death. Finally, a brief overview has been devoted to the contribution of mitochondria, nitric oxide, glutathione and intracellular levels of cations in addition to the activity of genes as cdk2, p53, Fas and members' of the Bcl2 family in modulating rat thymus cell death.     

Caspase-independent apoptotic pathways in T lymphocytes: a minireview

Cell death by apoptosis is involved in the maintenance of T cell receptor diversity, self tolerance, and T-cell number homeostasis. Until recently, apoptosis was thought to require caspase activation. Evidence is now accumulating that a caspase-independent pathway exists, shown by in vitro experiments with broad-range caspase inhibitors. Mature T lymphocytes readily undergo caspase-independent apoptosis in vitro, and recent data suggest that this type of apoptosis may be involved in the negative selection of thymocytes. Mitochondria likely release death triggers specific for both caspase-dependent and caspase-independent apoptotic pathways (cytochrome c and AIF respectively) in response to apoptotic stimuli. A caspase-independent pathway is triggered first in activated T lymphocytes subjected to apoptotic stimuli that do not rely on receptors with death domains. In this pathway, the early commitment phase to apoptosis involves cell shrinkage, peripheral DNA condensation and the translocation of mitochondrial AIF to the cytosol and nucleus. This process is reversible until mitochondrial cytochrome c is released and m dissipated. Only at this stage are caspases activated.     

Sialidase and malignancy: A minireview

Aberrant sialylation in cancer cells is thought to be a characteristic feature associated with malignant properties including invasiveness and metastatic potential. Sialidase which catalyzes the removal of sialic acid residues from glycoproteins and glycolipids, has been suggested to play important roles in many biological processes through regulation of cellular sialic acid contents. The altered expression of sialidase observed in cancer would, therefore, suggest its involvement in the malignant process. In mammalian cells, three types of sialidase cloned and characterized to date were found to behave in different manners during carcinogenesis. Recent progress in molecular cloning of these sialidases has facilitated elucidation of the molecular mechanisms and significance of these alterations. Herein we briefly describe our own studies on sialidase changes associated with malignant transformation and summarize the topic from both a retrospective and a prospective viewpoint. Sialidases are indeed closely related to malignancy and are thus potential targets for cancer diagnosis and therapy. Published in 2004. This revised version was published online in August 2006 with corrections to the Cover Date.     

Diurnal and ultradian rhythms in human endocrine function: a minireview

Rapidly accumulating evidence indicates that every hypothalamo-pituitary axis is influenced by both sleep (irrespective of the time of day when it occurs) and circadian rhythmicity (irrespective of the sleep or wake condition). Circadian effects seem to be exerted by a modulation of the amplitude of secretory pulses. Sleep may affect pulse frequency. Recent studies indicate that this complex temporal organization is not limited to pituitary and pituitary-dependent hormones but also underlies glucose regulation and insulin secretion.     

Human enteric viruses in the water environment: a minireview.

Water virology started around half a century ago, with scientists attempting to detect poliovirus in water samples. Since that time, other enteric viruses responsible for gastroenteritis and hepatitis, among a great variety of virus strains, have replaced enteroviruses as the main target for detection in the water environment. Technical molecular developments, polymerase-chain reaction (PCR) amplification being the method of choice, enable the detection of fastidious health-significant viruses. However, shortcomings of molecular procedures include their potential incompatibility with concentration methods, indispensable to reduce the water sample volume to assay for viruses, the inability to discern between infectious and non infectious material. On the other hand, these procedures are restrained to sophisticated laboratories and detection of alternative indicator organisms has been proposed. Bacterial indicators fail to give a reliable clue of the virological quality of water. Selected bacteriophage groups appear as a better choice for their use as virus indicators.     

Amyloid beta-peptide induces cholinergic dysfunction and cognitive deficits: a minireview

Amyloid beta-peptide (Abeta) plays a critical role in the development of Alzheimer's disease (AD). Much progress has been made in understanding this age-related neurodegenerative disorder, thus an insight into the cellular actions of Abeta and resulting functional consequences may contribute to preventive and therapeutic approaches for AD. In this review, recent evidence of Abeta-induced brain dysfunction, particularly of cholinergic impairment and memory deficits is summarized. Moreover, proposed mechanisms for Abeta-induced neurotoxicity such as oxidative stress, ion-channel formation, and Abeta-receptor interaction are discussed.     

Molecules inhibiting neurite growth: A minireview

Molecules and activities which repulse growing neurites or induce growth cone collapse and long-lasting growth inhibition have been defined over the last 10 years. Recently, specific guidance roles for developing axons and pathways could be associated with such repulsive effects. A high molecular weight membrane protein located in CNS myelin acts as potent neurite growth inhibitor and may play a role as a negative control element for sprouting, neurite growth and regeneration, and for the plasticity of the adult CNS. Interestingly, some guidance molecules can have positive, growth-promoting as well as negative, repulsive effects for specific types of neurons. These results underline the complex mechanisms involved in neurite guidance which depends on the interpretation of combinations of incoming signals by particular growth cones. Special issue dedicated to Dr. Hans Thoenen.     

The microbial degradation of azo dyes: minireview

The removal of dyes in wastewater treatment plants still involves physical or chemical processes. Yet numerous studies currently exist on degradation based on the use of microbes—which is a well-studied field. However progress in the use of biological methods to deal with this environmentally noxious waste is currently lacking. This review focuses on the largest dye class, that is azo dyes and their biodegradation. We summarize the bacteria identified thus far which have been implicated in dye decolorization and discuss the enzymes involved and mechanisms by which these colorants are broken down.     

Unstable nucleotide repeat minireview series: a molecular biography of unstable repeat disorders

Expansion of an unstable nucleotide repeat is a mutational mechanism that is apparently unique to humans and is known to cause a variety of neurological disorders. This collection of minireviews examines several of these unstable repeats, focusing on those where there is considerable molecular information on how the mutation alters function.     

Golgi/granule processing of peptide hormone and neuropeptide precursors: a minireview

Proteolytic processing of precursor proteins is a phylogenetically ancient and widely used mechanism for producing biologically active peptides. Proteolytic cleavage of proproteins begins only after transport to the Golgi apparatus has been completed and in most systems may continue for many hours within newly formed secretory vesicles as these are stored in the cytosol or transported along axons to more peripheral sites of release. Paired basic residues are required for efficient proteolysis in most precursors, suggesting that a small number of specialized tryptic proteases exist that have great site selectivity but can process many sites within the same precursor or in different precursors within the same cell, or in different cells or tissues. Cleavage-site choice may be strongly influenced by other factors, such as secondary and tertiary structure, but definitive structural information on precursor proteins is lacking. Modifications such as glycosylation, phosphorylation, and sulfation also are Golgi associated but are not known to influence proteolytic processing patterns. Golgi/granule processing also rarely occurs at sites other than pairs of basic amino acids, including single basic residues ( trypsinlike ), Leu-Ala, Leu-Ser, or Tyr-Ala bonds ( chymotrysinlike ) as well as other specialized nontryptic cleavages, suggesting that mixtures of proteases coexist in the Golgi/granule system. Cathepsin B-like thiol proteases, or their precursors, have been implicated as the major processing endopeptidases in several systems. Carboxypeptidase B-like enzymes also have been identified in secretion granules in several tissues and appear to be metalloenzymes similar in mechanism to the pancreatic carboxypeptidases, but with a lower pH optimum. The role of the Golgi apparatus in sorting newly formed secreted products from lysosomal hydrolases may have permitted the development in evolution of an intimate relationship between certain of the lysosomal degradative enzymes, such as cathepsin B or its precursors, and the Golgi/granule processing systems. The sequestration of the proteolytic products of precursors within secretion granules leads to the coordinate discharge of highly complex mixtures of peptides having related or overlapping biological activities. The cosecretion of nonfunctional peptide " leftovers ," such as the proinsulin C-peptide, can serve as useful markers of secretion or cellular localization, as well as of evolutionary relation ships. Errors in cleavage due to point mutations in precursors have been identified in several systems, leading to the accumulation of incorrectly processed materials in the circulation. These and/or defects (ABSTRACT TRUNCATED AT 400 WORDS)