Progress in human tumour immunology and immunotherapy

Studies of the administration of interleukin-2 to patients with metastatic melanoma or kidney cancer have shown that immunological manipulations can mediate the durable regression of metastatic cancer. The molecular identification of cancer antigens has opened new possibilities for the development of effective immunotherapies for patients with cancer. Clinical studies using immunization with peptides derived from cancer antigens have shown that high levels of lymphocytes with anti-tumour activity can be raised in cancer-bearing patients. Highly avid anti-tumour lymphocytes can be isolated from immunized patients and grown in vitro for use in cell-transfer therapies. Current studies are aimed at understanding the mechanisms that enable the cancer to escape from immune attack.

Recent progress in artificial receptors for phosphate anions in aqueous solution

A recent progress of artificial phosphate receptors is reviewed with special focus on macrocyclic polyamines and their metal complexes as a new prototype. In comparison to most of the previous artificial receptors most of them are organic molecules ,our system characteristically works in aqueous solution at neutral pH with extremely strong affinities with phosphate anions.

A Thymic Precursor to the NK T Cell Lineage

CD1d-restricted autoreactive natural killer (NK1.11) T cells function as regulatory cells in various disease conditions. Using improved tetramer tracking methodology, we identified a NK1.1– thymic precursor and followed its differentiation and emigration to tissues by direct cell transfer and in situ cell labeling studies.

COMPUTING: Successes and Challenges

In the last few years, the idea of a molecular computer that could execute computational steps at the scale of a single molecule has moved from the realm of science fiction into that of scientific publications.

Small Nucleolar RNAs: An Abundant Group of Noncoding RNAs with Diverse Cellular Functions

Small nucleolar RNAs represent an abundant, evolutionarily ancient group of noncoding RNAs which possess impressively diverse functions ranging from 2
-O-methylation of Various Classes of RNAs ylation and pseudouridylation of various classes of RNAs, through nucleolytic processing of rRNAs to the synthesis of telomeric DNA.

Lipases and HDL metabolism

Plasma levels of high-density lipoproteins (HDL) cholesterol are strongly inversely associated with atherosclerotic cardiovascular disease.Here,wefocus on new developments and insights into the role of secreted lipases on HDL metabolism and their relationship to atherosclerosis.

Ribosome structure:revisiting the connection between translational accuracy and unconventional decoding

This article proposes that the ribosome uses the structure of the codon–anticodon complex formed by the peptidyl-tRNA, especially its wobble interaction, to constrain the incoming aminoacyl-tRNA to the correct reading frame.

Signaling Networks That Link Cell Proliferation and Cell Fate

In this review, we will discuss our current understanding of the Rb/E2F pathway, the c-Myc transcription factor, and the Ras signaling molecule, followed by recent work showing interconnections between these pathways, leading to a more comprehensive picture of the network controlling the balance between cellular proliferation and apoptosis.

Adrenomedullin:An Autocrine/Paracrine Factor for Cardiorenal Protection

Since 1993, with the discovery of adrenomedullin (AM) by Kitamura and coworkers,we have gained many insights into the biology of this new peptide.We now know that AM circulates in plasma and is present in organs and tissues with increases in AM activity in heart failure, hypertension, and renal dysfunction.

NF-κB in Cancer: From Innocent Bystander to Major Culprit

Although the importance of NF-κB in immunity is undisputed, recent evidence indicates that NF-κB and the signalling pathways that are involved in its activation are also important for tumour development.

Death and Anit-Death:Tumor Resistantce to Apoptosis

Tumour cells often have faulty apoptotic pathways. These defects not only increase tumour mass, but also render the tumour resistant to therapy. So, what are the molecular mechanisms of tumour resistance to apoptosis and how can we use this knowledge to resensitize tumour cells to cancer therapy?

Danger — misfolding proteins

Protein folding is vital to living organisms because it adds functional flesh to the bare bones of genes. But errors in this process generate misfolded structures that can be lethal.

On the offensive

After decades of disappointment, and the investment of billions of dollars,is the ‘war on cancer’ about to gain real momentum? Alison Abbott sends a dispatch from the front line.

Mixed signals in heart failure:cancer rules

Perhaps the time has come to attempt to dissect the mixed signals for heart failure from the viewpoint of recent advances in cancer biology. On a molecular level, the failing heart represents the end result of multiple cues for the growth, death, and survival of cardiac myocytes, many of which are shared with signaling pathways in cancer biology.

Mitochondria, from cell death to proliferation

Mitochondrial signaling cascades have been implicated in the activation of programmed cell death and, more recently, control of cell proliferation. A nuclear gene encoding a mitochondrial Krebs-cycle protein, fumarate hydratase, is now shown to act as a major tumor-suppressor gene.

Embryo and stem cell research in the USA:a political history

Embryo and stem cell research in the USA is inextricably linked with the abortion debate since 1973, when elective abortions became legal. Research has continued in an unregulated private sector.Here, the unique US cultural, political and religious factors that have resulted in this situation are discussed.

Order and Disorder in the Nucleus

Fluorescence in situ hybridization combined with three-dimensional microscopy has shown that chromosomes are not randomly strewn throughout the nucleus but are in fact fairly well organized, with different loci reproducibly found in different regions of the nucleus.

Gene expression profiling diagnosis through DNA molecular computation

An Adleman DNA self-assembly computer that would use cDNA as input might be ideal for clinical cell discrimination and a neural network architecture would be appropriate for making the necessary classifications.

The emerging power of chemical genetics

Chemical genetic methods allow signal transduction pathways to be probed in a domain-specific manner. This subtle perturbation of function, when combined with classical genetic and biochemical data, allows for a better understanding of protein function.

How signaling proteins integrate multiple inputs: a comparison of N-WASP and Cdk2

Signal transduction proteins that can integrate multiple upstream signals play a critical role in the complex regulatory circuits that control cellular behavior. The two signaling node proteins cyclin-dependent kinase 2 and the actin regulator neuronal Wiskott–Aldrich syndrome protein have qualitatively similar signaling properties.

Proteomics of the nucleolus:more proteins,more functions?

The first encyclopedia of nucleolar proteins in a human cell is now available.Many of the 271 nucleolar proteins identified are involved in rRNA synthesis and processing, and in ribosome assembly, but others are indicative of more diverse nucleolar functions.

The angiotensin-converting enzyme gene family: genomics and pharmacology

Recently,genomic approaches have identified the first human homologue of ACE, termed ACEH (or ACE2).ACEH differs in specificity and physiological roles from ACE, which opens a potential new area for discovery biology.

Circular proteins – no end in sight

This article describes the discovery, structure, function and biosynthesis of the currently known circular proteins.

Protein microarray technology

Here,we discuss theoretical advantages and limitations of any miniaturized capture-molecule–ligand assay system and discusses how the use of protein microarrays will change diagnostic methods and genome and proteome research.

Heat-shock proteins as activators of the innate immune system

We discuss the similarities between the responses to HSPs and LPS and also, emphasize that care must be taken when working with preparations of HSPs in experimental settings and interpreting experimental data.

Medicinal chemistry and therapeutic potential of CpG DNA

The observation that oligodeoxynucleotides containing CpG dinucleotides (CpG DNA) exhibit several immunological effects has led to their use as therapeutic agents and adjuvants for various diseases.This article reviews recent progress in understanding the effects of CpG DNA, the medicinal chemistry of CpG DNA, and its possible therapeutic applications.

Seven-transmembrane receptors:crystals clarify

The X-ray structure of the photoreceptor rhodopsin has provided the first atomic-resolution structure of a seven-transmembrane (7-TM) G-proteincoupled receptor.

Skiing Toward Nonstop mRNA Decay

One well-studied assurance mechanism in gene expression in eukaryotes is nonsense-mediated messenger RNA (mRNA) decay (NMD). NMD prevents the synthesis of potentially deleterious truncated proteins when translation terminates prematurely.

Chemical Database Techniques in Drug Discovery

Database searches based on possible requirements for biological activity can identify compounds that might be suitable for further analysis or indicate novel ways to achieve the desired activity. What considerations are involved in the construction and searching of chemical databases?

Development of therapeutics: opportunities within complementary and alternative medicine

This article contrasts the regulatory framework for dietary supplements and drugs, outlines the challenges of evaluating dietary supplements for safety and clinical effectiveness, and describes the evolving drug model for botanicals.