Search

Poor penetration of anticancer drugs into tumors can be an important factor limiting their efficacy. We studied mouse tumor models to show that a previously characterized tumor-penetrating peptide, iRGD, increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing coadministered drugs to penetrate into extravascular tumor tissue. Importantly, this effect did not require the drugs to be chemically conjugated to the peptide. Systemic injection with iRGD improved the therapeutic index of drugs of various compositions, including a small molecule (doxorubicin), nanopartides (nab-paditaxel and doxorubicin liposomes), and a monoclonal antibody (trastuzumab). Thus, coadministration of iRGD may be a valuable way to enhance the efficacy of anticancer drugs while reducing their side effects, a primary goal of cancer therapy research. doi: 10.1126/science.1183057

The transcriptional regulatory protein p53 (1) activates the expression proteins that control cellular growth (2). Inhibition of its ability to activate transcription correlates with oncogenesis (3). There functional domains of [...], The adenovirus E4orf6 protein is shown here to interact with the cellular tumor suppressor protein p53 and to block p53-immediated transcriptional activation. The adenovirus protein inhibited the ability of ps to bad to human [TAF.sub.II]31, a component of transcription factor IID (TFIID). Earlier work demonstrated that the interaction of pa53 with [TAF.sub.II]31 involves a sequence near the [NH.sub.2]-terminus of p53, whereas the E4of6-p53 p53 interaction occurs within amino acids 318 to p53. Thus, the E4orf6 protein interacts at a site on p53 distinct from the domain that binds to [TAF.sub.II] 31 but nevertheless inhibits the p53-[TAF.sub.II]31 interaction.

Tumor Cells Exhibit Deregulation of the Cell Cycle Histone Gene Promoter Factor HiNF-D THE HUMAN H4 HISTONE GENE (FO108) proximal promoter contains two in vivo protein binding domains, sites I [...]

The biological functions of cell surface oligosaccharides have been difficult to elucidate owing to the complexity of achieving genetic control over a molecule that is the product of multiple enzymes [...], Poly-[Alpha]2,8-sialic acid (PSA) has been implicated in numerous normal and pathological processes, including development, neuronal plasticity, and tumor metastasis. We report that cell surface PSA expression can be reversibly inhibited by a small molecule, N-butanoylmannosamine (ManBut). Inhibition occurs through a metabolic mechanism in which ManBut is converted to unnatural sialic acid derivatives that effectively act as chain terminators during cellular PSA biosynthesis. N-Propanoylmannosamine (HanProp), which differs from ManBut by a single methylene group, did not inhibit PSA biosynthesis. Modulation of PSA expression by chemical means has a role complementary to genetic and biochemical approaches in the study of complex PSA-mediated events.

Radiotherapy has been used to successfully treat a variety of solid tumors. The conventional explanation for why radiotherapy is so effective is that tumor cells are the principal target of [...]

Due largely to the vigilance of cytotoxic [CD8.sup.+] T cells, most malignant tumors regress before reaching detectable size. Terabe et al. suggest that the activities of some specialized lymphocytes, called [...]

The activation of the tumor suppressor protein p53 can lead to cell cycle arrest or to apoptosis. Attardi et al. used subtractive hybridization to identify a gene involved specifically in [...]

Neurofibromatosis type I (NF1) affects about 1 in 3500 individuals worldwide (1). The hallmark clinical feature of the disease is development of multiple benign neurofibromas, which can be debilitating, severely [...], Neurofibromatosis type 1 (NF1) is a prevalent familial cancer syndrome resulting from germ line mutations in the NF1 tumor suppressor gene. Hallmark features of the disease are the development of benign peripheral nerve sheath tumors (neurofibromas), which can progress to malignancy. Unlike humans, mice that are heterozygous for a mutation in Nf1 do not develop neurofibromas. However, as described here, chimeric mice composed in part of [Nf1.sup.-/-] cells do, which demonstrates that loss of the wild-type NJ1 allele is rate- limiting in tumor formation. In addition, mice that carry [inked germ line mutations in Nf1 and p53 develop malignant peripheral nerve sheath tumors (MPNSTs), which supports a cooperative and causal rote for p53 mutations in MPNST development. These two mouse models provide the means to address fundamental aspects of disease development and to test therapeutic strategies.

Survival of the fittest is a rule that applies just as much to protein families as it does to organisms. The serpins are a protein family of highly adaptable serine [...]

Cancer is a potentially lethal disease in mammals and other complex organisms with renewable tissues. Tumors originate from cells that are actively dividing. Such cells are at much greater risk [...]

Tumors hungry for sustenance need new blood vessels to deliver the goods. Cancer researchers have spent years working to starve tumors by blocking this blood vessel growth, or angiogenesis, with [...]

In 1858, Rudolf Virchow published a series of lectures as a book entitled Cellular Pathology (1), which altered medical research by turning the focus from the diseased cell's form to [...]

Summary. Two dozen cellular proto-oncogenes nave been discovered to date through the study of retroviruses and the use of gene transfer. They form a structurally and functionally heterogeneous group. At [...]

Abstract. After subcutaneous injection, monoclonal antibodies directed against a tumor can enter local lymphatic vessels, pass to the draining lymph nodes, and bind to metastases there. Lymphatic delivery of antibody [...]

Abstract. Carcinoma cells and normal epithelial cells differ in the mitochondrial retention of a permeant cationic compound, rhodamine 123. The possibility of utilizing this difference in carcinoma chemotherapy was investigated. [...]

Tumor Formation Dependent on Proteoglycan Biosynthesis PROTEOGLYCANS OCCUR ON THE plasma membranes of mammalian cells and in the extracellular matrix. The various classes of proteoglycans are distinguished by differences in [...]

Absence of TGF-β Receptors and Growth Inhibitory Responses in Retinoblastoma Cells DURING THE PAST DECADE, SUBstantial advances have been made in understanding the genes and proteins that act to promote [...]

Cell and Environment Interactions in Tumor Microregions: The Multicell Spheroid Model BY THE TIME A TUMOR HAS GROWN TO A DETECTABLE SIZE the cancer cells and their local environments have [...]

Site-Specific Nick in the T-DNA Border Sequence as a Result of Agrobacterium vir Gene Expression Agrobacterium tumefaciens HARBORINGa Ti (tumor-inducing) plasmid induces tumors in plants by transferring and integrating a [...]

Thyroid Hormone Induction of an Autocrine Growth Factor Secreted by Pituitary Tumor Cells THYROID HORMONES ARE ESSENTIAL for normal growth and development and exert profound effects on cellular metabolism in [...]

Transforming Growth Factor- : A More Potent Angiogenic Mediator Than Epidermal Growth Factor TRANSFORMING GROWTH FACTORS (TGF's) are polypeptides that can confer phenotypic transformation to several normal cells (1). TGF- [...]

Alterations of myc, myb, and ras.sup.Ha Proto-oncogenes in Cancers Are Frequent and Show Clinical Correlation PROTO-ONCOGENES MAY BE ACTIVATED and contribute to neoplastic transformation of cells through point mutations, translocations, [...]

The ras genes constitute a multigene family that is highly conserved among eukaryotes, including mammals and yeast. These genes and their 21-kD protein products (p21) were first identified as the [...]

The immune system is involved not only in defense against infections but also against 'spontaneously derived' aberrant cells (1). This latter immune function appears to be essential for the removal [...]

Prooxidant States and Tumor Promotion In cellular prooxidant states the intracellular concentration of activated forms of oxygen is increased, presumably because cells either overproduce these reactive substances or are deficient [...]

Three types of B lymphocytic tumors arise in BALB/c mice after they receive intraperitoneal injections of pristane and Abelson virus. On the basis of their morphology and association with Abelson [...]

Development of a fully malignant tumor involves complex interactions between environmentla and endogenous factors. In addition, carcinogenesis often proceeds through several discernible stages (initiation, promotion, progression) (1). DNA transfection studies [...]

Certain oncogenes can change the normal morphology of cultured rodent fibroblasts towrad an oncogenic phenotype, enabling those that carry the genes to grow in soft agar and form tumors when [...]

Like the DNA's of other vertebrates (1), human DNA contains multiple germline copies of retroviral sequences. These endogenous structures were first identified and selected from a genomic DNA library through [...]

Carcinomas originate from internal and external body surfaces, including ducts and glandular structures. Hence, they arise in epithelial tissue, where rapid cell loss and regeneration are physiological and defects in [...]

The human type-C retrovirus known as human T-cell leukemia-lymphoma virus (HTLV) was first isolated from neoplastic cells derived from black patients in the United States with adult T-cell malignancies (1,2). [...]

Human Proto-Oncogene Nucleotide Sequences Corresponding to the Transforming Region of Simian Sarcoma Virus The simian sarcoma virus (SSV) is the only acutely transforming retrovirus (causing disease within a short latency [...]