Abstract：
:The Ras proteins, which regulate intracellular signaling by a cyclic process involving interconversion between active GTP-bound and inactive GDP-bound states, play an essential role in controlling the activity of several crucial signaling pathways regulating normal cellular proliferation. Mutational activation of RAS genes can induce cancer in humans and other mammals. About 30% of human tumors contain an altered oncogenic Ras; therefore, inhibitors of Ras activation are potentially antineoplastic drugs. In this work we describe original molecules acting as Ras inhibitors. Recently a new class of inhibitors of the Ras nucleotide exchange process was described by Taveras et al. These molecules are able to form a noncovalent complex with Ras-GDP, inhibiting the GDP-GTP nucleotide exchange. We synthesized molecule SCH-53870 and we found that it inhibits p21-hRas nucleotide exchange in vitro, but it has very low solubility in water and undergoes rapid degradation at room temperature when dissolved in water-DMSO mixtures. This chemical instability could prejudice pharmacological activity in vivo. With the aim to improve solubility and chemical stability, we designed and synthesized other original bioactive molecules that have been characterized in vitro using purified human and yeast Ras proteins and in vivo using suitable Saccharomyces cerevisiae strains. In the long term we hope that the knowledge we derive from these compounds will help in the development of an alternative therapy targeting Ras for a specific inhibition of transformed cell proliferation.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Colombo S,Peri F,Tisi R,Nicotra F,Martegani Edoi
10.1196/annals.1329.007subject
Has Abstractpub_date
2004-12-01 00:00:00pages
52-61eissn
0077-8923issn
1749-6632pii
1030/1/52journal_volume
1030pub_type
杂志文章abstract：:Adults with better jobs enjoy better health: job title was, in fact, the social gradient metric first used to study the relationship between social class and chronic disease etiology, a core finding now replicated in most developed countries. What has been less well proved is whether this correlation is causal, and if...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.2009.05338.x
更新日期：2010-02-01 00:00:00
abstract：:Of the approaches presently available for prevention of blood-transmitted hepatitis, most clearly effective is the avoidance of high-risk donor populations, such as most paid commercial donors. It should be emphasized that even after screening for hepatitis B antigen most paid donor blood carries with it a five-ten ti...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1975.tb53345.x
更新日期：1975-01-20 00:00:00
abstract：:Opsoclonus-myoclonus syndrome (OMS) is a rare neurologic disorder comprising the main symptoms of eye-movement disturbances, muscle jerks, and severe ataxia. In children and adults, some cases are associated with a tumor as a paraneoplastic syndrome, whereas in children the paraneoplastic form is almost exclusively as...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1196/annals.1423.027
更新日期：2007-09-01 00:00:00
abstract：:In an effort to identify novel targets for the development of nonhormonal male contraceptives, genome-wide transcriptional profiling of the rat testis was performed. Specifically, enzymatically purified spermatogonia plus early spermatocyctes, pachytene spermatocytes, round spermatids, and Sertoli cells was analyzed a...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1196/annals.1411.014
更新日期：2007-12-01 00:00:00
abstract：:Various biological activities of peptides have been found. In this study, the induction of apoptosis in a human lymphoma cell line (U937) by peptide fraction separated from anchovy sauce was studied using biochemical and flow cytometric methods. After U937 was treated with a hydrophobic peptide fraction of the anchovy...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1196/annals.1299.073
更新日期：2003-12-01 00:00:00
abstract：:In spite of increasing incidence of esophageal adenocarcinoma in the last few decades, esophageal squamous cell carcinoma (SCC) still remains the dominant subtype of esophageal cancer worldwide. Apart from conventional SCC, some rare unconventional tumors of esophageal squamous mucosa are also well known. This study p...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/nyas.13108
更新日期：2016-10-01 00:00:00
abstract：:Ovarian failure is heterogeneous, both in cause and in phenotype. Women whose menses cease prior to age 40 years and have menopausal FSH levels are traditionally considered by clinicians to have the diagnosis of "premature ovarian failure" (POF). In fact, however, the ovarian function in this disorder is in reality a ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1196/annals.1429.019
更新日期：2008-01-01 00:00:00
abstract：:Researchers in Utrecht, the Netherlands have studied the effects of different factors, such as oral contraceptives (OCs), on sex hormone binding globulin (SHBG) levels in blood. The SHBG levels in women who continuously used OCs consisting only of .05 mg of ethinyl estradiol (EE2) rose as high as 260% + or - 25% of t...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.1988.tb48872.x
更新日期：1988-01-01 00:00:00
abstract：:We have presented a perspective of progress in three areas of simulations of complex molecules: the development of force fields for molecular simulation; the application of computer graphics, molecular mechanics and molecular dynamics in simulations of DNA and DNA-drug complexes and the application of computer graphic...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1986.tb20954.x
更新日期：1986-01-01 00:00:00
abstract：:One hundred years after Santiago Ramon y Cajal provided critical evidence for the "neuron doctrine," his cellular view of the brain remains the basis of modern neural science. This article begins with a review of how the early work of Ramon y Cajal, Charles Sherrington, and John Eccles and their contemporaries laid ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.2001.tb05704.x
更新日期：2001-04-01 00:00:00
abstract：:Adolescence and emerging adulthood form a critical time period for the achievement of optimal health and nutrition across all stages of the life course. We undertook a review of published literature and global data repositories for information on nutrition levels, trends, and patterns among young people aged 10-24 yea...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,meta分析,评审
doi：10.1111/nyas.13336
更新日期：2017-04-01 00:00:00
abstract：:Four weeks immobilization of the right leg of aged rats (26 months old) caused a marked 31% and 27% reduction of muscle mass of the plantaris and soleus muscles, respectively. In animals treated with 0.6 mg/kg body weight of growth hormone (GH), the reduction of weight of the above muscles was only 14.7 and 16.1%, res...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1996.tb39082.x
更新日期：1996-06-15 00:00:00
abstract：:The observations described herein allow us to make several inferences about PKC and regulation of normal and CF Cl- channels. FIGURE 5 shows a model that summarizes these observations. In this model, for the sake of clarity, we refer to the channel as a single entity, but note that it may consist of multiple subunits ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1989.tb25131.x
更新日期：1989-01-01 00:00:00
abstract：:Atherosclerotic coronary heart disease and other forms of cardiovascular disease (CVD) are the major cause of mortality in type II diabetes (T2DM) as well as a major contributor to morbidity and lifetime costs. The purpose of this article is the identification of the biochemical parameters in plasma, which may serve a...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1196/annals.1372.001
更新日期：2006-11-01 00:00:00
abstract：:B lymphocytes contribute to the pathogenesis of autoimmune disorders since B-cell depletion treatment improves such diseases. However, B cells seem ambivalent. Murine strains of nonorgan-specific as well as organ-specific autoimmune conditions present with aggravated symptoms when B cells are depleted. It is thus like...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2009.04651.x
更新日期：2009-09-01 00:00:00
abstract：:The expression levels of GAP-43 and MAP-2, two proteins involved, respectively, in axonal and dendritic remodeling, in control adult (11 months), old (24 months), and vitamin E-deficient (11 months) rats were evaluated. mRNA levels were determined by means of a quantitative in situ hybridization procedure in subregion...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1196/annals.1297.008
更新日期：2004-06-01 00:00:00
abstract：:The effects of TCDD exposure on the developing immune system were investigated in Wistar/Fischer hybrid or Fischer rats. Fetal and neonatal rats were exposed to TCDD through maternal dosing (5 muk/kg) on day 18 of gestation and on days 0, 7, and 14 of postnatal life (group 1). Another group of neonatal rats was expose...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1979.tb56628.x
更新日期：1979-05-31 00:00:00
abstract：:Posttraumatic stress disorder (PTSD) is typically accompanied by both acute and chronic alterations in the stress response. These alterations have mostly been described in individuals under baseline conditions, but studies have also used a challenge model to assess the role of the hypothalamic-pituitary-adrenal (HPA) ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,随机对照试验
doi：10.1196/annals.1364.014
更新日期：2006-07-01 00:00:00
abstract：:In this chapter we examine whether rapists are sexually aroused by coercive, nonconsensual sex. This question is theoretically important because it speaks to a potential sexual motivation underlying rape. It is also clinically important in that it may reveal an important assessment and treatment target. We first revis...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2003.tb07307.x
更新日期：2003-06-01 00:00:00
abstract：:Constitutively active GPCR have revealed novel properties of drugs that exhibit classical competitive antagonism at the native forms of GPCR. These drugs reverse basal levels of constitutive activity, indicating that they have inverse agonist activity. We were interested in determining if competitive antagonists of th...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1998.tb10184.x
更新日期：1998-12-15 00:00:00
abstract：:The recovery of Nicotiana tabacum L. cv. Bright Yellow 2 (BY-2) cells in Linsmaire and Skoog medium after treatment at high hydrostatic pressure was investigated using an Evans Blue staining method to discriminate live from dead cells. The survival of BY-2 cells just after the high-pressure treatment at 5 degrees C an...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2009.05185.x
更新日期：2010-02-01 00:00:00
abstract：:Eight children with congenital adrenal hyperplasia and late initiation of corticosteroid treatment are included in the present study. Four of them received LHRHa treatment for the arrest of central precocious puberty, while the other four served as controls. The administration of LHRHa was effective in arresting the m...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1993.tb43873.x
更新日期：1993-05-28 00:00:00
abstract：:Microcinematography was applied to the analysis of the kinetics of apoptotic cell death. Apoptosis was found to be a process that proceeds in different cells at different times after an initial stress, and therefore kinetic studies of apoptotic events in bulk cultures can be problematic. Using single cell analysis we ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2000.tb05607.x
更新日期：2000-01-01 00:00:00
abstract：:A survey of rodents and hematophagous flies was conducted on three farms located in an area endemic for vesicular stomatitis to determine the species composition of each zoological group occurring in these areas. Eleven species of small rodents were collected and identified. Individuals from forty-nine species of hema...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2000.tb05325.x
更新日期：2000-01-01 00:00:00
abstract：:The influence of either short-term fasting or vitamin E administration on insulin action was studied in two groups of obese Type 2 diabetic patients. Twelve patients underwent 7 days of fasting (group A), whereas 600 mg of vitamin E was administered daily during 3 months in 9 diabetic patients (group B). Insulin actio...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1997.tb51870.x
更新日期：1997-09-20 00:00:00
abstract：:Based on the relation found to exist between low CSF 5-HIAA and suicide attempt, in particular violent suicide attempt, both in depressed and in so-called nondepressed suicide attempters, the conclusion was drawn that decreased central 5-HT metabolism is related to (auto)aggression, rather than to depression. We chall...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1986.tb27895.x
更新日期：1986-01-01 00:00:00
abstract：:Pentazocine and cyclazocine are two benzomorphans that were synthesized by the late Sydney Archer in 1962. These benzomorphans were synthesized as part of an effort to develop analgesics with little or no abuse potential. Pentazocine is used as an analgesic, often in individuals who have sever pain or in those who hav...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2000.tb06672.x
更新日期：2000-01-01 00:00:00
abstract：:The molecular archaeology of the mutation spectra of tumor suppressor genes generates hypotheses concerning the etiology and molecular pathogenesis of human cancer. The spectrum of somatic mutations in the p53 gene implicates environmental carcinogens and both endogenous agents and processes in the etiology of human c...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2000.tb06870.x
更新日期：2000-01-01 00:00:00
abstract：:Teaching primary care is an important, but as yet, incompletely fulfilled responsibility of medical schools. The current surge of interest will not provide the needed personnel if primary care is defined too broadly, and if it is made everybody's business, but nobody's in particular. Primary care must not neglect firs...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1978.tb22078.x
更新日期：1978-06-21 00:00:00
abstract：:Tight junctions (TJs) regulate paracellular barriers and claudins (Cld) form the backbone of TJ strands. To elucidate the molecular mechanism of claudin polymer formation, TJs were reconstituted by claudin transfection of TJ-free HEK293 cells. Therewith, typical TJ stands can be found at cell-cell contacts. In additio...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2012.06546.x
更新日期：2012-06-01 00:00:00
