Abstract:
:We performed a detailed and comprehensive study of the involvement of tumor suppressor genes in human prostate cancer. We utilized primers flanking either the restriction fragment length polymorphism (RFLP) or variable number of tandem repeat [VNTR; microsatellite or simple repeat site (SRS)] polymorphic sites to polymerase chain reaction (PCR) amplify the genomic DNA and detect loss of heterozygosity of the target genes. Quantitative reverse transcription (RT)-PCR was performed to measure the mRNA expression levels and PCR/single strand conformational polymorphism (SSCP) and DNA sequencing carried out to detect mutation of the tumor suppressor genes. We found that multiple tumor suppressor genes (e.g., p53, DCC, APC, MCC, BRCA1, and WAF1/CIP1) were inactivated at different frequencies via various mechanisms [e.g., loss of heterozygosity (LOH), loss of expression (LOE), mutation, and inactivation by cellular binding protein]. Several important and novel findings are as following: LOH and LOE of the DCC gene, LOH, LOE, and possible mutation of the APC/MCC genes, LOH of the BRCA1 locus, and mutation of the WAF1/CIP1 gene. For p53 tumor suppressor gene alone, multiple inactivation mechanisms (i.e., LOH, LOE, mutation, and amplification of the cellular inactivating protein MDM2) were identified. A possible involvement of genomic instability or mutator phenotype in human prostate cancer was investigated by microsatellite typing using PCR. A high frequency of microsatellite instability was detected and the microsatellite instability found to correlate with advanced stage and poor differentiation of prostate cancer, suggesting that genes functioning in DNA mismatch repair or general stabilization of the genome may be involved in prostate cancer. The results obtained in this study suggested that multiple tumor suppressor genes (both known and unknown genes) may share the role in prostate cancer; a pattern which has been found in a number of human malignancies such as cancers of the esophagus, colon and breast. In fact, we performed deletion studies aimed at localizing potential tumor suppressor loci on various chromosomal regions. A number of chromosomal regions (i.e., 6p12-24 and 17q21) were found to potentially harbor unidentified tumor suppressor genes. Detailed deletion mapping has localized the potential tumor suppressor loci to a < 2 Mb region centromeric to the BRCA1 gene on chromosome 17q. In addition, we identified a number of novel mechanisms of tumor suppressor gene inactivation, in prostate cancer such as loss of mRNA expression of the DCC, APC, MCC and p53 gene, and mutator phenotype. And for the very first time, we identified somatic mutations of the WAF1/CIP1 gene in primary human malignancy-human prostate cancer. This finding provides the first evidence in primary tumor that the WAF1/CIP1 gene may be a tumor suppressor gene and may be involved in prostate cancer. We identified 12-lipoxygenase (12-LOX) as a potential prognostic marker for human prostate cancer. mRNA expression levels of the 12-LOX gene was measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and semi-quantitative in situ hybridization (ISH) in 122 pairs of matched normal and tumor tissues from prostate cancer patients. We found that 12-LOX expression levels were elevated in approximately half of the patients analyzed and the 12-LOX elevation correlates with advanced stage, poor differentiation, and surgical margin positivity. Our data suggest that 12-LOX may serve as a correlative marker for a more aggressive phenotype of prostate cancer and therefore for poor prognosis. We are currently refining our assays for possible clinical applicability. Since not all patients with loss of expression of the DCC gene showed LOH of the DCC locus, there must be other mechanism(s) responsible for loss of expression of the DCC gene. When we analyzed the relationship between DCC loss of expression and 12-LOX elevation in prostate cancer pati
journal_name
Adv Exp Med Bioljournal_title
Advances in experimental medicine and biologyauthors
Gao X,Porter AT,Honn KVdoi
10.1007/978-1-4899-1813-0_7subject
Has Abstractpub_date
1997-01-01 00:00:00pages
41-53eissn
0065-2598issn
2214-8019journal_volume
407pub_type
杂志文章,评审abstract::Langerhans cells (LCs) are immune cells that reside in the stratified epithelium of the skin and mucosal membranes. They play a range of roles in the skin, including antigen presentation and maintenance of peripheral tolerance. Reports of LC numbers have been variable in different cancer types, with the majority of st...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-3-030-49270-0_8
更新日期:2020-01-01 00:00:00
abstract::Resistance to drugs is a major problem in cancer chemotherapy. Various cellular mechanisms of drug resistance have been identified in cultured tumor cell lines selected for growth in the presence of sublethal concentrations of various anticancer drugs. They involve drug transport and detoxification, qualitative or qua...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-0-387-39978-2_10
更新日期:2007-01-01 00:00:00
abstract::A difficult task for a novice modeler is beginning a modeling project. The methods described here delineate the modeling process step by step. Aristole is quoted as having said "One learns to play the flute by playing the flute," and the same principle holds somewhat for modeling. An excellent means for understanding ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4899-1959-5_2
更新日期:1998-01-01 00:00:00
abstract::Diagnosis of allergic conditions is based on skin prick- and/or intradermal tests and on serology. Both methods make use of allergenic preparations and the results mainly depend on the quality of the substances applied and on the reactivity of the subjects. Recombinant allergens can be produced as highly pure proteins...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4615-5855-2_15
更新日期:1996-01-01 00:00:00
abstract::The olfactory system throughout the animal kingdom is characterized by a large number of highly specialized neuronal cell types. Olfactory receptor neurons (ORNs) in the peripheral sensory epithelium display two main differentiation features: the selective expression of a single odorant receptor out of a large genomic...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-0-387-78261-4_6
更新日期:2008-01-01 00:00:00
abstract::An unknown, but significant subgroup (perhaps the majority), of patients who have undergone chemotherapy treatment for their cancer report a subsequent decline in cognitive performance (e.g., difficulty in balancing a checkbook; forgetting or mixing up names of friends or relatives, etc.). The condition has been terme...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:
更新日期:2010-01-01 00:00:00
abstract::Patient-derived human-induced pluripotent stem cells (iPSCs) have been critical in advancing our understanding of the underlying mechanisms of numerous retinal disorders. Many of these retinal disorders have no effective treatment and result in severe visual impairment and even blindness. Among the retinal degenerativ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-030-27378-1_91
更新日期:2019-01-01 00:00:00
abstract::The human platelet-activating factor receptor gene exists as a single copy on chromosome 1. Two 5'-noncoding exons (Exon 1 and 2) has distinct transcription initiation sites and promoters. These exons are alternatively spliced to a common splice acceptor site on exon 3 that contains a total coding regions. The transcr...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:
更新日期:1996-01-01 00:00:00
abstract::The cloning of the MEN1 gene in 1997 led to the characterization of menin, the protein behind the multiple endocrine neoplasia Type 1 syndrome. Menin, a novel nuclear protein with no homology to other gene products, is expressed ubiquitously. MEN1 missense mutations are dispersed along the coding region of the gene bu...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4419-1664-8_3
更新日期:2009-01-01 00:00:00
abstract::This review summarizes key aspects of what has been learned about the physiology of pancreatic islets and leptin deficiency from studies in obese ob/ob mice. ob/ob Mice lack functional leptin. They are grossly overweight and hyperphagic particularly at young ages and develop severe insulin resistance with hyperglycemi...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-90-481-3271-3_20
更新日期:2010-01-01 00:00:00
abstract::The de novo generation of hematopoietic stem and progenitor cells (HSPC) occurs solely during embryogenesis from a population of epithelial cells called hemogenic endothelium (HE). During midgestation HE cells in multiple intra- and extraembryonic vascular beds leave the vessel wall as they transition into HSPCs in a ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-981-10-3233-2_4
更新日期:2017-01-01 00:00:00
abstract::Model organisms are widely used in research that is ultimately aimed at understanding the causes and consequences of human disease. It may seem counterintuitive to expect clinically useful information to be obtained from species as diverse as fishes and insects, but because fundamental biological mechanisms share evol...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-62414-3_9
更新日期:2017-01-01 00:00:00
abstract::An overall view of the contractile process that has emerged from -temperature-studies on active muscle is outlined. In isometric muscle, a small rapid temperature-jump (T-jump) enhances an early, pre-phosphate release, step in the acto-myosin (crossbridge) ATPase cycle and induces a characteristic rise in force indica...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4419-6366-6_14
更新日期:2010-01-01 00:00:00
abstract::Acute leukaemia is the major subtype of paediatric cancer with a cumulative risk of 1 in 2000 for children up to the age of 15 years. Childhood acute lymphoblastic leukaemia (ALL) is a biologically and clinically diverse disease with distinctive subtypes; multiple chromosomal translocations exist within the subtypes a...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-981-10-3233-2_14
更新日期:2017-01-01 00:00:00
abstract::Cancer metabolism is a well-known target of cancer therapeutics. Classically, cancer metabolism has been studied in terms of the dependence of cancer cells on crucial metabolites, such as glucose and glutamine. But, the accumulating data show that iron metabolism in tumor microenvironment is also an important factor i...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-030-43093-1_3
更新日期:2020-01-01 00:00:00
abstract::Advances in the design of cochlear implants (CIs), as well as improved CI surgical techniques, have led to an increase in the number of patients who retain some residual low-frequency acoustic hearing in the implanted ear. Many of these patients also possess some hearing in the unimplanted ear. Although their low-freq...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4614-1590-9_28
更新日期:2013-01-01 00:00:00
abstract::Screening of chromogenic peptide substrates have shown that FXIIa readily splits substrates of D-Pro-Phe-Arg-pNA (S-2302) and -Gly-Arg-pNA (e.g. S-2222) types. The latter type is preferred in a system where kallikrein is present. By using the substrate S-2222 a method for the determination of beta FXIIa inhibitors has...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4757-0154-8_7
更新日期:1986-01-01 00:00:00
abstract::Taurine transport is important for volume regulation of cultured neurons and astroglial cells. Both cell types utilize similar mechanisms for taurine accumulation and efflux. However, taurine lost from cerebellar Purkinje cells in vivo is accumulated by adjacent astrocytes during hypoosmotic hyponatremia. To examine m...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/0-306-46838-7_23
更新日期:2000-01-01 00:00:00
abstract::Retinoids clearly show both prophylactic and therapeutic effects against many kinds of neoplasm. Vitamin A deficiency and vitamin A excess, which are very different states clinically and metabolically, should be separately considered relative to carcinogenesis. The anticancer effects of retinoids and related compounds...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4613-1835-4_28
更新日期:1986-01-01 00:00:00
abstract::During hematopoiesis, a variety of cells are generated from stem cells through successive rounds of cell fate determination processes. Studies in the last two decades have demonstrated the involvement of Runx transcription factor family members in differentiation of multiple types of hematopoietic cells. Along with ev...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-981-10-3233-2_24
更新日期:2017-01-01 00:00:00
abstract::The application of next generation sequencing technologies has opened the door to a new molecular epidemiology of tuberculosis, in which we can now look at transmission at a resolution not possible before. At the same time, new technical and analytical challenges have appeared, and we are still exploring the wider pot...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-64371-7_4
更新日期:2017-01-01 00:00:00
abstract::Feline infectious peritonitis (FIP) is caused by one of several strains of feline coronaviruses which are grouped into 2 general types of viruses. Infection of cats with FIP virus results in production of serum antibodies which may be protective in conjunction with cell mediated immunity, may provided no protection at...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4684-1280-2_72
更新日期:1987-01-01 00:00:00
abstract::The key purpose of phagocytosis is the destruction of pathogenic microorganisms. The phagocytes exert a wide array of killing mechanisms that allow mastering the vast majority of pathogens. One of these mechanisms consists in the production of reactive oxygen species inside the phagosome by a specific enzyme, the phag...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-030-40406-2_9
更新日期:2020-01-01 00:00:00
abstract::Plasma oxytocin (OT) levels are strongly correlated with inhibition of ingestion in many models of stimulated food and NaCl intake in rats, but peripheral administration of OT or OT antagonists has little or no effect on these behaviors. These findings led us to propose that central OT secretion from parvocellular neu...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:
更新日期:1995-01-01 00:00:00
abstract::Nerve conduction in myelinated axons is a fascinating subject due to the intricate structure and complex properties of the axon and its relation to the equally complex Schwann cells surrounding it. This chapter first deals with normal functional aspects of voltage-gated ion channels in the axon and Schwann cell membra...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-981-32-9636-7_7
更新日期:2019-01-01 00:00:00
abstract::The innate immune system senses pathogens largely through signals initiated by a collection of phylogenetically related proteins known as "Toll-like receptors" (TLRs), of which ten representatives are encoded in the human genome. The sensing role of the TLRs first came to light when one member of this family, TLR4, wa...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/0-387-24180-9_4
更新日期:2005-01-01 00:00:00
abstract::Assessment is a key element in education. Given its multiple methods, assessment contains the aspect of correctness and honesty from both the assessor and the assessed. These methods can be classified and their types are numerous, starting from single questions to tests and practical work. Concerning tests, their vast...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-3-319-56246-9_6
更新日期:2017-01-01 00:00:00
abstract::Single frog skeletal muscle fibres were stretched during fused tetanic contractions. The force increase during stretch exhibited a breakpoint at a mean critical length change of 16.6 nm per half sarcomere that was independent of stretch velocity and sarcomere length. The early decaying extra force after stretch (compo...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4684-4703-3_71
更新日期:1984-01-01 00:00:00
abstract::Alzheimer's disease, a type of dementia, affects memory, behavior, and cognitive processes in affected individuals. It is one of the prominent diseases, accounting for 60-80% of dementia cases and affecting a significant population of persons over the age of 65 years. While rare, Alzheimer's disease (AD) may affect th...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-96445-4_14
更新日期:2018-01-01 00:00:00
abstract::This review of the effects of hemidecortication in humans has been limited to studies of cognitive outcome published during the last 20 years. More directly than in the case of split-brain patients, the patients reviewed here attest to the remarkable ability of a single hemisphere, whether left or right, to support at...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4615-3420-4_8
更新日期:1992-01-01 00:00:00