Biomedical subjects

Yong Ben

Publications and source records attributed to Yong Ben.

7 recordsLinked to original sources

PubMed2006

[Abscopal effect on metastatic tumor induced by oncolytic virus of H101 combining with local heating].

BACKGROUND & OBJECTIVE: The abscopal effect on the tumors is a distant antitumor activity induced by local treatments. The study was to observe the induction of abscopal effect by the combination of H101 oncolytic virotherapy with local heating. METHODS: Five patients with histologically confirmed, surgically unresectable metastatic malignant tumors (2 nasopharyngeal carcinomas, 1 pulmonary carcinoma, 1 parosteal sarcoma and 1 bladder carcinoma) that had definitely failed to the conventional chemotherapy and radiotherapy or refused these therapies were enrolled in this experimental therapy. All patients were treated with local intra tumor injection of H101 (5x10(11) - 15x10(11) VP) combined with 60-min heating at 42 degrees C. RESULTS: Two patients were cured with complete regressions of both injected and non-injected tumors and have survived for a long period up to date. Three patients responded to the novel therapy variously and eventually died from the disease, who survived 29, 15 and 13 months, respectively. CONCLUSION: The abscopal antitumor effect could be induced by the combination of H101 local intratumoral injection with heating.

Adenocarcinoma↗

PubMed2004

Tolerance develops in spinal cord, but not in brain with chronic [Dmt1]DALDA treatment.

Previously, we reported that H-2',6'-dimethyltyrosine [Dmt(1)]-d-Arg-Phe-Lys-NH(2) (DALDA), an analogue of the naturally occurring opioid peptide dermorphin, is a highly potent and selective mu receptor agonist with low cross-tolerance to morphine. In the present study, we investigated the effect of treating mice chronically with [Dmt(1)]DALDA. The AD(50) of [Dmt(1)]DALDA (s.c.) increased eight-fold in animals given this drug chronically; in contrast, the AD(50) increased two-fold in mice chronically treated with morphine. The AD(50) of morphine (s.c.) in these [Dmt(1)]DALDA-treated animals was increased more than 120 times, while that of the more selective mu agonist [d-Ala(2)-MePhe(4)-Gly-ol(5)]enkephalin (DAMGO) given intrathecally was increased more than 240 times. However, the AD(50) of DAMGO given intracerebroventricularly was essentially the same in animals treated chronically with [Dmt(1)]DALDA as in naive animals. The dose of naloxone required to precipitate withdrawal in [Dmt(1)]DALDA-treated animals was 20 times lower than that in morphine-tolerant animals. Using real-time quantitative PCR, we found that expression of the mu opioid receptor, delta opioid receptor, preproenkephalin and preprodynorphin genes was upregulated in the brain by [Dmt(1)]DALDA treatment. No significant changes in expression of opioid receptor or opioid peptide genes were detected in the spinal cord of [Dmt(1)]DALDA-treated mice, nor in the brain or spinal cord of morphine-treated mice. We conclude that a high degree of tolerance to [Dmt(1)]DALDA develops in the spinal cord but not brain, and cannot be accounted for by changes in expression of opioid receptors or opioid peptides in these tissues.

Animals↗

PubMed2004

A molecular 'signature' of primary breast cancer cultures; patterns resembling tumor tissue.

BACKGROUND: To identify the spectrum of malignant attributes maintained outside the host environment, we have compared global gene expression in primary breast tumors and matched short-term epithelial cultures. RESULTS: In contrast to immortal cell lines, a characteristic 'limited proliferation' phenotype was observed, which included over expressed genes associated with the TGFbeta signal transduction pathway, such as SPARC, LOXL1, RUNX1, and DAPK1. Underlying this profile was the conspicuous absence of hTERT expression and telomerase activity, a significant increase in TbetaRII, its cognate ligand, and the CDK inhibitor, p21CIP1/WAF1. Concurrently, tumor tissue and primary cultures displayed low transcript levels of proliferation-related genes, such as, TOP2A, ANKT, RAD51, UBE2C, CENPA, RRM2, and PLK. CONCLUSIONS: Our data demonstrate that commonly used immortal cell lines do not reflect some aspects of tumor biology as closely as primary tumor cell cultures. The gene expression profile of malignant tissue, which is uniquely retained by cells cultured on solid substrates, could facilitate the development and testing of novel molecular targets for breast cancer.

Breast↗

PubMed2004

Aberrations of breast cancer susceptibility genes occur early in sporadic breast tumors and in acquisition of breast epithelial immortalization.

In the search for early deletion targets in sporadic breast cancer, the analysis of TP53, BRCA1, BRCA2, and ATM revealed loss of heterozygosity (LOH) in tumor cells at 1 or more genes in 18 of 24 cases examined. Notably, in more than 60% of such tumors, LOH was detectable in morphologically normal terminal ductal lobular units (TDLUs) adjacent to carcinoma (LOHint). At BRCA2 and ATM, LOHint was most frequent, particularly in TDLUs of women <or= 50 years old (7 of 10). In a novel preneoplastic model system, declining expression levels observed with increasing passage in culture supported the postulate that during the acquisition of continuous growth, elimination of these genes at an early stage confers a distinct selective advantage. The intimate role of these genes in DNA repair and their early deletion has implications for the possible transforming effects of DNA-damaging agents on unexcised breast tissue harboring LOHint within breast cancer patients.

Adult↗

PubMed2004

Temporal gene expression patterns in G93A/SOD1 mouse.

Amyotrophic lateral sclerosis (ALS) is a generally fatal degenerative disorder of motor neurons that has no known cure. Many pathological processes have been implicated. However, the early, initiating events in the disease are poorly understood. We performed multivariate analyses of gene expression of 21 selected genes from categories including glutamate neurotoxicity, oxidative stress, neuroinflammation, aberrant metal ion regulation, apoptosis, and abnormal microglial function on G93A SOD1 mice. These animals develop symptoms of motor neuron dysfunction at about 12 weeks of age, and die at age 18 to 20 weeks. We analyzed animals at both presymptomatic and symptomatic stages. Differential regulation of several genes involved in neuroinflammation, including TNF-alpha, IL- RA, CD86, CD200R and Groalpha, was observed in presymptomatic mice, aged 6-9 weeks, while expression of genes representative of other processes was not altered until the animals reached symptomatic stages. Analysis of expression of inflammatory genes and microglia related genes together also revealed a highly significant change in mutant mice relative to wildtype at 6-9 weeks. These changes were due to the presence of the mutant gene, and not simply to overexpression of a SOD1 gene. These findings are discussed in relation to possible roles of microglia function in the development of ALS.

Age Factors↗

PubMed2002

Morphine tolerance in spinal cord is due to interaction between mu- and delta-receptors.

When the opioid agonist morphine is given chronically and systemically to mice by pellet implantation for 3 days, the animals develop substantial tolerance to the antinociceptive effect of a test dose of morphine given systemically. When the test dose is administered to the spinal cord, however, very little tolerance is observed. We tested six strains of mice differing in the degree to which they develop systemic tolerance to morphine and found that none of them developed significant tolerance to spinal morphine. However, most of these strains did develop substantial spinal tolerance to antinociception induced by the selective mu-agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) and by the selective delta-agonist [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE). Moreover, in naïve animals, the antinociceptive effect of both DAMGO and DPDPE was blocked by D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2), a selective mu-antagonist, indicating that both agonists mediate antinociception in the spinal cord through mu-receptors. In addition to directly mediating antinociception, however, DPDPE potentiated the antinociceptive activity of DAMGO in the spinal cord of naïve animals, and this antinociception was blocked by the delta-antagonist H-TyrTicPsi[CH(2)NH]Phe-Thr-OH (TIPPpsi), indicating mediation through delta-receptors. In contrast, in tolerant animals, TIPPpsi enhanced the antinociception of DAMGO. These results thus demonstrate not only that mu- and delta-opioid receptors interact in naïve animals, but that the nature of this interaction changes during tolerance, from a potentiation to an inhibition. The lack of tolerance to spinal morphine may result from the ability of morphine to act as a partial antagonist at delta-receptors.

Analgesics, Opioid↗

PubMed2002

[Dmt(1)]DALDA is highly selective and potent at mu opioid receptors, but is not cross-tolerant with systemic morphine.

The clinical effectiveness of morphine is limited by several side effects, including the development of tolerance and dependence. Most of these side effects are believed to be mediated by central opioid receptors; therefore, hydrophilic opioids, which don't cross the blood-brain barrier, may have advantages over morphine in some clinical applications. We recently synthesized several analogues of DALDA (Tyr-D-Arg-Phe-Lys-NH2), a highly hydrophilic peptide derived from the endogenous opioid peptide dermorphin; all of them, particularly [Dmt(1)] DALDA (Dmt - 2',6'-dimethyl tyrosine), had high potency and selectivity at mu receptors, the target of morphine, in activity assays. Here we report the pharmacological characterization of [Dmt(1)] DALDA in the whole animal. [Dmt(1)]DALDA was 40 times more potent than morphine in inducing antinociception in mice when both drugs were given s.c., and 6-14 times more potent than DAMGO, a selective m agonist, when both drugs were given it. However, [Dmt(1)]DALDA showed poor cross-tolerance to morphine; thus chronic morphine treatment of animals increased the antinociceptive AD(50) of systemic [Dmt(1)]DALDA two fold or less, as compared to an 8-9-fold increase for morphine and a 4-5-fold increase for DAMGO. The antinociceptive activity of [Dmt(1)]DALDA (i.t) was blocked by CTAP, a selective mu antagonist, but not by TIPP psi, a selective delta antagonist, nor by nor-BNI, a selective kappa antagonist. [Dmt(1)]DALDA-induced antinociception was also blocked by naloxone methiodide, an antagonist that does not cross the blood-brain barrier, when agonist and antagonist were given i.t. or i.c.v., but not when they were given s.c. We conclude that [Dmt(1)] DALDA is a highly potent analgesic acting at mu receptors. Though it appears to penetrate the blood-brain barrier, it exhibits low cross-tolerance to morphine, suggesting that it may have advantages over the latter in certain clinical applications.

Analgesics, Opioid↗