Biomedical subjects

Ke Liu

Publications and source records attributed to Ke Liu.

62 records · Page 4Linked to original sources

PubMed2003

Breakthroughs in cancer gene therapy.

OBJECTIVES: To give oncology nurses an overview on the vectors and selected approaches used in the current clinical trials involving gene transfer to cancer patients. DATA SOURCES: Peer-reviewed scientific papers, review articles, and book chapters. CONCLUSION: Significant progress has been made in the field of cancer gene therapy. Different phases of clinical protocols derived from new generations of vectors and novel approaches are being tested for use in the treatment of patients with cancer. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses need to be familiar with current advances in the field of cancer gene therapy to expand their role as health care professional, patient educator, and advocate for the treatment of patients with cancer.

Clinical Trials as Topic↗

PubMed2003

A despecialization step underlying evolution of a family of serine proteases.

In the trypsin superfamily of serine proteases, non-trypsin-like primary specificities have arisen in only two monophyletic descendent subbranches. We have recreated an ancestor to one of these subbranches (granzyme) using phylogenetic inference, gene synthesis, and protein expression. This ancestor has two unusual properties. First, it has broad primary specificity encompassing the entire repertoire of novel primary specificities found in its descendents. Second, unlike extant members that have narrow primary specificities, the ancestor exhibits tolerance to mutational changes in primary specificity-conferring residues-that is, structural plasticity. Molecular modeling and mutagenesis studies indicate that these unusual properties are due to a particularly wide substrate binding pocket. These two crucial properties of the ancestor not only distinguish it from its extant descendents but also from the trypsin-like proteases that preceded it. This indicates that a despecialization step, characterized by broad specificity and structural plasticity, underlies evolution of new primary specificities in this protease superfamily.

Amino Acid Sequence↗

PubMed2003

Neuroprotective effects of hydroxysafflor yellow A: in vivo and in vitro studies.

Previous work has shown that hydroxysafflor yellow A (HSYA), extracted from Carthamus tinctorius L. markedly extended the coagulation time in mice and exhibited a significant antithrombotic effect in rats. The present study was conducted to demonstrate further its neuroprotective effects on cerebral ischemic injury in both in vivo and in vitro studies. In vivo, male Wistar-Kyoto (WKY) rats with middle cerebral artery occlusion (MCAO) were evaluated for neurological deficit scores followed by the treatment with a single dose of HSYA. Furthermore, the infarction area of the brain was assessed in the brain slices. In vitro, the effect of HSYA was tested in cultured fetal cortical cells exposed to glutamate and sodium cyanide (NaCN) to identify its neuroprotection against neurons damage. The results in vivo showed that sublingular vein injection of HSYA at doses of 3.0 mg/kg and 6.0 mg/kg exerted significant neuroprotective effects on rats with focal cerebral ischemic injury by significantly decreasing neurological deficit scores and reducing the infarct area compared with the saline group, HSYA at a dose of 6.0 mg/kg showed a similar potency as nimodipine at a dose of 0.2 mg/kg. Sublingular vein injection of HSYA at the dose of 1.5 mg/kg showed a neuroprotective effect, however, with no significant difference when compared with the saline group. Results in vitro showed that HSYA significantly inhibited neuron damage induced by exposure to glutamate and sodium cyanide (NaCN) in cultured fetal cortical cells. Noticeably, the neuroprotective action of HSYA on glutamate-mediated neuron injury was much better than that of HSYA on NaCN-induced neuron damage. All these findings suggest that HSYA might act as a potential neuroprotective agent useful in the treatment in focal cerebral ischemia. Abbreviations. HSYA:hydroxysafflor yellow A TTC:2,3,5-triphenyltetrazolium chloride MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide DMEM:Dulbecco's modified Eagle medium FCS:Fetal calf serum MCAO:middle cerebral artery occlusion ECA:external carotid artery ICA:internal carotid artery LDH:lactate dehydrogenase NMDA: N-methyl- D-aspartate

Animals↗

PubMed2003

[Clinical analysis of 22 cases of Bartholin gland cyst or abscess treated with trocar puncture].

This study was designed to observe the effects of trocar puncture in the treatment of Bartholin gland cyst or abscess. The cure rate of these 22 cases was 100%, and no relapse of the disease occurred during the follow-up lasting for 5 to 12 months. Trocar puncture proves to be effective in the treatment of bartholin gland cyst or abscess, especially when the size is less than 3.0 cm.

Abscess↗

PubMed2002

Synthesis, crystal structure, and ESR study of a novel phosphorylated lipophilic spin trap.

In this article, the synthesis of a novel alpha-phosphorus-containing spin trap DEPPEPO [2-(diethoxyphosphoryl)-2-phenethyl-3,4-dihydro-2H-pyrrole-1-oxide] and the evaluation of its ability to spin-trap radicals, especially superoxide and hydroxyl radicals, are described. Single crystal X-ray structure analysis reveals that there exist a lot of intramolecular nonbonded attractive interactions in the molecule. The phenethyl group is located away from the diethoxyphosphoryl group and the nitronyl plane, and only one face of the nitronyl plane is sterically hindered by the oxygen attached to the phosphorus with a double bond. The latter feature is responsible for the stereoselection of the free radical additions on the nitronyl moiety. The ability of DEPPEPO to trap the active superoxide anion radical generated in the HX/XO system and the stability of their spin adduct were investigated with that for DEPMPO. The half-life of DEPPEPO is about 13.4 min, and as a result, the DEPPEPO seems to be a promising lipophilic spin trap, perhaps in both in vitro and in vivo ESR investigation. Because DEPPEPO is a solid compound, it is quite easy to purify by recrystallization and to store the compound even at room temperature. In addition, an obvious increase in lipophilicity for DEPPEPO was found as a contribution of 2-substituted phenethyl.

Journal Article↗

PubMed2002

Delta tryptase is expressed in multiple human tissues, and a recombinant form has proteolytic activity.

Tryptases are neutral serine proteases selectively expressed in mast cells and have been implicated in the development of a number of inflammatory diseases including asthma. It has recently been established that the number of genes encoding human mast cell tryptases is much larger than originally believed, but it is not clear how many of these genes are expressed. A recent report suggested that the transcript for at least one of these genes, originally named mMCP-7-like tryptase, is not expressed. To further address this question, we screened tissue-specific RNA samples by RT-PCR, using primers designed to match the putative exonic sequence of this gene. We successfully generated and cloned the correctly sized RT-PCR product from mRNA isolated from the human mast cell-I cell line. Two distinct clones were identified whose nucleotide sequence matched the published sequence of the mMCP-7-like I and mMCP-7-like II genes. Transcripts were detected in a wide variety of human tissues including lung, heart, stomach, spleen, skin, and colon. A polyclonal antipeptide Ab that specifically recognizes the translated product of this transcript was used to demonstrate its expression in mast cells that reside in the colon, lung, and inflamed synovium. A recombinant form of this protein expressed in bacterial cells was able to cleave a synthetic trypsin-sensitive substrate, D-Ile-Phe-Lys pNA. These results suggest that the range of functional tryptases is larger than previously recognized. For simplicity, we suggest that the gene, transcripts, and corresponding protein product be named delta tryptase.

Adult↗

PubMed2002

Drs2p-dependent formation of exocytic clathrin-coated vesicles in vivo.

The small GTP binding protein ARF has been implicated in budding clathrin-coated vesicles (CCVs) from Golgi and endosomal membranes. An arf1 synthetic lethal screen identified DRS2/SWA3 along with a clathrin heavy-chain conditional allele (chc1-5/swa5-1) and SWA2, encoding the yeast auxilin-like protein involved in uncoating CCVs. Drs2p/Swa3p is a P-type ATPase and a potential aminophospholipid translocase that localizes to the trans-Golgi network (TGN) in yeast. Genetic and phenotypic analyses of drs2Delta mutants suggested that Drs2p was required for clathrin function. To address a potential role for Drs2p in CCV formation from the TGN in vivo, we have performed epistasis analyses between drs2 and mutations that cause accumulation of distinct populations of post-Golgi vesicles. We find that Drs2p is required to form a specific class of secretory vesicles that accumulate when the actin cytoskeleton is disrupted. Accumulation of these vesicles also requires clathrin and is perturbed by mutation of AP-1, but not AP-2, AP-3, or GGA adaptins. Most of the accumulated vesicles are uncoated; however, clathrin coats can be partially stabilized on these vesicles by deletion of SWA2. These data provide the first in vivo evidence for an integral membrane protein requirement in forming CCVs.

Adaptor Protein Complex 1↗

PubMedDate not supplied

Interleukin-2-independent proliferation of human melanoma-reactive T lymphocytes transduced with an exogenous IL-2 gene is stimulation dependent.

A major obstacle limiting the efficacy of adoptive T-cell transfer (adoptive immunotherapy) to treat patients with cancer is the short survival of the transferred cells. These in vitro activated T cells depend on the growth factor, interleukin (IL)-2, and may undergo apoptosis in vivo when they are transferred. The authors previously reported that the need for an exogenous source of IL-2 could be abrogated in vitro by retrovirally transducing antitumor T lymphocytes with an exogenous IL-2 gene. Here they report that this growth of IL-2 transductants depended on restimulation of the T-cell receptor complex and appeared to be regulated at the transcriptional level of the transduced IL-2 gene. The transduced IL-2 transcript was barely detectable in IL-2-transductants just before they died without restimulation, and they expressed a low level of the CD25 molecule, the alpha chain of the IL-2 trimeric receptor complex. Melanoma-specific tumor-infiltrating lymphocytes (either bulk or CD8+ cells alone), when transduced with an IL-2 retroviral vector, could produce IL-2 upon tumor stimulation and proliferated after the destruction of autologous tumor cells in the absence of added IL-2. Control vector-transduced tumor-infiltrating lymphocytes failed to do so under the same conditions. These findings provide a foundation for the development of clinical efforts to adoptively transfer melanoma-specific tumor-infiltrating lymphocytes transduced with an IL-2 retroviral vector for the treatment of patients with metastatic melanoma to evaluate the fate and therapeutic effect of these IL-2 gene-modified antitumor T lymphocytes in vivo.

Genetic Therapy↗