Biomedical subjects

Y N Chen

Publications and source records attributed to Y N Chen.

At least 37 records · Page 2Linked to original sources

PubMed1997

Ras-dependent apoptosis correlates with persistent activation of stress-activated protein kinases and induction of isoform(s) of Bcl-x.

Ras proteins are signal transducers for many cellular responses. However, it is not well established whether Ras-signaling also contributes to apoptosis. We have constructed H-RasR12-transformed Rat1 fibroblasts using tetracycline operator/repressor (TetO/TetR)-based conditional vectors. Rat1/TetO-RasR12 (Rat1-Ras) cells produced high levels of H-RasR12 protein and exhibited oncogenic transformation. Treatment of Rat1-Ras cells with 0.1% serum triggered massive apoptosis. Rat1-Ras cells expressed increased basal activities of extracellular response kinase (ERK) and p46/p54 stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Interestingly, Ras-dependent apoptosis correlated with further persistent activation of both p46 and p54 SAPK/JNK and concurrent inhibition of ERK. Differential modulation of SAPK/JNK and ERK was not detected in tetracycline-treated cells that did not commit apoptosis. Furthermore, two Bcl-x related proteins of 15 kDa and 18 kDa were highly induced in apoptotic Rat1-Ras cells. Our results establish a direct role for Ras in apoptosis, and suggest a functional relationship between H-Ras, SAPK/JNK, ERK and Bcl-x in regulating apoptosis.

Journal Article↗

PubMed1997

Regulation of Myc-dependent apoptosis by p53, c-Jun N-terminal kinases/stress-activated protein kinases, and Mdm-2.

Deregulated overexpression of c-Myc (Myc) confers susceptibility to apoptosis in several cell types, but the molecular regulation of these processes has not been well established. Here we have characterized several molecular changes that may modulate Myc-dependent apoptosis. Ectopic overexpression of Myc in both Rat1 fibroblasts and human osteosarcoma cells causes a dramatic increase of cellular p53 mRNA and protein, and this induction of p53 correlates with apoptosis triggered by withdrawal of serum. Stable transfection of a wild-type human p53 gene into Myc-transformed cells further potentiates apoptosis. Anticancer agents vinblastine and nocodazole also induce apoptosis in Myc-transformed Rat1 fibroblasts but are cytostatic to the same cells without Myc overexpression. We demonstrate that induction of Myc-dependent apoptosis in these cells is specifically associated with an activation of p46 c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activity, whereas this JNK/SAPK activation is absent in stress-treated cells without Myc overexpression. Moreover, overexpression of the Mdm-2 gene in Rat1-myc cells significantly inhibits apoptosis induced by low serum but has little effect on apoptosis triggered by chemotherapeutic drugs. Interestingly, differential inhibition by Mdm-2 paralleled differential activation of p46 JNK/SAPK. Thus, our data support a functional involvement of p53 in Myc-dependent apoptosis and implicate potential regulatory roles for JNK/SAPK and Mdm-2 pathways in the regulation of apoptosis in Myc-transformed tumor cells.

Animals↗

PubMed1996

Interaction of interleukin-11 with cytotoxic therapies in vitro against CEM cells and in vivo against EMT-6 murine mammary carcinoma.

Interleukin-11(rhIL-11) is a cytokine that has been shown to enhance the recovery of bone marrow and intestinal crypt cells after cytotoxic insult with radiation or anticancer drugs. The current study examined the effects of rhIL-11 on the response of CEM human lymphoblastic leukemia cells and on the EMT-6 murine mammary carcinoma in vivo to cytotoxic anticancer therapies. Exposure of CEM cells to rhIL-11 for 24 hr did not alter the cytotoxicity of melphalan or radiation, increased the cytotoxicity of CDDP (100 muM) and 4-hydroperoxycyclophosphamide (50 betaM) and decreased the cytotoxicity of 5-fluorouracil and ara-C toward the cells. Treatment of mice bearing the EMT-6 tumor with rhIL-11 twice daily for 4 days prior to and the day of cytotoxic therapy resulted in no significant change in the tumor cell killing or bone marrow CFU-GM killing by melphalan, cyclophosphamide, thiotepa, CDDP, radiation, 5-fluorouracil or ara-C. Administration of rhIL-11 twice per day on days 7-18 to EMT-6 tumor bearing animals receiving high dose chemotherapy (melphalan, thiotepa or cyclophosphamide) as a single dose on day 7 followed by mobilized peripheral blood cells on day 8 and rhG-CSF on days 8-20, tended to prolong the tumor growth delay produced by the drugs. This rhIL-11 treatment also resulted in a more rapid recovery of white blood cells and granulocytes in the animals. Furthermore, animals treated with rhIL-11 had improved survival rates compared with animals receiving all other normal tissue support without rhIL-11.

Animals↗

PubMed1995

Smooth muscle relaxing and hypotensive activities of synthetic calciseptine and the homologous snake venom peptide FS2.

The biological activities of synthetic calciseptine and FS2, a homologous peptide from snake venom, were determined using in vitro and in vivo preparations. Calciseptine and FS2 produced dose-dependent relaxation in pre-constricted rat aorta, pulmonary artery and trachea. The onset and duration pattern of these relaxing effects were similar to those caused by nifedipine, an L-type Ca2+ channel blocker. Calciseptine relaxed the contraction of rat aorta provoked by an L-type channel agonist, Bay K 8644. This relaxation was not affected by NG-nitro-L-arginine, indomethacin or propranolol. Calciseptine and FS2 inhibited the contraction caused by acetylcholine in guinea pig ileal longitudinal muscle. In case of in vivo study using anesthetized rats, calciseptine, FS2 and nifedipine showed depressor effects. The hypotensive effects of the two peptides were more potent and sustained than that of nifedipine. These findings show that both synthetic calciseptine and FS2 have similar biological activities like nifedipine, an L-type Ca2+ channel blocker. In addition, these two peptides with large molecular weights may be unique and useful tools for studying the Ca2+ channel.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1994

NF-IL6, a member of the C/EBP family of transcription factors, binds and trans-activates the human MDR1 gene promoter.

Revealing the regulatory mechanisms involved in P-glycoprotein expression is important to our understanding of multidrug resistance (MDR) in tumor cells. The MDR1 gene encoding P-glycoprotein contained a promoter sequence (-157 to -125) that was found to be homologous with other mdr gene promoters and that specifically interacted with a nuclear protein. The nuclear protein was identified, using a HeLa lambda gt11 cDNA expression library, to be the transcriptional regulator nuclear factor for interleukin-6 (NF-IL6), a member of the C/EBP family of transcription factors that bound an NF-IL-6-like consensus element 5'-TTTCGCAGT-3'. Furthermore, a glutathione S-transferase fusion protein (10.1-glutathione S-transferase) containing the partial NF-IL6 cDNA was also found to specifically interact with the MDR1 promoter sequence. Co-transfection of an NF-IL6 expression vector with a chloramphenicol acetyltransferase reporter gene driven by 1018 base pairs of MDR1 5'-flanking sequences demonstrated that NF-IL6 trans-activated the MDR1 promoter. This trans-activation was significantly reduced when the NF-IL6 element in the reporter gene construct was deleted or mutated. Identification of NF-IL6 as an important transcriptional regulator and the implications of its potential role in MDR1 gene induction in response to a variety of stimuli are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

Potentiation of cytotoxic cancer therapies by TNP-470 alone and with other anti-angiogenic agents.

The ability of TNP-470, a synthetic analog of fumagillin which has been described as an anti-angiogenic agent, to potentiate cytotoxic cancer therapies was investigated in vivo in the murine FSaIIC fibrosarcoma and the Lewis lung carcinoma. TNP-470 was more toxic toward FSaIIC tumor cells from tumors treated in vivo than toward bone-marrow CFU-GM from the same animals. TNP-470 had a dose-modifying effect on the toxicity of cyclophosphamide toward FSaIIC tumor cells which amounted to an 8-fold increase in tumor-cell killing at a cyclophosphamide dose of 500 mg/kg. Treatment with TNP-470 and minocycline increased the permeability of the FSaII fibrosarcoma in vivo to the fluorescent dye Hoechst 33342 and increased the killing of both the bright and the dim tumor cells by cyclophosphamide. TNP-470, especially in combination with minocycline, formed a highly effective modulator combination for treatment of the Lewis lung carcinoma with cytotoxic cancer therapies against primary and metastatic disease. The combination of TNP-470/minocycline and cyclophosphamide led to 40 to 50% long-term survivors in Lewis-lung-carcinoma-bearing animals. Our results indicate that the use of anti-angiogenic modulators in cancer therapy is a very promising area for further study.

Animals↗

PubMed1994

CAI: effects on cytotoxic therapies in vitro and in vivo.

CAI (NSC 609974; L651582), a new agent that has demonstrated antimetastatic activity in vitro and in vivo, was not very cytotoxic toward EMT-6 mouse mammary carcinoma cells in culture or toward FSaIIC fibrosarcoma cells in vivo. Coexposure of EMT-6 cells to CAI and antitumor alkylating agents under various environmental conditions did not markedly increase the cytotoxicity of cisplatin (CDDP), melphalan, or carmustine (BCNU). However, the combination of CAI and 4-hydroperoxycyclophosphamide (4-HC) produced much greater than additive killing of EMT-6 cells. CAI also increased the sensitivity of hypoxic EMT-6 cells to X-rays. CAI increased the cytotoxicity of cyclophosphamide toward FSaIIC tumor cells when animals were treated with single doses of both drugs. The effect of CAI on tumor cell killing by cyclophosphamide was greatest at high doses of the antitumor alkylating agent. CAI administration appeared to result in increased serum levels of prostaglandin E2 and leukotriene B4 in animals bearing the Lewis lung tumor. Administration of CAI on days 4-18 did not alter the growth of the Lewis lung carcinoma but did result in an increase in the tumor-growth delay produced by treatment with CDDP, cyclophosphamide, melphalan, BCNU, and fractionated radiation. Although CAI did not reduce the number of lung metastases present in Lewis lung carcinoma-bearing mice on day 20, it did appear to reduce the number of large (vascularized) metastases present on that day.

Aminoimidazole Carboxamide↗

PubMed1993

Synthesis of omega-agatoxin IVA and its related peptides.

A potent and selective P type calcium channel blocker isolated from the venom of the funnel web spider Agelenopsis aperta, omega-agatoxin IVA, and its related peptides were synthesized by the solution procedure. Synthetic omega-agatoxin IVA was found to block high-threshold P-type calcium current in rat Purkinje neuron with the same potency as that reported for the natural product. Its disulfide structure was determined by amino acid analysis, gas-phase sequencing and mass spectrometry of the proteolytic fragments. The N-terminus biotinylated and truncated peptides showed the same disulfide-bond-forming profile and the same activities as those of omega-agatoxin IVA, indicating that the N-terminal basic tripeptide, Lys-Lys-Lys, is not important for both the folding and the expression of the biological activity. However, the Trp residue in the molecule might be essential for the toxin to bind tightly with the channel pores.

Amino Acid Sequence↗

PubMed1993

Synthesis and evaluation of the antitumor activity of 4,5-diamino-substituted 1,2-benzoquinones.

A series of 4,5-diamino-substituted-1,2-benzoquinones were prepared from catechol and the corresponding secondary amines in high yield in a single step using copper complex formation to stabilize the intermediate. The cytotoxicity of the products under various conditions was evaluated using the EMT-6 mammary carcinoma cell line, and antitumor activity was tested in the L1210 murine leukemia. The 4,5-diaziridinyl-1,2-benzoquinone was a more potent cytotoxic agent than diaziquone (AZQ) and was very effective against the L1210 leukemia. The azetidine, pyrrolidine, and diethylamine derivatives were not effective antitumor agents.

Animals↗

PubMed1993

beta-cyclodextrin tetradecasulfate/tetrahydrocortisol +/- minocycline as modulators of cancer therapies in vitro and in vivo against primary and metastatic Lewis lung carcinoma.

Tetrahydrocortisol, beta-cyclodextrin tetradecasulfate, and minocycline used alone or in combination are not very cytotoxic toward EMT-6 mouse mammary tumor cells growing in monolayer. Tetrahydrocortisol (100 microM, 24 h) and beta-cyclodextrin tetradecasulfate (100 microM, 24 h) protected EMT-6 cells from the cytotoxicity of CDDP, melphalan, 4-hydroperoxycyclophosphamide, BCNU, and X-rays under various conditions of oxygenation and pH. Minocycline (100 microM, 24 h) either had no effect upon or was additive with the antitumor alkylating agents or X-rays in cytotoxic activity toward the EMT-6 cells in culture. The combination of the three modulators either had no effect upon or was to a small degree protective against the cytotoxicity of the antitumor alkylating agents or X-rays. The Lewis lung carcinoma was chosen for primary tumor growth-delay studies and tumor lung-metastases studied. Tetrahydrocortisol and beta-cyclodextrin tetradecasulfate were given in a 1:1 molar ratio by continuous infusion over 14 days, and minocycline was given i.p. over 14 days, from day 4 to day 18 post tumor implantation. The combination of tetrahydrocortisol/beta-cyclodextrin tetradecasulfate diminished the tumor growth delay induced by CDDP and melphalan and produced modest increases in the tumor growth delay produced by cyclophosphamide and radiation. Minocycline co-treatment increased the tumor growth delay produced by CDDP, melphalan, radiation, bleomycin, and, especially cyclophosphamide, where 4 of 12 animals receiving minocycline (14 x 5 mg/kg, days 4-18) and cyclophosphamide (3 x 150 mg/kg, days 7, 9, 11) were long-term survivors. The 3 modulators given in combination produced further increases in tumor growth delay with all of the cytotoxic therapies, and 5 of 12 of the animals treated with the 3-modulator combination and cyclophosphamide were long-term survivors. Although neither tetrahydrocortisol/beta-cyclodextrin tetradecasulfate, minocycline, nor the three modulator combination impacted the number of lung metastases, there was a decrease in the number of large lung metastases. Treatment with the cytotoxic therapies alone reduced the number of lung metastases. Addition of the modulators to treatment with the cytotoxic therapies resulted in a further reduction in the number of lung metastases. These results indicate that agents that inhibit the breakdown of the extracellular matrix can be useful additions to the treatment of solid tumors.

Animals↗

PubMed1993

[Specific curative effects of nitrosourea drugs on tumor cells with Mer--phenotype in Chinese].

O6-Methylguanine DNA methyltransferase (O6-MT) activity and cellular sensitivity to nitrosourea drugs of 10 kinds of tumor cell strains derived from Chinese patients were measured by 3H radioactivity and colony-forming ability, respectively. The results in vitro showed that nimustine (Nim) 25 micrograms.ml-1 and carmustine (Car) 20 micrograms.ml-1 exhibited specific killing effects on Mer-phenotype tumor cells characterized by low O6-MT activity. In vivo both Nim and Car (25 mg.kg-1.wk-1 x 4 wk, ip) had specific curative ability to Mer- tumor cells implanted in nude mice. These findings suggested that assay of O6- MT activity in tumor biopsy could be used as a predictable guide to human tumor chemotherapy with nitrosourea compounds.

Animals↗

PubMed1992

The functional role of tyrosine-200 in human testis angiotensin-converting enzyme.

The active site of angiotensin-converting enzyme (ACE) has been shown by chemical modification to contain a critical tyrosine residue, identified as Tyr-200 in human testis ACE (hTACE). We have expressed a mutant hTACE containing a Tyr-200 to Phe mutation. The mutant exhibits a marked decrease in kcat: 15-fold and 7-fold for the hydrolysis of furanacryloyl-Phe-Gly-Gly and angiotensin I, respectively, whereas its Km increases by only 1.6- and 2.2-fold, respectively. We conclude that Tyr-200 is not required for substrate binding. Instead, the effect on kcat together with a 100-fold decrease in affinity for the ACE inhibitor lisinopril indicates that Tyr-200 may participate in catalysis by stabilizing the transition state complex. Thus, Tyr-200 in hTACE has a role analogous to that of Tyr-198 in carboxypeptidase A.

Amino Acid Sequence↗

PubMed1992

The unique N-terminal sequence of testis angiotensin-converting enzyme is heavily O-glycosylated and unessential for activity or stability.

The testis-specific isozyme of angiotensin-converting enzyme (ACE) is identical, from residue 68 to the C terminus, to the second half or C-terminal domain of somatic ACE. However, the first 67 residues, comprising the signal peptide and a Ser-/Thr-rich 36-residue sequence that constitutes the N terminus of mature testis ACE, are unique. We have expressed a mutant human testis ACE lacking this 36-residue N-terminal sequence and find that compared to the wild-type protein the mutant is 15 kDa smaller due to the loss of greater than 90% of all O-linked sugars, but that it retains full enzymatic activity and is stable in culture. Heavy O-glycosylation is a property of testis ACE that is not shared by the somatic enzyme and is attributable to this unique sequence.

Amino Acid Sequence↗

PubMed1992

Demonstration of a relationship between white blood cell count, insulin resistance, and several risk factors for coronary heart disease in women.

In order to evaluate the relationship between peripheral white blood cell (WBC) count, insulin-mediated glucose uptake, and several risk factors for coronary heart disease (CHD), WBC, plasma glucose and insulin responses to a 75-g oral glucose challenge, fasting plasma cholesterol, high-density-lipoprotein (HDL)-cholesterol, and triglyceride concentration, and systolic and diastolic blood pressure were determined in 63 consecutive female volunteers with normal glucose tolerance. The results demonstrated the presence of statistically significant correlation coefficients between WBC count and both insulin-mediated glucose disposal (r = 0.50, P less than 0.001) and insulin response to oral glucose (r = 0.50, P less than 0.001). Furthermore, WBC count correlated with plasma glucose response to oral glucose (r = 0.48, P less than 0.001), fasting plasma triglyceride (r = 0.37, P less than 0.005) and HDL-cholesterol concentrations (r = -0.38, P less than 0.005), and systolic (r = 0.22, P less than 0.1) and diastolic (r = 0.27, P less than 0.05) blood pressure. However, the only two variables significantly correlated with WBC count in multivariate regression analysis were insulin resistance (r = 0.49, P less than 0.01) and insulin response (r = 0.35, P less than 0.05). These data indicate that WBC count is significantly correlated with changes in carbohydrate and lipoprotein metabolism and blood pressure that increase the risk of CHD. However, it appears that these relationships are secondary to resistance to insulin-mediated glucose uptake and hyperinsulinaemia.

Adult↗

PubMed1992

[The use of thoracoscopy in the diagnosis and treatment of chest diseases].

The procedure and results of thoracoscopy by using a fiberoptic bronchoscope and rigid cold-light thoracoscope in 76 cases with chest diseases of unknown causes were reported. The positive diagnostic rate was 89.5% (68/76). The histologic diagnosis following thoracoscopic biopsy in 65 patients was compared with the findings at follow-up, the results showed the sensitivity being 87.7%, specificity 100% and diagnostic accuracy 89.2%. 3 cases with persistent or recurrent spontaneous pneumothorax were cured by Nd-YAG laser transendoscopically. 5 patients with malignant pleural effusion were treated with intrapleural talcum powder under thoracoscopic control, 4 of them obtained complete pleurodesis. There were only minor complications: transient fever in 40 cases and local subcutaneous emphysema in 7. It was concluded that thoracoscopy is simple, safe, reliable and practical in the diagnosis and treatment of chest diseases. It should be popularized clinically.

Adolescent↗

PubMed1991

P-glycoprotein expression and schedule dependence of adriamycin cytotoxicity in human colon carcinoma cell lines.

Four human colon cancer cell lines (SW620, LS 180, DLD-I, and HCT-15) and Adriamycin-resistant sub-lines with varying degrees of P-glycoprotein expression were studied to evaluate the reversibility of Adriamycin resistance in human colon cancer. Two groups of cell lines were studied. In the first, including a series of Adriamycin-resistant SW620 and DLD-I sub-lines, and in parental HCT-15 cells, P-glycoprotein has a major role in Adriamycin resistance, as evidenced by a correlation between Adriamycin resistance, expression of the multidrug-resistance gene mdr-I and its product, P-glycoprotein (Pgp), decreased drug accumulation and reversibility by verapamil. In these cell lines, increasing doses of verapamil are required to fully reverse increasing levels of resistance. In the second group, including parental SW620, DLD-I and LS 180 cells and Adriamycin-selected LS 180 sub-lines, P-glycoprotein does not have a major role in Adriamycin resistance. There was correlation between the schedule dependence of Adriamycin cytotoxicity and the role of P-glycoprotein in modulating resistance. In the cell lines in which P-glycoprotein was a major determinant of Adriamycin resistance, the drug exposure (defined as the product of the concentration and the time of treatment) needed to achieve a given percent cell kill was reduced as much as 9-fold when cells were treated for 7 days as compared with 3 hr. By comparison, in cell lines in which P-glycoprotein played a lesser role, the drug exposure necessary to achieve a given percent kill increased under conditions of continuous treatment. In some human colon carcinoma cell lines Pgp appears to play a significant role in resistance to Adriamycin, and this can be overcome by the use of competitive inhibitors of Pgp. The increased sensitivity with continuous treatment observed in cell lines with P-glycoprotein-mediated resistance suggests that administration of drugs by continuous infusion may be valuable in reversing clinical drug resistance mediated predominantly by P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1991

Spontaneous solubilization of membrane-bound human testis angiotensin-converting enzyme expressed in Chinese hamster ovary cells.

The testis isozyme of angiotensin-converting enzyme (ACE; EC 3.4.15.1) is a membrane-bound protein that, apart from the first 35 N-terminal residues, is identical to the C-terminal half of somatic ACE and contains the same putative C-terminal membrane anchor. Stable transfection of Chinese hamster ovary (CHO) cells with an expression vector containing the full-length human testis ACE cDNA results in the expression of two forms of recombinant human testis ACE (hTACE): membrane-bound ACE and, surprisingly, large quantities (up to 3 mg/liter) of soluble hTACE in the conditioned medium. Both forms are fully active and are physicochemically similar. However, by phase separation in Triton X-114, the soluble enzyme is hydrophilic, as is an anchor-minus mutant hTACE recovered from the medium of CHO cells transfected with a vector that contains a 3'-truncated testis ACE cDNA lacking the sequence encoding the membrane anchor. In contrast, the membrane-bound hTACE is amphipathic but is converted to a hydrophilic form on treatment with trypsin. The data establish that in ACE the hydrophobic sequence near the C terminus is necessary for membrane anchoring. Moreover, in CHO cells, membrane-bound hTACE is apparently solubilized by proteolytic cleavage of this anchor. A similar mechanism may account for the release of endothelial ACE in vivo to generate serum ACE and more generally for the constitutive processing and solubilization of analogously anchored proteins such as the amyloid precursor protein, among others. The release of membrane-bound ACE in CHO cells may, therefore, provide a useful system for the study of membrane-protein-solubilizing proteases.

Amino Acid Sequence↗

PubMed1991

Purification and characterization of recombinant human testis angiotensin-converting enzyme expressed in Chinese hamster ovary cells.

Enzymatically active human testis angiotensin-converting enzyme (ACE) was expressed in Chinese hamster ovary (CHO) cells stably transfected with each of three vectors: p omega-ACE contains a full-length testis ACE cDNA under the control of a retroviral promoter; and pLEN-ACEVII and pLEN-ACE6/5, in which full-length and membrane anchor-minus testis ACE cDNAs, respectively, are under the control of the human metallothionein IIA promoter and SV40 enhancer. In every case, active recombinant human testis ACE (hTACE) was secreted in a soluble form into the culture media, up to 2.4 mg/liter in the media of metal-induced, high-producing clones transfected with one of the pLEN vectors. In addition, membrane-bound recombinant enzyme was recovered from detergent extracts of cell pellets of CHO cells transfected with either p omega-ACE or pLEN-ACE-VII. Recombinant converting enzyme was purified to homogeneity by single-step affinity chromatography of conditioned media and detergent-extracted cell pellets in 85 and 70% overall yield, respectively. Purified hTACE from all sources comigrated with the native testis isozyme on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with M(r) approximately 100 kDa. The native and recombinant proteins cross-reacted equally with anti-human kidney ACE antiserum on Western blotting. The catalytic activity of recombinant angiotensin-converting enzyme, in terms of angiotensin I and 2-furanacryloyl-Phe-Gly-Gly hydrolysis, chloride activation, and lisinopril inhibition, was essentially identical to that of the native enzyme. The facile recovery in high yield of fully active hTACE from the media of stably transfected CHO cells provides a suitable system for investigating structure-function relationships in this enzyme.

Animals↗