Biomedical subjects

Z H Chen

Publications and source records attributed to Z H Chen.

At least 37 records · Page 2Linked to original sources

PubMed2000

[Studies of transgenic tobacco plants expressing beta-1,3-glucanase and chitinase genes and their potential for fungal resistance].

Plant bivalent expression vector pBLGC for basic tobacco beta-1, 3-glucanase and bean chitinase genes were constructed, and the tobacco tissue was transformed. Transgenic tobacco plants were carried out for analysis by PCR, PCR-Southern blot, Dot blot, Western blot, etc., and the results showed that some transgenic plants gave strong positive signal, it suggested that foreign genes have been integrated into tobacco genome, and expressed correctly. Fungal challenge with Alternaria alternata showed that transgenic plants were much more resistant to this pathogenic fungus.

Chitinases↗

PubMed2000

An immunohistochemical study of the compartmentation of metabolism during the development of grape (Vitis vinifera L.) berries.

The compartmentation of key processes in sugar, organic acid and amino acid metabolism was studied during the development of the flesh and seeds of grape (Vitis vinifera L.) berries. Antibodies specific for enzymes involved in sugar (cell wall and vacuolar invertases, pyrophosphate: fructose 6-phosphate phosphotransferase, aldolase, NADP-glyceraldehyde-P dehydrogenase, cytosolic fructose 1,6-bisphosphatase), photosynthesis (Rubisco, fructose 1,6-bisphosphatase, sedoheptulose 1,7-bisphosphatase), amino acid metabolism (cytosolic and mitochondrial aspartate aminotransferases, alanine aminotransferase, glutamate dehydrogenase, glutamine synthetase), organic acid metabolism (phosphoenolpyruvate carboxylase, NAD- and NADP-dependent malic enzyme, ascorbate peroxidase), and lipid metabolism (acetyl CoA carboxylase, isocitrate lyase) were used to determine how their abundance changed during development. There were marked changes in the abundance of many of these enzymes in both the flesh and seeds. The intercellular location of some enzymes was investigated using immunohistochemistry. Several enzymes (e.g. phosphoenolpyruvate carboxylase and those involved in amino acid metabolism) were associated with tissues likely to function in the transport of imported assimilates, such as the vasculature. Although other enzymes (e.g. NADP-malic enzyme and soluble acid invertase, involved in the metabolism of sugars and organic acids) were largely present in the parenchyma cells of the flesh, their distribution was extremely heterogeneous. This study shows that when considering the metabolism of complex structures such as fruit, it is essential to consider how metabolism is compartmentalized between and within different tissues, even when they are apparently structurally homogeneous.

Amino Acids↗

PubMed2000

[Studies on transgenic oilseed rape (Brassica napus) plants transformed with beta-1,3-glucanase and chitinase genes and its resistance to Sclerotinia sclerotiorium].

By Agrobacterium-mediated method, the cotyledonary petiole of good quality rape variety H165 was transformed with plant expression vector pBLGC which constitutively express beta-1,3-glucanase and chitinase genes. We obtained some Kanamycin(Kan)-resistant regenerational green shoots, with these shoots, PCR identification was conducted. Results showed that 30% green shoots which grew in medium of Kan 15 mg/L and 53% green shoots in Kan 25 mg/L had positive reaction. We also made dot blot analysis with those green shoots, some of them gave positive signal, indicating that the foreign genes had integrated into rape genome. Fungal challenge of these transgenic plants showed that some plants were much more resistant to Sclerotinia sclerotiorium than non-transgenic control plants.

Ascomycota↗

PubMed2000

[Meiosis-like reduction in the culture system for somatic embryogenesis of Arabidopsis thaliana].

The somatic meiosis-like reduction was observed in some cells in the embryogenic calli of Arabidopsis thaliana. One type was somatic chromosome reductional grouping, in which the chromosomes in a cell either separated into two groups, or separated into more than two groups at prophase or metaphase. The chromosomes separated directly, the morphology of the chromosomes did not show any role of the spindle fibers. Chromosome reductional grouping happened more frequently in polyploid cells. The other type was somatic meiossi which was analogous to that existed in the process of gametogenesis, and characterized by the pairing and synapsis of homologues chromosomes. In the embryogenic calli cultured on dedifferentiation medium, about 3% of the observed cells contained haploid number of chromosomes, while the tetrad cells occurred at a frequency of about 4%. The somatic meiosis-like reduction could result in the recombination of chromosomes in the cells generated by these processes. The roles of somatic meiosis-like reduction in the somatic embryogenesis and somaclonal variations were discussed.

Arabidopsis↗

PubMed2000

Triptolide: a potent inhibitor of NF-kappa B in T-lymphocytes.

AIM: To study the effect of triptolide on the activity of nuclear factor-kappa B (NF-kappa B) and gene expression of I kappa B alpha, a major inhibitor of NF-kappa B, in human Jurkat T cell line. METHODS: Jurkat cells treated with or without PMA/PHA were incubated with varied doses of triptolide for different time periods. The activity of NF-kappa B in Jurkat cells was measured with electrophoretic mobility shift assays (EMSA), and the mRNA expression of I kappa B alpha in Jurkat cells was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: PMA/PHA treatment was found to induce NF-kappa B activation rapidly. Triptolide treatment decreased the activity of NF-kappa B in both PMA/PHA treated and untreated Jurkat cells. This effect of triptolide was in a dose-dependent manner and was more obvious in cells treated with PMA/PHA. The mRNA expression of I kappa B alpha were upregulated by triptolide, while this effect was more potent in cells without PMA/PHA treatment. CONCLUSION: Triptolide is a potent inhibitor of NF-kappa B activation in T lymphocyte and this effect is partly due to the upregulation of I kappa B alpha mRNA expression.

DNA-Binding Proteins↗

PubMed1999

Modulation of Xenopus oocyte-expressed phospholemman-induced ion currents by co-expression of protein kinases.

Phospholemman (PLM), the major sarcolemmal substrate for phosphorylation by cAMP-dependent kinase (PKA) protein kinase C (PKC) and NIMA kinase in muscle, induces hyperpolarization-activated anion currents in Xenopus oocytes, most probably by enhancing endogenous oocyte currents. PLM peptides from the cytoplasmic tail are phosphorylated by PKA at S68, by NIMA kinase at S63, and by PKC at both S63 and S68. We have confirmed the phosphorylation sites in the intact protein, and we have investigated the role of phosphorylation in the regulatory activity of PLM using oocyte expression experiments. We found: (1) the cytoplasmic domain is not essential for inducing currents in oocytes; (2) co-expression of PKA increased the amplitude of oocyte currents and the amount of PLM in the oocyte membrane largely, but not exclusively, through phosphorylation of S68; (3) co-expression of PKA had no effect on a PLM mutant in which all putative phosphorylation sites had been inactivated by serine to alanine mutation (SSST 62, 63, 68, 69 AAAA); (4) co-expression of PKC had no effect in this system; (5) co-expression of NIMA kinase increased current amplitude and membrane protein level, but did not require PLM phosphorylation. These findings point to a role for phosphorylation in the function of PLM.

Amino Acid Sequence↗

PubMed1999

Glucose transporter (GLUT1) allele (XbaI-) associated with nephropathy in non-insulin-dependent diabetes mellitus.

BACKGROUND: Although multiple factors contribute to the initiation and progression of diabetic nephropathy (DN), hyperglycemia and genetic predisposition are two major components implicated in the development of DN. Several pieces of experimental evidence suggest that glucose transporter (GLUT1) activity is an important modulator for the cell hypertrophy and extracellular matrix formation of glomerular mesangial cells. METHODS: To evaluate the role of the GLUT1 gene mutation in the development of DN in Chinese patients with non-insulin-dependent diabetes mellitus (NIDDM), the polymorphic XbaI site of GLUT1 gene was analyzed by polymerase chain reaction in 124 normal subjects and 131 patients with NIDDM, among whom 64 were complicated with DN. DN was defined as persistent albuminuria with or without impaired renal function with no known cause of renal disease other than diabetes. RESULTS: The frequencies of XbaI (+/-) genotype (75 vs. 44%, P < 0.01) and XbaI (-) allele (44 vs. 29%, P < 0.05) were significantly higher in NIDDM patients with DN than those without nephropathy. There were no significant differences for GLUT1 genotype and allele frequency between NIDDM patients without nephropathy and normal subjects. The presence of the XbaI (-) allele appeared to have a strong association with the development of DN. The odds ratio was 1.915, and the 95% confidence interval was 1.044 to 3.514. In addition, no strong association was found between GLUT1 gene polymorphism and retinopathy in NIDDM patients. CONCLUSION: Our results indicate that the XbaI (-) allele of the GLUT1 gene might be a genetic marker of NIDDM with DN, and this genetic susceptibility is independent of its retinopathy in Chinese subjects.

Adult↗

PubMed1999

Effects of copper-aspirin complex on plasma 6-keto-prostaglandin F(1alpha) level and platelet cytosolic calcium in rabbits.

Effects of copper-aspirin complex on washed platelet aggregation, thromboxane B(2) formation and 6-ketoprostaglandin F(1alpha) level were monitored by Born's and Terashita's methods, respectively. The influence of copper-aspirin complex on cytosolic free calcium was examined using the fluorescent indicator, Fura 2-AM. Copper-aspirin complex significantly inhibited arachidonic acid-induced aggregation in washed platelets. The IC(50) value was 9.6 micromol L(-1). Copper-aspirin complex significantly decreased arachidonic acid-induced thromboxane B(2) formation by 87.1% in washed platelets. Ten mg kg(-1) of copper-aspirin complex given intragastrically markedly increased the plasma level of 6-keto-prostaglandin F(1alpha). Aspirin, however, reduced both thromboxane B(2) formation and 6-keto-prostaglandin F(1alpha) level. In the presence of CaCl2 1 mmol L(-1), copper-aspirin complex (20, 40 and 80 micromol L(-1)) markedly lowered arachidonic acid-induced increase in platelet calcium from the resting level (270+/-36 nmol L(-1)) to 213+/-14, 170+/-20 and 135+/-17 nmol L(-1), respectively. In the presence of ethylene glycol-bis (beta-aminoethyl ether) N,N,N',N'-tetraacetic acid 1 mmol L(-1), copper-aspirin complex (20, 40 and 80 micromol l L(-1)) significantly suppressed the release of intracellular calcium induced by arachidonic acid from 127+/-23 nmol L-1 to 108+/-17, 93+/-12 and 70+/-13 nmol L(-1).

Journal Article↗

PubMed1999

Effect of protopine on cytosolic Ca2+ in rabbit platelets.

AIM: To study the influence of protopine (Pro) on the cytoplasmic free Ca2+ concentration ([Ca2+]i) in rabbit platelets. METHODS: Measurement of [Ca2+]i of platelets in vitro by Fura 2-AM fluorescence technique. RESULTS: In the presence of CaCl2 1 mmol.L-1, Pro 10, 20, and 40 mumol.L-1 attenuated the rise in [Ca2+]i evoked by ADP from (420 +/- 57) to (320 +/- 26), (264 +/- 21), and (180 +/- 14) nmol.L-1, respectively, by arachidonic acid (AA) from (280 +/- 36) to (210 +/- 17), (184 +/- 21), and (143 +/- 16) nmol.L-1, respectively, and by platelet-activating factor (PAF) from (350 +/- 42) to (282 +/- 31), (223 +/- 30), and (165 +/- 15) nmol.L-1, respectively. In the presence of egtazic acid 1 mmol.L-1, Pro 10, 20, and 40 mumol.L-1 reduced the Ca2+ release induced by ADP, AA, and PAF, respectively. Pro 10, 20, and 40 mumol.L-1 also decreased ADP-, AA-, and PAF-induced Ca2+ influx. CONCLUSION: Pro inhibited not only Ca2+ release but also the influx of Ca2+.

Adenosine Diphosphate↗

PubMed1999

Ion currents through mutant phospholemman channel molecules.

Phospholemman (PLM), a small membrane protein with a single transmembrane domain, is a major substrate for protein kinases in muscle. In lipid bilayers, PLM forms ion channels with two unusual features--selectivity for the zwitterion taurine, and switching among cation- and anion-selective conformations. To investigate the molecular determinants of channel behavior, we measured ion currents through (1) PLM channels with point mutations in the extracellular and cytoplasmic domains, (2) chimeric PLM channels with the transmembrane domain of IsK, a K channel subunit, and (3) truncated PLM channels lacking the cytoplasmic domain. Truncated channels and those with a mutation at the cytoplasmic face had altered selectivity. Channels with a point mutation near the extracellular face were non-selective. Switching among channel conformations was less frequent in truncated channels and in channels with point mutations in either the extracellular or cytoplasmic domain. Chimeric channels with a different transmembrane domain had only a small reduction in conductance. We conclude that both the extracellular and cytoplasmic domains play roles in channel selectivity and conformational changes. Cation-binding sites appear to lie in the cytoplasmic domain, and an anion-binding site may reside in the extracellular domain. The cytoplasmic domain may function as a "ball and chain" to regulate channel selectivity.

Amino Acid Sequence↗

PubMed1999

[Microdissection of M chromosome in Vicia faba and its library construction].

Microdissection and microcloning technique was employed to construct the library of M chromosome in Vicia faba. The M chromosomes were microdissected with a micromanipulator and were put into a 0.5 ml Eppendorf tube, then digested with Sau3A. Sau3A linker adaptors were ligated to the end of chromosome DNA fragments, and two rounds of PCR were carried out with one chain of linker adaptor as the primer. The PCR products ranged in size from 300 base pair (bp) to 3000 bp with predominant fragments from 500 bp to 1500 bp. Southern hybridization analysis confirmed that PCR products originated from Vicia faba genome. The second round PCR products were cloned and about 102,000 recombinants were obtained. 118 recombinants were selected randomly for analysis. The inserts ranged in size from 150 bp to 3000 bp with an average of 690 bp. Dot blot was carried out for 100 clones with DIG labeled Vicia faba genome DNA as probes. The result revealed that 51% were low and unique copy sequences, 49% were repetitive sequences. M chromosome DNA library has not been reported before.

Chromosome Mapping↗

PubMed1998

A HU-like protein binds to specific sites within nod promoters of Rhizobium leguminosarum.

Nodulation genes (nod) of rhizobia are essential for establishment of its symbiosis with specific legume hosts and are usually located on the Sym(biosis) megaplasmid. In this work we identified a new Sym plasmid independent protein in Rhizobium leguminosarum, Px, by its ability to bind to nod promoters and induce DNA bending. Depending upon its concentrations relative to DNA templates, Px could either stimulate or inhibit in vitro transcription of the major regulatory nodulation gene nodD. This may result from its property to bind to specific sites within nod promoters at lower concentration or in the presence of competitor calf thymus DNA but nonspecifically associate with DNA at higher levels or in the absence of competitors. Its binding sites within nodD and nodF promoters were determined by DNase I footprinting but showed no sequence consensus. N-terminal sequencing and Western blot revealed that Px belongs to the HU class of prokaryotic histone-like proteins. Its binding feature and functioning mechanism were discussed in the light of this discovery.

Bacterial Proteins↗

PubMed1998

Effects of copper-aspirin complex on platelet aggregation and thrombosis in rabbits and mice.

The effects of intragastric and intraduodenal copper-aspirin complex on rabbit platelet aggregation were observed by Born's method. Myers's method was used to evaluate the antithrombotic effect of copper-aspirin complex in mice. In-vitro copper-aspirin complex selectively inhibited arachidonic acid-induced platelet aggregation with an IC50 value (concentration resulting in 50% inhibition) of 13.2 microM (95% confidence limits 9.1-16.8 microM). Copper-aspirin complex (10 mg kg(-1) given intragastrically or intraduodenally) was more potent than aspirin in inhibiting arachidonic acid-induced platelet aggregation. Copper-aspirin complex (10 mg kg(-1)) had a stronger inhibitory effect and a longer duration of action when given intragastrically than when given intraduodenally. It was shown by radioimmunoassay that copper-aspirin complex significantly reduced the level of thromboxane B2 in plasma while markedly increasing that of 6-ketoprostaglandin F1alpha (6keto-PGF1alpha). Copper-aspirin complex (10 mg kg(-1) given intragastrically for 7 days) significantly reduced mouse mortality caused by intravenous injection of arachidonic acid. The results suggest that both in-vitro and in-vivo copper-aspirin complex is more potent in selectively inhibiting arachidonic acid-induced platelet aggregation than aspirin. When given intragastrically the complex has a more potent antiplatelet effect and a longer duration of action than when given intraduodenally. The antithrombotic effect of the complex was more potent than that of aspirin.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

[Effects of 17 beta-estradiol on delayed rectifier potassium channels in hippocampal pyramidal neurons of the rat].

In the present study, both cell-attached and inside-out patch-clamp techniques were used to detect the effects of 17 beta-estradiol (E2) on 42 pS delayed rectifier potassium channels in acutely dissociated hippocampal neurons of new-born SD rats. The results indicated that after application of 1.0 and 10.0 nmol/L E2, the open probabilities of K+ channels were decreased from (67.4 +/- 18.2)% to (41.2 +/- 12.5)% and from (56.3 +/- 15.8)% to (13.2 +/- 12.6)% respectively, the open frequencies were reduced from (43.40 +/- 6.7) Hz to (27.68 +/- 9.1) Hz and from (38.19 +/- 10.1) Hz to (15.79 +/- 3.5) Hz respectively. Meanwhile, there was a shortening of the mean open time and a lenghtening of the mean close time of the channels. The above results suggest that E2 has suppressive effects on the activities of the channels, which might be exerted through a direct action on the cellular membrane.

Animals↗

PubMed1997

Cancer-preventive selenocompounds induce a specific redox modification of cysteine-rich regions in Ca(2+)-dependent isoenzymes of protein kinase C.

Since protein kinase C (PKC) serves as a receptor for phorbol ester type tumor promoters and oxidants and has unique redox-active cysteine-rich regions, we have determined whether various chemopreventive selenocompounds could affect this enzyme. At lower concentrations, selenite decreased the kinase activity (IC50 = 0.5 microM), while at higher concentrations it decreased phorbol ester binding. However, when the catalytic and regulatory domains of PKC were separated by proteolysis, the catalytic domain retained its sensitivity to selenite, while the regulatory domain lost its sensitivity. Cysteine residues were quantitated in PKC modified with selenite by using 5,5'-dithiobis(2-nitrobenzoic acid) and also by using 2-nitro-5-thiosulfobenzoic acid after sulfitolysis. At lower concentrations, selenite induced a modification of four cysteine residues resulting in the formation of two disulfides, while at higher concentrations it induced a modification of seven to eight cysteine residues resulting in the formation of three to four disulfides. Contrary to selenite, selenocystine and selenodiglutathione (GSSeSG) readily inactivated the kinase activity, but not the phorbol ester binding. These two agents induced a two-stage modification of PKC; a limited modification at low concentrations leads to a loss of affinity for ATP, while an excessive modification at high concentrations leads to a loss of Vmax. Selenocystine and GSSeSG were 100,000-fold more potent than GSSG in inactivating PKC. The isoenzymes alpha, beta, and gamma exhibited an identical susceptibility to these selenocompounds. These results suggested that the cysteine residues present within the catalytic domain of these isoenzymes, although apart in the sequence, may be clustered in the tertiary structure to react with selenite, as well as may be in close proximity to some of the cysteines in the regulatory domain. Selenite did not affect protein kinase A, whereas GSSeSG and selenocystine inactivated the catalytic subunit after dissociation from the regulatory subunit at concentrations 100- and 800-fold, respectively, higher than that required for PKC inactivation. All three selenocompounds did not affect the activities of phosphorylase kinase and protein phosphatase 2A. Taken together, these results suggest that the accessible redox-active cysteine residues present in the PKC catalytic domain can react with certain specificity with redox-active selenocompounds such as selenite, selenocystine, and GSSeSG relative to other protein kinases tested.

Animals↗

PubMed1997

Selenocompounds induce a redox modulation of protein kinase C in the cell, compartmentally independent from cytosolic glutathione: its role in inhibition of tumor promotion.

Since selenite and other redox-active selenocompounds can modify protein kinase C (PKC) in the test tube, we have determined whether or not this redox regulation occurs inside the cell despite having high concentrations of GSH and the role of this regulation in the inhibition of tumor promotion. By using phorbol ester-promoted JB6 epidermal cell transformation assay, the concentrations of selenite, selenocystine, and selenodiglutathione which are optimal for chemopreventive activity were determined. At such concentrations (0.5 to 2 microM) in the cells treated with these agents, only a slight but transient decrease in PKC activity was observed when measured with a low (5 microM), but not with a high (100 microM) concentration of ATP. However, when the cells were serum starved or pretreated with 2-deoxyglucose, there was a pronounced but transient inactivation of PKC when assayed with both low and high concentrations of ATP. The inactivation was reversed in the cell by an endogenous mechanism or by treatment with thiol agents in the test tube. In spite of a substantial (90%) depletion of GSH in the cells by pretreatment with buthionine sulfoximine, there was no further increase in the redox modification of PKC by selenite as well as no change in the inhibitory effect of selenite on the phorbol ester-stimulated induction of ornithine decarboxylase, which is an intermediate marker related to cell transformation. While GSH is known to influence certain actions of selenium, it may not be required to mediate the effects of selenite tested in this study. The water-soluble cytosolic GSH did not interfere with the redox modification of PKC probably due to the shielding of the cysteine-rich region of the enzyme by a weak hydrophobic association with the membrane. Due to the presence of cofactors in the crude cell extracts, PKC was more sensitive to selenite than in the purified form and was inactivated by low concentrations of selenite (IC50 = 0.05 microM). This modification was reversed by thiol agents as well as by NADPH. A protein disulfide reductase, which can regenerate PKC, was present in the homogenate. Conceivably, selenite and other selenocompounds induce a redox modification of cellular PKC, compartmentally independent from the cytosolic GSH, but intimately connected to a NADPH-dependent reductase system, to mediate, at least in part, some of the cancer-preventive actions.

Animals↗

PubMed1997

In vitro culture of human dental pulp cells: some aspects of cells emerging early from the explant.

Cells emerging from a dental pulp explant were studied in order to elucidate the origin of precursor cells implicated in the formation of reparative dentin in vivo. Such cells observed at the very early stage of culture (days 5-10) were different from fibroblast-like cells obtained after one subculture. These early cells were round or elongated, with thin spinous processes, highly mobile, and contained numerous lipid vesicles. Incorporation of 1-[14C]palmitic acid did not show an increased incorporation of radiolabeled total lipids or triglycerides into these early cells compared to cells after four subcultures or control skin fibroblasts, suggesting that the lipids in vesicles were not synthesized by the cells. Since these cells also show a high level of fluid phase uptake via macropinocytosis, it is suggested that these lipids originate from macropinocytosis. Between days 10 and 20, these cells spontaneously start conversion into cells that have a fibroblast-like morphology, are less mobile, and lack lipid vesicles. Their morphology, movement, and macropinocytosis suggest that these cells, which migrate from the pulp explants, are mesenchymal cells related to mononuclear phagocytes/histiocytes.

Adolescent↗

PubMed1997

Expression of methylthioadenosine phosphorylase cDNA in p16-, MTAP- malignant cells: restoration of methylthioadenosine phosphorylase-dependent salvage pathways and alterations of sensitivity to inhibitors of purine de novo synthesis.

5'-Deoxy-5'-methylthioadenosine phosphorylase (MTAP) is involved in the salvage of adenine and methylthio moieties of 5'-deoxy-5'-methylthioadenosine, a byproduct of polyamine synthesis, to adenine nucleotides and methionine, respectively. The gene encoding MTAP, MTAP, is frequently codeleted along with the tumor suppressor gene p16 in malignant cells bearing homozygous deletions in the chromosome 9p21 region. p16-, MTAP- malignant cells have been shown to be more susceptible to the purine de novo inhibitory actions of antifolates such as methotrexate than are p16+, MTAP+ cells. To understand the underlying mechanism, we reintroduced MTAP activity into two p16-, MTAP- cell model systems, the MiaPaCa-2 and PANC-1 human pancreatic carcinoma cell lines, by transfection with MTAP cDNA. It was found that transfection with MTAP cDNA (i) restored both the MTAP-dependent adenine and methionine salvage pathways, (ii) decreased the rates of purine de novo synthesis (18-47% lower than the wild-type or sham-transfected counterparts), and (iii) decreased cellular sensitivity to the antipurine-related growth-inhibitory actions of methotrexate and azaserine. These data support the hypothesis that operation of the MTAP-dependent adenine salvage pathway renders MTAP+ cells less dependent on de novo purine synthesis and hence less susceptible than MTAP- malignant cells to the growth-inhibitory actions of agents (e.g. antifolates) whose mechanism of action in part involves the de novo purine pathway. These findings provide a theoretical basis for the relatively selective action certain antifolates may have against MTAP-deficient malignancies.

Adenosine↗