Comparison of the Effects of L-asparaginase and Pegaspargase in the Treatment of Adult Acute Lymphoblastic Leukemia

Objective:To compare the effect of L-asparaginase and pegaspargase in the treatment of adult acute lymphoblastic leukemia.Methods:In this study,96 patients who received treatment at the Shaanxi Provincial People’s Hospital from April 2019 to April 2021 were selected.The control group received L-asparaginase treatment,and the observation group received pegaspargase treatment.The curative effect and adverse reaction rate were compared between the two groups.Results:Comparing the experimental statistical results of the observation and the control groups,it can be concluded that the effect of the former group is better than that of the latter group in terms of clinical curative effect and statistics of adverse reactions.Conclusion:In the treatment of adult acute lymphoblastic leukemia,the application of pegaspargase therapy has a significantly better clinical effect and is worthy of further promotion.

Screening and characterization of extracelluar L-asparaginase producing Bacillus subtilis strain hswx88,isolated from Taptapani hotspring of odisha,India

Objective:To screen and isolate an eco-friendly,u thermophilic and potent L-asparaginase producing bacterium,with novel immunological properties that may obviates hypersensitivity reactions.Methods:In the present study baclerial strain isolated for extracellular L-asparaginase production from hotspring,identified by morphological,biochemical and physiological tests followed by t6S rDNA technology and the L-asparaginase production ability was tested by both semi quantitative and quantitative enzymatic assay.Result:The bacterial strain was identified as Bacillus sublilis strain hswx88(GenBank Accession Number JQ237656.1).The extracellular enzyme yielding capacity isolate Bacillus subtilis strain hswx88(23.8 IU/mL)was found to be 1.7 and 14.5 limes higher than the reference organism Pectobacterium carotovorum MTCC 1428(14.2 IU/mL)and Bacillus sp.BCCS 034(1.64 IU/mL).Conclusion:The isolate is eco-friendly and useful to produce bulk quantity of extracellular,thermophilic L-asparaginase for the treatment of various tumor cases and for preparation of acrylamide free fry food preparation.

L-asparaginase production by mangrove derived Bacillus cereus MAB5:optimization by response surface methodology

Objective:To isolate marine bacteria,statistically optimize them for maximum asparaginase production.Methods:In the present study,statistically based experimental designs were applied to maximize the production of L-asparaginase from bacterial strain of Bacillus cereus（B.cereus） MAB5（HQ675025） isolated and identified by 16S rDNA sequencing from mangroves rhizosphere sediment.Results:Plackett-Barman design was used to identify the interactive effect of the eight variables viz.yeast extract,soyabean meal,glucose,magnesium sulphate,KH2PO4,wood chips,aspargine and sodium chloride.All the variables are denoted as numerical factors and investigated at two widely spaced intervals designated as -1（low level） and +1（high level）. The effect of individual parameters on L-asparaginase production was calculated.Soyabean meal,aspargine,wood chips and sodium chloride were found to be the significant among eight variables.The maximum amount of L-asparaginase produced（51.54 IU/mL） from the optimized medium containing soyabean meal（6.282 8 g/L）,aspargine（5.5 g/L）,wood chips（1.383 8 g/L） and NaCl（4.535 4 g/L）.Conclusions:The study revealed that,it is useful to produce the maximum amount of L-asparaginase from B.cereus MAB5 for the treatment of various infections and diseases.

Asparagine Synthetase Is Partially Localized to the Plasma Membrane and Upregulated by L-asparaginase in U937 Cells

This study investigated the intracellular localization of asparagine synthetase （ASNS） in the relation with chemoresistance in leukemia. pIRES-GFP-ASNS-Flag/Neo expression vector was transiently tansfected into SK-N-MC cells and 297T cells respectively. Immunofluorescence and Western blot analysis were performed for cellular localization of ASNS respectively. U937 cells were treated with L-asparaginase for 48 h and examined for endogenous ASNS expression on plasma membrane by immunofluorescence staining. Immunofluorescence staining showed that the transiently expressed ASNS was partly localized on transfected-SK-N-MC cell surface. Moreover, Western blotting exhibited that ASNS expressed both in cytosol and on plasma membrane of transfected-293T cells. Immunofluorescence staining with anti-ASNS-specific monoclonal antibody revealed that endogenous ASNS was localized on the plasma membrane of U937 cells, except for its distribution in the cytosol. In addition, ASNS exhibited a higher expression on plasma membrane after treatment with L-asparaginase as compared with the untreated cells. It was concluded that the subcellular translocation of ASNS may play an important role in L-asparaginase resistance in leukemia cells.

Purification and Biochemical Characterization of Native and Pegylated Form of L-Asparaginase from Aspergillus terreus and Evaluation of Its Antiproliferative Activity

L-asparaginase is a chemotherapeutic drug used in the treatment of lymphoblastic leukemia. In the present study, the extracellular L-asparaginase produced by strain (PC-1.7A) of Aspergillus terreus was purified, characterized, and modified with polyethylene glycol. Moreover, its antiproliferative activity was evaluated. The apparent molecular weight of the enzyme was found to be 136 kDa. The optimal pH and temperature for the enzyme were 9.0℃ and 40℃, respectively. The enzyme retained 100% of the activity at 40℃ for 120 min. Pegylated L-asparaginase was more thermostable and more resistant to trypsin than native enzyme. Native L-asparaginase against human normal cells did not show cytotoxicity. However, in the leukemia cell lines RS4;11 and HL60 the antiproliferative effects of native L-asparaginase were observed after 96 and 72 h of incubation, respectively. For the first time, an L-asparaginase from fungus was evaluated as an antitumor agent in human cells lines and further investigations should be conducted to improve the knowledge about this enzyme.

Therapeutic Efficacy of L-asparaginase in the Treatment of Refractory Midfacial Peripheral T-Cell Non-Hodgkin’s Lymphoma

Objective: To improve the efficacy of refractory midfacial peripheral T-cell non-Hodgkin’s lymphoma (MPTC-NHL) with L-asparaginase (L-ASP) based salvage chemotherapy. Methods: 21 patients with refractory MPTC-NHL were analyzed. 11patients (L-ASP group) received L-asparaginase based salvage chemotherapy consisting of L-asparaginase, vincristine and dexame-thosone. 10 patients (control group) received salvage combination chemotherapy without L-asparaginase. Results: Complete remission rates were 45.6% for L-ASP group and 0.0% for control group (p<0.05). Overall response rates (CR+PR) were 63.6% for L-ASP group and 10.0% for control group, respectively (p<0.05). 2-year survival rates were 45.5% for L-ASP group and 0.0% for control group (p<0.05). The major adverse effects of L-ASP were leukopenia, elevation of serum bilirubin and hyperglycemia. Conclusion: The preliminary clinical study shows that the L-ASP based salvage chemotherapy may improve the response rate and 2-year survival rate of the patients with refractory MPTC-NHL. It is necessary to continue the study further.

Purification,characterization and antiproliferative activity of L-asparaginase from Aspergillus oryzae CCT 3940 with no glutaminase activity

Objective:To explore the anti-proliferative activity of purified L-asparaginase from Aspergillus oryzae CCT 3940(A.oryzae).Methods:L-asparaginase was produced by submerged fermentation and purified to electrophoresis homogeneity by ionic exchanged chromatography in a fast protein liquid chromatographic system.The purified enzyme was characterized and used for the antiproliferative assay against nine tumor cell lines and one non-tumor cell line.Results:The free glutaminase L-asparaginase was purified 28.6 fold.L-asparaginase showed high stability under physiological condition,remaining stable in the p H range7.0–8.0 after 1 h incubation at temperature range 30–45℃.The Km and Vmax values of purified L-asparaginase were estimated as 0.66 mmol/L and 313 IU/mL,respectively.The purified enzyme could inhibit the growth of a broad range of human tumor cell lines at the concentrations studied.Also,the enzyme from A.oryzae CCT 3940 could inhibit tumor growth of leukemia cell line(K562) with a total growth inhibition value of(3.2 ± 2.5) IU/mL and did not inhibit the non-carcinogenic human cell line growth at the concentrations studied.Conclusions:The sensitivity of the cells lines to purified L-asparaginase from A.oryzae CCT 3940 appeared to be concentration dependent affording a more significant decrease in cell growth than that observed for the commercial L-asparaginase from Escherichia coli.The L-asparaginase from A.oryzae CCT 3940 has a high potential for pharmaceutical exploitation in the treatment of leukemia.

Mathematical Simulation of Blood Purification for Leukemia by Immobilized L-asparaginase

Plasma was purified in an immobilized L-asparaginase column. The predicted results are in good agreement with experimental data. It is indicated that the mathematical model is suitable for the mass transfer and reaction of blood purification.

Batch, Fed Batch Production and Characterization of Glutaminase Free L-Asparaginase II of <i>Pectobacterium carotovorum</i>MTCC 1428 in <i>Escherichia coli</i>

The present study describes the production optimization of recombinant L-asparaginase II of Pectobacterium carotovorum MTCC 1428 in Escherichia coli BL21 (DE3) at batch and fed batch bioreactor level. Production of recombinant L-asparaginase II in batch and fed batch mode was found to be 1.34 and 5.38 folds higher, respectively as compared to shake flask culture. SDS-PAGE and native PAGE of the purified enzyme revealed that molecular mass of the subunits and native enzyme are ~37.5 kDa and ~150 kDa, respectively. Optimum range of pH and temperature for hydrolysis of L-asparagine were found to be 7.5 - 8.5 and 47°C - 52°C, respectively. The recombinant enzyme is very specific for its natural substrate, L-asparagine. The activity of recombinant L-asparaginase II is improved by mono cations and diverse effectors including Na+, K+, L-cystine, L-histidine, glutathione and 2-mercaptoethanol whereas, it is moderately inhibited by different divalent cations and thiol group blocking reagent. The kinetic parameters Km, Vmax, kcat and Km/Kcat of purified recombinant L-asparaginase II were determined. The purified L-asparaginase II possesses no partial glutaminase activity, which is prerequisite to reduce the possibility of side effects during the course of anti-cancer therapy.

Side Effects of Vincristine and L-Asparaginase in Patients with Acute Lymphoblastic Leukemia in a Mexican Pediatric Hospital

Background: The treatment used to combat acute lymphoblastic leukemia (ALL) is multidrug;therefore it is important to use active pharmacovigilance to detect, assess and analyze the likely adverse reactions which may occur during the same period. Objective: To determine the frequency of adverse reactions to chemotherapeutic drugs in children with ALL. Material and Methods: Intensive pharmacovigilance was used to record the reports of adverse reactions to vincristine, L-asparaginase and the vincristine-L-asparaginase combination in children with ALL in a paediatric hospital. For each notification, the adverse reactions were analyzed in order to verify causality. Results: Forty patients were evaluated. Twenty children were female (50.0%) and 20 were male (50%). The children had a mean age, weight and height (±standard deviation: SD) of 8.1 (±3.4) years, 31.4 (±13.9) kg and 1.3 (±0.2) m, respectively. Vincristine was administered to 19 patients, vincristine plus L-asparaginase were given to 19 patients and only 2 patients used L-asparaginase. One-hundred-ninety adverse reactions were detected in the patients, with an average (±SD) of 4.8 (±2.6). Ondansetron was the drug administered for the treating of nausea and vomiting. One hundred eighty-one (95.3%) adverse reactions were identified as “definite”, 5 (2.6%) as “probable” and 4 (2.1%) as “doubtful”. Conclusions: There is a high incidence of adverse reactions by the administration of vincristine and L-asparaginase;the reactions of highest incidence were: nausea, vomiting, neutropenia, diarrhea, constipation, mucositis, headache, and abdominal pain. It is important to promote the detection, collection, reporting, assessment and treatment of ARD’s in children. It is necessary to promote the conduct further studies on pharmacovigilance with this type of treatments and to increase the duration of the studies.

Purification of L-asparaginase II by crystallization

Here a case study ofL-asparaginase II out of a recombinant Escherichia coli is presented. The target protein was obtained by simple cell disintegration and acetone precipitation. The L-asparaginase II has been crystallized in three different forms in the following microbatch crystallization. The rod-shaped crystals （-400 μm edge length） were obtained at either 8℃ or 22℃ after 17h by addition of PEG6ooo. The rectangular-shaped crystals were obtained after further recrystallization of the rod-shaped crystals. The rhombic-shaped crystals formed at 8℃ after 12 days when cold ethanol was used instead of PEG6000. All crystallizations were performed in tris-acetate buffer （50mmol-L-1, pH 5.1）. By crystallization, the specific activity of L-asparaginase II has increased 5-fold. The protein content and the purity of the crystals were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis （SDS-PAGE）. The more concentrated L- asparaginase II out of an extract mixture and the presence of only less minor proteins after crystallization demonstrates that crystallization is an effective and mild method to purify the target protein. The single crystal X-ray diffraction pattern reveals that the crystals are proteins and the X-ray powder diffraction （XRPD） pattern shows clearly that the crystals forming in PEG600o and ethanol have different crystal structures.

Withania somnifera (Ashwagandha):a Novel Source of L-asparaginase

Different parts of plant species belonging to Solanaceae and Fabaceae families were screened for L-asparaginase enzyme （E.C.3.5.1.1.）. Among 34 plant species screened for L-asparaginase enzyme. Withania somnifera L. was identified as a potential source of the enzyme on the basis of high specific activity of the enzyme. The enzyme was purified and characterized from W. somnifera, a popular medicinal plant in South East Asia and Southern Europe. Purification was carried out by a combination of protein precipitation with ammonium sulfate as well as Sephadex-gel filtration. The purified enzyme is a homodimer, with a molecular mass of 72 ± 0.5 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresisand size exclusion chromatography. The enzyme has a pH optimum of 8.5 and an optimum temperature of 37 ℃. The Km value for the enzyme is 6.1 × 10^-2 mmol/L. This is the first report for L-asparaginase from W. somnifera, a traditionally used Indian medicinal plant.

Chemical modification of L-asparaginase with N, O-carboxymethyl chitosan and its effects on plasma half-life and other properties

<正> E.coli L-asparaginase,an antitumor enzyme,was chemically modified with N,O-carboxymethyl chitosan to lower its artigenicity and increase its plasma half-life.The results showed that the modified L-asparaginase has almost the same apparent Km value as that of native enzyme.The modified L-asparaginase also showed a higher protease stability against trypsin and a-chymotrypsin.After being modified,the enzyme exhibited the complete loss of antigenicity towards antiasparaginase serum.In addition,the higher the molecular weight of modifying reagents,the better the effects on reduction of antigenicity.When tested in vivo,the plasma half-life of the modified enzyme (t1/2=40 h) was over 33 times longer than that of the native enzyme (t1/2=1.2 h).

TYROSINE MICRO-REGION OF E.COLI L-ASPARAGINASE

The relationship between conformation change and activity of E. coli L-asparaginase hasbeen studied with circular dichroism spectra and microcaloric methods. In many papers [1-4],it has been pointed out that the active site of L-asparaginase isclosely related to tyrosyl residues. The present authors[5] have studied the effects of L-cysteine on the activity and the conformation of L-asparaginase with UV difference spectraand kinetic methods. Moreover, we have studied the space arrangement of tyrosyl residuesin the enzyme molecule. The results show that every enzyme molecule contains about 56 tyrosylresidues,20 of which are in the hydrophobic core of the enzyme molecule, another 20 at thesurface of the enzyme molecule, and the rest in the rifts and hollows of the enzyme molecule.Meanwhile, further study has also been made to determine the relationship between the changesof the enzyme activity and the ionization of tyrosyl residues as well as their chemical modifica-tion. By Zou Chenglu’s graphical method we have proved that two tyrosyl residues at thesurface of the enzyme molecule are the essential groups.

左旋门冬酰胺酶、培门冬酶对急性淋巴细胞白血病患儿的治疗效果比较

目的 对比左旋门冬酰胺酶、培门冬酶对急性淋巴细胞白血病(ALL)患儿的治疗效果。方法 回顾性收集2016年6月至2022年9月无锡市儿童医院收治的所有ALL患儿临床资料,根据治疗方法不同随机选取左旋门冬酰胺酶组和培门冬酶组,例数各37例。两组均进行常规基础治疗,在此基础上,左旋门冬酰胺酶组采用左旋门冬酰胺酶进行治疗,培门冬酶组采用培门冬酶进行治疗,两组均治疗46天,并随访3个月。统计两组治疗46天的临床疗效及治疗期间不良反应发生情况,比较两组治疗前、治疗21天、46天后、随访3个月后糖脂代谢指标及治疗前、治疗21天、46天后细胞因子、凝血功能、肝功能。结果 治疗46天后,与左旋门冬酰胺酶组比较,培门冬酶组总缓解率差异无统计学意义(P>0.05),而完全缓解率更高(χ^(2)=4.874,P<0.05)。治疗前及治疗21天、46天后、随访3个月后,两组血清胰岛素、C肽水平呈降低趋势,不同时间点比较,差异具有统计学意义(P<0.05);治疗21天后,培门冬酶组高于左旋门冬酰胺酶组(t=3.372、3.704,P<0.05)。治疗46天后、随访3个月后,两组血清甘油三酯(TG)水平较治疗前、治疗21天后升高,培门冬酶组高于左旋门冬酰胺酶组(t=7.181、5.635,P<0.05)。治疗前、治疗21天、46天后,两组血清肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素-8(IL-8)、白介素-10(IL-10)、干扰素-γ(IFN-γ)、铁蛋白(SF)水平呈先升高后降低趋势,不同时间点比较,差异具有统计学意义(P<0.05);治疗21天后培门冬酶组高于左旋门冬酰胺酶组(t值介于3.785~7.921之间,均P<0.05);治疗46天后培门冬酶组低于左旋门冬酰胺酶组(t值介于2.983~7.000之间,均P<0.05)。两组凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)时长呈先升高后降低趋势,培门冬酶组治疗21天后长于左旋门冬酰胺酶组(t=2.985,P<0.05);两组血浆纤维蛋白原(FIB)水平呈先降低后升高趋势,培门冬酶组治疗21天后低于左旋门冬酰胺酶组(t=5.711,P<0.05);两组血清D-二聚体(D-D)、纤维蛋白原降解产物(FDP)、丙氨酸氨基转移酶(ALT)、总胆汁酸(TBil)水平呈先升高后降低趋势,培门冬酶组治疗21天、46天后高于左旋门冬酰胺酶组(t值介于3.566~40.745之间,均P<0.05)。治疗期间,培门冬酶组总不良反应发生率高于左旋门冬酰胺酶组(χ^(2)=7.341,P<0.05)。结论 与左旋门冬酰胺酶相比,采用培门冬酶治疗ALL患儿对患儿胰岛功能和肝功能、凝血功能影响较大,安全性相对较差,但其在降低患者机体炎症反应方面应用效果更好,同时疗效更好,临床可根据患儿具体情况选取合适的药物进行治疗。

构建转天冬酰胺酶基因菌株及其固体发酵产酶培养基优化

构建一株转L-天冬酰胺酶基因的里氏木霉重组菌株,并采用固体发酵的方法研究其发酵产酶。首先以贝莱斯芽孢杆菌质粒为骨架重组天冬酰胺酶基因,验证其天冬酰胺酶的表达;随后探讨不同培养基配方(配方1和配方2)发酵产酶效果,通过单因素和正交试验优化其优势产酶培养基。结果表明:构建的里氏木霉可以正确表达天冬酰胺酶;在固体培养基配方1和配方2中,重组的里氏木霉菌株发酵产天冬酰胺酶分别为4.52 U/g和2.21 U/g,配方1产酶量远高于配方2。因此,以配方1作为优选配方,通过单因素及正交试验对其进一步优化。配方1中,当麦麸与玉米芯的比例为3∶1、初始含水量为1∶4.4、初始pH值为5.5时,该里氏木霉转L-天冬酰胺酶基因重组菌株发酵产酶活力为5.965 U/g,与原配方相比,优化后的固体培养基发酵产酶活力提高了24.22%。

基于Fosmid文库筛选山羊瘤胃微生物源蛋白酶基因及其表达验证

【目的】利用Fosmid文库功能筛选法,获得山羊瘤胃微生物源蛋白酶基因并进行原核表达。【方法】利用功能底物筛选法从山羊瘤胃微生物源Fosmid文库中筛选具有蛋白酶活性的克隆子,对其进行Illumina二代测序,对预测到的基因进行功能注释,根据基因丰度结果确定后续研究的功能基因。利用大肠杆菌BL21(DE3)对功能基因进行诱导表达,对表达产物进行酶活性测定。通过CRISPR/Cas9基因编辑技术,将密码子优化后的功能基因分别敲入枯草芽孢杆菌C6基因组ctc位点并进行表达验证。【结果】从Fosmid文库1700个克隆子中筛选到1个具有蛋白酶活性的阳性克隆Pro4-C5。通过二代测序技术,鉴定出3个潜在的蛋白酶基因gene0833(内肽酶,EC编号:EC3.4.21.53)、gene0196(金属内肽酶,EC编号:EC3.4.24)和gene0585(羧肽酶,EC编号:EC3.4.17.14)以及1个L-天冬酰胺酶基因(gene0683,EC编号:EC3.5.1.1)。以pET-28a(+)为表达载体,通过大肠杆菌BL21(DE3)原核诱导表达发现,gene0585和gene0196未表达;gene0833表达的蛋白分子质量为87 ku,蛋白酶活性为10.45 U/mL;gene0683表达的蛋白分子质量为37 ku,L-天冬酰胺酶活性为88.52 U/mL,同时发现该蛋白也具有蛋白酶活性,酶活性为5.25 U/mL。将密码子优化后的gene0683和gene0833定点敲入枯草芽孢杆菌C6基因组中表达发现,gene0833未表达,gene0683表达的蛋白酶活性为109.72 U/mL,相比原始菌株(100.97 U/mL)显著提高了8.67%(P<0.01);L-天冬酰胺酶活性为31.63 U/mL,相比原始菌株(22.79 U/mL)显著提高了30.06%(P<0.01)。【结论】从山羊瘤胃微生物源Fosmid文库中筛选和鉴定出了2个具有蛋白酶活性的功能基因(gene0833和gene0683),均来源于微小杆菌属(Exiguobacterium),其中gene0683在大肠杆菌和枯草芽孢杆菌中的表达产物具有较高的蛋白酶和L-天冬酰胺酶酶活性。

结外自然杀伤/T细胞淋巴瘤鼻型的治疗研究进展

结外自然杀伤(NK)/T细胞淋巴瘤鼻型(ENKTL)是一种侵袭性恶性肿瘤,多见于亚洲和南美洲人群。EB病毒(EBV)感染与ENKTL的发病和患者预后密切相关。NK细胞淋巴瘤预后指数-EB病毒(PINK-E)模型是目前临床上较实用的ENKTL患者预后评估模型。ENKTL的治疗方案包括放疗、含L-天冬酰胺酶的非蒽环类化疗、造血干细胞移植、靶向程序性细胞死亡蛋白-1/程序性细胞死亡蛋白-1配体(PD-1/PD-L1)轴治疗,已取得显著疗效。未来,新的治疗方案包括抗EBV治疗、信号通路治疗和表观遗传学治疗等具有极大治疗潜力,有待临床试验加以验证。

培门冬酶注射液联合CAG方案化疗方案用于加速期慢性粒细胞白血病患者的效果

目的:观察培门冬酶注射液联合CAG方案化疗方案用于加速期慢性粒细胞白血病(CML)患者的效果。方法:选取2021年3月至2023年2月该院收治的98例加速期CML患者进行前瞻性研究,按照随机数字表法将其分为观察组与对照组各49例。对照组给予CAG方案化疗,观察组在对照组基础上联合培门冬酶注射液治疗,比较两组临床疗效,治疗前后凝血功能指标水平、Th1/Th2淋巴细胞因子水平,以及不良反应发生率。结果:观察组治疗总有效率为73.47%,明显高于对照组的53.06%,差异有统计学意义(P<0.05);治疗后,两组纤维蛋白原、D-二聚体水平均低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05);治疗后,两组血清白细胞介素(IL)-10、IL-4水平均低于治疗前,且观察组低于对照组,两组血清IL-2、γ干扰素水平均高于治疗前,且观察组高于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:培门冬酶注射液联合CAG方案化疗方案用于加速期CML患者可提高治疗总有效率,降低其纤维蛋白原、D-二聚体水平,改善其Th1/Th2淋巴细胞因子水平,效果优于单纯CAG方案化疗。

L-天冬酰胺酶在肿瘤中的研究进展

氨基酸代谢与细胞氧化应激、细胞增殖和细胞凋亡等多种细胞过程相关,参与糖尿病、衰老、肿瘤等生理病理过程。L-天冬酰胺酶(L-asparaginase,L-ASP)是氨基酸代谢途径中的关键酶,能够水解天冬酰胺生成天冬氨酸和氨,参与细胞增殖、凋亡、迁移以及侵袭等生物过程。研究表明,L-天冬酰胺酶影响白血病、乳腺癌、胃癌、肺癌、胰腺癌、肝癌等多种肿瘤的发生和发展。本文主要从L-天冬酰胺酶的结构、酶学作用、与其他药物联用对多种肿瘤治疗的潜力进行综述。