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Effect of TNF-$\alpha$ Gene Transfer to Respiratory Cancer Cell Lines on Sensitivity to Anticancer drugs (호흡기계암세포주에서 TNF-$\alpha$ 유전자의 이입이 항암제 감수성에 미치는 효과)

  • Mo, Eun-Kyung;Lee, Jae-Ho;Lee, Kye-Young;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Choi, Hyung-Seok
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.3
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    • pp.302-313
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    • 1995
  • Background: Tumor necrosis factor(TNF) showed antitumor cytolytic effects on sensitive tumor cells in numerous in vivo and in vitro studies. But it could not be administered systemically to human because of severe systemic adverse effects at effective concentrations against tumor cells. Many studies showed that a high concentrations of TNF in the local milieu may evoke in vivo TNF-responsive mechanisms sufficient to suppress tumor growth. Recently developed technique of TNF gene transfer to tumor cells using retrovirus vector could be a good candidate for local TNF administration. TNF is also known to synergistically enhance in vitro cytotoxicity of chemotherapeutic drugs targeted to DNA topoisomerase II against TNF-sensitive tumor cell lines. In this study the in vitro chemosensitivity against DNA topoisomerase II targeted chemotherapeutic drugs was evaluated using some respiratory cancer cell lines to which TNF gene had been transferred. Method: NCI-H2058, a human mesothelioma cell line, A549, a human lung adenocarcinoma cell line and WEHI 164 cell line, a murine fibrosarcoma cell line were treated with etoposide and doxorubicin, which are typical topoisomerase II - targeted chemotherapeutic agents, at different concentration. The resultant cytotoxicity was measured by MIT assay. Then the cytotoxicity of the same chemotherapeutic agents was measured after TNF-$\alpha$ gene-transfer and the two results were compared. Results: The cytotoxicity was not increased significantly in WEHI164 cell line and A549 cell line but statistically significant increase was observed in H2058 cell line when TNF-$\alpha$ gene was transferred(p<0.05). Conclusion: These findings show that TNF-$\alpha$ gene transfer to respiratory cancer cell lines results in variable effects on chemosensitivity against topoisomerase II inhibitor among different cell lines in vitro and can be additively cytotoxic in certain selective tumor cell lines.

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Microtubule-damaging Chemotherapeutic Agent-mediated Mitotic Arrest and Apoptosis Induction in Tumor Cells (미세소관-손상 항암제 처리에 의한 세포주기의 정지 및 에폽토시스 유도)

  • Jun, Do Youn;Kim, Young Ho
    • Journal of Life Science
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    • v.26 no.3
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    • pp.376-386
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    • 2016
  • Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

Intensity Modulated Whole Pelvic Radiotherapy in Patients with Cervix Cancer: Analysis of Acute Toxicity (자궁경부암 환자에서 전골반 강도변조방사선치료에 의한 급성부작용)

  • Choi, Young-Min;Lee, Hyung-Sik;Hur, Won-Joo;Cha, Moon-Seok;Kim, Hyun-Ho
    • Radiation Oncology Journal
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    • v.24 no.4
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    • pp.248-254
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    • 2006
  • $\underline{Purpose}$: To evaluate acute toxicities in cervix cancer patients receiving intensity modulated whole pelvic radiation therapy (IM-WPRT). $\underline{Materials\;and\;Methods}$: Between August 2004 and April 2006, 17 patients who underwent IM-WPRT were analysed. An intravenous contrast agent was used for radiotherapy planning computed tomography (CT). The central clinical target volume (CTV) included the primary tumor, uterus, vagina, and parametrium. The nodal CTV was defined as the lymph nodes larger than 1 cm seen on CT and the contrased-enhanced pelvic vessels. The planning target volume (PTV) was the 1-cm expanded volume around the central CTV, except for a 5-mm expansion from the posterior vagina, and the nodal PTV was defined as the nodal CTV plus a 1.5 cm margin. IM-WPRT was prescribed to deliver a dose of 50 Gy to more than 95% of the PTV. Acute toxicity was assessed with common toxicity criteria up to 60 days after radiotherapy. $\underline{Results}$: Grade 1 nausea developed in 10 (58.9%) patients, and grade 1 and 2 diarrhea developed in 11 (64.7%) and 1 (5.9%) patients, respectively. No grade 3 or higher gastrointestinal toxicity was seen. Leukopenia, anemia, and thrombocytopenia occurred in 15 (88.2%). 7 (41.2%), and 2 (11.8%) patients, respectively, as hematologic toxicities. Grade 3 leukopenia developed in 2 patients who were treated with concurrent chemoradiotherapy. $\underline{Conclusion}$: IM-WPRT can be a useful treatment for cervix cancer patients with decreased severe acute toxicities and a resultant improved compliance to whole pelvic irradiation.

Comparative Assessment of the Half-lives of Benfuresate and Oxolinic Acid Estimated from Kinetic Models Under Field Soil Conditions (포장조건에서 Kinetic Models로부터 산출한 Benfuresate 및 Oxolinic Acid의 토양중 반감기 비교평가)

  • Yang, Jae-E.;Park, Dong-Sik;Han, Dae-Sung
    • Korean Journal of Environmental Agriculture
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    • v.14 no.3
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    • pp.302-311
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    • 1995
  • Benfuresate or oxolinic acid, as an experimental pesticide, was applied to the different textural paddy or upland soil respectively under the field condition and the residual concentrations were determined. Six kinetic models were employed to characterize the best-fit kinetic model describing the residual pattern of benfuresate or oxolinic acid and the $t\frac{1}{2}$ estimated from each model was comparatively assessed. All of the six models explained significantly the residual patterns of the pesticides but the empirical models such as PF, EL, and PB were not recommendable for the $t\frac{1}{2}$ estimation. Among theoretical models, the residual patterns were followed in the orders of the second-order(SO)>first-order(FO)>zero-order(ZO) kinetics, judging from the size and significance of coefficient of determination and standard error. However, the multiple FO model, consisting of the fast and slow decomposition steps, was better than the single FO model for the residual pattern and the $r^2$ in this case became similar to that of SO kinetic model. Thus the multiple FO and SO models were represented as the best fit model of the experimental pesticide. The $t\frac{1}{2}$ of benfuresate estimated from the single FO kinetic model in Weolgog and Cheongwon series was 49 and 63 days, respectively, which were 20 and 13% longer than the respective $t\frac{1}{2}$ from the SO kinetic model. The $t\frac{1}{2}$ of oxolinic acid from the FO model in Yonggye and Ihyeon series were 87 and 51% longer than those from the SO kinetic model, respectively. These results demonstrated that the best-fit model representing the residual pattern of a pesticide and the resultant $t\frac{1}{2}$ might be variable with the kinds of pesticides and the environmental conditions. Therefore it is recommended that the half-life of a pesticide be assessed from the best-fit model rather than from the FO kinetic model uniformly.

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Closed Interlocking Intrmedullary Nailing of Metastatic Diaphyseal Fractures of the Humerus (상완골 간부 악성 병적골절의 비관혈적 고합성 골수강내 금속정 고정술)

  • Bahk, Won-Jong;Rhee, Seung-Koo;Kang, Yong-Koo
    • The Journal of the Korean bone and joint tumor society
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    • v.9 no.1
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    • pp.1-11
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    • 2003
  • Purpose: To analysis of the result of the treatment of metastatic diaphyseal fracture of the humerus with closed interlocking intrameduallry nailing. Materials and Methods: Among surgically treated 29 patients with pathologic or impending fracture of diaphysis of the humeurs, 13 patients (16 cases) treated with closed intramedullary interlocking nail were selected for the study. The final result of pain relief and functional recovery was evaluated by modified rating system of Perez et al. Results: Primary cancer was diagnosed after fracture was developed in 2 patients and pathologic or impending fracture was occurred average period of 28.9 months after primary cancer was diagnosed. The main primary malignancies were multiple myeloma, lung cancer and breast cancer. Mean survival after humeral metastasis was 11.7 months. The final result was superior to fair in 13 of 16 cases, and poor in 3 cases with progression of tumor spread or distant dissemination to the ipsilateral fingers. Except the latter 3 patients and other 3 patients, who died before 3 months postoperatively, bony union was achieved in 10 cases. There were no complications related to surgery. Conclusion: Closed interlocking intrameduallry nailing is accomplished with brief operative time, small amount of bleeding and provides immediate stability with resultant early return of function to the arm. Additionally it allows early postoperative irradiation. However, some of our cases shows that intramedullary nailing can accelerate tumor spread and metastases elsewhere, so that serious consideration must be given in planning this treatment. In conclusion, the functional status before fracture, life expectancy, type of tumor and extent of involvement should be carefully considered to decide operative treatment of metastatic disease.

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A study on the menstrual patterns and menstrual discomforts in women university students (일부 여대생들의 월경양상과 월경시 불편감에 관한 조사연구)

  • Lee In Sook
    • Journal of Korean Public Health Nursing
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    • v.12 no.1
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    • pp.116-131
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    • 1998
  • This study was undertaken to obtain the menstrual patterns and menstrual discomforts in women university students. For the data collection, self-administered questionnaire survey was made from December 10, 1996 to January 20, 1997 among the 180 women university students in Seoul. The resultant data were processed by SAS program for frequency, proportion, and chi-square test. The results of this study are as follows ; 1) The mean age of the subjects was 20.6 years old. The mean height was 162cm and weight was 52.3Kg. $26.9\%$ of the subjects responded that they had experienced the unbalanced diet, $56\%$ the irregular meal, $39.6\%$intermittent dizziness, and $63.4\%$ the premenstrual syndrome. $53.7\%$ had feeling that skin temperature of their four extremities was 'a little lower than others'. The mean BMI(Body Mass Index) was 19.8, 'normal level' was $41.8\%$. $18.7\%$ responded that their characters were 'introspective ones'. The mean age of menache was 13.8 years old. The subjects responded that the mean number of pads they used per day during menstrual periods was 4.6 sheets. The mean duration of menstruation was 5.4 days, $10.4\%$ responded that their menstrual cycles were 'extremely regular', $44.8\%$ was 'regular', $36.6\%$ was 'a little irregular', and $8.2\%$ was 'extremely irregular'. Out of them who had experienced the dysmenorrhea, $21.3\%$ had family history of dysmenorrhea in connection with their mother and $35.0\%$ in their sisters. The mean of the first time that they experienced dysmenorrhea was 15 years old. $94\%$ of the subjects responded that they had experienced the dysmeorrhea. $47.6\%$ of the subjects responded that they experienced the dysmenorrhea 'monthly' and $52.4\%$ 'intermittently'. $53.0\%$ of them who had experienced dysmenorrhea responded that dysmenorrhea was the severest 'on the first menstrual day' and $22.4\%$ 'on the second day'. $48.8\%$ of them who had experienced dysmenorrhea responded that the most painful region was 'low abdomen'. $40\%$ of them who had experienced dysmenorrhea responded that they used 'analgesics' to soothe dysmenorrhea, $24.8\%$ used nothing, $18.4\%$ lay in their beds or slept, and $12\%$ made their 'low abdomen' warm. $70.3\%$ who had used analgesics because of dysmenorrhea took analgesics 'one or two times per month', $25.7\%$ 'intermittently', and $4.0\%$ more than 3 times per month. The analgesics which they used were 'geworin$(33.8\%)$,' 'penzal$(32.4\%)$', 'tyrenol$(18.9\%)$', and 'aspirin$(4.2\%)$'. $(47.9\%)$ of them who took analgesics because of dysmenorrhea responded that the duration of analgesics effect was '4 to 8 hours'. $15.1\%$ of them who experienced dysmenorrhea responded that they had visited the hospital. 2) The incidence of premenstrual syndrome was no significant difference according to the BMI, unbalanced diet, pattern of meal, skin temperature of four extremites, and characters. 3) The incidence of dysmenorrhea was significant difference according to the BMI, unbalanced diet, pattern of meal, skin temperature of four extremites, and characters. 4) The incidence of analgesics usage was significant difference according to the BMI, subjects with low BMI took more analgesics than those with normal BMI (p<.05). The incidence of analgesics usage was significant difference in accordance with pattern of meal. The women who had a meal regularly took more analgesics than those who had a meal irregularly(p<.05). But the incidence of analgesics usage was no significant difference in accordance with the unbalanced diet, characters, the incidence of dizziness, skin temperature of four extremities, the incidence of premenstrual syndrome.

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Patient Position Verification and Corrective Evaluation Using Cone Beam Computed Tomography (CBCT) in Intensity.modulated Radiation Therapy (세기조절방사선치료 시 콘빔CT (CBCT)를 이용한 환자자세 검증 및 보정평가)

  • Do, Gyeong-Min;Jeong, Deok-Yang;Kim, Young-Bum
    • The Journal of Korean Society for Radiation Therapy
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    • v.21 no.2
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    • pp.83-88
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    • 2009
  • Purpose: Cone beam computed tomography (CBCT) using an on board imager (OBI) can check the movement and setup error in patient position and target volume by comparing with the image of computer simulation treatment in real.time during patient treatment. Thus, this study purposed to check the change and movement of patient position and target volume using CBCT in IMRT and calculate difference from the treatment plan, and then to correct the position using an automated match system and to test the accuracy of position correction using an electronic portal imaging device (EPID) and examine the usefulness of CBCT in IMRT and the accuracy of the automatic match system. Materials and Methods: The subjects of this study were 3 head and neck patients and 1 pelvis patient sampled from IMRT patients treated in our hospital. In order to investigate the movement of treatment position and resultant displacement of irradiated volume, we took CBCT using OBI mounted on the linear accelerator. Before each IMRT treatment, we took CBCT and checked difference from the treatment plan by coordinate by comparing it with the image of CT simulation. Then, we made correction through the automatic match system of 3D/3D match to match the treatment plan, and verified and evaluated using electronic portal imaging device. Results: When CBCT was compared with the image of CT simulation before treatment, the average difference by coordinate in the head and neck was 0.99 mm vertically, 1.14 mm longitudinally, 4.91 mm laterally, and 1.07o in the rotational direction, showing somewhat insignificant differences by part. In testing after correction, when the image from the electronic portal imaging device was compared with DRR image, it was found that correction had been made accurately with error less than 0.5 mm. Conclusion: By comparing a CBCT image before treatment with a 3D image reconstructed into a volume instead of a 2D image for the patient's setup error and change in the position of the organs and the target, we could measure and correct the change of position and target volume and treat more accurately, and could calculate and compare the errors. The results of this study show that CBCT was useful to deliver accurate treatment according to the treatment plan and to increase the reproducibility of repeated treatment, and satisfactory results were obtained. Accuracy enhanced through CBCT is highly required in IMRT, in which the shape of the target volume is complex and the change of dose distribution is radical. In addition, further research is required on the criteria for match focus by treatment site and treatment purpose.

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A study on transferring the effects of brand reputation and level of service satisfaction of an offline channel company when it is expanding to an online distribution channel (온라인 유통채널 확장시 오프라인 채널의 브랜드 명성, 서비스 만족도의 이전 효과에 관한 연구)

  • Hwang, Hee-Joong;Lee, Sun-Mi
    • Journal of Distribution Science
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    • v.9 no.2
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    • pp.31-36
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    • 2011
  • I conducted empirical analyses of what happens when an offline channel expands to an online channel and whether the pre-existing offline channel's competitive assets (e.g. brand reputation and level of service satisfaction) can be linked to online channel preference. I found that an offline channel's brand reputation and level of service satisfaction can have a direct influence on offline channel preference and a second-hand influence on online channel preference. Thus, if the competitiveness of the online channel is strong enough and its customers have a higher preference for the offline channel, they will be committed and loyal to the company. The resultant enhanced competitiveness of the offline channel will present opportunities for both present and future success. The main results are the following. First, the management of the distribution channel service quality is more important than that of the brand reputation. Customers' experiences of service and subjective evaluations are not important only as the leading factors in the long-term brand reputation management but also as influential factors in channel preference. SoThus, given that the service quality of the pre-existing channel is not the customers' main concern, a strategy of improving the level of service satisfaction aimed at present customers is more valuable than a wide brand positioning strategy aimed at general and new customers. Second, when an offline channel company establishes an internet shopping mall on an online channel, it is highly likely that the preference and subjective evaluation of the present customers will influence the online channel. This applies not only to the special case of an expansion from an offline intermediary channel to an online one, but also to an online channel acting as an expansion of the business model of a conventional manufacturing or service company: both cases are vertical integrations of marketing channels in an expansion of the distribution channel. My theory applies to a wide range of contexts. Third and finally, any business strategy can grasp the meaning of 'channel expansion. Fundamentally, it is an expansion of the sales activity channel and marketing activity. However, it is also a way of enhancing marketing and sales competitiveness through an expansion to an online or offline channel. The expansion of an offline company to an online channel could be seen not as improvement but as an innovation of the business process by which two goals are achieved with one technique. The former is expected to increase the sales of the offline company, and the latter is also expected to increase sales while also contributing to cost reduction.

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Analysis of the Characteristics of the Seismic source and the Wave Propagation Parameters in the region of the Southeastern Korean Peninsula (한반도 남동부 지진의 지각매질 특성 및 지진원 특성 변수 연구)

  • Kim, Jun-Kyoung;Kang, Ik-Bum
    • Journal of the Korean Society of Hazard Mitigation
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    • v.2 no.1 s.4
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    • pp.135-141
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    • 2002
  • Both non-linear damping values of the deep and shallow crustal materials and seismic source parameters are found from the observed near-field seismic ground motions at the South-eastern Korean Peninsula. The non-linear numerical algorithm applied in this study is Levenberg-Marquadet method. All the 25 sets of horizontal ground motions (east-west and north-south components at each seismic station) from 3 events (micro to macro scale) were used for the analysis of damping values and source parameters. The non-linear damping values of the deep and shallow crustal materials were found to be more similar to those of the region of the Western United States. The seismic source parameters found from this study also showed that the resultant stress drop values are relatively low compared to those of the Western United Sates. Consequently, comparisons of the various seismic parameters from this study and those of the United States Seismo-tectonic data suggest that the seismo-tectonic characteristics of the South eastern Korean Peninsula is more similar to those of the Western U.S.

Enzymatic characterization of Paenibacillus amylolyticus xylanases GH10 and GH30 for xylan hydrolysis (Paenibacillus amylolyticus 유래 xylanase GH10 및 GH30의 xylan 가수분해 특성)

  • Nam, Gyeong-Hwa;Jang, Myoung-Uoon;Kim, Min-Jeong;Lee, Jung-Min;Lee, Min-Jae;Kim, Tae-Jip
    • Korean Journal of Microbiology
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    • v.52 no.4
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    • pp.463-470
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    • 2016
  • The enzymatic degradation of xylans is the most versatile way to obtain the high value-added functional compounds or the fermentable sugars for renewable energy. The endo-${\beta}$-xylanases are the major enzymes which hydrolyze the internal ${\beta}$-1,4-linkages of xylan backbones to produce the mixtures of xylooligosaccharides including xylobiose and xylotriose. Among them, glucuronoxylanase GH30 can exclusively hydrolyze the internal ${\beta}$-1,4-linkages of xylans decorated with methylglucuronic acid branches. In the present study, two xylanolytic enzyme (PaXN_10 and PaGuXN_30) genes were cloned from Paenibacillus amylolyticus KCTC 3005, and expressed in Escherichia coli, respectively. PaXN_10 (38.7 kDa) belongs to the endo-${\beta}$-xylanases GH10 family, while PaGuXN_30 (58.5 kDa) is a member of glucuronoxylanase GH30. They share the same optimal reaction conditions at $50^{\circ}C$ and pH 7.0. Enzymatic characterization proposed that P. amylolyticus can utilize the hardwood glucuronoarabinoxylans via the cooperative actions of xylanases GH10 and GH30. The extracellular PaGuXN_30 is secreted into the medium and hydrolyzes glucuronoarabinoxylans to release a series of aldouronic acid mixtures with a methylglucuronic acid branch. The resultant products being transported into the microbial cell are successively degraded into the smaller xylooligosaccharides by the intracellular PaXN_10, which will be utilized for the cellular metabolism.