ulinastatin oncology proposal

MEDICCA PRESS A MEDICAL CONTENT COMPANY

Anthology of Clinical Evidences: Ulinastatin in oncology Proposal for BSVL

Anthology of Clinical Evidences: Ulinastatin in

Oncology

Details of Deliverables

Type of input: Booklet

Title of the input: Anthology of Clinical Evidences: Ulinastatin in Oncology

Target customers: Oncologist

Periodicity: One-time

Issue details: 24+4 pages; centre pinning; A4 size; 4-color job

Molecule and indication: Ulinastatin for the treatment of cancer

Contents

The booklet will include re-written articles on the efficacy and safety of

ulinastatin in the treatment of cancer.

The articles in the booklet will be presented under the following sections:

Section 1 : Clinical studies on the efficacy and safety of ulinastatin in cancer

Section 2 : In vitro and experimental studies on the efficacy and safety

of ulinastatin in cancer.

Relevant figures, graphs and tables and the key messages will be

highlighted.



Sample references

Clinical studies

Nan Fang Yi Ke Da Xue Xue Bao. 2007 Jan;27(1):81-3.

[Effect of ulinastatin on inflammatory responses induced by oesophagectomy].

Lu XY1, Zeng WA, Lin WQ, Chen BX, He WX.

Abstract

OBJECTIVE:

To examine the effect of ulinastatin (UTI) on the inflammatory responses induced by

oesophagectomy.

METHODS:

Forty patients with esophageal cancer (without serious hypertension, heart disease, or

respiratory function impairment, including 34 men and 6 women aged 46 to 70 years)

scheduled for oesophagectomy via left thoracotomy were randomly divided into control

group (n=20) and UTI group (n=20). Anesthesia induction and perioperative management

followed the same protocols in the two groups, and in UTI group, patients received 5000 U/kg

UTI while those in the control group were given the same volume of saline. Before operation

(T(1)), 10 min after recovery of two-lung ventilation (T(2)), and 24 h (T(3)) and 48 h (T(4)) after

operation, the venous blood sample was taken from the internal jugular vein and the plasma

was separated and stored at -70 degrees C for later analysis of IL-6 and IL-8 with enzyme-

linked immunosorbent assay (ELISA). The bronchoalveoar lavage fluid (BAFL) was also

collected at T(1) and T(2) for IL-6 and IL-8 detection.

RESULTS:

IL-6, IL-8 levels in the plasma and BALF collected at T(2)-T(4) increased significantly as

compared with those in samples collected at T(1), and their peak concentration inplasma and

BALF samples were similar. IL-6 and IL-8 levels in the UTI group were significantly lower than

those in the control group during the time points of T(2)-T(4).

CONCLUSION:

Inflammatory responses occur during and after oesophagectomy, which can be inhibited with

UTI.

Med Oncol. 2015 Jan;32(1):405. doi: 10.1007/s12032-014-0405-x. Epub 2014 Dec 12.

Protective effect of ulinastatin in patients with non-small cell lung cancer after radiation

therapy: a randomized, placebo-controlled study.

Bao P1, Zhao W, Li Y, Liu Y, Zhou Y, Liu C.

Abstract



Radiation-induced lung injury (RILI) is a frequent, sometimes life-threatening complication of

radiation therapy for the treatment of lung cancer. The anti-inflammatory role

of ulinastatin has been well documented, and the potential application of ulinastatin in

management of acute lung injury has been suggested in multiple animal studies. In this article,

we described a double-blind, randomized, placebo-controlled study in patients with non-

small cell lung cancer. A total of 120 patients were randomized into two groups: the trial

group was treated with ulinastatin for 3 days prior to and for the first 7 days of radiation

therapy and the control group was treated with placebo for 10 days following the same

schedule. The results from follow-up studies showed that the incidence and grade of RILI were

significantly lower in the trial group than in the control group. Reduction in pulmonary

function from baseline was significantly smaller in the trial group than that in the control

group. Production of serum TGF-1, TNF- and IL-6 decreased significantly in the trial group

promptly following radiation therapy. However, no difference in survival or tumour response

rate was found between the two groups. The results indicated that ulinastatin exerted a

protective effect on radiation-induced lung injury. Treatment with ulinastatin could be an

effective management strategy and greatly improve the clinical efficacy of radiation therapy

for patients with lung cancer.

World J Surg Oncol. 2013 Apr 10;11:84. doi: 10.1186/1477-7819-11-84.

Preventive effect of ulinastatin on postoperative complications, immunosuppression, and

recurrence in esophagectomy patients.

Zhang L1, Wang N, Zhou S, Ye W, Yao Q, Jing G, Zhang M.

Abstract

BACKGROUND:

To evaluate the potential efficacy of preventive effect of ulinastatin in esophagectomy

patients.

METHODS:

Eighty patients with esophageal cancer were preoperatively allocated at random into two

equal groups. Ulinastatin was administered to the treatment group (U) whereas the control

group (C) received a placebo. The arterial oxygen tension and carbon dioxide tension were

measured and the respiratory index (RI) was calculated. Plasma levels of circulating T

lymphocyte subsets and interleukin 6 (IL-6) were measured and clinical courses of patients in

the two groups were compared.

RESULTS:

RI in the U group was significantly lower than that in the C group. The rate of postoperative

complications and the duration of ICU stay were significantly lower in the U

group. Ulinastatin significantly increased the rate of CD3+ and CD4+ cells, and ratio of

CD4+/CD8+, but decreased the rate of CD8+ cells and release of IL-6 compared to the C group

on postoperative days 1 and 3. Patients within the C group showed worse recurrence free



survival. Multivariate analysis revealed that ulinastatin administration significantly decreased

the incidence of recurrence.

CONCLUSIONS:

Ulinastatin had a preventive effect on postoperative complications and immunosuppression

in esophagectomy patients, thereby prolonging recurrence free survival.

PLoS One. 2011;6(12):e29053. doi: 10.1371/journal.pone.0029053. Epub 2011 Dec 22.

Safety of postoperative administration of human urinary trypsin inhibitor in lung

cancer patients with idiopathic pulmonary fibrosis.

Yamauchi Y1, Izumi Y, Inoue M, Sugiura H, Goto T, Anraku M, Ohtsuka T, Kohno M, Soejima

K, Nomori H.

Abstract

BACKGROUND:

Patients with idiopathic pulmonary fibrosis (IPF) undergoing pulmonary resection for lung

cancer carry risks of acute exacerbations of IPF (AE) postoperatively. Currently, agents which

may attenuate AE are actively sought. Urinary trypsin inhibitor, ulinastatin, is a synthetic

glycoprotein which may potentially inhibit various inflammatory factors associated with the

development and progression of IPF. The present study was done to evaluate the effects of

administration of high dose ulinastatin in lung cancer patients with IPF immediately following

lung resection.

METHODS:

Patients with IPFs radiologically diagnosed on high resolution CT, and histologically diagnosed

resectable lung cancers, were eligible for the study. The effects of escalating doses

of ulinastatin 310(5), 610(5), and 910(5) units/body/day, administered postoperatively for

3 days were evaluated. The endpoints were safety and feasibility.

RESULTS:

Nine patients were evaluated, in cohorts of 3 patients per dosage. Postoperative follow up

ranged from 3 to 12 months (median 9 months). The postoperative courses were uneventful

in all patients. No subjective adverse events such as abdominal symptoms or skin rashes, or

objective adverse events as per serum laboratory tests, such as liver or kidney dysfunctions

potentially attributable to ulinastatin administration were observed. AE was seen in one

patient at 3 months after surgery, but since this occurred shortly after administration of

chemotherapy, it was considered to be attributable to the chemotherapy rather than surgery.

DISCUSSION:

Ulinastatin administration after lung resection in lung cancer patients with IPF was considered

to be safe and feasible. Further study is planned at the highest dose of this study to evaluate

efficacy.



Nan Fang Yi Ke Da Xue Xue Bao. 2007 Jan;27(1):81-3.

[Effect of ulinastatin on inflammatory responses induced by oesophagectomy].

Lu XY1, Zeng WA, Lin WQ, Chen BX, He WX.

Abstract

OBJECTIVE:

To examine the effect of ulinastatin (UTI) on the inflammatory responses induced by

oesophagectomy.

METHODS:

Forty patients with esophageal cancer (without serious hypertension, heart disease, or

respiratory function impairment, including 34 men and 6 women aged 46 to 70 years)

scheduled for oesophagectomy via left thoracotomy were randomly divided into control

group (n=20) and UTI group (n=20). Anesthesia induction and perioperative management

followed the same protocols in the two groups, and in UTI group, patients received 5000 U/kg

UTI while those in the control group were given the same volume of saline. Before operation

(T(1)), 10 min after recovery of two-lung ventilation (T(2)), and 24 h (T(3)) and 48 h (T(4)) after

operation, the venous blood sample was taken from the internal jugular vein and the plasma

was separated and stored at -70 degrees C for later analysis of IL-6 and IL-8 with enzyme-

linked immunosorbent assay (ELISA). The bronchoalveoar lavage fluid (BAFL) was also

collected at T(1) and T(2) for IL-6 and IL-8 detection.

RESULTS:

IL-6, IL-8 levels in the plasma and BALF collected at T(2)-T(4) increased significantly as

compared with those in samples collected at T(1), and their peak concentration inplasma and

BALF samples were similar. IL-6 and IL-8 levels in the UTI group were significantly lower than

those in the control group during the time points of T(2)-T(4).

CONCLUSION:

Inflammatory responses occur during and after oesophagectomy, which can be inhibited with

UTI.

Zhonghua Wei Chang Wai Ke Za Zhi. 2005 Nov;8(6):487-9.

[Protective efficacy and probable mechanism of ulinastatin in patients with

gastrointestinal cancer undergoing adjuvant chemotherapy].

He YL1, Deng YH, Huang MJ, Zhao JZ, Cai SR, Zhang CH, Zhan WH.

Abstract

OBJECTIVE:

To investigate whether ulinastatin can alleviate the side effect in patients with

gastrointestinal cancer undergoing adjuvant chemotherapy, and to explore the probable

mechanism of its protective efficacy.



METHODS:

Forty consecutive patients with gastrointestinal cancer who underwent surgical operations

from May 2004 to October 2004 were recruited. The patients were randomly divided into

therapeutic group and control group, receiving ulinastatin 150,000 U per day or 250 ml

hydrochloric sodium before chemotherapy for 5 continuous days respectively. The prevalence

of side effects and the levels IL-6 and TNF-alpha were compared between the two groups.

RESULTS:

There were no differences in the clinicopathological characteristics between the two groups.

The prevalences of white blood cell decline (41.2% versus 13.1%), pigmentation (23.5% versus

4.3%), baldness (17.6% versus 4.3%) were higher in the control group than those in

therapeutic group (all P< 0.05). In therapeutic group, IL-6 level was significantly decreased

after ulinastatin treatment, but not in the control group while the levels of TNF-alpha were

not changed in the both groups.

CONCLUSION:

Ulinastatin can reduce the common side effects of chemotherapy, and the mechanism may

be associated with the decrease of IL-6.

Dis Esophagus. 2005;18(3):151-4.

Use of low dose dopamine, gabexate mesilate and ulinastatin reduces the water balance

and pulmonary complication in thoracic esophagectomy patients.

Sato A1, Kuwabara Y, Shinoda N, Kimura M, Ishiguro H, Fujii Y.

Abstract

SUMMARY:

In spite of improvements in surgical technique and perioperative care, severe lung

complication remains as the leading cause of morbidity in thoracic esophageal cancer patients

who undergo esophagectomy. The purpose of this study was to evaluate the safety and

effectiveness of postoperative drug therapy using low dose dopamine, gabexate mesilate,

and ulinastatin on postoperative lung complication in esophageal cancer patients. Sixty-one

patients operated for esophageal cancer from 1996 to 2000 were treated postoperatively

with low dose dopamine (300 microg/kg/h), gabexate mesilate (80 mg/h), and ulinastatin(300

000 unit/day) as a study group. Seventy-four patients operated from 1987 to 1994 served as

an historical control group. Various preoperative and perioperative medical parameters and

water balance were analyzed. Postoperative pulmonary complications were observed in 26

patients (35.1%) in the control group and three patients (4.9%) in the study group,

respectively (P < 0.0001). Preoperative and perioperative variables were not significantly

different between the groups. Water balance from operation to postoperative day 3 in the

study group was significantly lower than the control group. Postoperative use of low dose

dopamine, gabexate mesilate, and ulinastatin significantly reduced pulmonary complications



after esophagectomy. This may be partly attributable to negative water balance during the

early postoperative days.

Chinese Journal of Digestive Surgery 2009 Vol. 8 No. 5 pp. 374-376

Effects of ulinastatin on pulmonary and hepatorenal function of elderly patients undergoing

resection of esophageal cancer.

Xiong XueMei; Wu Wei; Xia Mei; Wang Hua

Abstract

The objective of this study was to investigate the effects of ulinastatin on pulmonary and

hepatorenal function of elderly patients who underwent resection of oesophageal cancer.

The clinical data of 40 elderly patients with oesophageal cancer who were admitted to

Southwest Hospital from January 2005 to 2008 were retrospectively analysed. All the patients

were randomly divided into control group (n=20) and ulinastatin group (n=20) according to

random number table. Patients were administered with total parenteral nutrition and

patients in ulinastatin group were additionally instilled with 4105 U/d of ulinastatin. The

levels of PaO2, PaCO2, PaO2/FiO2, alanine aminotransferase (ALT), aspartate aminotransferase

(AST), total bilirubin (TBil), blood urea nitrogen, creatinine and uric acid were detected

preoperatively and at postoperative day two and day six. All the data were analysed by f-test

and chi-square test. The levels of PaO2 and PaO2/FiO2 were (87.34.2) mm Hg (1mmHg=0.133

kPa) and (41620) mmHg in ulinastatin group, which were significantly higher than (79.04.3)

mmHg and (37620) mmHg in control group (t=6.2, 6.2, P



Objective To investigate the effects of ulinastatin on cytokines in patients with liver cancer

during the treatment of high intensity focused ultrasound (HIFU). Methods Twenty ASA class

or liver cancer patients, scheduled for the treatment of HIFU, were randomly divided

into two groups with 10 cases each. The patients in group U received intravenous infusion of

ulinastatin after anesthesia induction and the same amount of normal saline was given

instead of ulinastatin in group C. Plasma concentrations of CRP and TNF- were measured

before the treatment (T1), at the end of the treatment (T2) and 24 h after the treatment (T3).

Results In group C, plasma concentrations of CRP,IL-6,IL-8,IL-10 and TNF- were significantly

increased at T2 and T3 compared with those at T1 (P0.05 or P0.01). In group U, although

plasma concentration of CRP was also increased at T2 and T3 compared with those at T1

(P0.05),the increase of CRP was significantly lower than that in group C at T3 (P0.05). Plasma

concentration of IL-10 in group U was increased at T2 and T3 compared with that at T1 (P0.05

or P0.01) and was significantly higher than that in group C at T2 (P0.05).Plasma concentrations

of IL-6,IL-8 and TNF- at T1 were not significantly different from those at T2 and T3 in group

U. Conclusion The treatment of HIFU increased cytokine production of patients. Ulinastatin

can decrease proinflammatory factor and increase antiinflammatory factor during the

treatment of HIFU in the patients with liver cancer.

Journal of Xinxiang Medical College 2012-12

Effect of ulinastatin on inflammatory response in patients undergoing resection of liver cancer

SUN Fen-fen,ZHAO Zhen-long,TANG Jing,GU Miao-ning,XIAO Jin-fang(Department of

Anesthesiology,Nanfang Hospital,Southern Medical University,Guangzhou

510515,Guangdong Province,China)

Objective To study the anti-inflammatory effect of ulinastatin in patients undergoing

resection of liver cancer. Methods Forty adult patients of American Society of

Anesthesiologists class- who were scheduled for resection of liver cancer were divided

into two groups according to random digits table, including ulinastatin group and normal

saline group and twenty patients in each group. After general anaesthesia, the patients in

ulinastatin group were treated with ulinastatin 10 000 Ukg-1 dissolved in 20 mL normal

saline, while the patients in normal saline group were treated with 20 mL normal saline,

intravenous drip infusion, within 20 minutes after the start of surgery. Before operation (T1),

after operation (T2),6 hours(T3) and 24 hours(T4) after operation, the venous blood samples

were taken from internal jugular vein. After separation of the serum, the levels of interleukin

(IL)-6, IL-8, IL-10 and tumor necrosis factor- (TNF-) were detected with LiquiChip system.

Results There was no statistically significant difference in the levels of serum IL-6,IL-8,IL-10

and TNF- at T1 between the two groups(P0.05).There was no significant difference in the

levels of serum IL-8 and TNF- at the same time point between the two

groups(P0.05).Compared with normal saline group, at T2,T3 and T4,the level of IL-6 was lower



in ulinastatin group(P0.05),but the level of IL-10 was higher significantly(P0.01).There was no

significant difference in serum TNF- level among all time points between the two

groups(P0.05).The levels of IL-6,IL-8 and IL-10 in the two groups at T2,T3 and T4 were higher

than those at T1(P0.01),and the levels of IL-6 and IL-8 increased with the development of

time(P0.05).However, there was no significant difference in IL-10 values among T2,T3 and T4

in the two groups(P0.05).Conclusion Inflammatory response exist in patients undergoing

resection of liver cancer. Ulinastatin can inhibit the generation of pro-inflammatory cytokines

in serum, while promoting the production of anti-inflammatory factors.

Journal of Taishan Medical College 2008-04

Effect of ulinastatin on perioprative cytokine in elderly patients with thoracic tumor

CAO Ling-min,MA Gui-fen(Taian City Central Hospital,Taian 271000,China)

Objective: To observe the effect of ulinastatin on perioprative cytokine in the elderly patients

with thoracic tumor. Methods: Thirty patients undergone elective radical operation for

esophogas and cardia cancer were randomly assigned into two groups with 15 cases each.

The patients in the ulinastatn group (U) received ulinastatin 30ku in 30 min before skin

incision, and the patients in the control group(C) the same volume of normal Saline as in group

U instead of ulinastatin. Blood samples were taken before induction of anesthesia (T1),at the

end of operation(T2), at 1(T3),3(T4),5(T5) day after the end of surgery for the measurements

of interleukin-6(IL-6),IL-8 and tumor necrosis factor alpha(TNF-) by radioimmunoassay.

Results: IL-6 and TNF-increased significantly during the period of T2T4,compared with that

at T1 in group C(P0.05).In group U, the IL-6 and TNF- almost returned to baseline values at

T4.At T2T4,IL-6 and TNF-were significantly higher in group C than those in group

U(P0.05).IL-8 was strikingly higher at T2 and T3 than that at T1 in group C(P0.05),and IL-8 at

T2 and T3 in group C was also significantly higher compared with that in group U. Conclusion:

Ulinastatin can effectively depresss the perioprative cytokine IL-6,IL-8,andTNF- in elderly

patients with thoracic tumor.

In vitro and experimental studies

Onco Targets Ther. 2014 Feb 18;7:305-14.

Synergism from the combination of ulinastatin and curcumin offers greater inhibition

against colorectal cancer liver metastases via modulating matrix metalloproteinase-9 and

E-cadherin expression.

Shen F1, Cai WS1, Li JL1, Feng Z1, Liu QC2, Xiao HQ1, Cao J1, Xu B1.

Abstract

Liver metastasis is a major cause of mortality in colorectal cancer (CRC). The current study

was to investigate the ability of ulinastatin (UTI) and curcumin (CUR) to inhibit CRC liver



metastases via modulating matrix metalloproteinase-9 (MMP-9) and E-cadherin expression.

Human CRC HCT-116 cells were treated with compounds individually and in combination in

order to understand the effect on cell migration and invasion. The HCT-116 cell line was

established to stably express luciferase and green fluorescent protein (GFP) by lentiviral

transduction (HCT-116-Luc-GFP). We identified an anti-metastasis effect of UTI and CUR on a

CRC liver metastasis mouse model. Tumor development and therapeutic responses were

dynamically tracked by bioluminescence imaging. Expression of MMP-9 and E-cadherin in

metastatic tumors was detected by immunohistochemical assay. Results of wound healing

and cell invasion assays suggest that treatment with UTI, CUR, and UTI plus CUR, respectively,

significantly inhibit HCT-116 cell migration and invasion. Furthermore, results of CRC hepatic

metastasis on a nude mouse model showed that treatment with UTI, CUR alone, and a

combination notably inhibited hepatic metastases from CRC and prolonged survival of tumor-

bearing mice, especially in the UTI plus CUR group. These results suggest that the combination

of UTI and CUR together may offer greater inhibition against metastasis of CRC.

Cancer Biother Radiopharm. 2013 Apr;28(3):218-25.

Ulinastatin exerts synergistic effects with taxotere and inhibits invasion and metastasis of

breast cancer by blocking angiogenesis and the epithelial-mesenchymal transition.

Gao F1, Sun Z, Sun X, Zhang Y, Wang H, Zhong B, Luo J, Zhao X.

Abstract

Urinary trypsin inhibitor (UTI) ulinastatin as a broad-spectrum protease inhibitor has been

widely used to treat acute pancreatitis and shock and to improve the surgical outcome in the

clinic. In the present study, we investigated the potential antihuman breast cancer effects of

UTI and its combination with taxotere (TXT). Human primary breast cancer cells and

breast cancer cell line MDA-MB-231 cells were treated with UTI with or without TXT, and

invasion and metastasis ability of these cells were evaluated, respectively, by a transwell

assay. Reverse transcription-polymerase chain reaction was used to detect fibroblast growth

factor, vascular endothelial growth factor c, epidermal growth factor, epidermal growth

factor receptor, transforming growth factor-1, and protein kinase B/AKT. We also

investigated the in vivo role of UTI by using a xenograft mouse model, and

immunohistochemical assay was employed to show the expression of factors involved in

either angiogenesis or the epithelial-mesenchymal transition (EMT). Our results showed that

UTI inhibited invasion and metastasis in both primary and MDA-MB-231 cells both in vivo and

in vitro. Especially, UTI presented the significant combined effects with TXT on these cells in

terms of angiogenesis blocking and EMT inhibition. These results suggest that UTI and its

combination with TXT present therapeutic potential against breastcancer and deserve further

preclinical and clinical studies.



Cancer Biother Radiopharm. 2012 May;27(4):252-8.

Additive effects of ulinastatin and docetaxel on growth of breast cancer xenograft in nude

mice and expression of PGE2, IL-10, and IL-2 in primary breast cancer cells.

Zhong B1, Shen H, Sun X, Wang H, Zhang Y, Sun Z.

Abstract

Ulinastatin is a broad-spectrum enzyme inhibitor extracted from urine. Previous data from

our group suggested that ulinastatin could significantly inhibit proliferation of human breast

MDA-MB-231 cells, growth of tumor xenograft in nude mice, and expression of interleukin

(IL)-6 and IL-8. In the present study, we investigated whether there is an additive effect

of ulinastatin and docetaxel on growth of breast cancer xenografts in nude mice and its

possible mechanisms. Nude mice and primary human breast cancer cells were treated with

phosphate buffered saline (PBS), ulinastatin, docetaxel, or ulinastatin plus docetaxel,

respectively. Their effects on xenograft growth; expressions of cyclooxygenase-2 (COX2),

prostaglandin E2 receptor 2 (EP2), IL-10, and IL-2; and secretion of prostaglandin E2 (PGE2)

were examined using variety of methods, including semi-quantitative reverse transcription-

polymerase chain reaction (RT-PCR), Western blot, enzyme-linked immunosorbent (ELISA)

assay, and immunohistochemistry SP method. The treatment with ulinastatin, docetaxel,

or ulinastatin plus docetaxel could significantly (1) inhibit COX2 and IL-10 expression in

primary tumor cells at both mRNA and protein levels, (2) reduce PGE2 secretion in culture

supernatant (p



METHODS:

The cell lines cultured were divided into four groups: 1) control group, 2) UTI group, 3) TXT

group, and 4) UTI+TXT group. The method of MTT essay, flow cytometry, and RT-PCR were

used to detect cell proliferation, cell apoptosis, and expression of IGF-1R, PDGFA, NGF, NF-B,

JNk-2, respectively. The growth of xenografted tumor in nude mice was used to calculate the

anti-tumor rate. Immunohistochemistry staining (SP) was used to detect the expression of

IGF-1R, PDGFA, NGF, ki-67, caspase-3, JNk-2, and NF-B.

RESULTS:

Proliferation of human breast cancer cells and MDA-MB-231 cell lines, and growth rate of

xenografted tumor decreased in order of UTI+TXT > TXT > UTI > control, apoptosis increased

in the order control < UTI < TXT < UTI+TXT. The gene expression and protein expression of

IGF-1R, PDGFA, NGF, NF-B and JNk-2 in breast cancer cells was inhibited by UTI and TXT.

CONCLUSIONS:

UTI 1) inhibits the proliferation of human breast cancer cells and the growth of xenografted

tumors, 2) induces cancer cell apoptosis, and 3) enhances the anti-tumor effect of TXT. This

mechanism might be related to decreasing signal transduction of JNk-2 and NF-B, and then

expression of IGF-1R, PDGFA, NGF.

ulinastatin oncology proposal

Documents

safety of ulinastatin

effect of ulinastatin

uti group n

oncology proposal

cancer section

control group n

esophageal cancer

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