Current status and outlook of medical treatment for KRAS-mutated non-small cell lung cancer / 中华肿瘤杂志

Lung cancer remains the leading cause of cancer-related deaths in men and women worldwide, and 85% of these patients have non-small cell lung cancer. In recent years, the clinical use of targeted drug therapy and immune checkpoint inhibitors has dramatically changed the treatment landscape for advanced NSCLC. The mechanism and the value of targeted therapies have been a hot topic of research, as KRAS is one of the earliest discovered and most frequently mutated oncogenes, which is activated by binding to GTP and triggers a series of cascade reactions in cell proliferation and mitosis. The KRAS protein acts as a molecular switch and is activated by binding to GTP, triggering a series of cascade responses in cell proliferation and mitosis. Clinically, patients with KRAS mutated NSCLC have poor response to systemic medical therapy and poor prognosis. Since the first report of KRAS gene in 1982, research on KRAS targeted therapeutics has been slow, and previous studies such as farnesyltransferase inhibitors and downstream protein inhibitors of KRAS signaling pathway have not achieved the expected results, making KRAS long defined as a "non-druggable target". The deeper understanding of the crystal structure of KRAS has led to the discovery of potential therapeutic sites for KRAS and the development of several drugs directly targeting KRAS, especially KRAS G12C inhibitors such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have shown encouraging results in clinical trials. In recent years, studies on the therapeutic efficacy of immune checkpoint inhibitors for KRAS-mutated NSCLC have made some progress. In this review, we systematically introduce the basic understanding of RAS gene and clinical characteristics of KRAS mutated NSCLC patients, summarize the medical treatments for KRAS mutated NSCLC, including chemotherapy, anti-vascular drug therapy and tumor immunotherapy, and focus on the review and outlook of the research progress of KRAS targeted therapy.

ADAMTS9-AS1-SEMA3G affects the infiltration of immune cells in pancreatic cancer / 医学研究生学报

ObjectiveThe mechanism that affects the infiltration of immune cells in pancreatic cancer has not yet been clarified. This study aims to investigate the lncRNA mRNA regulatory pathways that affect immune infiltration in pancreatic cancer.MethodsTCGA and GEO gene expression data were used to screen common differential lncRNAs. We perform survival analysis, target gene prediction, GO, KEGG enrichment analysis, immune infiltration analysis, gene set enrichment analysis (GSEA) on the selected differential lncRNAs to identify the relevant pathways of immune infiltration.ResultsThe pancreatic cancer patients with high expression of ADAMTS9 AS1 have a higher survival rate when compared to patients with low expression (P=0.010). The combined analysis of TCGA and GSE86436 revealed the difference and survival-related ADAMTS9 AS1. The functional prediction of ADAMTS9 AS1 was related to immunity. Using the TIMER database, the lncRNA affected the infiltration of immune cells in pancreatic cancer tissues. The clinical analysis was demonstrated that the ADAMTS9 AS1 was related to pathological grade. The target gene SEMA3G was screened by co-expression analysis using the IMMPORT database and TIMER database. Lastly, GSEA analysis of ADAMTS9-AS1 showed that the lncRNA was also related to tumor metabolism.ConclusionThese results indicate that ADAMTS9-AS1-SEMA3G is associated with the prognosis and immune invasion level of pancreatic cancer, which can provide a theoretical basis for subsequent genetic verification experiments and immune research.

Analysis of Risk Factors Affecting the Chemotherapy-related Infections in Patients with ALL / 中国实验血液学杂志

OBJECTIVE@#To analyze the risk factors affecting the chemotherapy-related infections in patients with acute lympho-blastic leukemia (ALL).@*METHODS@#The clinical data of 102 patients with ALL from January 2014 to December 2018 were collected and retrospectively studies. The risk factors of chemotherapy-related infections were analyzed by univa-riate and multivariate logistic regression.@*RESULTS@#A total of 386 courses of chemotherapy were completed, out of which the infection occurred in 201 course, with the infection rate of 52.07%, identified infection number was 215 case-times, including perianal infection of 13.95% (30/215), oral infection of 13.49% (29/215), blood flow infection of 1721% (37/215), lower respiratory tract infection of 37.21% (80/215), urinary infection of 3.26% (7/215), skin infection of 3.72% (8/215), digestive and intra abdominal infection of 9.30% (20/215), and other infections of 1.86 (4/215). Totally 88 strains of pathogenic bacteria were detected, including 29 Gram-positive bacteria (32.95%), 52 Gram-negative bacteria (59.09%) and 7 fungi (7.95%). Gram-positive bacteria mainly were Staphylococcus haemolyticus and Enterococcus faecium, susceptible to tegacycline, vancomycin and linezolid; Gram-negative bacteria mainly were Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae, susceptible to tegacycline, amikacin, piperacillin/tazobactam and imipenem; Candida was the dominant fungus. Living in an ordinart ward, neutrophil defi-ciency for more than 7 days after chemotherapy and incomplete remission were independent risk factors of related infections during the induction chemotherapy in ALL inpatients, and hospitalization time also closely related with chemo-therapy-related infections in ALL inpatients (P<0.05). Neutrophil deficiency for more than 7 days after chemotherapy was an independent risk factor of chemotherapy-related infections in ALL inpatients in the consolidation chemotherapy (P<0.05).@*CONCLUSION@#Patients with ALL are prone to chemotherapeutic-related infections, and those who lack neutrophils for more than 7 days after chemotherapy and who do not reach complete remission are more prone to infection. Living in laminar flow ward and reducing hospitalization stay can help reduce the incidence of infection.

Upregulation of Neural Precursor Cell Expressed Developmentally Downregulated 4-1 is Associated with Poor Prognosis and Chemoresistance in Lung Adenocarcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The E3 ubiquitin ligase neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) negatively regulates phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein levels through polyubiquitination and proteolysis, but its significance in lung cancer is still unclear. This study investigated the expression and the role of NEDD4-1 in tumor development and chemosensitivity of lung adenocarcinoma (ADC).</p><p><b>METHODS</b>We retrospectively investigated the expression and significance of NEDD4-1, PTEN, and p-Akt proteins in 135 paired ADC and adjacent noncancerous tissue specimens using immunohistochemistry. Furthermore, we evaluated the relationship between NEDD4-1 expression and clinicopathologic characteristics and prognosis. The effects of small interfering RNA against NEDD4-1 on proliferation and chemosensitivity were examined in A549 cells in vitro using 3- (4,5-dimethylthiazol-2-yl) -5-(3-carboxymethoxyphenyl) -2-(4-sulfophenyl)- 2H-tetrazolium method. The ability of migration and invasion of A549 cells was tested by transwell assay. Moreover, reverse-transcription quantitative polymerase chain reaction and Western blotting analyses were used to determine the expression of NEDD4-1, PTEN, phosphoinositide 3-kinase (PI3K)/Akt activity, and its downstream target proteins.</p><p><b>RESULTS</b>NEDD4-1 protein was significantly upregulated in lung ADC tissues, whereas it was weak or negative in normal lung epithelial cells. The expression of NEDD4-1 in ADC (78.5%, 106/135) was significantly much higher than that in adjacent normal lung tissue (13.3%, 29/135, P < 0.01), and it was associated with lymph node metastasis, tumor-node-metastasis (TNM) stage, and chemotherapy resistance. PTEN expression was downregulated in lung ADC (60.7% vs. 100.0% in noncancerous specimens, P = 0.007), and was negatively correlated with lymph node metastasis, histological variants, clinical stage, chemoresistance. In addition, expression of p-Akt in ADC tissues (71.1% 96/135) was much higher than that in adjacent lung epithelial cells (6.7%, 9/135, P < 0.01). Kaplan-Meier and multivariate analysis demonstrated that expressions of NEDD4-1 and PTEN were both independent risk factors for survival in patients with lung ADC. NEDD4-1 knockdown in vivo decreased proliferation, migration, and invasion and improved chemosensitivity to cisplatin and paclitaxel in A549 cells. NEDD4-1 knockdown also significantly enhanced PTEN expression and inhibited p-Akt activity and downstream target proteins.</p><p><b>CONCLUSIONS</b>NEDD4-1 upregulation may contribute to the progression of lung ADC. NEDD4-1 may regulate the proliferation, invasion, migration, and chemoresistance of lung ADC cells through the PI3K/Akt pathway, suggesting that it may be regarded as a therapeutic target for the treatment of lung ADC.</p>

Development of Two-Dimensional Liquid Chromatography Coupled with Tandem Mass Spectrometry for Identification of Extracted Proteins of Rice Leaves: Hydrophilic Interaction-Reversed-phase Approach / 分析化学

A two-dimensional liquid chromatography method was developed for the analysis of rice leaves proteomics based on the coupling of hydrophilic interaction liquid chromatography-reversed-phase liquid chromatography with online tandem mass spectrometry. The influence of pH value of chromatographic mobile phase on the orthogonality of the hydrophilic interaction-reversed-phase two-dimensional liquid chromatography was evaluated by the changes of standard peptide retention. The results indicated that the better orthogonality (R2=0.34113) was achieved from the system with hydrophilic interaction columns(pH 9.3) in the first and C18columns(pH 3.3) in the second LC dimension. Coupled with multiple fraction concatenation strategy,the orthogonality of two-dimensional liquid chromatography was further evaluated in the analysis of complex rice leaf proteins. The results showed that more than 50% of the total peptides were identified less than two times, and the peptides obtained from first-dimension were well distributed across the elution window,indicating that the method showed significant orthogonality in the identification of complex rice leaf proteins. Based on the proteome discoverer software,207345 peptides belonged to 2930 protein clusters were identified.

Role of adjuvant chemoradiotherapy in treatment of resectable esophageal carcinoma: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The effectiveness and influence of surgery followed by adjuvant chemoradiotherapy (CRT) on the survival of patients with resectable esophageal carcinoma are still under debate. The outcomes of clinical trials have not been consistent. This study aimed to perform a meta-analysis of eligible published clinical trials to compare CRT with surgery without adjuvant chemoradiotherapy (non-CRT) for resectable esophageal carcinoma.</p><p><b>METHODS</b>Computerized bibliographic and manual searches were undertaken to identify all eligible literature between 1990 and 2012. PubMed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang databases were our primary sources for published clinical trials. The quality of the methodology and reliability of the data from all of the clinical trials were assessed. All data were extracted by three independent researchers.</p><p><b>RESULTS</b>Seven studies that included a total of 523 patients were selected. It was found that CRT significantly improved survival. The odds ratio (OR) in comparing CRT and non-CRT groups was 1.75 (95% confidence intervals (CI): 1.17 - 2.60, P = 0.006) for 1-year survival, 2.07 (95%CI: 1.45 - 2.96, P < 0.0001) for 3-year survival, and 2.17 (95%CI: 1.45 - 3.26, P = 0.0002) for 5-year survival. There have been no CRT treatment-related deaths reported in the literature. The incidence of related complications was high in the cases with CRT. Patients treated with CRT had a lower incidence of local-regional cancer recurrence (OR: 0.49, 95%CI: 0.31 - 0.76, P = 0.002) and a similar incidence of distant cancer recurrence (OR: 0.90, 95%CI: 0.60 - 1.34, P = 0.60).</p><p><b>CONCLUSIONS</b>It was found that patients with resectable esophageal carcinoma could gain a survival benefit from CRT. However, CRT was associated with a high incidence of related complications.</p>

Upregulation of glucosylceramide synthase protein in papillary thyroid carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Glucosylceramide synthase (GCS) can reduce ceramide levels and help cells escape ceramide-induced apoptosis, thus leading to multidrug resistance (MDR). However, its expression and clinical significance in thyroid neoplasms still remain unclear. We aimed to elucidate the expression of GCS and explore its correlation with the clinicopathological characteristics in papillary thyroid carcinomas (PTCs).</p><p><b>METHODS</b>We retrospectively investigated GCS protein expression level in tissue specimens obtained from 108 consecutive PTC patients by immunohistochemistry and Western blotting.</p><p><b>RESULTS</b>GCS was weakly positive or negative in normal follicular cells, but it was frequently overexpressed in PTC cells. GCS overexpression was associated with primary tumor size, local infiltration, lymph node metastasis, and local recurrence, but not associated with gender, age, pathological variants, tumor multifocality, tumor stage or distant metastasis. Western blotting also showed that GCS protein levels were much higher in PTCs' tissues than in normal thyroid tissues.</p><p><b>CONCLUSION</b>GCS was upregulated in PTCs and might be an independent factor affecting prognosis.</p>

Effects of Baidanhuang lavage fluid nasal irrigation on the postoperative patients with chronic rhinosinusitis with nasal polyps / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy of Baidanhuang lavage fluid nasal irrigation (BLFNI) on postoperative patients with chronic sinusitis with nasal polyps (CRwNP).</p><p><b>METHODS</b>Ninety postoperative patients with CRwNP were randomly assigned to two groups, the treatment group (60 cases) and the control group (30 cases). After nasal endoscopic surgery, all patients received routine therapies, while the nasal cavity perfusion device was used to irrigate. Patients in the treatment group were treated with BLFNI, while those in the control group were irrigated with physiologic saline with dexamethasone and gentamycin. The physic liquor was maintained in the nasal cavity for 15 min, 14 days as one therapeutic course: once per 3 days in first treatment course; once per 5 days in the second treatment course; once per 7 days in the third treatment course. The irrigation times gradually reduced as time went by. The VAS scoring was performed in four clinical symptoms, such as nasal obstruction, rhinorrhea, olfaction disorders, discomforts or pain in the face or head. The Lund-Kenenedy quantification scoring method was used for nasal endoscopy to assess the polyps size, mucous membrane, scar, surface scab, and quality of life (QOL). The SNOT-20 rating scales were filled to investigate the QOL. All the assessments were carried out before surgery, 1.5, 3, and 6 months, respectively. The comprehensive efficacy assessment was conducted 1 year later.</p><p><b>RESULTS</b>The 1-year cure rate was 79.25% in the treatment group and 76.92% in the control group, and the total effective rate was 90.57% in the treatment group and 84.62% in the control group. There was no statistical difference between the two groups (P > 0.05). The nasal cavity cleaning time and the epithelization time was (2.15 +/- 0.13) weeks and (9.17 +/- 1.67) weeks respectively in the treatment group, earlier than those in the control group [(2.65 +/- 0.15) weeks and (10.71 +/- 3.12) weeks, P < 0.05]. At week eight 22 patients in the treatment group ended the lavage due to recovery, while 5 patients in the control group ended the lavage, showing statistical difference (P < 0.05). Compared with the control group, better results were obtained in the treatment group in relieving the total VAS score at postoperative 6 weeks and 3 months, in the single score of symptoms at 3 months after operation, the rhinorrhea at postoperative 6 months and 1 year (P < 0.05). The total endoscopic score, and the single score for nasal mucous membrane edema, and nasal secretion at postoperative 1.5 month were lower in the treatment group than in the control group (P < 0.05). The total score of SNOT-20 questionnaire, and the integrals for five major indicators at postoperative 1.5 and 3 months were lower in the treatment group than in the control group (P < 0.05).</p><p><b>CONCLUSIONS</b>The perioperative application of BLFNI could alleviate postoperative mucosal inflammation, shorten the cavity cleaning time, speed up the process of epithelization, improve the QOL, and elevate the operative efficacy. Its therapeutic roles were more prominent within perioperative 1.5-3 months.</p>

Related factors of central lymph node metastasis in papillary thyroid carcinoma / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the related factors of central lymph node (CLN) metastasis in papillary thyroid carcinoma (PTC),the indications and the extent of central neck dissection (CND).</p><p><b>METHODS</b>A total of 153 cases treated between Jan. 2009 and Dec. 2010 was analysed retrospectively. Of the cases 28 males and 125 cases females, with a mean age of (44 ± 14) years. T1, T2, and T3 diseases accounted for 51, 10 and 81 cases, respectively; I, II, III and IV diseases for 88, 3, 26 and 36 cases, respectively. Multifocal tumors were found in 63 cases. The related clinicopathologic factors were analyzed, including sex, age, tumor size, extrathyroidal extension, and multifocal tumor.</p><p><b>RESULTS</b>All the cases had total/near total thyroidectomy and CND, of them 64 cases had unilateral neck dissection and 18 cases had bilateral neck dissection. CLN metastases existed in 68.6% (105/153) cases, 37.2% (57/153) for unilateral and 31.4% (48/153) for bilateral respectively. The rates of CLN metastasis were 86.6% (71/82) in cN1 cases and 47.9% (34/71) cN0 cases, respectively,and the rates of bilateral CLN metastases were 45.1% (37/82) in cN1 cases and 15.5% (11/71) in cN0 cases. Multivariate analysis showed that extrathyroidal extension (P = 0.002, OR = 3.502) was an independent risk factor for CLN metastasis and that lateral neck lymph node metastasis (P = 0.028, OR = 3.080), surrounding tissue invasion (P = 0.014, OR = 3.113), and maximum tumor diameter greater than 1 cm (P = 0.012, OR = 3.732) were independent risk factors for bilateral CLN metastases.</p><p><b>CONCLUSIONS</b>It is indicated that ipsilateral CND should be obligatory for PTC. Intraoperative frozen section examination should be routine. Bilateral CND should be conducted when ipsilateral CLN metastases accompanied by one of following issues such as more invasive tumor (surrounding tissue invasion, T3 or T4 disease), maximum tumor diameter greater than 1 cm, and lateral neck lymph node metastasis.</p>

Littoral cell angioma of the spleen: report of three cases and a review of the literature / 中华医学杂志(英文版)

Littoral cell angioma is a recently described rare vascular tumor of the spleen. The clinical course of this benign tumor is asymptomatic in most patients. Herein, we described three patients with littoral cell angioma detected during physical examination. A brief discussion and review of a handful of cases of splenic littoral cell angioma, which have been previously reported in the English language literature, are performed in this paper.

Inhibitory effect of photodynamic therapy combined with paclitaxel on the proliferation of esophageal carcinoma Eca-109 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of photodynamic therapy (PDT) in combination with paclitaxel (PCT) on proliferation in esophageal carcinoma Eca-109 cells line.</p><p><b>METHODS</b>Eca-109 cells were treated with PCT alone, HPD alone at different doses, or their combinations. For the combined treatments, the cells were exposed to PCT for 12 h followed by incubation with HPD at high, middle or low concentrations for 4 h. PDT was then performed on these treated cells and fluorescence microscopic observation was made before and after PDT. The cell survival was measured by MTT assay, and the cell apoptosis rate analyzed by flow cytometry after a 24-h cell incubation following PDT.</p><p><b>RESULTS</b>The fluorescence excitation of the cells was weakened after PDT. Combined treatments resulted in significantly lowered cell survival rate and increased cell apoptosis rates as compared to those of the control cells and the cells treated with PCT alone and low-dose HPD (P<0.01). Significant differences were also noted among the cells exposed to HPD at different concentrations (P<0.05).</p><p><b>CONCLUSION</b>PDT combined with PCT have significant synergetic effects in inhibiting the proliferation of human esophageal carcinoma cells and inducing their apoptosis in vitro.</p>

Effect of actovegin on intestinal mucosa and expression of bcl-2/bax genes in rats with acute radiation enteritis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effect of actovegin (Nycomed, deproteinized hemoderivative of calf blood injection) on intestinal mucosa in rats with acute radiation enteritis, and observe the changes of expression of apoptosis-related bcl-2/bax genes.</p><p><b>METHODS</b>An abdominal irradiation in a dose of 9.0 Gy X-ray of linear accelerator was performed once on a group of Wistar rats to establish a model of acute intestinal radiation enteritis. The experimental rats were randomly divided into five groups. Group 1 was normal control group; group 2 was model control group; groups 3, 4 and 5 were treated with low, middle and high dose of actovegin, respectively. After the model was established, actovegin injection was given intraperitoneally for successive 4 days. Corresponding intestinal tissues were taken for morphological examination with an image analysis system. The expression of apoptosis related bax and bcl-2 protein in the intestinal mucosal epithelial cells was determined by immunohistochemistry.</p><p><b>RESULTS</b>The groups 4 and 5 had significantly higher height of intestinal villi, the depth of crypt, the thickness of the mucosa and entire wall (254.66/261.71 microm, 166.47/165.41 microm, 510.44/511.71 microm, 610.38/608.98 microm), compared with those of the model control group (239.12 microm, 151.45 microm, 420.27 microm and 579.32 microm), respectively (P < 0.05). Treatment with middle and high doses of actovegin also significantly down-regulated the expression of activating apoptosis protein bax (24.54/23.24) compared with that of model control group (59.32) (P < 0.05) and up-regulated the expression of inhibiting apoptosis protein bcl-2 (55.54/52.21) compared with that of model control group (20.32) (P < 0.05). The ratio of bcl-2/bax was significantly higher in the groups 4 and 5 (2.2632, 2.1275) compared with that in the model control group (0.3425) (P < 0.01).</p><p><b>CONCLUSION</b>Actovegin accelerates the recovery of the acute radiation-injured intestinal mucosal epithelium by decreasing apoptosis via down-regulation of the expression of activating apoptosis protein bax and up-regulation of inhibiting apoptosis protein bcl-2.</p>

Detecting the haplotype of three Y-STR loci by fluorescent multiplex amplification / 法医学杂志

OBJECTIVE@#To establish a fluorescent multiplex PCR system for typing Y-STR loci Y-GATA-A7.1, DYS456 and DYS443, and investigate their haplotype frequencies in Chinese Han population.@*METHODS@#203 unrelated males of Han population living in Zhengzhou were typed by fluorescent multiplex amplification system and ABI 3100 genetic analyzer.@*RESULTS@#In Zhengzhou Han population, 5,6 and 6 different alleles were observed for Y-GATA-A7.1, DYS456 and DYS443 loci, and their gene diversity (GD) were 0.669 2, 0.583 9 and 0.705 3 respectively. A total of 44 different haplotypes formed by these three loci was identified and the haplotype diversity (HD) reached 0.952 3.@*CONCLUSION@#The fluorescent multiplex system for these three Y-STR loci will be very powerful for forensic individual identification and paternity testing in Chinese Han population.

Abnormal expression of hMSH2 mRNA and mutation P53 protein in acute lymphoblastic leukemia / 中国实验血液学杂志

In order to investigate the mechanism of acute lymphoblastic leukemic cell malignant proliferation, the expressions of hMSH2 mRNA and mutation P53 (mtP53) protein in bone marrow cells of de novo acute lymphoblastic leukemia (ALL) were determined by in situ hybridization and immunocytochemical methods. The results showed the that percentage of positive cell with hMSH2 mRNA expression was (32.88 +/- 11.46)% in the de novo ALL group and (64.22 +/- 8.51)% in the control group. The percentage of positive cell with mtP53 protein expression was (29.25 +/- 9.45)% in the de novo ALL group, and (12.63 +/- 6.66)% in the control group. There was a significant negative correlation between the positive percentages of hMSH2 mRNA expression and mtP53 protein expression (r = -0.45, P < 0.05). It is concluded that defective MSH2 mRNA expression plays an important role in the pathogenesis of acute lymphoblastic leukemia, mtP53 protein mutation plays an important role in the development of acute lymphoblastic leukemia, the hMSH2 mRNA defect can lead to accumulation of the mutant P53 protein in acute lymphoblastic leukemia, and both jointly promote the pathogenesis of ALL.

Reversal of multidrug resistance property of carcinoma cells by down-regulating transcription of mdr-1 / 中华病理学杂志

<p><b>OBJECTIVE</b>To reverse the multidrug resistance (MDR) property of carcinoma cells by blocking transcription of activating sites of mdr-1.</p><p><b>METHODS</b>Breast carcinoma cells were transinfected with several antisense oligonucleotide (ASODN) complementary to mdr-1 by lipofectin. RT-PCR was used to detect the production of mdr-1mRNA. The expression of P-glycoprotein (gp) was then detected by immunohistochemistry and the function of P-gp was detected by rhodamine123 retention.</p><p><b>RESULTS</b>Forty-eight hours after transfection, mdr-1 index of cells treated by ASODN complementary to MA zone (major initiation start zone), MI (minor initiation start zone), C zone (CAAT box), G zone (GC box) of mdr-1 gene was 1.4, 1.9, 1.6 and 2.1 respectively. The rate of P-gp protein expression in treated cells was 14%, 43%, 26% and 39% respectively. The intracellular Rh123 retention in treated cells was 125%, 83%, 102% and 77% respectively. There was significant difference between cells treated by ASODN complementary to MA zone and C zone and drug-resistant cells.</p><p><b>CONCLUSIONS</b>The ASODN complementary to MA zone and C zone of mdr-1 gene can reverse MDR of drug-resistant cells to various extent, amongst which the former is more effective. Down-regulating transcription of mdr-1 by blocking transcription activating sites can reduce the expression of mdr-1mRNA and P-gp, and thus reversing MDR of carcinoma cells. The ASODN complementary to MI zone, G zone of mdr-1 however do not significantly reverse the MDR property.</p>