Biological Clock Genes are Crucial and Promising Biomarkers for the Therapeutic Targets and Prognostic Assessment in Gastric Cancer.

BACKGROUND: Gastric cancer is one of the major public health problems worldwide. Circadian rhythm disturbances driven by circadian clock genes play a role in the development of cancer. However, whether circadian clock genes can serve as potential therapeutic targets and prognostic biomarkers for gastric cancer remains elusive. METHODS: In this study, we comprehensively analyzed the potential relationship between circadian clock genes and gastric cancer using online bioinformatics databases such as GEPIA, cBioPortal, STRING, GeneMANIA, Metascape, TIMER, TRRUST, and GEDS. RESULTS: Biological clock genes are expressed differently in human tumors. Compared with normal tissues, only PER1, CLOCK, and TIMELESS expression differences were statistically significant in gastric cancer (p < 0.05). PER1 (p = 0.0169) and CLOCK (p = 0.0414) were associated with gastric cancer pathological stage (p < 0.05). Gastric cancer patients with high expression of PER1 (p = 0.0028) and NR1D1 (p = 0.016) had longer overall survival, while those with high expression of PER1 (p = 0.042) and NR1D1 (p = 0.016) had longer disease-free survival. The main function of the biological clock gene is related to the circadian rhythms and melatonin metabolism and effects. CLOCK, NPAS2, and KAT2B were key transcription factors for circadian clock genes. In addition, we also found important correlations between circadian clock genes and various immune cells in the gastric cancer microenvironment. CONCLUSIONS: This study may establish a new gastric cancer prognostic indicator based on the biological clock gene and develop new drugs for the treatment of gastric cancer using biological clock gene targets.

Association of TNF-α, IGF-1, and IGFBP-1 levels with the severity of osteopenia in mice with nonalcoholic fatty liver disease.

BACKGROUNDS: Nonalcoholic fatty liver disease (NAFLD) exhibits a close association with osteoporosis. This work aims to assess the potential effects of NAFLD on the progression of osteopenia in animal models. METHODS: Forty-eight C57BL/6 female mice were randomly divided to wild-type (WT) group and high-fat diet (HFD) group. The corresponding detections were performed after sacrifice at 16, 24 and 32 weeks, respectively. RESULTS: At 16 weeks, an remarkable increase in body weight and lipid aggregation in the hepatocytes of HFD group was observed compared to the WT group, while the bone structure parameters showed no significant difference. At 24 weeks, the levels of TNF-α and IL-6 in NAFLD mice were significantly increased, while the level of osteoprotegerin mRNA in bone tissue was decreased, and the level of receptor activator of nuclear factor Kappa-B ligand mRNA was increased. Meanwhile, the function of osteoclasts was increased, and the bone microstructure parameters showed significant changes. At 32 weeks, in the HFD mice, the mRNA levels of insulin-like growth factor-1 (IGF-1), runt-related transcription factor 2, and osterix mRNA were reduced, while the insulin-like growth factor binding protein-1 (IGFBP-1) level was increased. Simultaneously, the osteoblast function was decreased, and the differences of bone structure parameters were more significant, showing obvious osteoporosis. CONCLUSIONS: The bone loss in HFD mice is pronounced as NAFLD progresses, and the changes of the TNF-α, IL-6, IGF-1, and IGFBP-1 levels may play critical roles at the different stages of NAFLD in HFD.

New target DDR1: A "double-edged sword" in solid tumors.

Globally, cancer is a major catastrophic disease that seriously threatens human health. Thus, there is an urgent need to find new strategies to treat cancer. Among them, identifying new targets is one of the best ways to treat cancer at present. Especially in recent years, scientists have discovered many new targets and made breakthroughs in the treatment of cancer, bringing new hope to cancer patients. As one of the novel targets for cancer treatment, DDR1 has attracted much attention due to its unique role in cancer. Hence, here, we focus on a new target, DDR1, which may be a "double-edged sword" of human solid tumors. In this review, we provide a comprehensive overview of how DDR1 acts as a "double-edged sword" in cancer. First, we briefly introduce the structure and normal physiological function of DDR1; Second, we delineate the DDR1 expression pattern in single cells; Next, we sorte out the relationship between DDR1 and cancer, including the abnormal expression of DDR1 in cancer, the mechanism of DDR1 and cancer occurrence, and the value of DDR1 on cancer prognosis. In addition, we introduced the current status of global drug and antibody research and development targeting DDR1 and its future design prospects; Finally, we summarize and look forward to designing more DDR1-targeting drugs in the future to make further progress in the treatment of solid tumors.

HIF1α: A Novel Biomarker with Potential Prognostic and Immunotherapy in Pan-cancer.

Cancer is a catastrophic disease that seriously affects human health. HIF1α plays an important role in cancer initiation, progression, and prognosis. However, little is known about the specific role of HIF1α in pan-cancer. Therefore, we systematically and comprehensively analyzed HIF1α using GEPIA, HPA, GeneMANIA, STRING, SMPDB, cBioPortal, UALCAN, and TISDB databases and also 33 cancer and normal tissues in TCGA downloaded from the Genome Data Commons (GDC) data portal. Data and statistical analysis were performed using R software v4.0.3. Our results found that there were differences in the mRNA expression levels of HIF1α in human pan-cancer and its corresponding normal tissues. The expression level of HIF1α correlated with tumor stage in LIHC and also significantly correlated with prognosis in LIHC, LUSC, STAD, OV, PAAD, PRAD, THCA, LUAD, MESO, and READ. The small molecule pathways involved in HIF1α include succinate signaling, fumarate, and succinate carcinogenesis-related pathways. The highest mutation frequency of the HIF1α gene in pan-cancer was head and neck cancer, and the HIF1α methylation level in most tumors is significantly reduced. HIF1α was not only associated with immune cell infiltration but also with immune checkpoint genes and immune regulators TMB and MSI. There were currently 5 small molecule drugs targeting HIF1α.

Respiratory exposure to carbon black nanoparticles may induce testicular structure damage and lead to decreased sperm quality in mice.

Environmental carbon black nanoparticles (CBNPs) can enter into various organs including testes through the respiratory tract. However, there are few studies describing reproductive toxicity of CBNPs after respiratory exposure. In this study, male KM mice were exposed to CBNPs in their natural breathing state. Four-, 8-, and 12-week-old mice were exposed to 0, 9, 18 and 27 mg/m3 of CBNPs for 4 weeks in order to examine the relationship between CBNP exposure and age. Eight-week-old mice were exposed to CBNPs at the same four concentrations for 1-4 weeks in order to examine the effects of CBNP exposure time. After CBNP exposure, testicular oxidative stress and inflammation increased significantly, and these effects varied with exposure time. Seminiferous tubule diameter (STD), seminiferous epithelium height (SEH), the number of spermatogenic and Leydig cells, sperm motility, and sperm speed decreased significantly, and these effects varied with exposure dose. Data analyses suggested that increased oxidative stress and inflammation in testes damaged testicular morphology, spermatogenesis, and testosterone secretion, and decreased sperm quality. Morphological damage to the testes was also closely related to decreased the sperm quantity. These findings are of significance for evaluating the reproductive toxicity of CBNPs.

Prognostic value and therapeutic implications of ZHX family member expression in human gastric cancer.

Despite significant advances in the early diagnosis and effective treatment of gastric cancer, it remains the fourth most common cancer and the second leading cause of cancer-related deaths worldwide. The zinc-fingers and homeoboxes (ZHX) family of transcriptional repressors has been shown to play a role in multiple types of cancer. However, the prognostic significance of ZHX expression in patients with gastric cancer remains unclear. This work studied the association between differential expression of ZHX mRNA and outcomes in patients with gastric cancer using data from the Oncomine, CCLE, Kaplan-Meier-plotter, and cBioPortal databases. Expression of ZHX3 protein was also measured by immunohistochemistry (IHC) in gastric cancer tissues. We found that increased expression of ZHX1 mRNA and decreased expression of ZHX2 and ZHX3 were correlated with better overall survival (OS) in patients with gastric cancer. Further subgroup analyses identified significant associations between ZHX1 expression and survival in select gastric cancer patients. IHC staining confirmed that the over-expression of ZHX3 was associated with worse OS, and multivariate analyses identified ZHX3 expression as an independent prognostic factor. These results suggest that the ZHX family members may serve as distinct biomarkers and prognostic factors for patients with gastric cancer.

Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A.

Ewing's sarcoma, the second most common type of malignant bone tumor, generally occurs in children and young adults. The current treatment of Ewing's sarcoma comprises systemic anti­cancer chemotherapy with complete surgical resection. However, the majority of patients with Ewing's sarcoma develop resistance to chemotherapy. The present study revealed an oncogenic role of lactate dehydrogenase­A (LDHA) in the resistance of Ewing's sarcoma to cetuximab. LDHA was shown to be upregulated at the protein and mRNA level in cetuximab­resistant Ewing's sarcoma tissues and a cell line. In addition, a link between LDHA­induced glycolysis and cetuximab resistance in Ewing's sarcoma cells was revealed. Of note, inhibition of LDHA by either small interfering RNA or LDHA inhibitor oxamate significantly re­sensitized cetuximab­resistant cells to cetuximab. Combined treatment with LDHA inhibitor and cetuximab synergistically reduced the viability of cetuximab-resistant cells through the suppression of LDHA. The present study revealed a novel mechanism of cetuximab resistance from the perspective of cancer­cell metabolism and provided a sensitization approach, which may aid in the development of anti-chemoresistance strategies for the treatment of cetuximab-resistant Ewing's sarcoma.

[Effect of airway humidification on lung injury induced by mechanical ventilation].

OBJECTIVE: To explore the effect of airway humidification on lung injury as a result of mechanical ventilation with different tidal volume (VT). METHODS: Twenty-four male Japanese white rabbits were randomly divided into four groups: low VT with airway humidification group, high VT with airway humidification group, low VT and high VT group without humidification, with 6 rabbits in each group. Mechanical ventilation was started after intubation and lasted for 6 hours. Low VT denoted 8 mL/kg, while high VT was 16 mL/kg, fraction of inspired oxygen (FiO2) denoted 0.40, positive end-expiratory pressure (PEEP) was 0. Temperature at Y piece of circuit in airway humidification groups was monitored and controlled at 40 centigrade. Arterial blood gas analysis, including pH value, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), lung mechanics indexes, including peak airway pressure (P(peak)) and airway resistance (Raw), and lung compliance was measured at 0, 2, 4, 6 hours of mechanical ventilation. The levels of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in plasma and bronchoalveolar lavage fluid (BALF) were determined by enzyme linked immunosorbent assay (ELISA). The animals were sacrificed at the end of mechanical ventilation. The wet to dry (W/D) ratio of lung tissues was calculated. Histopathologic changes in the lung tissueies were observed with microscope, and lung injury score was calculated. Scanning and transmission electron microscopies were used to examine the integrity of the airway cilia and the tracheal epithelium. RESULTS: Compared with low V(T) group, pH value in high V(T) group was significantly increased, PaCO2was significantly lowered, and no difference in PaO2was found. P(peak), Raw, and lung compliance were significantly increased during mechanical ventilation. There were no significant differences in blood gas analysis and lung mechanics indexes between low V(T) with airway humidification group and low V(T) group. Compared with high V(T) group, PaCO2in high V(T) with airway humidification group was significantly decreased, Ppeak raised obviously, and no difference in pH value, PaO2, Raw and pulmonary compliance was found. Compared with low V(T) with airway humidification group, no difference in blood gas analysis (PaCO2, mmHg, 1 mmHg=0.133 kPa) was found, but Ppeak (cmH2O, 1 cmH2O=0.098 kPa), Raw (cmH2O), and lung compliance (mL/cmH2O) were increased significantly in high V(T) with airway humidification group (PaCO2at 2 hours: 27.96 ± 4.64 vs. 36.08 ± 2.11, 4 hours: 28.62 ± 2.93 vs. 34.55 ± 5.50, 6 hours: 29.33 ± 2.14 vs. 35.01 ± 5.53; Ppeak at 0 hour: 14.34 ± 1.97 vs. 8.84 ± 1.32, 2 hours: 17.33 ± 0.52 vs. 11.17 ± 2.14, 4 hours: 17.83 ± 0.98 vs. 12.67 ± 2.06, 6 hours: 18.67 ± 1.22 vs. 13.50 ± 2.16; Raw at 0 hour: 37.36 ± 5.14 vs. 27.0 5 ± 2.93, 2 hours: 43.94 ± 6.58 vs. 31.95 ± 3.56, 4 hours: 48.04 ± 6.07 vs. 35.24 ± 3.50, 6 hours: 50.33 ± 6.34 vs. 36.66 ± 3.64; pulmonary compliance at 6 hours: 2.28 ± 0.18 vs. 1.86 ± 0.37, all P<0.05). The lung W/D ratio in high VT group was significantly higher than that of the low V(T) group (6.17 ± 2.14 vs. 3.50 ± 1.52, P<0.05). W/D in high V(T) with airway humidification group was higher than that of low V(T) with airway humidification group but without statistically significant difference (5.17 ± 2.14 vs. 3.00 ± 1.10, P>0.05). Microscopic observation showed that cilia were partially detached, adhered and sparse in low V(T) group, while cilia in high V(T) group showed serious detachment and lodging. Remaining cilia were sparse, with lodging, and cellular structure was damaged. Lung tissue pathological injury score in the high V(T) group was significantly higher than that of low V(T) group (6.17 ± 2.14 vs. 3.50 ± 1.52, P<0.05). Cilia density and cellularity were normal in low V(T) with airway humidification group, and no difference in lung tissue pathological injury score was found compared with low V(T) group (3.00 ± 1.10 vs. 3.50 ± 1.52, P>0.05). Cilia were severely detached, adhered and lodging, and cellularity were not obvious in high V(T) with airway humidification group, and lung tissue pathological injury score was elevated significantly than that of the low V(T) with airway humidification group but without statistically significant difference (5.17 ± 2.14 vs. 3.00 ± 1.10, P>0.05). TNF-α and IL-8 concentrations showed no change in plasma and BALF in all groups during ventilation, and no significant difference was found among the groups. CONCLUSIONS: Airway humidification can alleviate pathological lung injury, damage of cilia and cellular structure in trachea caused by mechanical ventilation with low and high V(T). High V(T) with humidification can result in serious pulmonary edema.

[Treatment of distal comminuted humeral fracture with serious osteoporosis by total elbow arthroplasty].

OBJECTIVE: To analyse short-term clinical effect of total elbow arthroplasty in treatment of distal comminuted humeral fracture with serious osteoporosis in geratic patients. METHODS: From April 2006 to October 2007, five cases of distal comminuted humeral fractures were treated by total elbow arthroplasty with bone cement. Of them, there were 2 males and 3 females, aging 50-76 years old (mean 67.6 years old), including 4 cases of closed fracture and 1 case of open fracture (II type Gustilo-Anderson). All fractures were caused by tumbling. According to classification of AO, there were 2 cases of type C1, 2 cases of type C2 and 1 case of type C3. The Barnett index of osteoporosis was 0.40-0.45. The time from injury to operation was 4 to 18 days (mean 7.2 days). The rehabilitation exercise of function was done after 2 days of operation. RESULTS: The operative time was from 120 to 180 minutes (mean 150 minutes), the bleeding amount was from 150 to 250 mL (mean 200 mL). All incision achieved primary healing. No complication occurred. Five cases were followed up for 19 to 36 months (mean 24.5 months). The mean motion range of elbow joint include 141.6 degrees for flection, 6.5 degrees for extention, 10.2 degrees for the degree of ectropion, 81.7 degrees for revolve forward, and 73.8 degrees for revolve behind respectively after 4 months of operation. The length discrepancy of upper limb was less than 1.5 cm, the muscle force for flexion and extention of finger and wrist was normal. The X-ray films showed that the position of artificial joint was satisfactory without prosthesis dislocation or loosening. According to Mayo elbow performance score, the excellent and good rate was 80% (excellent in 1 case, good in 3 cases, and fair in 1 case). CONCLUSION: Total elbow arthroplasty with bone cement is an effective method in treatment of distal comminuted humeral fracture with serious osteoporosis obviously in the geratic patients, but indication and technique of operation should be mastered strictly.

[Primary anterior focus debridement and bone autograft with internal fixation via transperitoneal approach for tuberculosis of lumbosacral junction].

OBJECTIVE: To evaluate the clinical outcomes of primary anterior focus debridement, bone autograft, and internal fixation via transperitoneal approach in treating tuberculosis of the lumbosacral junction. METHODS: From February 2002 to April 2007, 16 patients with tuberculosis of the lumbosacral junction underwent anterior radical debridement, autologous iliac bone graft (two pieces of iliac bone, 5 cm x 3 cm in size), and internal fixation via transperitoneal approach, including 4 males and 12 females aged 27-63 years old (average 38 years old). The course of the disease ranged from 6 to 18 months (average 10 months). All patients experienced various degrees of pain in the lumbosacral area and toxic symptoms of the tuberculosis. Nine cases were complicated with radicular pain in the lower extremities, and 3 cases had saddle area anaesthesia. Two cases were initially diagnosed as lumbar intervertebral disc protrusion and treated accordingly. The segments involved by the tuberculosis were L5-S1 level in all cases. The average erythrocyte sedimentation rate (ESR) was 61 mm/hour. Imaging examination confirmed the diagnosis of spinal tuberculosis. All cases received four antitubercular drugs and nutrition support for nerve before operation. Operation was performed when hepatorenal function was normal, and the toxic symptom of the tuberculosis was under control or ESR was decreased. RESULTS: Operation was performed safely in all cases without injuries of abdominal viscera, major blood vessel, cauda equina nerve and ureter. All wounds healed by first intention. No recurrence of tuberculosis and formation of sinuses occurred. All cases were followed up for 12-37 months (average 21 months). No such complications as tuberculous peritonitis and intestinal obstruction occurred. No postoperative erectile dysfunction and retrograde ejaculation occurred in the 4 male patients. ESR was recovered to normal 3-6 months after operation, and regular X-ray and CT exams showed no displacement of grafted bone. All patients achieved bony fusion 12 months after operation without the occurrence breakage and loosening of titanium plate and screw. The radical pain in the lower extremities and the saddle area anaesthesia disappeared. Four patients had pain in the iliac donor site, 2 patients had mild pain in the lumbosacral area, and the pain was eliminated after symptomatic treatment. The therapeutic effect was graded as excellent in 14 cases and good in 2 cases according to the therapeutic effect evaluation criteria of Chen and co-workers. CONCLUSION: The surgical treatment of tuberculosis of the lumbosacral junction with primary anterior focus debridement, bone autograft, and internal fixation via transperitoneal approach can achieve satisfying bony fusion and reconstruct spinal stability.

[Repair and reconstruction for severe fracture and dislocation of ankle joint].

OBJECTIVE: To summarize the technique and effect of the therapy for severe fracture and dislocation of ankle joint by operation. METHODS: From March 2003 to February 2006, 76 cases were treated with primary open restoration and internal fixation for dislocated ankle joint fracture, with 47 males and 29 females, with the average age of 36.4 years (ranging from 18 years to 65 years). According to AO criterion, these fresh fractures were classified into 13 cases for type C3-1, 45 cases for type C3-2 and 18 cases for type C3-3. Based on the Gustilo-Anderson standard, 23 open fractures were classified into 17 cases for type II and 6 cases for type III A. The operation was delayed from 1 hours to 24 hours after the injury. RESULTS: All incisions healed at the first stage except 4 cases which delayed union because of simple infection by revision with ointment. A total of 72 cases were followed up, with the average time of 18.5 months (from 12 months to 35 months). The time of bone union was from 12 weeks to 24 weeks. The screws of fixation for lower tibia-fibula joint were found to be ruptured in 2 cases when further consultation was performed in the 16th and 20th week after the operation, respectively, and were broken within 1 year after the operation. These screws were taken out 12 weeks postoperative in 28 cases, while the whole internal fixations of the rest cases were taken out 1 year after the operation. The postoperative function of malleolus extended from 21.7 degrees to 26.8 degrees and flection from 38.5 degrees to 44.7 degrees. Assessed by the American Orthopaedic Foot and Ankle Society Clinical Rating Scales, 23 cases were excellent, 36 good, 13 fair, and the choiceness rate reached 81.94%. CONCLUSION: These procedures, together with reduction by twist after hospital, open and internal fixation in time, and parenchyma managed with internal fixation, are important to attain satisfactory effect for the treatment of severe fracture and dislocation of ankle joint.

[Treatment of intertrochanteric comminuted fracture in aged patients by replacement of artificial long-stem bipolar femoral head].

OBJECTIVE: To discuss the clinical effect of hip arthroplasty for the treatment of intertrochanteric comminuted fracture in aged patients. METHODS: From February 2004 to March 2006, 89 cases with intertrochanteric comminuted fractures were treated by replacement of artificial long-stem bipolar hip hemiarthroplasty with bone cement, including 34 males and 55 females, with the average age of 82.6 years (ranging from 70 years to 92 years). There were fresh fractures in 76 cases and old fractures in 13 cases. According to improving-classification of Evans-Jensen, there were 32 cases with type III fracture and 57 with type IV. Osteoporosis was graded by Singh-index, and there were 24 cases with level IV, 46 with level III and 19 with level II. The operation was delayed from 4 days to 36 days (6.5 days on average) after the injury. RESULTS: The surgery time lasted from 50 minutes to 70 minutes (62 minutes on average). Bleeding volume was from 100 mL to 250 mL (150 mL on average). The time in hospital was from 16 days to 25 days (18.6 days on average). All incision primarily healed except 1 case which delayed union by revision with infection. Steel wire rupture occurred in 1 case, invalidation in 1 case. They were not treated because there were no uncomfortable symptoms. The consciousness disability happened in 2 cases 2 to 3 days after the operation, 2 case with the infection for the system of urine and breath 1 week after operation, were healed through the treatment. Eighty-five cases were followed up for 14 months to 39 months (26.5 months on average). The function of the hip was graded by the system of Harris and the choiceness rate was 84.7% (excellent in 16 cases, good in 56 cases, fair in 12 cases and poor in 1 case). CONCLUSION: The treatment of intertrochanteric comminuted fracture in the aged patients by replacement of long-stem bipolar femoral head prosthesis is effective, but indications and techniques of the operation must be paid much attention to.

[Influence of artificial pneumoperitoneal media on colon carcinoma cell proliferation in vitro].

OBJECTIVE: To evaluate the influence of different pneumoperitoneal media on colon carcinoma LS-174T cell proliferation in vitro. METHODS: The artificial pneumoperitoneum was established. The proliferation of LS-174T cells was detected by MTT assay and soft agar clone formation assay. Expression of HIF-1alpha and VEGF was examined by immunohistochemistry. Apoptosis of LS-174T cells was analyzed by AO/EB double fluorescein stain and flow cytometry. RESULTS: The growth speed and proliferating capacity of LS-174T cells in CO(2) pneumoperitoneum group[A:0.37 +/- 0.02,formation (32.8 +/- 3.6)%] were significantly higher than those in control group [A:0.33 +/- 0.01,formation (28.4 +/- 2.3)%] and He group [A:0.30 +/- 0.01,formation (23.5 +/- 2.7)%], meanwhile the He group was the lowest (P<0.01). Positive expression of HIF-1alpha and VEGF in CO(2) and He artificial pneumoperitoneum up-regulated significantly as compared to control group(P<0.01), meanwhile the above expression was higher in CO(2) group (P<0.01). The G(0 )/G(1) ratio in CO(2) group was the lowest as compared to control group and He group (P<0.01), and G(0 )/G(1) ratio in He group was higher than that of control group(P<0.01). Aapoptosis rate in He group was the highest as compared with the other two groups(P<0.01). CONCLUSION: CO(2) pneumoperitoneum has stronger effect on the proliferation of colon carcinoma cell LS-174T as compared to He pneumoperitoneum in vitro.

[Expression of multidrug resistance-associated protein 1 in osteosarcoma and its relationship with clinicopathologic characteristics].

OBJECTIVE: To detect the expression of multidrug resistance-associated protein 1 (MRP1) in human ostesarcoma and to explore its relationship with clinicopathologic characteristics. METHODS: Six normal bone specimens and 45 osteosarcomas from patients were analysed for MRP1 expression by immunohistochemistry. The expression levels of MRP1 with the clinicopathologic parameters of the patients were examined using Chisquare test. RESULTS: The expression of MRP1 was observed in 32 (71.11%) osteosarcoma specimens. More(P < 0.05) specimens expressed MRP1 in high-grade osteosarcomas(30/38, 78.95%) than in low-grade osteosarcomas (2/7, 28.57%). The correlation coefficient between expression of MRP1 and grade of pathology was 0.844. In a limited number of patients, the expression of MRP1 was not related to the the age and sex of the patients, Enneking surgical stage, osteosarcoma size, serum concentration of ALP and duration before diagnosis. No expression of MRP1 in 6 normal bone specimens was observed. CONCLUSION: MRP1 is expressed in osteosarcoma and its expression is positively correlated with the malignancy of osteosarcoma.