Investigation on nutrition status and clinical outcome of patients with common cancers in Chinese patients: a multicenter prospective study protocol

Background:Malnutrition is common in patients with cancer, whichadversely affectsthesurvival and quality of life ofcancer patients.However, there is no national data on the prevalence of malnutrition inChinese cancer patients. Thisstudy aims to evaluate the prevalenceof malnutrition and quality of life(QOL)ofChinese patients with localregional, recurrentor metastatic cancer,to address the prognostic value of nutritional status and QOLon the survival of cancer patients in China and to validate the patient-generated subjective global assessment (PG-SGA) questionnaire in Chinese cancer patients.Methods:Thisisanobservational,multi-centered,and hospital-based prospective cohort study.We aimed to recruit 50,000 cancer patients (age 18and above)overan 8-year period.Data collection will occur within 48hrafter patientsare admitted to hospital, 30-days after hospital admission, and the follow-up will be conducted1-8years after enrolment. The primary outcomeisoverall survival, and secondaryoutcomes arelength of hospital stay and hospital costs. Factors measured are demographic characteristics, tumor characteristics, anthropometry measurements,hematological measurement, body composition, PG-SGAscores,Karnofsky performance status scores,and QLQ C30 scores. This protocol wasapproved by local ethical committees of all the participant hospitals.Conclusions: This multi-centered, large-scale, long-time follow-up prospective study will help diagnose malnutrition in cancer patients in China, and identify the related risk factors associated with the negative outcomes. The anticipated results will highlight the need for a truly scientific appraisal of nutrition therapy, and help to improve outcomes among cancer patients in China.Trial Registration: The trial has been registered with the Chinese Clinical Trial Registry, ChiCTR1800020329. Registered on 19 December 2018

Expression and diagnostic value of serum miR-26a/b in patients with gastric cancer / 中国肿瘤临床

Objective:To discuss the diagnostic value of miR-26a/b and relationship of this microRNA with clinicopathological features in patients with gastric cancer. Methods:The expression of serum miR-26a/b was detected in 121 patients with gastric cancer and 116 healthy controls using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationship of miR-26a/b and clinicopathological parameters of patients were analyzed. The receiver operating curve (ROC) was constructed to in vestigate the value of miR-26a/b in the diagnosis of gastric cancer. Results:The relative expression levels of serum miR-26a and miR-26b in patients with gastric cancer were lower than those in the control group (1.60±1.02 vs. 5.35±0.44;1.44±0.71 vs. 5.35±0.71;P<0.05). The relative expression level of miR-26a/b correlated with TNM stage, and the relative expression level of miR-26a also correlated with invasion depth and lymph node metastasis (P<0.05), but not with sex, age, tumor size, or histological type (P>0.05). The area under the ROC curve of miR-26a was 0.828 (95％CI:0.776～0.881), with sensitivity of 73.3％and specificity of 81.0％, while the area under the ROC curve of miR-26b was 0.853 (95％CI:0. 801～0.906), with sensitivity of 68.1％and specificity of 99.2％. Conclusion:The expression of miR-26a/b significantly reduced in patients with gastric cancer, and its expression level correlated with the clinical stage, invasion depth, and lymph node metastasis. MiR-26a/b has potential diagnostic value for gastric cancer.

miR-143 suppresses the proliferation and migration of SGC7901 gastric cancer cells / 中国肿瘤临床

Objective:To investigate the role and mechanism of miR-143 in the proliferation and migration of gastric cancer (GC) cells. Methods:Western blot was performed to detect the expression level of avian erythroblastosis oncogene B-3 (ERBB3) in GC tissues, paired non-cancerous tissues, and SGC7901 GC cells. RT-qPCR was conducted to determine the mRNA and miR-143 of ERBB3 quantita-tively. Bioinformatics tools were used to predict the target gene of miR-143. Luciferase reporter assay was carried out to confirm the predicted target gene. Transwell and EdU assays were applied to observe the migration and proliferation of SGC7901 GC cells transfect-ed with miR-143 mimics/inhibitor/NC mimics/inhibitor. Results:Compared with the expression levels of ERBB3 and miR-143 in the paired non-cancerous tissues, the expression level of ERBB3 was upregulated and the expression level of miR-143 was downregulated in GC tissues. In the prediction of the potential target gene, miR-143 could bind to a specific sequence of the 3′-untranslated regions (UTR) of the mRNA of ERBB3. This finding was supported by luciferase reporter assay results. In vitro, ERBB3 protein expression and cell migration and proliferation were suppressed significantly in the SGC7901 cells transfected with miR-143 mimics. By contrast, these processes were remarkably enhanced when the cells were transfected with miR-143 inhibitor. Conclusion:miR-143 can suppress the migration and proliferation of GC cells by downregulating the expression of ERBB3.

Serum microRNA profiles as novel biomarkers for the post-operative evaluation and survival of patients with glioblastoma multiform / 中国肿瘤临床

Objective:To investigate the differentially expressed miRNAs in serum collected post operation and compared these miR-NAs with those collected pre-surgery among patients suffering from glioblastoma multiform (GBM) and undergoing regular clinical fol-low-up. These miRNAs may be potential biomarkers for the post-operative evaluation of patients with GBM. Methods:Forty-eight pa-tients with GBM and clinical pathological diagnosis were enrolled in this study. In the initial biomarker screening stage, total RNAs were extracted and subjected to Solexa sequencing to select miRNAs with significantly altered expression pre-and post-operation. Some of these differentially expressed miRNAs were chosen and verified through TaqMan probe-based qRT-PCR assay. A t-test was performed to determine the miRNAs that satisfied the two criteria, namely, fold change>2 and P<0.05. All of the patients were fol-lowed-up, and survival data were collected. The patients were then classified into two groups, namely, long-and short-survival groups, on the basis of the median of the miR-30e expression levels in the sera collected post-operation. Kaplan-Meier method and Log-rank test (SPSS version 19.0, IBM) were employed to determine the possible relationships between miR-30e expression levels in the sera collected post-operation and patients' overall survival. Results: Solexa revealed 63 differentially expressed miRNAs. Four miRNAs, namely, miR-26b, miR-30e, miR-129-3p, and miR-206, were selected on the basis of previous and present findings. These miRNAs were then verified in the RT-qPCR phase. Among these miRNAs, only miR-30e was significantly upregulated post-operation. The serum miR-30e expression level post-operation was not significantly associated with the overall survival of the patients. A low miR-30e expression level corresponded to prolonged survival. Conclusion:miR-30e was upregulated in the sera collected post-operation from patients with GBM. This miRNA may be negatively related to the tumor load of these patients. The miR-30e expression level in the serum col-lected post-surgery serum was not significantly associated with overall survival. Therefore, miR-30e may serve as a novel potential non-invasive biomarker for the post-operative evaluation of patients with GBM.

Analysis of the maintenance treatment and prognostic factors of metastatic colorectal cancer patients with stable disease symptoms after induction chemotherapy / 中国肿瘤临床

Objective: To investigate the survival and individualized therapy of metastatic colorectal cancer (mCRC) patients who achieved a stable disease state after induction chemotherapy. Methods:Data were reviewed from 204 metastatic colorectal cancer pa-tients, who presented a stable disease state after first-line and second-line chemotherapy at Tianjin Medical University Cancer Insti-tute and Hospital. The clinical and pathological characteristics were analyzed. Moreover, we analyzed the significance of maintenance treatment in patients with certain mCRC characteristics. Results:Univariate analysis indicated that the line of chemotherapy, levels of CA724, CEA, and CA19-9, and platelet-to-lymphocyte ratio (PLR) were considered prognostic factors of treatment after induction che-motherapy. According to the multivariate analysis, first-line chemotherapy, as well as low levels of CA19-9 and PLR, with maintenance treatment after the induction chemotherapy was significantly associated with better survival. Among the patients with high levels of PLR, those who underwent maintenance treatment achieved a progression-free survival of 13.43 months (versus 10.63 months in pa-tients from the observation group, P=0.003). Conclusion:The levels of CA19-9 and PLR, and treatment after chemotherapy were signif-icant prognostic factors for mCRC patients who achieved a stable disease state after induction chemotherapy. These patients, especial-ly those with high PLR, could benefit from the maintenance treatment.

The choices of advanced gastric cancer / 中国肿瘤临床

Gastric cancer is a malignant cancer with high morbidity and mortality in China. The main aim for advanced gastric cancer is improvement of life quality and overall survival. Chemotherapy is the backbone for advanced gastric cancer's treatment. There are some new evidences in the recent years. We review the chemotherapy options for advanced gastric cancer.

miR-10a inhibits cell proliferation and promotes cell apoptosis by targeting BCL6 in diffuse large B-cell lymphoma

The BCL6 (B-Cell Lymphoma 6) gene is a proto-oncogene that is often expressed in diffuse large B-cell lymphomas (DLBCLs). BCL6 loss of function can kill DLBCL cells, demonstrating that BCL6 is necessary for the survival of DLBCL cells and could be a therapeutic target. In this study, we found that BCL6 protein levels were consistently upregulated in DLBCL tissues, whereas its mRNA levels varied randomly in tissues, suggesting that a post-transcriptional mechanism was involved in BCL6 regulation. We used bioinformatics analysis to search for miRNAs, which potentially target BCL6, and identified specific targeting sites for miR-10a in the 3'-untranslated region (3'-UTR) of BCL6. We further identified an inverse correlation between miR-10a levels and BCL6 protein levels, but not mRNA levels, in DLBCL tumor tissue samples. By overexpressing or knocking down miR-10a in DLBCL cells, we experimentally validated that miR-10a directly recognizes the 3'-UTR of the BCL6 transcript and regulated BCL6 expression. Furthermore, we demonstrated that negatively regulating BCL6 by miR-10a suppressed the proliferation and promoted apoptosis of DLBCL cells.

Onco-miR-24 regulates cell growth and apoptosis by targeting BCL2L11 in gastric cancer

Gastric cancer is one of the most common malignancies worldwide; however, the molecular mechanism in tumorigenesis still needs exploration. BCL2L11 belongs to the BCL-2 family, and acts as a central regulator of the intrinsic apoptotic cascade and mediates cell apoptosis. Although miRNAs have been reported to be involved in each stage of cancer development, the role of miR-24 in GC has not been reported yet. In the present study, miR-24 was found to be up-regulated while the expression of BCL2L11 was inhibited in tumor tissues of GC. Studies from both in vitro and in vivo shown that miR-24 regulates BCL2L11 expression by directly binding with 3'UTR of mRNA, thus promoting cell growth, migration while inhibiting cell apoptosis. Therefore, miR-24 is a novel onco-miRNA that can be potential drug targets for future clinical use.

Progress on exosomal transmission of microRNAs in cancer research / 中国肿瘤临床

Exosomes are cell-derived vesicles that contain protein and RNA from the same source and function. The vesicle has a diam-eter between 30 and 100 nm. Exosomes are the natural carriers and have been recently used as drug delivery system for cancer treat-ment. MicroRNAs (miRNAs) function in RNA silencing and regulation of gene expression. They can exist as intracellular and extracellu-lar miRNAs. Extracellular miRNAs can function as secreted signaling molecules that affect receptor cell phenotype. They can also re-flect molecular changes in donor cells. Therefore, extracellular miRNAs can be potentially used for diagnosis and therapeutics. Studies show that the volume of exosomes in cancer patients' blood is higher than that in normal controls. The ability to package cancer-relat-ed miRNAs is a biological function of exosomes. In conclusion, specific miRNAs transferred by exosomes may play an important role in the pathogenesis of tumor or cancer. This paper presents a summary of research on exosomes as the carrier of miRNAs in the develop-ment and treatment of cancer.

Research progress on differences between left-and right-sided colon cancers / 中国肿瘤临床

In recent years, the incidence and mortality of colorectal cancer have gradually increased in China. This review sum-marized the differences in pathogenic factors, clinical manifestations, pathological features, gene expression, therapeutic modalities, and other aspects between left-and right-sided colon cancers. Results showed that the onset of both left-and right-sided colon cancers is associated with gender and age. Significant differences existed among the clinical manifestations and pathological features. Differenc-es in gene expression, allelic deletion, and DNA mismatch repair affected the occurrence, metastasis, and prognosis of left-and right-sided colon cancers. Moreover, the location of primary tumor is a potential predictor of targeted drug efficacy. Differences in survival rates are possibly related to TNM stage. Hence, new ideas for individualized treatment should be provided by analyzing the differences between left-and right-sided colon cancers.

Effect of chemotherapy on the phenotype of secreted protein, acidic and rich in cysteine in gastric cancer / 中国肿瘤临床

Objective:To investigate the influence of chemotherapy on the phenotype of secreted protein, acidic and rich in cysteine (SPARC) in gastric cancer (GC). Methods:Immunohistochemistry was used to analyze SPARC expression in 132 GC patients. Among these patients, 54 with preoperative chemotherapy and 78 without preoperative chemotherapy were selected to analyze the effect of chemotherapy on SPARC phenotype by comparing the postoperative specimens of the two cohorts. Results:SPARC expression was higher in GC lesions than in the desmoplastic stroma surrounding the tumor cells and noncancerous tissues. High SPARC expression was related to invasion depth, lymph node metastasis, and TNM staging. SPARC expression was lower in patients with preoperative chemotherapy than in controls ( P<0.05). Gross type, histology, depth of invasion, lymph node metastasis, TNM staging, and SPARC phenotype correlated with the overall survival of the patients with preoperative chemotherapy. Further multivariate analysis suggested that lymph node metastasis, histology, and SPARC phenotype after chemotherapy were independent prognostic indicators of GC. Conclusion:SPARC expression was associated with invasion depth, lymph node metastasis, TNM staging and GC prognosis. Preoperative chemotherapy may change the phenotype of SPARC in GC patients.

Clinical analysis of intestinal neuroendocrine tumors / 中国肿瘤临床

Objective:To analyze the clinico-pathological features of intestinal neuroendocrine tumors (NET), as well as the treat-ment protocols and survival of intestinal NET patients. Methods:Clinico-pathological features of 82 intestinal NET patients were retro-spectively reviewed. Results:The male to female ratio was 1.41:1 in the group of patients, and the mean age was 48.72 ± 13.26. Up to 72 cases were NET, 7 were neuroendocrine cancer, and 3 were mixed adeno-neuroendocrine carcinoma. The most commonly observed organ exhibiting primary lesion of the tumors was the rectum. The overall five-year survival rates were 78%and 80%among all the pa-tients and among the NET patients, respectively. Tumors of different histological types demonstrated statistically significant differences in terms of primary site, pT stage, and metastasis (P<0.05). The pT stage, histological classification, age, and primary site of the tumors were associated with the metastasis of the intestinal NETs (P<0.05). Age was the main risk factor of metastasis in the tumors. Conclu-sions:Intestinal neuroendocrine neoplasms usually occur in males, and the most commonly involved organ is the rectum. Age is an im-portant factor of neuroendocrine tumor metastasis.

Development of target therapy for advanced gastric cancer / 中国肿瘤临床

The efficacy of conventional chemotherapy for gastric cancer is extremely limited because of its relatively low chemo-sensitivity and obvious heterogeneity. Molecular phenotype-directed target therapy is important for the improvement of the effi-cacy of conventional chemotherapy in treating advanced gastric cancer. Trastuzumab has been confirmed to have a survival benefit when added to chemotherapy for HER-2 positive gastric cancer. Ramucirumab can increase the survival of gastric cancer patients as second line treatment compared with a placebo. The anti-c-MET monoclonal antibody Rilotumumab indicates promising results in phaseⅡtrial. However, most of the targeting drugs in gastric cancer clinical trials have failed. Therefore, further efforts are required to explore critical targeted genes and effective agents.

Development of adjuvant treatment of gastric cancer / 中国肿瘤临床

Multidisplinary treatment is the mordent means of local-regional gastric cancer therapy, and individualized treatment decisions are dependent on the patient's characteristics. Stage II patients previously treated with standard D2 resection should receive oral administration of S-1 or combination chemotherapy of XELOX. However, patients at stage IIIb or at a more advanced stage should receive combination treatment as priority. Concurrent radiochemotherapy was recommended to treat patients that had been operated by D0 or D1 resection. Perioperative chemotherapy is more reasonable than pure neoadjuvant chemotherapy. No evidence has verified that perioperative or neoadjuvant chemotherapy leads to better survival compared with postoperative adjuvant chemotherapy. The value of chemotherapy before operation is rest with the effect of downstaging and conversion of the unresectable tumor to a resectable one. Con-current radiochemotherapy prior to an operation needs further investigation to affirm its high efficacy of downstaging and conversion.

CCL21-CD40L fusion gene induce augmented antitumor activity in colon cancer / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the anti-tumor activity of CCL21-exCD40L eukaryotic expression vector.</p><p><b>METHODS</b>CCL21-exCD40L fusion gene were constructed by overlap PCR connecting CCL21 and exCD40L through a flexible linker (Gly3Ser)4, and then was cloned into expression vector pcDNA3.1(+). pcDNA3.1(+)/CCL21 and pcDNA3.1(+)/exCD were constructed as negative control. Wsestern blot was used to identify the fusion protein. CHO cells was transfected with pcDNA3.1(+)/CCL21-exCD, pcDNA3.1(+)/CCL21 and pcDNA3.1(+), respectively. The chemotatic function of the expressed product was detected by Transwell method and its anti-tumor activity was tested with vivo transfection.</p><p><b>RESULTS</b>Gene sequencing and restrictive digestion proved the successful construction of pcDNA3.1(+)/CCL21-exCD40L,and its expression was conformed by western blot. The transfectant supernantes of pcDNA3.1(+)/CCL21-exCD40 group had a significant chmotactic function to DCs, of which the cell numbers passing through the film was 14.95 times of blank control every high power microscope visual field. After tumor orthotoic injection of plasmid carrying fusion gene in Balb/c mouse, the tumor mass reduced remarkablely, and all the mouse in fusion gene group survived after 4 weeks.</p><p><b>CONCLUSION</b>CCL21-exCD40L fusion protein had a remarkable function to DCs and it can inhibit tumor growth and prolong the mouse survival time, which is more effective than all control group.</p>

A phase II prospective randomized controlled trial of weekly paclitaxel combined with S-1 or fluorouracil for advanced gastric carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma.</p><p><b>METHODS</b>Two hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-1, while those in the control arm received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m(2) by intravenous infusion, day 1, 8, 15; S-1 80 - 120 mg/day given by oral administration, day 1 - 14. The regimen of control arm was fluorouracil 500 mg/m(2) by intravenous infusion continuously, day 1 - 5; CF 20 mg/m(2) by intravenous infusion, day 1 - 5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed.</p><p><b>RESULTS</b>Two hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set (experimental arm 100 patients, control arm 92 patients). The overall response rates of experimental and control arms were 50.0% and 28.3% (P = 0.002), and the disease control rates were 82.0% and 70.7% (P = 0.064), respectively. The primary endpoints of experimental arm were non-inferior to that of the control arm. The secondary endpoint of experimental arm in terms of median progression free survival was significantly better than that of control arm (5 months versus 4 months, P = 0.006). The experimental arm had a higher incidence of grade III-IV bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different.</p><p><b>CONCLUSIONS</b>Oral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.</p>

Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial / 癌症

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.

The Association of Thrombocytosis with the Prognosis of Patients with Gastric Cancer / 中国肿瘤临床

Objective: To analyze the association of thrombocytosis with the prognosis of patients with gastric cancer.Methods: The clinical materials of 782 patients with gastric cancer who underwent initial surgery in our hospital between January 1995 and December 1999 were retrospectively analyzed.Kaplan- Meier and Log-Rank test were used to analyze the data.Prognostic factors were analyzed by multivariate Cox proportional hazards model.Results: Thrombocytosis oc-curred in 11.4% (87/782) patients.The platelet level was not significantly different among patients of different gender, tumor stage, and histological differentiation (P>0.05).However, a significant difference was observed in the platelet level among patients with different age and surgical approach (P<0.05).The 1-, 3-, and 5-year survival rates were 75.0%, 40.1% and 28.9% in patients without thrombocytosis and 52.8%, 16.9%, and 13.5% in patients with thrombocytosis (P=0.002).Univari-ate analysis showed that histological differentiation, pathological stage, surgical approach and thrombocytosis significantly affected the survival of patients.While age and gender had no significant impact on patient survival.Multivariate analysis showed that pathological stage, surgical approach, and thrombocytosis were independent prognostic factors for gastric can-cer.The relative risk of death of patients with thrombocytosis was elevated by 1.454 times (RR=1.454, 95% CI: 1.135～1.861, P=0.005).Conclusion: Thrombocytosis is an independent prognostic indicator for the survival of initially treated pa-tients with gastric cancer.

Construction of murine CCL21 eukaryotic expression plasmid and chemotactic function of its products / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To construct the murine CCL21 eukaryotic expression plasmid, and to investigate the chemotactic function of its products.</p><p><b>METHODS</b>Murine CCL21 cDNA was amplified by RT-PCR from murine total RNA, and was inserted into eukaryotic expression plasmid pcDNA3.1 after confirmation of sequencing. The recombinant CCL21 plasmid was transferred into mouse forestomach carcinoma (MFC) cells and the chemotactic function of expressed products was detected by chemotaxis assay.</p><p><b>RESULT</b>Gene sequencing, gel electrophoresis of PCR products and restrictive digestion proved the successful construction of CCL21, and its expression was confirmed by Western Blot. The transfected tumor cells had a significant chemotactic function to DC.</p><p><b>CONCLUSION</b>The recombinant murine CCL21 eukaryotic expression plasmid has been successfully constructed, and its expression products in tumor cells have a marked chemotactic function to DC.</p>

Down-regulation of PGC-1alpha expression in human hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the effect of PGC-1alpha in human liver carcinogenesis, and explore the regulatory role of PGC-1alpha in the development of liver cancer.</p><p><b>METHODS</b>The changes of PGC-1alpha mRNA level in normal human liver tissues and human liver tumors was examined by quantitative RT-PCR. PGC-1alpha mRNA level was interfered by siRNA in human liver cell line L02 in vitro, and their morphological changes were observed by pathology with HE staining. The ultrastructure of cells was observed by electron microscopy. In addition, the gene expression pattern of decreasing PGC-1alpha in L02 cells and liver tumor tissue was compared by human genome 70-mer oligonucleotide microarray analysis.</p><p><b>RESULTS</b>PGC-1alpha expression was weaker in the malignant liver tumors compared with that in normal liver tissues. When PGC-1alpha expression was suppressed in human liver L02 cells, the cells became smaller with enlarged nuclei, and myelin figures were observed in mitochondria by electron microscopy, similar with the ultrastructure of liver cancer cells. Microarray analysis showed that the decrease of PGC-1alpha in L02 cells induced up-regulation of some oncogenes and adhesive genes, and down-regulation of a number of tumor suppressor genes and cell proliferation suppressor genes. The changes of decreasing expression pattern of PGC-1alpha gene in L02 cells were similar to those in human liver cancer tissue.</p><p><b>CONCLUSION</b>The results of the present study show that PGC-1alpha is down-regulated in liver cancers and is involved in the malignant transformation in human normal liver cells in vitro, suggesting an important regulatory role of PGC-1alpha in the development of liver cancer.</p>