Correlation and expression analysis of hypoxia-inducible factor 1α, glucose transporter 1 and lactate dehydrogenase 5 in human gastric cancer.

The development and identification of novel potential targeting sites for intervention therapy are essential in the search for improved treatment methods for gastric cancer (GC). Previously, it has been reported that hypoxia inducible factor-1α (HIF-1α) is a potential target gene involved in the endogenous hypoxic response and bioenergetic metabolism of GC cells. In the present study, with the assumption of a close interplay among HIF-1α, glucose transporter 1 (GLUT1) and lactate dehydrogenase-5 (LDH-5), 85 patients with GC were recruited and the protein and gene expression levels of HIF-1α, GLUT1 and LDH-5 in tumor tissues were evaluated in order to assess clinical correlations and co-expression patterns, using Immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction. The results demonstrated that the protein and gene expression levels of HIF-1α were significantly associated with the depth of invasion, nodal metastasis, clinical stage, differentiation and distant metastasis. Consistent with the protein expression results, the mRNA expression levels of the genes coding for GLUT1 and LDH-5 were clearly associated with tumor size, depth of invasion, distant metastasis, clinical stage and differentiation. Correlation analysis of HIF-1α with GLUT1 and LDH-5 at the protein and mRNA expression levels in gastric carcinoma indicated that HIF-1α expression was positively correlated with the expression of GLUT1 (P<0.01, r=0.765 for mRNA expression; P<0.01, r=0.697 for protein expression) and LDH-5 (P<0.01, r=0.892 for mRNA expression; P<0.01, r=0.783 for protein expression) at the mRNA and protein levels. Therefore, it may be concluded that HIF-1α, GLUT1 and LDH-5 are potential target genes involved in the endogenous tumor response to hypoxia and the inhibition of tumor energy metabolism, highlighting a novel therapeutic target for GC.

[Effect of HIF-1α Gene Silence on Biological Characteristics of Human Colon Cancer Cells SW480].

OBJECTIVE: To investigate changes in proliferation and apoptosis of human colon cancer SW480 cells after silencing hypoxia inducible factor-lα (HIF-1α) expression. METHODS: siRNA interference technology was performed to silence the expression of HIF-1α using lipofectamine mediation to transfect siRNA into human colon cancer SW480 cells. The siRNA interfered SW480 cells were compared with a negative control group, an empty vector group, and a blank control group. Real-time PCR and Western blot were used to measure the expressions of HIF-lα protein and mRNA. MTT and flow cytometry (FCM) were used to evaluate the apoptosis and proliferation of SW480 cells. RESULTS: The interfered SW480 cells had a higher level of silence of HIF-lα mRNA (> 80%) compared with those of in the three control groups (P < 0.05). Higher levels of apoptosis and lower levels of proliferation were detected in the interfered cells compared with those in the control groups (P < 0.01). CONCLUSION: HIF-lα silencing promotes apoptosis and inhibits the proliferation of SW480 cells in vitro.

[Necessity of splenectomy in radical resection of gastric cancer: a meta-analysis].

OBJECTIVE: To evaluate the necessity of splenectomy in radical resection of gastric cancer. METHODS: Twelve studies comparing outcomes after radical resection of gastric cancer with or without splenectomy were identified. Both fixed effect model and random effect model were used. RESULTS: There were 2628 patients in total. There were significant differences in complications between splenectomy group and spleen-preserving group(OR=1.91, 95% CI:1.28-2.87, P<0.05), while no significant difference in 5-year survival rate was noticed(HR=0.90, 95% CI:0.73-1.11, P>0.05). CONCLUSION: Radical resection of gastric cancer combined with splenectomy is not associated with improved survival but increased postoperative complications.

Synchronous incidental gastrointestinal stromal and epithelial malignant tumors.

AIM: To investigate the incidence of incidental gastrointestinal stromal tumor (GIST) and its etiopathogenesis. METHODS: From January 1, 2000 to December 31, 2007, 13804 cases of gastrointestinal epithelial malignant tumor (EMT) and 521 cases of pancreatic adenocarcinoma (PAC) were successfully treated with surgery at the Department of General Surgery and the Department of Thoracic Surgery, West China Hospital, Sichuan University, China. The clinical and pathologic data of 311 cases of primary GIST, including 257 cases with clinical GIST and 54 cases of incidental GIST were analyzed. RESULTS: Of the 311 patients, 54 had incidental GIST, accounting for 17.4%. Of these tumors, 27 were found in 1.13% patients with esophageal squamous cell carcinoma (ESCC), 22 in 0.53% patients with gastric adenocarcinoma (GAC), 2 in 0.38% patients with PAC, 2 in 0.03% patients with colorectal adenocarcinoma, and 1 in one patient with GAC accompanying ESCC, respectively. Patients with incidental GIST presented symptoms indistinguishable from those with EMT. All incidental GIST lesions were small in size, and the majority had a low mitotic activity while only 1.9% (5/257) of clinical GIST lesions had a high risk. CONCLUSION: Incidental GIST may occur synchronously with other tumors and has a high prevalence in males. Surgery is its best treatment modality.

[Expression of glucose transporter 1 in human breast carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression of glucose transporter 1 (Glut1) in human breast cancer and its relationship to proliferating cell nuclear antigen (PCNA) protein, other tumor biomarkers and clinical pathologic factors. METHODS: Imunohistochemical staining (SP) was applied to measure the expression of Glut1 and PCNA in 20 cases of human breast fibroadenoma, 20 cases of usual hyperplasia and 80 cases of breast carcinoma. RESULTS: Glut1 was not found expressing in breast fibroadenoma and hyperplastic lesions. In contrast, the total positive rate of Glut1 in breast carcinoma was 58.8% (47/80); that in the ductal carcinoma in situ (DCIS) was 45.0% (9/20), that in the well-differentiated invasive carcinoma was 50.0% (15/30) and that in the poorly differentiated was 76.7% (23/30). The total positive rate of PCNA in breast carcinoma was 75% (60/80), that in DCIS was 65% (13/20) and that in invasive carcinoma was 78.3% (47/60). There was a positive correlation between Glut1 and PCNA level (r = 0.742, P (< 0.01). CONCLUSION: The overexpression of Glut1 play important roles in carcinogenesis and progression of breast carcinoma and closely correlate with cell proliferation of breast carcinoma, may suggest different therapeutic approaches or the need for closer follow-up, and be wished to become a new target for treatment of breast carcinoma.

Effects of short-term application of low-dose growth hormone on trace element metabolism and blood glucose in surgical patients.

AIM: To investigate the effects of short-term application of low-dose growth hormone on trace element metabolism and blood glucose in surgical patients. METHODS: A total of 48 consecutive patients undergoing abdominal operations were randomized to receive either subcutaneous rhGH (0.15 IU/kg) or placebo (menstruum) injections daily for 7 d after surgery. The two groups had similar nutrition intake. Blood, feces, urine and drain samples were collected to measure zincum, cuprum and ferrum as well as glucose levels. Accumulative intake, excretion and balance of zincum, cuprum and ferrum, apparent absorption (AA) and apparent utilization (AU) of zincum, cuprum and ferrum, blood glucose levels and adverse events were estimated. RESULTS: There were no differences in accumulative intake and drain excretion between the two groups. The feces excretion and accumulative excretion of cuprum were lower in the rhGH group (P < 0.05). The urinary excretion of zincum, cuprum and ferrum was all significantly decreased in the rhGH group (P < 0.05) and the accumulative balance of zincum, cuprum and ferrum was improved compared with the placebo group (P < 0.05). AA of cuprum in the rhGH group was almost twice as much as the placebo group (P < 0.05), and AU of zincum, cuprum and ferrum was all improved in the rhGH group (P < 0.05). The mean blood glucose level was significantly higher in the rhGH group than in the placebo group from d 3 to d 6 after operation (P < 0.05). CONCLUSION: Postoperative low-dose rhGH treatment improves the retention of zincum, cuprum and ferrum and decreases the excretion of zincum, cuprum and ferrum, improves the balance of zincum, cuprum and ferrum, and promotes the AA and AU of zincum, cuprum and ferrum. rhGH can be well tolerated without significant adverse effects and the blood glucose level can be well controlled.

Clear cell adenocarcinoma of colorectum: a case report and review of the literature.

Primary clear cell adenocarcinoma of the colorectum is a rare neoplasm, which differs from ordinary carcinomas of the colorectum in morphological features, but shares some traits of clear cell carcinoma of other organs. The tumor is usually composed of polygonal or oval cells with abundant granular and clear cytoplasm. The nuclei are often in hyperchromatic shapes with vesicular nucleoli. We report the first case of clear cell adenocarcinoma of the colorectum in China and review the related published cases. The tumor was located in descending colon of a 37-year-old man, and was rich in glycogen but poor in mucin. By immunoperoxidase and histochemical staining, we clarified the clinicopathological characteristics, diagnosis and differential diagnoses, and pursued its potential pathogenesis. In our case, necrosis, high mitotic activity and lymph node metastasis may suggest a highly malignant tumor and an advanced pathological stage. Nevertheless, the patient has survived for one year with the help of operation and postoperative adjuvant chemotherapy. Regardless of the stage and differentiation, surgical therapy and proper adjuvant chemotherapy are effective means to treat the clear cell adenocarcinoma of the colorectum.

[HIF-1alpha expression and relationship involving tumor cell proliferation and angiogenesis in human breast carcinoma].

OBJECTIVE: To investigate the expression of hypoxia- inducible 1 alpha (HIF-1alpha) in human breast cancer and its relationship with vascular endothelial growth factor (VEGF) protein, proliferating cell nuclear antigen (PCNA ) protein, other tumor biomarkers and clinical pathologic factors. METHODS: The immunohistochemical staining (SP) was used to measure the expression of HIF-1alpha, VEGF and PCNA in human breast fibroadenoma, usual hyperplasia and breast carcinoma. RESULTS: HIF-1alpha was not found expressing in breast fibroadenoma and hyperplastic lesions. In contrast, the positive rate of HIF-1alpha was found in the ductal carcinoma in situ 55% (DCIS, 11/20) and the invasive breast carcinoma 85% (51/60). VEGF positivity in breast carcinoma was 81.3% (65/80). The total positive rate of PCNA in breast carcinoma was 75% (60/80), that in DCIS was 65% (13/20) and that in invasive carcinoma was 78.3% (47/66). Increased levels of HIF-1alpha were statistically significantly associated with increased expression of VEGF (r = 0.762, P <0.01) and PCNA (r = 0.693, P < 0. 01). Conclusion The upregulated expression of HIF-1alpha and VEGF in breast carcinoma has a close relationship with tumor angiogenesis, tumor cell proliferation, lymph node metastasis, ER status and stages of histology. This suggests that HIF-1alpha plays an important role in the carcinogenesis and progression of breast carcinoma; is wished to become a new target for radiotherapy, chemotherapy and biotherapy of tumor, which will offer the new ways to diagnosis and treatment of tumor.