Molecular mechanism of chemosensitization to paclitaxel in human melanoma cells induced by targeting the EGFR signaling pathway / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the molecular mechanism of epidermal growth factor receptor (EGFR) signaling pathway in mediating paclitaxel-resistance and improving paclitaxel sensitivity in human melanoma A375 cells.</p><p><b>METHODS</b>Human melanoma cell line A375 cells were treated with different concentrations of paclitaxel with or without 20 µmol/L AG1478 (EGFR inhibitor), 40 µmol/L PD98059 (extracellular signal conditioning kinase (ERK) 1/2 blockers) or 10 µmol/L LY294002 (PI3K inhibitor). MTT method was used to measure the proliferation of A375 cells. Flow cytometry was used to detect cell cycle and apoptosis in the A375 cells. The expressions of P-EGFR, P-ERK and P-AKT proteins were determined by Western blot analysis.</p><p><b>RESULTS</b>Paclitaxel (0.001 µmol/L to 0.1 µmol/L) inhibited the growth of A375 cells (P < 0.01) and induced apoptosis (P < 0.05) in a dose- and time-dependent manner. AG1478 (20 µmol/L) increased the 0.01 µmol/L paclitaxel-induced inhibition rate from 38.5% to 62.6% at 72 h. Different doses of paclitaxel induced apoptosis in A375 cells by different ways, in which G0/G1 phase cells were decreased and mitotic phase was prolonged at 0.01 µmol/L, and cell cycle arrest at G2/M phase by 0.1 µmol/L paclitaxel. When DNA damage occurred in A375 cells exposed to paclitaxel, expression of P-EGFR, P-ERK and P-AKT proteins was increased. When EGFR signaling pathway was blocked, paclitaxel did not activate MAPK signaling pathway or PI3K/AKT signaling pathway and did not change its effect on cell cycle in vitro. When EGFR was inhibited by 20 µmol/L tyrophostin AG1478, the 0.001 and 0.01 µmol/L paclitaxel-induced early apoptosis rate in A375 cells was increased by 1.73- and 1.80-fold, respectively. When the ERK signaling was blocked by 40 µmol/L PD98059, the 0.001 and 0.01 µmol/L paclitaxel-induced early apoptosis rate in A375 cells was increased by 2.73- and 2.25-fold, respectively. When the AKT signaling was blocked by 10 µmol/L LY294002, the 0.001 and 0.01 µmol/L paclitaxel-induced early apoptosis rate in A375 cells was increased by 2.02- and 1.46-fold, respectively.</p><p><b>CONCLUSIONS</b>Human melanoma A375 cells produce resistance to paclitaxel (0.001 to 0.1 µmol/L) by activating MAPK signaling and PI3K/AKT signaling pathways. Targeting EGFR, ERK and AKT signaling pathways significantly enhances the cytotoxic effect of paclitaxel on human melanoma cells.</p>

Clinicopathological characteristics and prognostic factors in patients with stage III gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics and prognostic factors of stage III gastric cancer.</p><p><b>METHODS</b>A retrospectively study of 1007 patients with Stage III gastric cancer in a single institute in China was performed. The patients underwent surgical resection from January 1991 to December 2005. Univariate and multivariate analyses were performed using log-rank test and Cox proportional hazards model to access the prognostic factors in stage III gastric cancer patients who received curative (R0) gastric resection.</p><p><b>RESULTS</b>The mean age of the 1007 patients was 58.7 years and the male-to-female ratio was 2.6:1.0. There were 242 patients with stage IIIA disease, 403 patients with stage IIIB, and 362 patients with stage IIIC. R0, R1, and R2 resection were performed in 754 patients (74.9%), 56 patients (5.5%), and 197 patients (19.6%), respectively. The 5-year survival rate (37.8%) of patients who received R0 resection was significant higher than that of patients who received R1(21.2%) and R2(8.9%) resection (P<0.05). Multivariate analysis revealed that pN stage, pT stage, and Borrmann type were independent prognostic factors (all P<0.01).</p><p><b>CONCLUSIONS</b>Stage III gastric cancer patients have certain clinicopathological characteristics and R0 resection should be performed if possible. Lymph node count, depth of tumor invasion, and Borrmann type are independent prognostic factors in stage III gastric cancer patients undergoing R0 resection.</p>

Prognostic value of metastatic lymph node ratio in gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVES</b>To evaluate the value of the metastatic to examined lymph nodes (rN) ratio in gastric cancer patients who underwent radical resection.</p><p><b>METHODS</b>In this retrospective study, data were collected from the medical records of 710 patients who underwent radical gastrectomy (R0) for gastric cancer from 1980 to 2006 in the Department of Surgical Oncology at the First Affiliated Hospital of China Medical University. The patients were divided into 2 groups according to the number of examined lymph nodes: Group 1 consisted of 327 patients with <15 examined lymph nodes and Group 2 consisted of 383 patients with ≥15 lymph nodes. rN categories staging and pN categories were divided separately according to the metastatic lymph node ratio and the examined lymph nodes. The prognostic factors were analyzed by univariate (Log-rank) and multivariate (Cox model) analysis methods.</p><p><b>RESULTS</b>The median survival time was 74 months (95% CI:55.6-92.4 months) in Group 1 and 96 months (95% CI:77.8-119.2 months) in Group 2, and the difference was not statistically significant (P>0.05). On multivariate analysis, the N ratio remained as an independent prognostic factor in both Group 1 (P<0.01, RR=1.225, 95% CI:1.102-1.362) and Group 2 (P<0.01, RR=1.421, 95% CI:1.269-1.592). However, pN stage was an independent prognostic factor only in Group 1. When the rN ratio classification was applied, there were no significant differences between each categories (P>0.05). However, the overall survival of patients with pN1 disease in Group 1 was significantly shorter than that in Group 2 according to the pN stage classification (P<0.01).</p><p><b>CONCLUSIONS</b>The metastatic lymph node ratio is an independent prognostic factor of the prognosis of gastric cancer. The staging system based on metastatic lymph node ratio (rN) is more reliable than the system based on the number of metastatic lymph nodes in the prediction of the prognosis of gastric cancer.</p>

Clinical analysis of superficial spreading early gastric cancer:a report of 62 cases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To clarify the clinicopathological features and prognosis, and to evaluate the rational surgical therapy for superficial spreading early gastric cancer (EGC).</p><p><b>METHODS</b>Superficial spreading EGC was defined as tumor invading the mucosa or submucosa layer with the diameter> or =50 mm, and common EGC as tumor with diameter < 50 mm. The clinicopathological data of 62 patients with superficial spreading EGC and 224 patients with common EGC were collected and analyzed retrospectively.</p><p><b>RESULTS</b>No significant differences in age, sex, differentiation, depth of invasion, growth manner, vessel involvement and lymph node metastasis were found between superficial spreading and common EGC(P>0.05), but significant differences were seen in tumor site, macroscopic type, scope of gastrectomy and lymphadenectomy between the two groups(P<0.05). Superficial spreading EGC located in the middle or the whole of stomach accounted for 45.2%, and presented mixed macroscopic type more frequently(48.4%), such as II(C+II(A 5 cases, II(C+II(B 9 cases and II(C+III( 16 cases, and more total gastrectomy and more D(2) lymphadenectomy(16.1% and 40.3% respectively) were executed, compared with common EGC. Due to cancer residual,two patients underwent enlargement of the scope of gastrectomy,two underwent total gastrectomy and one underwent operation again after surgery. The 5-, 10-year tumor-free survival rates for superficial spreading EGC were 98.4% and 91.4%, while 97.0% and 91.2% for the common EGC (chi(2)=1.16,P=0.282).</p><p><b>CONCLUSIONS</b>Special clinicopathological features can be seen in superficial spreading EGC, and the lesion is superficial and extensive. Prevention of cancer residual in remnant stomach is the key point and D(2) lymphadenectomy is suitable enough for operation.</p>

Clinicopathologic features and prognosis of gastric cancer in young adults / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathologic features and prognosis of young patients with gastric cancer by comparing with older patients.</p><p><b>METHOD</b>The clinicopathologic data of 157 younger adults (age, </= 40 years) with gastric cancer and 1761 cases of elder gastric cancer patients (age, > 40 years) was analyzed and compared retrospectively. All of the 1918 patients were surgically treated between January 1980 and December 2000.</p><p><b>RESULTS</b>The rates of poorly differentiation, diffusive growth, Borrmann 4 type, whole-stomach invasion were significantly higher in younger cases than those in the elder counterparts (P < 0.05), especially in young female patients. The rate of early gastric cancer was significantly higher in young patients than that in older patients (P < 0.05), especially in young male patients. There was significant difference between the survival rate of younger male cases (median survival, 35 months) and younger female cases (median survival, 19 months) (P = 0.0219), but no significant difference was found between elder male and elder female (median survival, 26 vs. 30 months). TNM stage, operative curability, gross type were independent predictive factors of survival for younger patients.</p><p><b>CONCLUSIONS</b>Younger female gastric cancer patients tends to have worse prognosis than older patients, while younger male patients have better prognosis due to higher percentage of early gastric cancer when diagnosed. Pathologic staging and operative curability are the independent predictive factors of survival for younger patients.</p>

Features of metastasis in different lymph node groups and their significance in lymph node dissection in total gastrectomy for gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To summarize the features of metastasis in different lymph node groups (from 1 to 16 groups) in gastric cancer patients treated by total gastrectomy, and evaluate their clinical significance in lymph node dissection.</p><p><b>METHODS</b>The data of 73 gastric cancer patients with total gastrectomy and lymph node dissection from January 2004 to April 2006 were analyzed retrospectively. The lymph nodes were divided into 16 groups according to the 13(th) edition of gastric cancer treatment guideline of JGCA (The Japan Gastric Cancer Association). The metastatic rate and degree of dissected lymph nodes in these patients were compared.</p><p><b>RESULTS</b>The metastatic rates of lymph node groups in these patients from lower to higher were as follows: group 15, 13/16, 14v, 12, 10, 9, 11, 8, 2, 6/7, 5, 1, 4, 3. The lowest was the 15(th) group lymph nodes (1.4%), the highest was the 3rd group (65.8%), with a statistically significant difference between those two groups (P < 0.01). The metastatic degrees of the lymph node groups from lower to higher were as follows: 13, 16, 1, 7, 6, 5, 12, 4, 11, 8, 2, 15, 9, 3, 10, 14v. There was a statistically significant difference between the lowest group of lymph node (13(th) group, 10.7%) and the highest (14v(th), 56.3%, P < 0.01).</p><p><b>CONCLUSION</b>In the radical total gastrectomy for patients with gastric cancer, it is suggested that the regional lymph nodes with higher metastatic rate should be resected necessarily, and the group with a higher metastatic degree should be dissected completely. If the result of sentinel lymph node biopsy in the 3(rd) or 14v(th) group is negative, the operation extent can be reduced. If positive, it should be extended. When the biopsy result in the 13(th) or 16(th) is positive, palliative operation may be indicated. However, if the biopsy result is negative in the 13(th) or 16(th), but positive in the 14v(th) group, extended operation is indicated.</p>

Lymphadenectomy adjacent to inferior mesenteric artery root during radical operation and prognosis in rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of lymphadenectomy adjacent to inferior mesenteric artery root on the prognosis of rectal cancer.</p><p><b>METHODS</b>Clinicopathological data of 260 cases with rectal cancer undergone radical operation were analyzed retrospectively. The patients were divided into two groups. Group D(2): the lymph nodes adjacent to mesenteric artery root were not excised (n=188). Group D(3): the lymph nodes adjacent to mesenteric artery root were excised (n=72). Prognosis of two groups was compared during the follow-up period.</p><p><b>RESULTS</b>In group D(2), the 1-, 3-, 5-year total survival rates (TS) were 97.3%, 87.2% and 77.1%, and tumor-free survival rates (TFS) were 93.1%, 83.0% and 76.8% respectively. In group D(3 ), the 1-, 3-, 5-year total survival rates (TS) were 94.4%, 79.2% and 73.6%, and tumor-free survival rates (TFS) were 86.1%, 76.4% and 71.0% respectively. The differences of TS and TFS between two groups were not significant according to Kaplan-Meier analysis (P>0.05). Multivariate analysis revealed that the excision of lymph nodes adjacent to mesenteric artery root was not statistically correlated with the recurrence, metastasis and survival time after radical operation of rectal cancer.</p><p><b>CONCLUSION</b>Excision of lymph nodes adjacent to inferior mesenteric artery root has no significant impact on prognosis and it is unnecessary in the radical operation of rectal cancer.</p>

Assessment on different modes of lymphadenectomies in the treatment for early gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of different modes of lymphadenectomies in the surgical treatment for early gastric cancer (EGC) in order to provide evidence for reasonable selection of lymphadenectomy for the ECG.</p><p><b>METHODS</b>The clinicopathological data of 325 EGC patients were reviewed. The lymph node metastasis (LNM) rate of different levels and the efficiency of different modes of lymphadenectomies were analyzed, and the correlation between LNM and clinicopathological features were analyzed either.</p><p><b>RESULTS</b>The overall LNM rate in the EGC was 14.8%, and the overall LNM degree was 3.0%. In the ECG located in the lower third of the stomach, the rate of first level nodal involvement was 14.5%, which was detected in the No. 3, No. 4, No. 5, No. 6 station of draining lymph nodes for the stomach; and it was 6.9% in the second level lymph nodes which were seen in the No.7 and No. 8a station. There was rare metastasis in the No. 1, No. 9, No. 11p, No. 12a and No. 14v station. In the ECG located in the middle third of the stomach, the rate of first level nodal involvement was 13.8% , which was found in the No. 1, No. 3, No. 5 and No. 6 station, and it was 6.9% in the second level nodes only seen in the No. 7 and No. 8a station. The LNM rate was significantly higher in the lesion larger than 3.0 cm in diameter, or having submucosa invasion, or being poorly differentiated, or with lymphatic involvement than that of the lesion smaller than 3.0 cm in diameter, without mucosa invasion or lymphatic involvement, or being well differentiated (P < 0.05).</p><p><b>CONCLUSION</b>Based on our data, it is suggested that the D1 or D1 + lymphadenectomy of the No. 7 station of lymph node may be suitable for the lesion smaller than 1.0 cm in diameter or only located in the mucosa; the D1 + lymphadenectomy of the No. 7 and No. 8a station of lymph nodes may be suitable for the lesion larger than 1.0 cm in diameter, or being depressed type or with submucosa invasion in the middle and/or lower third of the stomach. For the lesion larger than 3.0 cm in diameter, the No. 1 and No. 9 station lymph node should be dissected. It is also suggested that regular D2/ D3 lymphadenectomy should be avoided in the surgical treatment for the early gastric cancer whenever the tumor situation is suitable.</p>

Retrospective analysis of extended gastrectomy and lymphadenectomy in early gastric cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To objectively evaluate the practical significance of different extended surgeries in early gastric cancer(EGC) patients, and to choose reasonable gastrectomies and lymphadenectomies.</p><p><b>METHODS</b>A total of 217 EGC patients were investigated undergone normalized D2 or above extended surgery and their clinicopathological data were recorded in detail. The efficiency of the extended lymphadenectomies, complications and operation causes were analyzed, and the correlation between the group 2 lymph node metastasis (LNM) and clinicopathological factors were assessed, too.</p><p><b>RESULTS</b>There was no nodal involvement in the No.5 and No.6 lymph nodes among the total gastrectomy in the upper third of the stomach, neither was in the No.10, 11p and 11d lymph nodes among the combined splenectomy, and neither was in the No.15 lymph nodes among the combined transverse mesocolon resection in the lower third of the stomach. There was no distant nodal involvement in the EGC. Above all, most of them were mistaken for advanced gastric cancer preoperatively and intraoperatively, the operation time was longer and the blood loss was more during operation. Among the resected nodes of group 2 in the lower third of the stomach, metastasis was not found in the No.11p, 12a and 14v lymph nodes. The rate of the No.7 and 8a nodal involvement in the submucosa cancer was higher than that in the mucosa cancer(P<0.05) and so did the No.7 in the lymphatic penetration positive(P<0.001). The No.1 and No.13 nodal involvement were only seen in the high risk cases, such as submucosa cancer, the lesion diameter more than 3.0 cm, depressed type and lymphatic involvement.</p><p><b>CONCLUSION</b>It is not necessary to execute total gastrectomy in the upper third of the stomach, combined organ resection (such as splenectomy, transverse mesocolon resection), and distant lymph node dissection in the EGC. In the lower third of the stomach, the No.11p 12a and 14v lymph nodes shouldn't be dissected. With respect to the high risk nodal involvement cases in the lower third of the stomach, the No.1 lymph nodes should be dissected and so does the No.13 lymph nodes if it's tumefied. It is the key point of reasonable operation to exactly diagnose the EGC before and during the surgery.</p>

Study on lymph node metastasis in 292 patients with early gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the status of lymph node metastasis (LNM) and reasonable procedure in early gastric cancer (EGC).</p><p><b>METHODS</b>Two hundred and ninety-two patients with histologically proven mucosal or submucosal gastric cancer who underwent gastrectomy/lymphadenectomy were included in this study. The numbers of total dissected lymph node were all above 15 in all patients. The clinical characteristics, pathologic features, and LNM were assessed by univariate and multivariate analysis.</p><p><b>RESULTS</b>LNM were observed in 43 of 292 cases (14.7%), and 6.4% in mucosal lesions and 22.4% in submucosal lesions. The LNM was identified in 12.7% at the first level, 7.2% at the second level and 0.34% at the third level. The LNM frequency was found in the 6, 3, 4, 1, 5 lymph node (from high to low) consequently at the first level and the 7, 8a lymph node at the second level. The EGC with nodal involvement and the tumors < 2.0 cm in diameter were all depressed type. The diameter of elevated type with LNM was no less than 3.0 cm in this series. The depth of invasion and lymphatic vessel involvement were independent influencing factors in LNM on multivariate analysis (P<0.05).</p><p><b>CONCLUSIONS</b>Less extensive surgery might be considered for the elevated type EGC, and tumors <or= 2.0 cm in diameter and mucosal lesions. Gastrectomy with D1 plus No.7, 8a lymphadenectomy might be carried out in the depressed type/<or= 3.0 cm in diameter, or in the elevated type/> 3.0 cm in diameter. With respect to the depressed type EGC/tumors > 3.0 cm in diameter, gastrectomy with D2 lymphadenectomy is proper.</p>

Expression and significance of interleukin-8 cyclooxygenase-2 and trefoil family factor 1 in the remnant stomach mucosa / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the expression and significance of interleukin-8 (IL-8), cyclooxygenase-2 (COX-2) and trefoil family factor 1 (TFF1) in the remnant stomach mucosa.</p><p><b>METHODS</b>Patients after gastrectomy were examined by upper gastrointestinal endoscopy. Biopsy specimens were obtained from stoma and the greater curvature of the upper corpus to be assessed for Hp (by H.E. and Giemsa staining) and conduct real-time semi-quantitative PCR. mRNA was extracted from the biopsy specimens to determine the IL-8, COX-2 and TFF1 gene mRNA levels by real-time PCR method.</p><p><b>RESULTS</b>In the stoma, COX-2 level in Hp-positive patients was significantly higher than that in Hp-negative patients, but the difference of IL-8 levels between them was not significant. In the corpus, IL-8 and COX-2 levels in Hp-positive patients were significantly higher than those in Hp-negative patients. In Hp-negative patients, IL-8 and COX-2 levels in the stoma were significantly higher in B II anastomosis than in B I anastomosis cases; COX-2 level in the stoma was significantly higher in B II anastomosis than in B I anastomosis cases, but the difference of IL-8 levels between them was not significant. TFF1 level in the remnant stomach mucosa showed no significant difference between Hp-positive and Hp-negative patients.</p><p><b>CONCLUSION</b>Hp infection and bile reflux are important risk factors for the secondary stomach carcinogenesis. Expression of IL-8 and COX-2 in the remnant stomach mucosa is related to the risk of secondary stomach carcinogenesis. The relationship between the TFF1 expression and secondary stomach carcinogenesis in the remnant stomach mucosa is still unclear and should further be studied.</p>

Double-mutant dihydrofolate reductase gene transfection into bone marrow cells protects mice from chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the feasibility of transfecting DHFR (human double-mutant dihydrofolate reductase) gene into mouse bone marrow cells and the effect of resistance to high dose MTX chemotherapy.</p><p><b>METHODS</b>After DHFR gene was transfected into mouse bone marrow cells with retroviral vector, the cells were treated with methotrexate (MTX) and then CFU-GM (granulocyte-macrophage colony-forming unit) assay was performed. Peripheral blood leucocytes and platelets, body weight and survival rate were observed. After treatment with high dose MTX, the expression of drug resistance gene was checked by RT-PCR in the transfected bone marrow cells.</p><p><b>RESULTS</b>SFG-F/S-NeoR gene-transfected mice bone marrow cells yielded drug-resistance colonies to MTX (donor mice: 15.8%, recipient mice: 18.0%, control: 0) The peripheral blood leucocytes and platelets, body weight recovered gradually and the survival rate was 83.3% at the 40th day, while 0 in controls in gene transfected mice after large dose MTX treatment. RT-PCR of transgenic mouse marrow cells showed the band of F/S gene (400 bp).</p><p><b>CONCLUSION</b>DHFR gene can not only be integrated and expressed in bone marrow cells but also improve their drug-resistence to MTX.</p>

Gene expression patterns in gastric cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify gene expression patterns in distinct stages of intestinal-type gastric cancer(GC).</p><p><b>METHODS</b>Gene expression patterns of distinct stages of intestinal-type GC samples from 3 patients were compared with cDNA microarray, which contained 576 genes. There were 506 target genes, which included 51 genes identified from our previous experiment with suppression subtractive hybridization(SSH) and other 455 genes chosen for their important roles in cancers. Hierarchical clustering was performed to clarify genes in association with distinct stages of GC.</p><p><b>RESULTS</b>One hundred and eighty-one differentially expressed genes with average Cy5:Cy3 ratios higher than 2.0 or lower than 0.5 in at least one stage of GC were identified by cDNA microarray. Among them, 48 genes were up-regulated and 133 down-regulated. Hierarchical clustering analysis separated the differentially expressed genes in different stages of GC into 5 main characteristic groups. Some important differentially expressed genes in different stages of GC were identified, such as SEC23IP, LIPF, ES(BQ291520), SLC5A1, PG(encoding similar to pepsin A precursor), CXCR4, DICER1, SH3GL2, and IGF2R.</p><p><b>CONCLUSION</b>The differentially expressed gene patterns and some important genes were identified, which might be useful in further study on carcinogenesis, progression and metastasis of intestinal-type GC.</p>

Classification of breast microcalcifications: radiological-pathological correlation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Microcalcifications play a very important role in detection of breast cancer, especially early stage breast cancer. However, ambiguity still exists in understanding the relationship between radiological and pathological characteristics of microcalcifications. The definitive indication of a biopsy has not been established. The purpose of this study is to evaluate the relationship of classification of breast microcalcifications using full-field digital mammography to the pathological characteristics.</p><p><b>METHODS</b>For all the women an open biopsy had been conducted. One hundred and three mammographs showing clustered microcalcifications from 98 consecutive patients were reviewed along with their pathological records. To investigate the value of each criterion for the detection of cancer, univariate and multivariate analyses were performed on the entire sample and then on morphological subgroups.</p><p><b>RESULTS</b>Pathological examination showed 67 malignant lesions (65.05%) and 36 benign lesions (34.95%). In the univariate analysis, four radiological variables were significant: morphological type (P = 0.001), complicated by a mass (P = 0.002), number of microcalcifications per cluster (P = 0.02) and linear or triangular distribution of clusters (P = 0.009). In the multivariate analysis, two criteria remained significant: morphological type (P < 0.001) and complicated by a mass (P = 0.001). The percentage of malignancy was 37.0%, 60.0%, 78.8%, and 88.9%, respectively, for type 2 (regularly punctiform), type 3 (dusty), type 4 (irregularly punctiform) and type 5 (vermicular) microcalcifications (Le Gal's classification). The malignancy was 78.6% for microcalcifications complicated by a mass and 48.9% without a mass. The difference was significant (P < 0.05). The relationship between morphological types of microcalcifications and the pathological characteristics was also studied. In subgroups, type 3 (dusty) microcalcifications complicated by a mass (P = 0.001) or with the number of microcalcifications more than 10 (P = 0.024); and type 2 (regularly punctiform) with a diameter of the area over 20 mm (P = 0.024) or complicated by a mass (P = 0.025) were statistically significant as criteria for malignant tumour.</p><p><b>CONCLUSIONS</b>Most cases of microcalcifications of type 4 or 5; type 3 complicated by a mass or with the number of microcalcifications more than 10; type 2 complicated by a mass or with a diameter of the area over 20 mm; are indicative of cancer. Open biopsy is recommended to acquire definitive pathological diagnosis for these cases. For the remainder of the morphological types, stereotaxic biopsy or followup should be considered.</p>

Evaluation of the correlations of cell proliferation activity with lymphatic and vascular invasion and prognosis in gastric carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate bromodeoxyuridine/DNA (BrdUrd/DNA) double-parametric flow cytometric analysis in detection of gastric carcinoma and to study the correlations of cellular BrdUrd labeling index (LI), G(2)/M phase fraction (G(2)/MPF) and DNA content, with lymphatic and vascular invasion and prognosis.</p><p><b>METHODS</b>Sixty cases of fresh tumor samples were examined by BrdUrd/DNA double-parametric flow cytometry.</p><p><b>RESULTS</b>BrdUrd LI and G(2)/MPF values were both significantly higher in patients with lymphatic invasion than those without invasion (P < 0.01). There was statistically significant difference between the 5-year survival rates in cases with and without lymphatic invasion (P < 0.01). Both BrdUrd LI and G(2)/MPF values were significantly higher in patients with lymph node metastasis than those in cases without metastasis (P < 0.01). There was a significant difference in 5-year survival rates between patients with and without lymph node metastases. The incidence of lymph node metastasis was significantly higher in aneuploid carcinoma (P < 0.05), and the patients with aneuploidy had significantly poor prognosis. BrdUrd LI was significantly higher in patients with more than 5 metastatic lymph nodes than those with 1-4 metastatic lymph nodes (P < 0.05) and no metastasis (P < 0.01). G(2)/MPF values in cases with more than 5 and 1-4 metastatic lymph nodes were higher than that in cases with no metastasis (P < 0.01 and P < 0.05, respectively). There were significant differences in 5-year survival rates among patients with no lymph node metastasis, 1-4 nodes metastasis and more than 5 nodes metastasis. G(2)/MPF values were significantly higher in patients with and without vascular invasion (P < 0.01).</p><p><b>CONCLUSION</b>Correlations exist among cellular BrdUrd LI, G(2)/MPF, DNA content and lymphatic involvement, vascular invasions and prognosis in gastric carcinoma.</p>

The study of the minimum number of examined lymph nodes for the TNM classification of gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To determine the minimum number of lymph nodes that should be examined for the UICC/AJCC TNM classification of gastric cancer.</p><p><b>METHODS</b>The clinical and pathological data of four hundred and thirty-six patients underwent curative resection for gastric cancer were analyzed by Chi-square and Student-Newman-Keuls test.</p><p><b>RESULTS</b>The pN0 patients with 1 to 4, 5 to 9 examined nodes showed significantly lower survival rate than those with 10 to 14, 15 or more examined nodes (P < 0.05), and the patients with 10 to 14 examined nodes had as good a prognosis as those with 15 or more examined nodes. In the pN1, pN2 categories, the patients with 1 to 4, 5 to 9 and 10 to 14 examined nodes tended toward significantly lower survival rates than those with 15 or more examined nodes (P < 0.05). Among the patients who were classified as stage II, the survival rate of those with 10 to 19 examined nodes was significantly lower than that with 20 or more examined nodes. Among the patients classified as stage III, those with 5 to 9, 10 to 19 and 20 to 29 examined nodes had significantly lower survival rates than those with 30 or more examined nodes (P < 0.05).</p><p><b>CONCLUSIONS</b>The number of lymph nodes examined has significant prognostic impact within each pN category of gastric carcinoma. The minimum number of lymph nodes to examine in order to determine pN0 classification can be reduced from 15 to 10. For tumor with lymph node metastasis, the minimum number should be 15. In stage II, 20 or more nodes should be examined, and in stage III and IV 30 or more.</p>

The relationship between the expressions of interleukin-8 and cyclooxygenase-2 and the type of anastomosis in the remnant stomach / 中华外科杂志

<p><b>OBJECTIVE</b>To study the expressions and the significance of interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) in the remnant stomach.</p><p><b>METHODS</b>Fifty-eight patients with gastrectomy were examined by upper gastrointestinal endoscopy. Two biopsy specimens were obtained from the stoma and the upper corpus gastric mucosa in the remnant stomach. mRNA was extracted from biopsy specimens to measure the IL-8 and COX-2 gene mRNA levels by real-time PCR method.</p><p><b>RESULTS</b>IL-8 and COX-2 levels were higher in stoma than in corpus, IL-8 levels in BI anastomosis were significantly higher in stoma than in corpus (P< 0.05). In Hp-negative patients, IL-8 and COX-2 levels in stoma were significantly higher in BII anastomosis than in BI anastomosis (P < 0.05). In Hp-positive patients, IL-8 and COX-2 levels in stoma showed no significant differences between BII anastomosis and BI anastomosis. In corpus, IL-8 and COX-2 levels in Hp-positive patients were significantly higher than those in Hp-negative patients, (P < 0.05), including in BI anastomosis and in BII anastomosis.</p><p><b>CONCLUSIONS</b>The risk of the secondary stomach carcinogenesis in stoma after distal gastrectomy is higher than that in corpus; The types of anastomosis may influence the risk for the secondary stomach carcinogenesis in the remnant stomach mucosa.</p>

Screening and analysis of associated genes in the carcinogenesis and progression of gastric cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen and analyze the important associated genes in different stages of gastric cancer.</p><p><b>METHODS</b>Using suppression subtractive hybridization (SSH) to screen differentially expressed genes; detecting the expression of genes in different stages of gastric cancer with dot blot hybridization; and verifying the results with semi-quantitative reverse transcriptase-polymerase chain reaction(RT-PCR).</p><p><b>RESULTS</b>Twenty-six differentially expressed gene fragments were obtained by means of SSH. Among them,24 were known genes, 1 was a new expressed sequence tags(EST), and 1 was a hypothetical gene. The results of dot blot hybridization demonstrated that the expressions of Annexin A2, RPS29, RPS12 etc. in dysplasia were higher than those in normal mucosa; the expressions of RPS12 etc.in early cancer were higher than those in normal mucosa;the expressions of cytochromosome C oxidase II, ferritin light chain, RPS12 etc. in advanced gastric cancer and lymph node metastases were consistently higher than those in normal mucosa. The expression of proteasome 26S subunit gene in advanced gastric cancer was higher than that in normal mucosa. The expression of RPS12 was consistently higher in different stages of gastric cancer. It was demonstrated by RT-PCR that the expression of RPS12 in gastric cancer was higher than that in normal mucosa.</p><p><b>CONCLUSION</b>The authors have identified some important genes that might be involved in the carcinogenesis and progression of gastric cancer, and RPS12 may play more important roles in gastric cancer.</p>

Mice transduced with double-mutant dihydrofolate reductase-cytidine deaminase fusion gene attained protection from high dose chemotherapy / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the feasibility of transferring fusion gene of dihydrofolate reductase (DHFR) gene and cytidine deaminase (CD) gene into mouse bone marrow cells in order to observe the drug resistance of high dose methotrexate (MTX) and cytosine arabinoside (Ara-C) in the bone marrow cells and to improve the tolerance of myelosuppression following combination chemotherapy.</p><p><b>METHODS</b>Human double-mutant dihydrofolate reductase-cytidine deaminase fusion gene was transferred into two mice bone marrow cells by retroviral vector. Resistant colony-forming unit granulocyte-macrophage (CFU-GM) assays were performed in mouse bone marrow cells by retroviral infection and after treatment by drugs (Ara-C, MTX, and Ara-C + MTX). DNA was extracted from mouse bone marrow cells. The expression of drug resistant genes in mouse bone marrow cells after transferring by retroviral vector was checked by polymerase chain reaction (PCR).</p><p><b>RESULTS</b>Bone marrow cells after coculture with the retroviral producer cells transduced with the genes (SFG-F/S-CD) showed the drug resistance colonies yield (Colony formation after exposure to Ara-C, MTX and Ara-C + MTX were 56%, 22% and 14%, respectively) and the increase in drug resistant to both MTX and Ara-C (P < 0.005). Expression of DHFR and CD gene in extracted DNA of transfected mice were demonstrated by PCR.</p><p><b>CONCLUSIONS</b>Double drug resistant gene can not only integrate and co-express in mice bone marrow cells but also increase the drug resistance to MTX and Ara-C.</p>

Relations of proliferative activities of gastric carcinoma cells to lymphatic involvement, venous invasion and prognosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>This study was to evaluate bivariate bromodeoxyuridine (BrdUrd)/DNA flow cytometric analysis in detection of gastric carcinoma and to study the relations of cellular BrdUrd labeling indices (LI), G2/M-phase fraction (G2/MPF) and DNA ploidy pattern to lymphatic involvement, venous invasion and prognosis.</p><p><b>METHODS</b>Fresh tumor samples from 60 patients with gastric carcinoma were analyzed by bivariate BrdUrd/DNA flow cytometry. The results were correlated with lymphatic vessel invasion, lymphatic node metastasis, the number of metastatic lymphatic nodes, and venous invasion. Propidium iodide (PI) was used as a fluorescent probe for total cellular DNA, and a monoclonal antibody against BrdUrd was used as a probe for BrdUrd incorporated into DNA. Fluorescent-labeled goat anti-mouse antibody was used as a second antibody. S-phase fractions were measured by in vitro BrdUrd labeling, and DNA ploidy and G2/MPF were also measured. Comparison of survival was performed with the log-rank test, the Chi-square test for qualitative data, and Student's t test for quantu data.</p><p><b>RESULTS</b>BrdUrd LI and G2/MPF values were significantly higher in tumors with lymphatic vessel invasion than in those without invasion respectively (P < 0.01); the patients who had tumors with lymphatic vessel invasion showed a significantly poor prognosis (P < 0.01). Both BrdUrd LI and G2/MPF values were significantly higher in tumors with lymphatic node metastasis than in those without metastasis (P < 0.01). A statistical significant difference was noted in the 5-year survival rates between the patients with lymph node metastasis and those without metastasis. Compared with diploid carcinoma, the incidence of lymph node metastasis was significantly higher in aneuploid carcinoma (P < 0.05), and the patients with aneuploid carcinoma showed a significantly poor prognosis (P < 0.05). BrdUrd LI was significantly higher in patients with more than 5 metastatic lymph nodes than those with 1 - 4 metastatic lymph nodes (P < 0.05) and those without metastasis (P < 0.01). G2/MPF values in those patients either with more than 5 metastatic lymph nodes or 1 - 4 metastatic lymph nodes were higher than those without metastasis (P < 0.01 and P < 0.05). A statistical significance was seen in the 5-year survival rates among the patients with no metastatic lymph node, 1 - 4 metastatic nodes and more than 5 metastatic nodes (P < 0.01). G2/MPF values were significantly higher in patients with venous invasion than in those without invasion (P < 0.01).</p><p><b>CONCLUSIONS</b>Positive correlations exist between cellular BrdUrd LI, G2/MPF with lymphatic involvement and prognosis, and DNA aneuploid with lymphatic involvement and prognosis. The same was true between G2/MPF value and venous invasion in gastric carcinoma.</p>