1.P-glycoprotein as an intermediate end point of drug resistance to neoadjuvant chemotherapy in locally advanced gastric cancer.
Hyun Cheol CHUNG ; Soo Jung GONG ; Nae Choon YOO ; Sung Hoon NOH ; Joo Hang KIM ; Jae Kyung ROH ; Jin Sik MIN ; Byung Soo KIM ; Kim Beom LEE
Yonsei Medical Journal 1996;37(6):397-404
The expression of p-glycoprotein (p-gp) was evaluated in pre- and post-chemotherapy states after the administration of adriamycin-based chemotherapy in 24 gastric cancer patients. Among them, group A was composed of twelve patients who relapsed after surgery plus adjuvant chemotherapy and group B was composed of another twelve patients who received neoadjuvant chemotherapy plus surgery. Pre-chemotherapy p-gp was evaluated in 18 out of 24 patients (6 patients had no pre-chemotherapy paraffin blocks) and post-chemotherapy p-gp was evaluated from all 24 patients. Pre- and post-chemotherapy p-gp was expressed in 5 of 18 patients (27.8%), and 9 of 24 patients (37.5%), respectively, with immunohistochemical stain using monoclonal antibody JSB-1. No differences of disease-free survivals were observed in Group A based on post-chemotherapy p-gp expression from relapsed lesions. In Group B, there was a higher relapse rate (p = 0.04) and a lower one-year disease-free survival rate (p = 0.04) in post-chemotherapy p-gp positive patients when adjuvant treatment was done with the same regimen as neoadjuvant chemotherapy. In all patients studied, post-chemotherapy p-gp expression correlated with a higher systemic recurrence (p = 0.04). These data suggest that p-gp can be induced by an adriamycin-based chemotherapy in gastric cancer. Thus, we suggest that the prognosis of gastric cancer may be poor if a multidrug resistance (MDR)-related regimen is used in the presence of p-gp after neoadjuvant chemotherapy with an adriamycin-based regimen, even if the initial response is good.
Adult
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Aged
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Combined Modality Therapy
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Dose-Response Relationship, Drug
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Doxorubicin/administration & dosage/*therapeutic use
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Drug Resistance
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Female
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Human
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Immunohistochemistry
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Male
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Middle Age
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Neoplasm Recurrence, Local
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P-Glycoprotein/*metabolism
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Stomach Neoplasms/*drug therapy/*metabolism/surgery
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Survival Analysis
2.Expression of HER-2 and leptin in gastric cancer and their clinical significance.
Yi-ting GENG ; Jin-rong QIU ; Rong WANG ; Yun-tao SU ; Yong-qian SHU ; Yong-mei YIN
Chinese Journal of Oncology 2011;33(10):764-769
OBJECTIVETo assess the expression of HER-2 and leptin in gastric cancer and evaluate their relationship with VEGF expression and clinicopathological features, and their prognostic value for gastric cancer patients.
METHODSOne hundred and ten gastric cancer specimens and the corresponding metastatic lymph nodes were detected for HER-2 by immunohistochemistry (IHC). All primary cancer tissues were detected for leptin, OB-Rb and VEGF. Ninty-six specimens of normal gastric mucosa served as the control.
RESULTSThe expression level of HER-2, leptin and OB-Rb in gastric cancer tissues were significantly higher than those in normal tissues (19.1% vs. 8.0%, 49.1% vs. 34.0%, and 60.9% vs. 46.0%, P < 0.05). HER-2 overexpression was moderately homogenous in primary gastric cancer and matastatic lymph nodes (P = 0.607, Kappa = 0.581). There was a correlation between the expression of HER-2 and leptin, both of which were significantly correlated with tumor invasion depth, metastatic lymph nodes ratio (NR), distal metastasis, TNM stage and VEGF expression. However, there was no significant correlation between OB-Rb expression and the clinicopathological features evaluated. Cox regression multivariate analysis showed that tumor size, histological grade, NR, stage, chemotherapy and HER-2 expression were independent prognostic factors.
CONCLUSIONSHER-2 is stably expressed in primary gastric cancer and metastatic lymph nodes. HER-2 and leptin play an important role in the progression and angiogenesis of gastric cancer. High expression of HER-2 is a prognostic factor for poor outcome.
Adenocarcinoma ; drug therapy ; metabolism ; pathology ; surgery ; Adult ; Aged ; Aged, 80 and over ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gastrectomy ; Humans ; Leptin ; metabolism ; Lymph Nodes ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Proportional Hazards Models ; Receptor, ErbB-2 ; metabolism ; Receptors, Leptin ; metabolism ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Survival Rate ; Tumor Burden ; Vascular Endothelial Growth Factor A ; metabolism
3.Impact of S100P expression on clinical outcomes of gastric cancer patients with adjuvant chemotherapy of oxaliplatin and its mechanisms.
Xiao-Mu ZHAO ; Zhi-Gang BAI ; Xue-Mei MA ; Zhong-Tao ZHANG ; Xiao-Yan SHI
Chinese Journal of Surgery 2010;48(13):1004-1008
OBJECTIVETo investigate the impact of the expression of S100P on the prognosis and tumor chemosensitivity in patients with resectable gastric cancer and its mechanisms.
METHODSThe expression of S100P was analyzed in 121 resected primary gastric cancer tissues by using tissue array of immunohistochemistry excised from January 2003 to December 2007. The patients received adjuvant chemotherapy with oxaliplatin. The pEGFP-S100P plasmid was constructed and was transfected into BGC823 cell line to establish gastric cancer cell line with over-expression of human S100P, BGC823-S100P. The expression level of S100P was determined by real-time PCR and Western blot assay. The chemosensitivity of BGC823-S100P cell line to oxaliplatin was detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay.
RESULTSThe S100P was positively expressed in 64 tumors (52.9%, 64/121). Although there was no significant relation between the expression of S100P and tumor T staging (P = 0.683), N staging (P = 0.472), M staging (P = 0.770) and differentiation (P = 0.553), Wilcoxon test showed that the 5-year cumulative survival rate of patients with positive S100P expression was significantly higher than that of patients with negative expression (20.3% vs. 3.5%, P = 0.034). Furthermore, overexpressed of S100P was found in the BGC823 cell line, BGC823-S100P. The mRNA and protein level of S100P in pEGFP transfected BGC823-S100P cell lines were significantly higher than those in control group (8.42 ± 1.38 vs. 0.83 ± 0.11 and 3.52 ± 0.48 vs. 0.97 ± 0.19, all P < 0.05). It indicated with MTT assay that the half-inhibitory concentration (IC(50)) to oxaliplatin decreased in BGC823-S100P cells, and was significantly lower than that in vector-only transfected cells [(142 ± 16) mg/L vs. (266 ± 11) mg/L, P = 0.032].
CONCLUSIONSS100P may also be a potentially novel independent prognostic factor in gastric cancer patients following curative resection. And it could improve the cumulative survival of the patients through enhancing the chemosensitivity of tumor cell line to oxaliplatin.
Adult ; Aged ; Aged, 80 and over ; Calcium-Binding Proteins ; metabolism ; Chemotherapy, Adjuvant ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; Organoplatinum Compounds ; administration & dosage ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Treatment Outcome
4.GRP78 expression in gastric cancer and its clinical significance.
Lei YANG ; Shu-yun YANG ; Jian-mei JI ; Yong-feng CAO ; Cong-fei JI ; Jin-feng JI ; Wei-wei XU ; Jian-hong WANG
Chinese Journal of Oncology 2013;35(11):837-842
OBJECTIVETo investigate the clinical value of the expression of glucose regulated protein 78 (GRP78) for assessment of severity, chemoresistance and prognosis in patients with gastric adenocarcinoma ( GC) .
METHODSA cohort of 237 patients with gastric cancer was included in this study. 160 patients of them were treated by D2 radical gastrectomy and adjuvant chemotherapy. The GRP78 expression was detected by immunohistochemistry and 80 patients of them were tested in vitro for cancer chemosensitivity by ATP-tumor chemosensitivity assay (ATP-TCA). In addition, the relationships were analyzed between GRP78 and age, gender, tumor differentiation, invasion, disease stage, lymph node metastasis and chemoresistance as well as disease-free survival (DFS).
RESULTSThe positive rate of GRP78 expression in the gastric adenocarcinoma was 68.8% before the initiation of chemotherapy. The positive GRP78 expression was significantly correlated with tumor invasion depth, poor differentiation, TNM stages, and lymph node metastasis (all P < 0.05), not correlated with gender and age, and high GRP78 expression was associated with the chemoresistance of the gastric cancer cells to chemotherapeutic agents. Negative GRP78 expression was associated with higher sensitivity to both drugs and regimens. The DFS of GRP78-positive group and GRP78-negative group was (53.6 ± 0.9) months and (38.3 ± 0.8) months, respectively (P = 0.041). Interestingly, subgroup analysis revealed that the DFS in GRP78-negative and-positive patients treated with taxane-containing chemotherapy was (58.6 ± 2.6) months and (49.1 ± 2.7) months, respectively, but the difference was statistically not significant (P = 0.111). In contrast, in the subset of GRP78-negative and- positive patients treated with taxane-containing regimens, the DFS was (45.5 ± 1.9) months and (35.1 ± 2.2) months, respectively, showing a significant difference (P = 0.038). In the group of patients with positive GRP78 expression, the patients treated with taxane-containing chemotherapy had a longer DFS [(49.1 ± 2.7) months] than those without that treatment [(35.1 ± 2.2) months], showing a significant difference (P = 0.017). Univariate analysis revealed that DFS was correlated with histological grade, GRP78 expression and lymph node metastasis (all P < 0.05). Multivariate analysis showed that GRP78 expression and TNM staging were independent influencing factors for gastric cancer (both P < 0.05).
CONCLUSIONSThe results of our study suggest that GRP78 may be a novel biomarker for assessment of malignant degree and prediction of chemoresistance in gastric cancer, and may be helpful to chemotherapy planning and prognosis prediction in patients with gastric cancer.
Adenocarcinoma ; drug therapy ; metabolism ; pathology ; surgery ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Bridged-Ring Compounds ; administration & dosage ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Female ; Gastrectomy ; Heat-Shock Proteins ; metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Taxoids ; administration & dosage
5.Clinicopathological and molecular genetic characteristics of childhood diffuse large B cell lymphoma.
Hui HUANG ; Wen-ping YANG ; Hong-yan XU
Chinese Journal of Oncology 2012;34(3):209-211
Adolescent
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Antigens, CD20
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metabolism
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Antineoplastic Combined Chemotherapy Protocols
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therapeutic use
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Burkitt Lymphoma
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drug therapy
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metabolism
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pathology
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surgery
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Child
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Child, Preschool
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Cyclophosphamide
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therapeutic use
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DNA-Binding Proteins
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metabolism
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Doxorubicin
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therapeutic use
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Female
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Follow-Up Studies
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Genes, myc
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Humans
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Hyaluronan Receptors
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metabolism
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Ki-67 Antigen
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metabolism
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Lymphoma, Large B-Cell, Diffuse
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drug therapy
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genetics
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metabolism
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pathology
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surgery
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Male
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Neoplasm Staging
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Neprilysin
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metabolism
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Peritoneal Neoplasms
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drug therapy
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genetics
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metabolism
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pathology
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surgery
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Prednisone
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therapeutic use
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Proto-Oncogene Proteins c-bcl-2
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metabolism
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Proto-Oncogene Proteins c-bcl-6
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Stomach Neoplasms
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drug therapy
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genetics
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metabolism
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pathology
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surgery
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Translocation, Genetic
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Vincristine
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therapeutic use
6.Inhibitory effect of somatostatin analogue octreotide on the expression of p53 and Ras in human gastric cancer.
Journal of Southern Medical University 2011;31(7):1245-1248
OBJECTIVETo investigate the inhibitory effect of somatostatin (SST) analogue octreotide on human gastric cancer.
METHODSFifty gastric cancer patients were randomly assigned into 2 equal groups. The patients in the control group received no medication before surgical resection of gastric cancer, and those in octreotide group were given daily subcutaneous injection of 100 µg octreotide for 7 days before the surgery. The resected specimens were examined histologically and the expressions of p53 and Ras protein were detected by immunohistochemistry.
RESULTSCompared with the control group, gastric cancer tissue in octreotide group showed significantly increased necrosis (P<0.05) and enhanced proliferation of fibrous tissues (P<0.05) with lowered expressions of p53 and Ras protein (P<0.05).
CONCLUSIONOctreotide can inhibit the expressions of p53 and Ras and suppress the growth of the human gastric cancer.
Adenocarcinoma ; drug therapy ; metabolism ; surgery ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Octreotide ; therapeutic use ; Proto-Oncogene Proteins p21(ras) ; genetics ; metabolism ; Somatostatin ; analogs & derivatives ; Stomach Neoplasms ; drug therapy ; metabolism ; surgery ; Tumor Suppressor Protein p53 ; genetics ; metabolism
7.Effect of intensive insulin therapy on the clinical results of postoperative patients with gastric cancer.
Shou-gen CAO ; Yan-bing ZHOU ; Cai-kun ZHANG ; Dong CHEN ; Yun-yun YU ; Lian-fang LU
Chinese Journal of Surgery 2008;46(12):918-920
OBJECTIVETo investigate the influence of intensive insulin therapy on the results of postoperative patients with gastric cancer.
METHODSForty-six patients with gastric cancer underwent radical operation were randomly divided into two groups: intensive group (n=23, to control blood glucose at 4.4 to 6.1 mmol/L) and conventional group (n=23, to control blood glucose at 10.0 to 11.1 mmol/L). Fasting blood glucose( FBG), fasting insulin (FINS), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C reaction protein (CRP) in 46 patients were detected dynamically during perioperative period. Insulin resistance index (HOMA-IR) were calculated using Homeostasis Model Assessment (HOMA) to evaluate insulin sensitivity. Postoperative complications and other clinical data were recorded.
RESULTSNo hypoglycemia occurred in the two groups. Compared with conventional group, morbidity and postoperative duration of fever, antibiotic use and the length of hospital stay in intensive group were significantly reduced (P < 0.05). On the day 1 and 3 after surgery, HOMA-IR and serum levels of TNF-alpha, IL-6 and CRP in patients of intensive group were significantly lower than those in conventional group (P < 0.05).
CONCLUSIONSIntensive insulin therapy could counteract the state of high-inflammation and then improve the outcome of postoperative patients.
Blood Glucose ; metabolism ; C-Reactive Protein ; metabolism ; Female ; Humans ; Hypoglycemic Agents ; therapeutic use ; Insulin ; blood ; therapeutic use ; Interleukin-6 ; blood ; Male ; Middle Aged ; Perioperative Care ; Stomach Neoplasms ; blood ; drug therapy ; surgery ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; blood
8.Effects of a Home-based Exercise Program for Patients with Stomach Cancer Receiving Oral Chemotherapy after Surgery.
Journal of Korean Academy of Nursing 2012;42(1):95-104
PURPOSE: The purpose of this study was to identify the effects of a home based exercise program for patients with stomach cancer who were undergoing oral chemotherapy. METHODS: The home-based exercise program was developed from the study findings of Winningham (1990) and data from the Korea Athletic Promotion Association (2007). The home-based exercise program consisted of 8 weeks of individual exercise education and exercise adherence strategy. Participants were 24 patients with stomach cancer who were undergoing oral chemotherapy following surgery in 2007 or 2008 at a university hospital in Seoul. Patients were randomly assigned to either the experimental group (11) or control group (13). The effects of the home-based exercise program were measured by level of cancer related fatigue, NK cell ratio, anxiety, and quality of life. Data were analyzed using SPSS/WIN 13.0 version. RESULTS: The degree of cancer related fatigue and anxiety in the experimental group decreased compared to the control group. The NK cell ratio and the degree of quality of life of experimental group increased while that of the control group decreased. CONCLUSION: This study result indicate the importance of exercise and provide empirical evidence for continuation of safe exercise for patients with cancer during their chemotherapy.
Administration, Oral
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Adult
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Aged
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Antineoplastic Agents/*therapeutic use
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Anxiety
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*Exercise Therapy
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Fatigue
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Female
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Humans
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Killer Cells, Natural/immunology/metabolism
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Male
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Middle Aged
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Program Evaluation
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Quality of Life
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Stomach Neoplasms/*drug therapy/surgery
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Treatment Outcome
9.Primary gastrointestinal diffuse large B-cell lymphoma: an immunohistochemical and prognostic study of 90 cases.
Li LIN ; Min MIN ; Cheng-Feng BI ; Xiao-Qing WANG ; Tian-You LUO ; Sha ZHAO ; Wen-Yan ZHANG ; Wei-Ping LIU
Chinese Journal of Pathology 2011;40(4):220-226
OBJECTIVETo study the immunophenotype and prognostic significance of primary gastrointestinal diffuse large B-cell lymphoma, with reference to Hans, Choi and Tally algorithms.
METHODSThe clinicopathologic features and follow-up data in 90 cases of primary gastrointestinal diffuse large B-cell lymphoma were analyzed by Kaplan-Meier method, Log-rank test and Cox regression model. Immunohistochemistry was carried out using EliVision and EnVision methods for CD20, CD3ε, CD10, bcl-6, MUM-1, CD5, bcl-2, GCET1, FOXP1, LMO2, BLIMP1 and Ki-67.
RESULTSThe age of patients ranged from 27 to 83 years (mean = 58 years). The male-to-female ratio was 1.31:1. Amongst the 90 cases studied, 64.4% (58/90) involved the stomach and 35.6% (32/90) involved the intestine. The immunohistochemical findings were as follows: 100% positivity for CD20, 0% for CD3ε and CD5, 17.8% (16/90) for CD10, 75.6% (68/90) for bcl-6, 52.2% (47/90) for MUM-1 (cut off was 30%), 43.3% (39/90) for MUM-1 (cut off was 80%), 50.0% (45/90) for GCET1, 45.6% (41/90) for FOXP1, 23.3% (21/90) for LMO2, 42.2% (38/90) for bcl-2 and 8.9% (8/90) for BLIMP1. The Ki-67 index ranged from 20% to 95% (median = 80%). According to Hans algorithm, 51.1% of the cases belonged to germinal center B-cell (GCB) subtype and 48.9% belonged to non-GCB subtype. In contrast, Choi algorithm classified 55.6% cases as GCB subtype and 44.4% as activated B-cell (ABC) subtype. According to Tally algorithm, 34.4% were of GCB subtype and 65.6% of non-GCB subtype. Most of the patients (67.8%, 61/90) received chemotherapy and 68.9% (62/90) underwent surgical resection. The overall 2, 3 and 5-year survival rates were 58.5%, 52.8% and 49.8%, respectively. The overall 2, 3 and 5-year survival rates in the CHOP therapy group were 68.5%, 61.2% and 52.9%, respectively.
CONCLUSIONSThere is no significant difference in ratio between the GCB and non-GCB/ABC subtypes by Hans and Choi algorithms. The non-GCB subtype seems to be more prevalent according to Tally algorithm. Although there is no significant difference in survival between GCB and non-GCB/ABC subtypes by the 3 algorithms, GCB subtype tends to show a better survival. In univariate analysis, LDH level, international prognostic index, chemotherapy, surgical resection, B symptoms, number of involved sites and clinical stage are found to have prognostic significance. In multivariate analysis, Choi algorithm, Tally algorithm, chemotherapy, surgical resection, LDH level and clinical stage are independent prognostic factors.
Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; DNA-Binding Proteins ; metabolism ; Doxorubicin ; therapeutic use ; Female ; Forkhead Transcription Factors ; metabolism ; Germinal Center ; pathology ; Humans ; Immunophenotyping ; Interferon Regulatory Factors ; metabolism ; Intestinal Neoplasms ; classification ; drug therapy ; metabolism ; pathology ; surgery ; Kaplan-Meier Estimate ; LIM Domain Proteins ; Lymphoma, Large B-Cell, Diffuse ; classification ; drug therapy ; metabolism ; pathology ; surgery ; Male ; Metalloproteins ; metabolism ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neprilysin ; metabolism ; Prednisone ; therapeutic use ; Proportional Hazards Models ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Repressor Proteins ; metabolism ; Serpins ; metabolism ; Stomach Neoplasms ; classification ; drug therapy ; metabolism ; pathology ; surgery ; Survival Rate ; Vincristine ; therapeutic use
10.Effect of shenqi fuzheng injection on pre/post-operational change of argyrophilic-nucleolar organizer regions in peripheral T-lymphocyte in patients with gastric carcinoma.
Jin-quiang YANG ; Yong LI ; Qun ZHAO ; Gang KUANG ; Liqiao FAN ; Lili WANG ; Hui ZHANG ; Kun JIAO ; Hongwei ZHOU
Chinese Journal of Integrated Traditional and Western Medicine 2005;25(7):626-628
OBJECTIVETo investigate the pre-post operational change of argyrophilic-nucleolar organizer regions (Ag-NORs) in peripheral T-lymphocyte of patients with gastric carcinoma (GC), and to explore the effect of shenqi fuzheng injection(SFI) on it.
METHODSEighty five patients were divided into two groups according to the operation performed was radical or non-radical, and the two groups were subdivided into two by additional intravenous dripping of SFI was given to them or not. The content of Ag-NORs in peripheral T-lymphocyte in all patients before and after operation as well as in 12 healthy subjects was determined.
RESULTSContent of Ag-NORs in GC patients was significantly lower than that in the healthy subject (P < 0.01), which significantly increased after patients underwent radical operation (P < 0. 01 or P < 0.05), especially in those treated with SFI (P < 0.01). While in patients underwent non-radical operation but not treated with SFI, it showed insignificant change after operation, however it did significantly increase in those treated with SFI (P < 0.05).
CONCLUSIONThe immune function of T lymphocyte was low in patients with gastric carcinoma, post-operational adjuvant treatment of SFI can significantly improve the cellular immunity of patients.
Adjuvants, Immunologic ; therapeutic use ; Adult ; Aged ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Injections ; Male ; Middle Aged ; Nucleolus Organizer Region ; metabolism ; Phytotherapy ; Silver Staining ; Stomach Neoplasms ; drug therapy ; immunology ; surgery ; T-Lymphocytes ; immunology