The diffuse large B cell lymphoma (DLBCL) is the most common adult non-hodgkin lymphoma.At present,rituximab in combination with CHOP program has significantly improved the prognosis of DLBCL,and about 50％ of the DLBCL can be cured.However,due to the heterogeneity of the tumor,the refractory and relapsed DLBCL is still lack of effective treatment methods.With the application of gene expression profile (GEP) and the thorough research of the activation of lymphoma cells signal way,a lot of potential therapeutic targets have been found.

Object To evaluate the efficacy and toxicity of L-asparaginase based regimen for extranodal nasal type NK/T cell lymphoma (ENKTL).Methods 36 patients were treated with L-asparaginase based regimen from February 2008 to November 2011. 20 stage Ⅰ /Ⅱ patients were administered with VLD regimen based chemo-radiotherapy. 4 of 16 stage Ⅲ/Ⅳ patients received modified SMILE regimen chemotherapy, followed by involved field radiation therapy (IFRT), while others received modified SMILE regimen chemotherapy alone.Results Among 36 patients,35 were eligible for treatment response evaluation.The overall response rate (RR) was 68.6％ (24/35) with complete response (CR) rate of 54.3％ (19/35).After the median follow-up of 13.5 (range 3-31) months,for all patients,the 1-year overall survival (OS) rate was 82 ％,and the rate of progression-free survival (PFS) at 1 year was 65 ％.The patients who attained response with treatment showed better 1-year OS (93 ％) and PFS (80 ％) as compared with patients without response (35 ％; 33 ％),and the differences were statistically significant (x2=13.909,P =0.000; x2=8.216,P =0.004).The major adverse event was myelosuppression. No chemotherapy-related mortality occurred. Conclusion L-asparaginase based regimen is obviously effective and well tolerant for ENKTL. The large prospective clinical trials of L-asparaginase based regimen in the first-line treatment for ENKTL are worth for further investigation.

Objective To evaluate the clinical outcome of autologous hemopoietic stem cell transplantation (AHSCT) for hematological malignancies. Methods Data of 61 patients with hematological malignancies who underwent AHSCT in Xiangya Hospital from April 1994 to August 2008 were retrospectively analyzed. There were 30 acute non-lymphoblastic leukemias (ANLL), 25 non-Hodgkin lymphoma (NHL), 3 Hodgkin lymphoma (HL), and 3 plasmacytoma. Mel 160 mg/m2 + Ara-C 2.0/2.5 g × 2 +Cy 1.8 g/m2 × 2, or TBI 8-10 Gy + Cy 1.8 g/m2 × 2 were mainly included in pretreatment regimens. Results All patients had rapid hemopoietic reconstitution. There was one patient who died of heart failure during the transplantation process. The rate of AHSCT related death was 1.6 %. The median follow up duration was 52(2-211) months. Forty-seven of 61 patients were still alive during the analysis. The probabilities of disease free survival (DFS) at 5 years were significantly different between these two groups: (77.5±5.5) % for AHSCT groups and (31.6±7.3) % for synchronous intensive chemotherapy groups(P ＜0.01). Conclusion AHSCT can be safely performed as an important treatment constituent for hematological malignancies.

OBJECTIVE: To explore the reversal effect and mechanism of lobeline on the multidrug-resistance (MDR) of human breast cancer cells MCF-7/ADM. METHODS: In human breast cancer cell line MCF-7/ADM, MTT assay was used to determine the cell growth inhibiting ratio of MCF-7/ADM by ADM and Fu. Fluorospectorphotometer was employed to investigate the intracellular concentration of rhodamine123 to reflect the effect of lobeline on the activity of MDR-related protein P-glycoprotein (P-gp). Taking untreated MCF-7/ADM cells as controls, flow cytometry was applied to detect the intracellular concentration of rhodamine123 in MCF-7/ADM cell intervened with lobeline of 20 micromol/L. RESULTS: The sensitivity of MCF-7/ADM to ADM and Fu was significantly increased by lobeline in a dose-dependent manner. The inhibitive concentration 50 (IC(50)) of ADM declined from (44.81+/-0.43) mg/L to (16.72+/-0.75) mg/L with a reversion index of 2.68. The IC(50) of Fu declined from (53.12+/-1.60) mg/L to (38.90+/-1.43) mg/L with a reversion index of 1.37. The fluorescence intensity of lobeline-treated cells was significantly higher than that of the controls, when the concentration of lobeline was more than 10 micromol/L. With fewer side effects, the reversal efficacy of 20 micromol/L lobeline was 71.6% of the classical MDR reversal agent of verapamil at the same concentration. CONCLUSION Lobeline can reverse the MDR of MCF-7/ADM cells by inhibiting the activity of P-glycoprotein.
Breast Neoplasms ; pathology ; Cell Line, Tumor ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Female ; Glycoproteins ; antagonists & inhibitors ; Humans ; Lobeline ; pharmacology

OBJECTIVE: To investigate the relationship between the expression of leptin, p-mTOR protein and the pathogenesis, development and clinicopathological features in colon carcinoma. METHODS: The expression of leptin and p-mTOR protein was evaluated by immunohistochemical methods in 40 normal colon mucosas, 40 colon adenomatous polyps and 108 cases of colon carcinomas. The relationship between the staining pattern and clinicopathogical features was examined. RESULTS: The positive rates of detection of leptin in normal colon mucosa, adenomatous polyps and colon carcinomas were 10% (4/40), 27.5% (11/40), and 71.3% (77/108), respectively; with significant differences among the three groups (P<0.05). The positive rates of p-mTOR protein in the normal colon mucosa, the adenomatous polyps, and the colon carcinomas were 2.5% (1/40), 20% (8/40), and 61.1% (66/108), respectively; with significant differences among the three groups (P<0.05). The expression of leptin and p-mTOR proteins were related to invasive depth, TNM stages, lymph node metastasis, distant metastasis and tumor differentiation (P<0.05), but not to age, sex, or site (P>0.05). In colon carcinoma tissues, leptin expression was positively correlated with p-mTOR expression (P<0.01). CONCLUSION Leptin and p-mTOR proteins may play important roles in the occurrence and development of colon carcinoma. The detection of leptin and p-mTOR may be helpful for evaluation of the prognosis of the patient with colon carcinoma.
Adenocarcinoma ; metabolism ; pathology ; Adenomatous Polyps ; metabolism ; pathology ; Aged ; Colon ; metabolism ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Humans ; Intestinal Mucosa ; metabolism ; Leptin ; metabolism ; Male ; Middle Aged ; Neoplasm Metastasis ; Phosphorylation ; Prognosis ; TOR Serine-Threonine Kinases ; metabolism

OBJECTIVE: To analyze the clinical characteristics of primary gastric lymphoma (PGL) and to improve its diagnosis and treatment. METHODS: The clinical manifestations, diagnosis, treatments and history of 50 PGL patients, who were hospitalized from September 2005 to September 2009, were reviewed and analyzed. RESULTS: The main manifestation of PGL was epigastric pain with infrequent systemic symptoms, such as stomach ache, abdominal discomfort, vomit, black stool, loss of appetite, fever, feeble, and skinny. Pathological examination indicated that only 1 patient had T cell lymphoma while the rest 49 had B cell lymphoma. Fourteen had mucosa-associated lymphoid tissue lymphoma (MALT), 35 had diffuse large B cell lymphoma (DLBCL), and 2 had both DLBCL and MALT (DLBCML). All the 50 patients received chemotherapy, and 12 underwent surgical treatment besides chemotherapy. Fourteen out of the 49 patients with B cell lymphoma received rituximab together with chemotherapy, and 35 received chemotherapy alone. The 2-year survival rate in the patients receiving rituximab together with chemotherapy was higher than that in the patients receiving chemotherapy alone (85.7% vs 77.1%, P< 0.05). The 2-year survival rate in patients of clinical stage I-II was higher than that in patients of clinical stage III-IV (90.9% vs 71.4%, P< 0.05). CONCLUSION The main clinical manifestation of PGL patients is non-specific gastrointestinal symptoms, among which abdominal pain is most common. The clinical examination mainly relies on pathological examinations, and the most common pathological type of primary gastric lymphoma is DLBCL. The main treatment is chemotherapy, and the prognosis is related to the clinical stage and the use of rituximab. After the treatment, the 2-year survival rate in the 50 patients reaches 80.0%.
Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Humans ; Lymphoma, B-Cell, Marginal Zone ; Lymphoma, Large B-Cell, Diffuse ; Lymphoma, Non-Hodgkin ; diagnosis ; drug therapy ; pathology ; Prognosis ; Retrospective Studies ; Rituximab ; Stomach Neoplasms ; diagnosis ; drug therapy ; pathology ; Survival Rate

OBJECTIVE: To analyze the impact of β-tubulin-III (TUBB3), thymidylate synthase (TS) and excision repair cross complementation group 1 (ERCC1) mRNA expression on chemoresponse and clinical outcome of patients with advanced gastric cancer treated with TXT/CDDP/FU (DCF) regimen chemotherapy. METHODS: The study population consisted of 48 patients with advanced gastric cancer. All patients were treated with DCF regimen palliative chemotherapy. The mRNA expressions of TUBB3, TS and ERCC1 of primary tumors were examined by multiplex branched-DNA liquid chip technology. RESULTS: The patients with low TUBB3 mRNA expression had higher response rate to chemotherapy than patients with high TUBB3 expression (P=0.011). There were no significant differences between response rate and TS or ERCC1 expression pattern. Median overall survival (OS) and median time to progression (TTP) were significantly longer in patients with low TUBB3 mRNA expression (P=0.002, P<0.001). TS or ERCC1 expression was not correlated with TTP and OS. In the combined analysis including TUBB3, TS and ERCC1, the patients with 0 or 1 high expression gene had better response rate, TTP and OS than the remaining patients (all P<0.001). Multivariate analysis revealed that ECOG (Eastern Cooperative Oncology Group)≥2 (HR=2.42, P=0.009) and TUBB3 (HR=2.34, P=0.036) mRNA expression significantly impacted on OS. CONCLUSION High TUBB3 mRNA expression is correlated with resistance to DCF regimen chemotherapy. TUBB3 might be a predictive and prognostic factor in patients with advanced gastric cancer treated with TXT-based chemotherapy. The combined evaluation of TUBB3, TS and ERCC1 expression can promote the individual treatment in advanced gastric cancer.
Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Drug Resistance, Neoplasm ; Endonucleases ; genetics ; metabolism ; Humans ; RNA, Messenger ; genetics ; metabolism ; Stomach Neoplasms ; drug therapy ; genetics ; Thymidylate Synthase ; genetics ; metabolism ; Treatment Outcome ; Tubulin ; genetics ; metabolism

Objective To investigate the optimal thresholds of the passing rate with different gamma measurement criteria (percent dose difference/DTA) based on the Delta 4 three-dimensional dosimetric verification system in the verification of volumetric modulated arc-therapy (VMAT) plan for cervical cancer.Methods Thirty clinically-approved dual-arc VMAT plans using the RapidArcTM (Varian Medical Systems Inc.) for cervical cancer were randomly selected.The gamma analysis and dose-volume histogram (DVH) evaluation were performed using Delta 4.All the plans were classified according to the following two criteria:1.If the absolute percentage dose errors of all specific dosimetry indices on the DVH were less than 5％,the plan was regarded as clinically acceptable.2.If the gamma passing rate was 90％ or 95％ under the criteria of 2％/2 mm and 3％/3 mm,the plan was regarded as acceptable.The sensitivity and specificity analyses were conducted based on the classification results and the receiver operating characteristic (ROC) curve was plotted.By calculating the Youden Index,the optimal thresholds under different Gamma criteria (global and local 2％/2 mm and 3％/3 mm) were investigated.Finally,the ability of distinguishing the plan was clinically acceptable or not between the conventional and optimal thresholds was quantitatively compared according to the sensitivity and specificity analyses.Results The optimal thresholds under the global 3％/3 mm and 2％/2 mm criteria were 98.3％ and 87.05％;and 97.55％ 、86.05％ for the local gamma analysis.Compared with the conventional thresholds,the sensitivity of the optimal thresholds was 0.93 by using the global and local gamma analyses under the 3％/3 mm criterion.Under the 2％/2 mm criterion,the sensitivity of the optimal thresholds was 0.65 and the specificity was 0.49 by using the global gamma analysis.The sensitivity was 0.7 and the specificity was 0.46 by using the local gamma analysis,suggesting that the sensitivity and the specificity were more balanced under the 2％/2 mm criterion.Conclusions Application of the optimal thresholds in the verification of VMAT plans can maintain the balance between the sensitivity and specificity,prevent the harm of clinically unacceptable plans to patients to certain extent and reduce the probability of increasing the daily work load for physicists due to the misjudgement of clinically acceptable plans.

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.