A dye combination for the staining of pollen coat and pollen wall.

The pollen coat, which forms on the pollen surface, consists of a lipid-protein matrix. It protects pollen from desiccation and is involved in adhesion, pollen-stigma recognition, and pollen hydration during interactions with the stigma. The classical methods used for pollen coat observation are scanning and transmission electron microscopy. In this work, we screened a collection of fluorescence dyes and identified two fluorescent brighteners FB-52 and FB-184. When they were used together with the exine-specific dye, Basic fuchsin, the pollen coat and the exine structures could be clearly visualized in the pollen of Brassica napus. This co-staining method was applied successfully in staining pollen from Fraxinus chinensis, Calystegia hederacea, and Petunia hybrida. Using this method, small pollen coat-containing cavities were detected in the outer pollen wall layer of Oryza sativa and Zea mays. We further showed these dyes are compatible with fluorescent protein markers. In the Arabidopsis thaliana transgenic line of GFP-tagged pollen coat protein GRP19, GRP19-GFP was observed to form particles at the periphery of pollen coat. This simple staining method is expected to be widely used for the studies of the palynology as well as the pollen-stigma interaction.

Development of the Middle Layer in the Anther of Arabidopsis.

The middle layer is an essential cell layer of the anther wall located between the endothecium and tapetum in Arabidopsis. Based on sectioning, the middle layer was found to be degraded at stage 7, which led to the separation of the tapetum from the anther wall. Here, we established techniques for live imaging of the anther. We created a marker line with fluorescent proteins expressed in all anther layers to study anther development. Several staining methods were used in the intact anthers to study anther cell morphology. We clarified the initiation, development, and degradation of the middle layer in Arabidopsis. This layer is initiated from both the inner and outer secondary parietal cells at stage 4, stopped cell division at stage 6, and finally degraded at stage 11. The neighboring cell layers, the epidermis, and endothecium continued cell division until stage 10, which led to a thin middle layer. The degradation of the tapetum cell wall at stage 7 lead to its isolation from the anther wall. This work presents fundamental information on the development of the middle layer, which facilitates the further investigation of anther development and plant fertility. These live imaging methods could be useful in future studies.

AUXIN RESPONSE FACTOR17 Directly Regulates MYB108 for Anther Dehiscence.

The timely release of mature pollen following anther dehiscence is essential for reproduction in flowering plants. AUXIN RESPONSE FACTOR17 (ARF17) plays a crucial role in pollen wall pattern formation, tapetum development, and auxin signal transduction in anthers. Here, we showed that ARF17 is also involved in anther dehiscence. The Arabidopsis (Arabidopsis thaliana) arf17 mutant exhibits defective endothecium lignification, which leads to defects in anther dehiscence. The expression of MYB108, which encodes a transcription factor important for anther dehiscence, was dramatically down-regulated in the flower buds of arf17 Chromatin immunoprecipitation assays and electrophoretic mobility shift assays showed ARF17 directly binds to the MYB108 promoter. In an ARF17-GFP transgenic line, in which ARF17-GFP fully complements the arf17 phenotype, ARF17-GFP was observed in the endothecia at anther stage 11. The GUS signal driven by the MYB108 promoter was also detected in endothecia at late anther stages in transgenic plants expressing promoterMYB108::GUS Thus, the expression pattern of both ARF17 and MYB108 is consistent with the function of these genes in anther dehiscence. Furthermore, the expression of MYB108 driven by the ARF17 promoter successfully restored the defects in anther dehiscence of arf17 These results demonstrated that ARF17 regulates the expression of MYB108 for anther dehiscence. Together with its function in microcytes and tapeta, ARF17 likely coordinates the development of different sporophytic cell layers in anthers. The ARF17-MYB108 pathway involved in regulating anther dehiscence is also discussed.

HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer.

BACKGROUND: In the Trastuzumab for GAstric cancer (ToGA) study, trastuzumab plus chemotherapy improved median overall survival by 2.7 months in patients with human epidermal growth factor receptor 2 (HER2)-positive [immunohistochemistry (IHC) 3+/fluorescence in situ hybridization-positive] gastric/gastroesophageal junction cancer compared with chemotherapy alone (hazard ratio 0.74). Post hoc exploratory analyses in patients expressing higher HER2 levels (IHC 2+/fluorescence in situ hybridization-positive or IHC 3+) demonstrated a 4.2-month improvement in median overall survival with trastuzumab (hazard ratio 0.65). The ToGA study provides the largest screening dataset available on HER2 overexpression/amplification in this indication. We further analyzed correlation(s) of HER2 overexpression/amplification with clinical and epidemiological factors. METHODS: HER2-positivity was analyzed by histological subtype, tumor location, geographic region, and specimen type. Exploratory efficacy analyses were performed. RESULTS: The HER2-positivity rate was 22.1 % across analyzed tumor samples. Rates were similar between European and Asian patients (23.6 % vs. 23.9 %), but higher in intestinal- vs. diffuse-type (31.8 % vs. 6.1 %), and gastroesophageal junction cancer versus gastric tumors (32.2 % vs. 21.4 %). Across all IHC scores, variability in HER2 staining (≤30 % stained cells) was observed in almost 50 % of cases, with increasing rates in lower IHC categories, and did not affect treatment outcome. The polysomy rate was 4 %. CONCLUSIONS: HER2 expression varies by tumor location and type. All patients with advanced gastric or gastroesophageal junction cancer should be tested for HER2 status, preferably using IHC initially. Due to the unique characteristics of gastric cancer, specific testing/scoring guidelines should be adhered to.

Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p><p><b>METHODS</b>Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival.</p><p><b>RESULTS</b>Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively.</p><p><b>CONCLUSIONS</b>Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p>

R-CHOP regimen can significantly decrease the risk of disease relapse and progression in patients with non-germinal center B-cell subtype diffuse large B-cell lymphoma / 癌症

To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma(DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen(R-CHOP regimen) significantly decreased the risk of disease relapse and progression in CD10-negative patients (P=0.001), Bcl-6-negative patients (P=0.01), and MUM-1-positive patients (P=0.003). The risk of disease relapse in patients with non-GCB subtype (P=0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P=0.042). Although univariate analysis found that both Bcl-2-positive and -negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P=0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.

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

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

Clinical characteristics and treatment of desmoplastic small round cell tumor / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics and treatment of desmoplastic small round cell tumor.</p><p><b>METHODS</b>Five patients with DSRCT were diagnosed and treated in our Hospital from January 1999 to May 2009. Forty-eight cases with complete clinical data were collected and reviewed from 23 published reports. Therefore totally 53 patients with DSRCT were analysed. The survival rate was calculated by Kaplan-Meier method and compared by log-rank test.</p><p><b>RESULTS</b>The median age of all cases was 23 (1.5 - 66) years old at the time of diagnosis. 75.5% of patients were male. The most common presenting complaint was intra-abdominal mass or pain (77.4%). In 46 patients (86.8%), the primary tumor was located in the abdomen or pelvis. Fifteen (28.3%) had positive lymph nodes or distant parenchymal metastases. The median follow-up was 1.8 years (range, 0.1 - 10.0 years). The overall 1-, 3- and 5-year survivals were 45.8%, 20.8% and 5.7%, respectively. Forty-seven patients underwent surgery. Complete tumor resection was significantly correlated with long survival. The 1- and 3-year survival rates were 70.5% and 53.7% in patients treated with complete tumor resection compared to 37.2% and 4.8% in the incomplete tumor resection cohort (P = 0.0020). Thirty-four patients received chemotherapy and the 1- and 3-year survival rates were 60.1% and 35.2%, respectively, however, only 29.7% and 12.7% in patients without chemotherapy (P = 0.0396). Twelve patients had radiotherapy and the 1- and 3-year survival rates were 75.0% and 38.9%, respectively, compared with 36.9% and 14.8% in those without radiotherapy (P = 0.0314).</p><p><b>CONCLUSION</b>Complete tumor resection results in improved survival in patients with DSRCT. Chemotherapy and radiotherapy correlate with improved patient outcome. Multimodal therapy may improve the survival in patients with DSRCT.</p>

Assessment of the protective effect of calcium-magnesium infusion and glutathione on oxaliplatin-induced neurotoxicity / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the efficacy of calcium-magnesium (Ca/Mg) infusion and glutathione (GSH) for preventing the neurotoxicity induced by oxaliplatin.</p><p><b>METHODS</b>This is a randomized, double blind, placebo controlled clinical trail. The patients receiving FOLFOX4 chemotherapy for their solid tumor were randomized to receive Ca/Mg, GSH or normal saline with chemotherapy simultaneously. The incidence and severity of oxaliplatin-induced neurotoxicity were observed. The ECOG performance status was recorded and compared among the 3 groups.</p><p><b>RESULTS</b>Ninety-three patients admitted in our department from Mar 2006 to Dec 2007 were entered into this study, including 29 patients in the Ca/Mg group, 33 in the GSH group and 31 in the chemotherapy alone group. The incidences of acute neurotoxicity were 82.8%, 90.9% and 93.5%, respectively. At the third cycle, the incidences of grade 1-2 chronic neurotoxicity were 37.9%, 48.5% and 42.0%, respectively. No grade 3 neuropathy was observed. After 6 cycles, the incidence of grade 1-2 neuropathy was increased to 68.2%, 88.9% and 85.2%, respectively. A lower percentage was observed in Ca/Mg arm without a statistically significant difference, and grade 3 neuropathy occurred in 5 patients. After 9 cycles, the incidence of grade 1-2 neuropathy was increased to 81.3%, 90.0% and 92.9%, respectively. Grade 3 neuropathy occurred in another 2 patients. No statistically significant difference was observed among the 3 arms. Changes of patient's ECOG score after chemotherapy were similar.</p><p><b>CONCLUSION</b>This study didn't provide evidence that Ca/Mg infusion and GSH can prevent the oxaliplatin-induced neurotoxicity.</p>

Prognostic analysis of patients with liver metastases from colorectal cancer treated with different modes of therapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the potential prognostic factors for patients with liver metastases from colorectal cancer treated with different modes of therapy.</p><p><b>METHODS</b>The clinicopathological data of 300 patients with liver metastases from colorectal cancers were retrospectively reviewed and analyzed.</p><p><b>RESULTS</b>The median survival of patients with recurrence (MSR) treated with complete and palliative resection of liver metastases and unresectable patients was 48, 19 and 18 months, respectively (P = 0.000). In patients with unresectable liver metastases, systemic chemotherapy plus regional therapy demonstrated a median survival time of 23 months, significantly longer than the 6 months in untreated patients (P = 0.000). Patients who showed response to the first-line therapy demonstrated an improved survival versus the patients who had no response, with a median survival time of 24 vs. 16 months (P = 0.000). Univariate analysis revealed that resection modes of primary diseases and liver metastases, treatment modality for liver metastases, and response to first-line therapy were prognostic factors. Multivariate analysis showed that resection modes of liver metastases, multimodality treatment after liver metastases, and the response to first-line therapy were all independent prognostic factors for patients with liver metastases from colorectal cancer.</p><p><b>CONCLUSION</b>Resection of liver metastases, multimodality treatment after liver metastases, and response to first-line chemotherapy are all independent prognostic factors for patients with liver metastasis from colorectal cancer.</p>

Analysis of first-line chemoresistance and prediction of chemo-response in non-small cell lung cancer by comparative genomic hybridization / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the association between chromosomal disequilibrium and chemoresistance/chemosensitivity in non-small cell lung cancer (NSCLC) using comparative genomic hybridization (CGH).</p><p><b>METHODS</b>Genomic DNA samples were prepared from the tumor tissues in paraffin-embedded sections derived from 88 patients with advanced NSCLC (18 with chemosensitivity and 16 with chemoresistance). The DNAs were first amplified by a degenerate oligonucleotide prime-polymerase chain reaction protocol and then labeled with fluorescence as probes for CGH analyses. The correlations of the resulting chromosomal imbalances with the chemo-sensitivity and other pathological features of the patients were analyzed.</p><p><b>RESULTS</b>A total of 640 abnormal chromosome regions including 96.12% gains and 3.88% losses were detected in 88 specimens. The results indicated that the most frequently gained chromosome regions were 19p13.1-13.3 (39/88, 44.12%), followed by 9q12-q22 (26/88, 29.41%), 22q12-q13 (26/88, 29.41%), and Xq (29/88, 32.35%). The total number of abnormal regions related with chemo-sensitivity was 188( 182 gains and 6 losses), while the number of the abnormal regions linked to the chemoresistance was 452 (431 gains and 21 losses) (P=0.005). Gains of 14p12-p13 and 19p were significantly correlated with the chemosensitivity of the NSCLC (P=0.006). Gains of 1q12-q22, 10q25-q26, 5p15.1-p15.3, 19q13.2-13.4, 20p11.2-p12, 21q22, and Xp 21-p22.1 were also significantly correlated with the chemoresistance (P]0.005, 0.029, 0.039, 0.029, 0.039, 0.016, and 0.006, respectively). No correlation between the chromosome abnormalities and other clinical features was observed.</p><p><b>CONCLUSIONS</b>The specific gains and losses of chromosome region is correlated with platinum-based first-line chemotherapy in NSCLC patients,as confirmed by CGH detection. This finding is useful for further identifying the chemosensitivity-related functional genes, predicting clinical effectiveness, and achieve individualized treatment in the future.</p>

Analysis of prognostic factors in 300 colorectal cancer patients with liver metastases / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyse the clinical characteristics and potential prognostic factors of colorectal cancer patients with liver metastases.</p><p><b>METHODS</b>The clinical and pathological data of 300 colorectal cancer patients with liver metastases were retrospectively reviewed and analyzed.</p><p><b>RESULTS</b>The median survival time of these patients was 19.0 months. The 1-, 2- and 5-year survival rates after liver metastases were 79.0%, 29.0% and 3.0%, respectively. Univariate analysis revealed that performance status (KPS), histological grading, primary tumor, N status, lymphatic and vascular invasion, stage at diagnosis, the number, size and distribution of liver metastases and other accompanied metastases were prognostic factors. Multivariate analysis showed that KPS, lymphatic and vascular invasion, the number and size of liver metastases were independent prognostic factors of colorectal cancer with liver metastases.</p><p><b>CONCLUSION</b>Performance status, lymphatic and vascular invasion, the number and size of liver metastases are independent prognostic factors of colorectal cancer with liver metastases.</p>

Comparison of the efficiency of CHOP-based regimen with or without high dose consolidation treatment combined with hematopoietic stem cell transplantation in 63 lymphoblastic lymphoma patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To retrospectively analyze and compare the treatment efficiency of CHOP-based regimens with or without high-dose consolidation treatment combined with hematopoietic stem cell transplantation (HDT-HSCT) in the patients with lymphoblastic lymphoma (LBL).</p><p><b>METHODS</b>From 1989 to 2004, totally 63 patients with LBL were initially treated with a standard CHOP-based regimen. Forty-two of the 63 patients achieved complete response (CR), 26 of those subsequently received consolidation HDT-HSCT, while the other 16 had 6-8 cycles of standard CHOP-based treatment only.</p><p><b>RESULTS</b>Of the 63 patients, 57 had a T-LBL and 6 B-LBL, with a median age of 20 years, 19 (30.2%) had a stage I-II diseases and 44 (69.8%) stage III-IV diseases, 61.9% presented with a mediastinal mass. Bone marrow involvement presented in 28.6% of the patients. Fourteen percent had central nervous system involvement. The median follow-up period was 24 months, and the estimated 5-year overall survival and disease-free survival of this series was 31.2% and 29.3%, respectively. Of the 42 patients who achieved CR, the 5-year OS rate of the patients who received HDT-HSCT as a consolidation therapy was 59.8% versus 14.6% of the patients treated by CHOP-based regimens alone (P=0.004). Bone marrow involvement, age > or =20 years, short response duration and primary refractory disease were factors significantly associated with poor outcome. Among the 18 patients with bone marrow involvement, 3 received allogeneic HSCT and were all still alive at the follow up time of 22, 32 and 37 months, respectively, while another 4 received auto-HSCT and all died of the disease within 14 months.</p><p><b>CONCLUSION</b>Short term treatment with a CHOP-based regimen is not sufficient for the patients with lymphoblastic lymphoma. High-dose consolidation treatment and hematopoietic stem cell transplantation may improve overall survival and disease free survival. Bone marrow involvement, age >20 years, and short response duration and primary refractory disease are all the factors significantly associated with poor outcome. For the patients with bone marrow involvement, allohematopoietic stem cell transplantation is superior to auto-hematopoietic stem cell transplantation.</p>

Relationship between the level of RRM1 expression and the sensitivity to gemcitabine in the esophageal squamous cell carcinoma cell lines / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Ribonucleotide reductase subunit M1 (RRM1) is the intracellular target of gemcitabine (GEM). The aim of this study is to explore the relationship between the level of RRM1 expression and the sensitivity to GEM in the esophageal squamous cell carcinoma cell lines.</p><p><b>METHODS</b>Four esophageal squamous cell carcinoma cell lines (Kyse-150, Kyse-450, 9706 and Eca-109) were cultured in vitro. In the same period, RRM1 expression level was measured by RT-PCR and Western blot, and cell sensitivity to GEM was determined by CCK-8 assay. The relation between cell sensitivity and RRM1 expression was further analyzed. Kyse-450 cells were continuously cultured in the medium containing 50 nM GEM. RRM1 expression was measured at different time points to monitor the dynamic changes in the surviving cells. Inhibition of RRM1 expression by RNAi method was applied and the effect on GEM-sensitivity was further examined.</p><p><b>RESULTS</b>The IC(50) of Eca-109, Kyse-150, Kyse-450 and 9706 cells were (0.92 +/- 0.17), (0.48 +/- 0.11), (0.29 +/- 0.06) and (0.02 +/- 0.01) mmol/L, respectively. The expressions of RRM1 protein and mRNA of Eca-109 cell line were the highest detected by Western blot and RT-PCR, followed by Kyse-150 and Kyse-450, and the lowest one was 9706 cell line. When Kyse-450 cells were continuously treated with 50 nmol/L GEM, the level of RRM1 protein was increasing in the surviving cells. RRM1 siRNA could effectively knock down the expression of RRM1 and significantly increase the cell sensitivity to GEM (P = 0.035).</p><p><b>CONCLUSION</b>The level of RRM1 expression correlates with the cell sensitivity to gemcitabine. The cells with a lower level of RRM1 expression are more sensitive to gemcitabine.</p>

Phase III clinical study of zoledronic acid in the treatment of pain induced by bone metastasis from solid tumor or multiple myeloma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of zoledronic acid in the treatment of bone pain in patients with bone metastasis from solid tumor or multiple myeloma.</p><p><b>METHODS</b>A randomized, double-blind, double-simulated and multi-center phase III clinical trail with pamidronate as control was conducted. Patients with moderate to severe bone pain (VAS > 50 mm) induced by solid tumor or multiple myeloma were randomized to receive intravenous zoledronic acid 4 mg or pamidronate 90 mg. Then the change of VAS and urinary NTX/Cr and CTX/Cr were observed in two groups.</p><p><b>RESULTS</b>From July 2005 to September 2006, 228 patients with bone pain induced by bone metastasis from 15 cancer centers were randomize into two groups: 116 patients in zoledronic acid group and 112 patients in pamidronate group. The VAS value was decreased gradually after treatment in these two groups. Significant improvement in bone pain after treatment were observed both in zoledronic acid group and the control group when compared with baseline VAS on D8 (-11.77% vs. -10.87%), D15 (-24.60% vs. -21.06%) and D28 (-32.37% vs. -31.26%) (P< or =0.0001), but no significant difference existed between two groups (P =0.6587). Compared with baseline, urine NTX/Cr and CTX/Cr level were decreased rapidly after treatment in both groups, the nadir was on D8, the median decreased on D28, which was -36.9% vs. -32.1% for NTX/Cr (P = 0.7922) and -63.2% vs. -47.9% for CTX/Cr (P =0.834). The frequently observed adverse events were pyrexia (19.0% vs. 31.3%), vomiting (6.0% vs. 8.9%), nausea (4.3% vs. 4.5%), fatigue (3.4% vs. 2.7%) and constipation (2.6% vs. 1.8%) in the two groups. Compared with baseline, the serum creatinine level was not significantly increased throughout the study.</p><p><b>CONCLUSION</b>Intravenous injection of 4 mg zoledronic acid can significantly reduce bone pain and bone resorption marker in urine in the Chinese patients with bone metastasis from solid tumor or multiple myeloma, which is tolerable and also comparable to pamidronate in the efficacy and safety.</p>

Multicenter phase II clinical trial of uroacitides injection in the treatment for advanced malignant tumors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the efficacy, safety and the life quality improvement of uroacitides injection in the treatment for patients with advanced malignant tumors.</p><p><b>METHODS</b>A total of 160 patients with advanced stage cancers were enrolled into this multicenter, open and non-randomized phase II clinical trial, including cancers of the lung (33 cases), liver (45 cases), breast (17 cases), esophagus (11 cases), stomach (18 cases), colon (19 cases), pancreas (3 cases) and kidney (4 cases), and glioma (10 cases). Uroacitides was administrated in a dose of 300 ml daily via the superior vena cava catheter for consecutive 4-8 weeks.</p><p><b>RESULTS</b>Of the 160 patients, 21 dropped out and one patient died during the trial. Efficacy could be evaluated in 138 patients and safety in 160. The total objective response rate (ORR, CR + PR)) and tumor control rate (CR + PR + MR + SD) of the 138 evaluable patients were 5.8% and 65.2%, respectively. Clinical benefit response (CBR) rate was 57.2%. Major adverse effects were grade I - II and reversible nausea/vomiting (21.9%) and pain (6.3%).</p><p><b>CONCLUSION</b>Uroacitides injection is effective in the control for various kinds of advanced cancers with mild, reversible and tolerable adverse effects, and can also improve the patient's quality of life. It is worth being studied further.</p>

Combined-modality therapy for 150 cases of early-stage Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the efficacy of chemotherapy alone, radiotherapy alone and combined-modality therapy in the treatment for early-stage Hodgkin's lymphoma (HL).</p><p><b>METHODS</b>From 1999 to 2002, totally 150 patients with stage I or II HL were treated in our hospital. They were stratified into several groups based on initial treatment strategy: chemotherapy alone (CT group, n = 22), radiotherapy alone (RT group, n = 18), combined-modality therapy (CMT group, n = 109) and surgical resection (SR group, n = 1). Chemotherapy regimens were mainly ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) and MOPP (mechlorethamine, vincristine, procarbazine and prednisone). Radiotherapy modes included involved field radiotherapy (IFRT), extended field radiotherapy (EFRT) and sub-total nodal irradiation (STNI).</p><p><b>RESULTS</b>The pathological types included nodular sclerosis (NS, n = 84), mixed-cellularity (MC, n = 39), lymphocyte-predominant (LP, n = 23), lymphocyte-depleted (LD, n = 3) and nodular lymphocyte predominant Hodgkin's disease (NLPHD, n = 1). Of those, 72 were evaluble in terms of prognostic factors. No poor prognostic factor was found in 36.1% or 29.2% of the patients according to EORTC or GHSG criteria, respectively. There were 33 patients with complete response (CR), 109 with partial response (PR), 5 with stable disease (SD) and 3 with progressive disease (PD) after initial therapy. The median follow-up period was 71.5 months. The overall 7-yr survival rate was 89.3%, and treatment failure rate at 6 years was 18.8%. The response rate of CMT group was superior to that of CT group, and the patients with nodular sclerosis or mixed-cellularity type had significantly lower risk of treatment failure (P = 0.009 and 0.019, respectively). The multivariate analysis revealed that the treatment strategies affected the prognosis significantly. The risk of failure of chemotherapy alone was 2.52 times higher than that of combined-modality therapy (P = 0.004). No predictive factor affecting OS was identified by either univariate or multivariate analysis. The patients in CMT group suffered more adverse effects than those in either CT or RT groups, which mainly consisted of leucopenia, alopecia and gastrointestinal symptoms.</p><p><b>CONCLUSION</b>Combined-modality therapy is more effective than chemotherapy alone or radiotherapy alone in the treatment for early stage Hodgkin's lymphoma. Though its acute adverse effects are more severe than that of chemotherapy or radiotherapy alone, it may reduce the risk of treatment failure.</p>

Phase II multicenter clinical trial of nedaplatin in the treatment of malignant tumors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate and compare the efficacy and safety of Nedaplatin (NDP)-based regimen and cisplatin (DDP)-based regimen for head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), esophageal cancer and ovary epithelial cell carcinoma.</p><p><b>METHODS</b>Single agent group: NDP was administered at a dose of 100 mg/m(2) on D1, every 3 weeks for at least 2 cycles. Combination chemotherapy group: combined with 5-Fu, NVB, VDS + 5-Fu, PTX or CTX respectively, NDP 80 mg/m(2) on D1 or DDP 30 mg/m(2) on D1-3, every 3 weeks for at least 2 cycles was given.</p><p><b>RESULTS</b>Of 237 patients in this trial, 37 were treated by single Nedaplatin, 139 by NDP-based regimen, 61 by DDP-based regimen in the control group. The response rate of single Nedaplatin chemotherapy for advanced NSCLC was 10.5% (2/19), for ovary carcinoma (1/3) and HNSCC (1/1). For NSCLC and ovary carcinoma patients who had failed in the previous DDP-based chemotherapy, the response rates by single NDP chemotherapy were still 9.1% and 33.3%. The response rate of NDP-based combination regimen for NSCLC, ovary carcinoma, HNSCC and esophageal cancer was 33.9% (21/62), 44.8% (13/29), 20.0% (3/15) and 18.2% (4/22), respectively, which was not statistically different from the rate of controlled group treated by DDP-based regimen. For chemonaive NSCLC, the effect of NDP-based combination regimen (35.7%) was significantly superior to the effect of DDP-based regimen (17.1%) (P = 0.045). The most common adverse events of nedaplatin were myelosuppression (leukopenia, thrombocytopenia, anemia), nausea and vomiting. The myelosuppression and renal toxicity of NDP-based regimen were similar to that of DDP-based regimen, but vomiting was milder than that of DDP-based regimen (54% vs. 75.4%), and grade I/II liver toxicity was more common in the NDP-based regimen than in DDP-based regimen (10.8% vs. 0).</p><p><b>CONCLUSION</b>Nedaplatin is effective in the treatment for HNSCC, NSCLC and ovary carcinoma. Compared with the control group treated by DDP-based regimen, nedaplatin-based combination chemotherapy has similar effect on HNSCC, NSCLC, ovary carcinoma and esophageal cancer. Gastrointestinal reaction of nedaplatin is milder than that of cisplatin but the liver function during chemotherapy must be monitored closely.</p>

Expression of serum breast drug-resistance protein in predicting chemosensitivity of NSCLC / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate expression of serum breast cancer resistance protein (BCRP) in non-small cell lung cancer patient (NSCLC) and healthy adult, and its correlation with chemosensitivity as one passible value of BCRP in clinical application.</p><p><b>METHODS</b>Venous blood specimens of 44 advanced NSCLC patients and 30 healthy adults were collected. Antibody of BCRP was used to detect its expression in the experiment. Part of venous specimens were randomly selected for Western-blot, and all specimens were examined by ELISA at last. Chemotherapy response of these patients was observed in order to analyze the correlation between BCRP expression level and chemosensitivity.</p><p><b>RESULTS</b>Western blot result showed that BCRP expression can be detected both in NSCLC patient and normal adult. The expression level in NSCLC patients detected by ELISA was significantly higher than that in the healthy adults (P = 0.00); which was also significantly higher in chemo-resistant patients than that in the chemosensitive (P = 0.02) and the healthy adults (P = 0.00); however, BCRP expression in chemo-sensitive patients was not significantly different from that in the healthy adults (P = 0.08).</p><p><b>CONCLUSION</b>Breast cancer resistance protein (BCRP) is found to be expressed at high level in the serum of NSCLC patient, the intensity of BCRP expression may be correlated with chemotherapy resistance in NSCLC, and the high level expressing of BCRP may indicate resistance to the platinum-based chemotherapy regimen. Detection of serum BCRP may someday become a useful bio-marker in predicting chemosensitivity of NSCLC.</p>

Correlation between the expression of PCDGF in serum and the chemotherapeutic sensitivity in NSCLC / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of PC cell-derived growth factor (PCDGF) in the serum of non-small cell lung cancer (NSCLC) patients and healthy adults, and it's correlation with chemotherapeutic sensitivity.</p><p><b>METHODS</b>The venous blood samples of 44 advanced NSCLC patients and 30 healthy adults were collected, and PCDGF mono-antibody was used for detection in the experiment. A part of specimens were randomly selected for Western-blot, and all specimens were eventually examined by ELISA. Chemotherapeutic response of these patients was recorded in order to analyze the correlation between PCDGF expression level and chemotherapeutic sensitivity.</p><p><b>RESULTS</b>Western blot results indicated that there was PCDGF expression both in NSCLC patients and healthy adults, and the expressing intensity of PCDGF in NSCLC patients was higher than that in healthy adults. The result of ELISA showed PCDGF expression in the patients whoever was chemoresistant or chemosensitive was significantly higher than that in healthy adults (P < 0.01), However, in chemoresistant patients, it was significantly higher than that in chemosensitive with a borderline statistical difference (P < 0.05).</p><p><b>CONCLUSION</b>PC cell-derived growth factor is found to be not only expressed in healthy adult but also in NSCLC patient at a high level in the serum, which may indicate metastasis and active proliferation in NSCLC. The intensity of PCDGF expression may be correlated with chemotherapy response and the high level expressing of PCDGF may indicate resistant to platinum-based chemotherapeutic regimen.</p>