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The tumor suppressor gene, PTEN, has previously been demonstrated to be involved in breast tumorigenesis and tumor progression. The aim of the present study was to investigate the expression and significance of PTEN in breast carcinomas, to detect the mutation frequency of PTEN in sporadic breast carcinoma tissues and to determine the association between PTEN promoter methylation and gene expression. Immunohistochemical methods were used to analyze the expression of the PTEN gene in 146 cases of breast carcinoma and 10 cases of normal breast tissue closely adjacent to the carcinoma. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis was used to analyze conformation polymorphisms in 45 breast carcinoma and 10 normal breast tissues. Point mutations of abnormal single stranded conformation were detected by DNA sequencing. The methylation of the PTEN promoter was analyzed by methylation-specific PCR. Expression of PTEN was detected in 57.5% (84/146) of patients with breast carcinoma. By contrast, PTEN expression was detected in 100% of normal samples. Expression of PTEN was found to negatively correlate with the tumor size, the pathological stage and the expression of the estrogen receptor (ER) and the progesterone receptor (PR) in breast cancer. The 2-year disease-free survival of patients with a high expression of PTEN was higher compared with those with low PTEN expression (P

Objective To evaluate the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermis growth-factor receptor 2(HER-2), to determine the phenotype transformation of these receptors before and after recurrence and/or metastasis, and to explore the effects of expression and phenotype transformation of receptors on the treatment efficacy and clinical prognosis of patients with breast cancer. Methods Based on the phenotype transformation of ER, PR, and HER-2 receptor, 211 breast cancer patients were assigned to 3 groups. Twenty patients of Group A were with primary triple-negative breast cancer (TNBC, defined as lacking expression of ER, PR and HER2) which transformed into non-TNBC after recurrence and/ or metastasis, 73 of Group B were with primary non-TNBC which transformed into TNBC after recurrence and/or metastasis, and 118 of Group C were with primary TNBC which was still TNBC after recurrence and/or metastasis. The phenotype transformation of receptors, recurrence/metastasis, and efficacy and clinical prognosis were analyzed following collection of general information of the patients. Results The median age of 211 recurrent patients was 52 years (range, 22 to 78 years). Most of the patients exhibited solitary metastasis. The most common locations of the initial metastasis were lymph node, bone and skin. The median disease-free survival for Groups A, B, and C was 34.0, 25.0, and 20.0 months, respectively. The clinical effect of Groups B and C was better than that of Group A for first-line, second-line, and third-line rescuing therapy (P=0.030, 0.003, 0.001). However, the clinical benefit rate of Group A was higher than those of Groups B and C for rescuing endocrine therapy. The median follow-up time of the 211 patients was 68 months (range, 20 to 127 months), and the median survival after recurrence for Groups A, B, and C was 63.1, 33.7, and 25.8 months respectively (P=0.000). The median overall survival for Groups A, B, and C was 156.7, 67.8, and 47.4 months respectively (P=0.000). Conclusions The phenotype transformation of ER, PR and HER-2 may influence the clinical prognosis of patients with breast cancer. Therefore, the expression of ER, PR and HER-2 should be determined to ensure the efficacy of rescuing therapy.

The effect of trastuzumab on patients with HER-2/neu (HER2)-positive gastric cancer has been confirmed in a phase III clinical trial (ToGA study). However, the optimized sequence and synergic mechanism of trastuzumab and chemotherapy are not clear. Our study investigated the effects and mechanisms of trastuzumab in combination with 5-Fluorouracil (5-Fu) or cisplatin (DDP) on gastric cancer cell lines. Flow cytometry was used to determine HER2 expression and cell cycle. MTT assay was performed to evaluate cytotoxicity. Western blotting and RT-PCR were used to analyze signaling transduction and mRNA expression. Sequential 5-Fu followed by trastuzumab and trastuzumab plus DDP followed by trastuzumab produced the best inhibitory effects. Inhibition of HER2-PI3K-AKT signal transduction, downregulation of nucleotide excision repair cross-complementation 1 (ERCC1), and interference with cell cycle distribution may elucidate the synergism between trastuzumab and chemotherapy. These results provide some evidence for designing a rational regime when trastuzumab is being considered to be used in patients with gastric cancer.

Mutations in the breast cancer susceptibility gene BRCA1 predispose individuals to breast and ovarian cancers. Cofactor of BRCA1 (COBRA1), a novel protein, was isolated as a BRCA1-interacting protein. However, the role of COBRA1 in breast cancer is poorly understood. In this study, we demonstrate that COBRA1 mRNA was differentially expressed in breast cancer cell lines by semi-quantitative reverse transcription-polymerase chain PCR (RT-PCR). We developed a highly specific rabbit polyclonal anti-COBRA1 antibody using GST-COBRA1 fusion protein. In most cases, the levels of COBRA1 protein in breast cancer cell lines detected by Western blotting with the anti-COBRA1 antibody correlated with those of COBRA1 mRNA. Immunofluorescence analysis indicated that COBRA1 was a nuclear protein. Endogenously expressed COBRA1 interacted with the nuclear protein BRCA1 in human breast cancer cells. These data suggest that the COBRA1 antibody may be a useful tool to investigate functions of COBRA1 in cancers and that, like BRCA1, COBRA1 may regulate various nuclear events in breast cancer cells. IUBMB Life, 56: 161-166, 2004

To analyze the factors affecting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients.A retrospective cohort study was carried out to analyze the clinical data of 141 breast cancer patients treated with neoadjuvant chemotherapy. The factors affecting pCR and the changes of tumor receptor status before and after treatment were analyzed.Among all the 141 patients, 21 patients (14.9%) achieved pCR. The rate of pCR achieved by regimens of anthracycline combined with taxane was higher (16.8%, 19/113) than that by anthracycline-containing regimens (7.1%, 1/14). The dose intensity of anthracycline had a significant correlation with pCR rate (P0.05). The pCR rate in the relative dose intensity of taxane ≥ 0.85 arm was higher than that of0.85 arm (P = 0.02). Eighty patients (56.7%) had completed more than 4 cycles of chemotherapy and the median time to achieve pCR was 6 (3 to 10) cycles. The pCR rate had a significant difference between patients6 and ≥ 6 cycles (7.1% vs. 22.5%,P = 0.01). Multivariate analysis showed that tumor size measured by palpation ≤ 5 cm and ≥ 6 chemotherapy cycles were significantly related with pCR rate (P0.05). In all the 21 pCR patients, the pre-treatment ER(-), PR(-), HER-2(-) statuses were in 14, 14 and 17 patients, respectively. The status of ER, PR, HER-2 of most patients (74.2%, 69.7% and 87.7%, respectively) was not changed after treatment. Among the patients with changes in receptor status, ER changed from negative to positive was in the majority (37.1%, 13/35 vs. 12.9%, 4/31, P0.05), and the percentage of changes in PR and HER-2 status had no significant differences.The regimens of anthracycline combined with taxane can achieve a higher pCR rate. The lymph node and receptor status before therapy have no significant correlation with pCR. Patients who have primary tumor size ≤ 5 cm, ≥ 6 chemotherapy cycles and enough dose intensity are easier to achieve pCR. The receptor status before and after therapy should be determined, and according to any positive results, physicians can chose HER-2 targeted therapy and/or endocrine therapy after surgery to benefit the patients.

To observe the preliminary efficacies and adverse events of sunitinib in the treatment of metastatic breast cancer ulcer.From December 2008 to May 2010, patients with advanced breast cancer ulcer took a single sunitinib. The dosage was adjusted on the basis of adverse events. And clinical response was evaluated.Nine patients with advanced breast cancer ulcer finished the treatment. The objective response and the clinical benefit time to progression of sunitinib were 3 and 7 patients with metastatic breast cancer ulcer, and the median time to progression (TTP) was 2.0 months. The most common adverse events included fatigue, hand-foot syndrome, neutropenia, thrombocytopenia and hypertension.Single-agent sunitinib treatment of refractory advanced breast cancer ulcer has marked efficacies. However, neutropenia, thrombocytopenia and hypertension are the major dose-limited toxicities.

To evaluate the predictive factors for efficacy and prognosis of retreatment trastuzumab in the patients with HER2 positive metastatic breast cancer (MBC) developing successive resistance to multi-line targeting therapies.The data of 29 patients with HER2 positive MBC were collected from July 2008 to July 2010 at our department. All patients were treated with trastuzumab, lapatinib and retreated with trastuzumab sequentially. Twenty-one patients progressed during the initial trastuzumab therapy. All patients were treated with lapatinib to disease progression and retreated with trastuzumab to disease progression or death subsequently. A Log-rank test was used for univariate analysis and a Cox regression model was employed for multivariate analysis.The efficacy showed no significant difference between the patients with progression or those without progression during the initial trastuzumab therapy. The time-to-progression (TTP) of prior lapatinib therapy was an influencing factor of median progression-free survival (PFS) (P0.0001) and the duration from discontinuation of lapatinib to trastuzumab retreatment an influencing factor of median overall survival (OS) (P = 0.008) of trastuzumab retreatment in our univariate analysis. The median PFS of trastuzumab retreatment for patients with TTP of lapatinib therapy12 weeks (hazard ratio (HR) = 0.02, P = 0.003) or whose duration of double trastuzumab treatment ≤ 1 year (HR = 0.26, P = 0.03) was significantly prolonged in multivariate analysis. Meanwhile, the death risk of patients whose duration from discontinuation of lapatinib to trastuzumab retreatment ≤ 4 weeks decreased 89% as compared with trastuzumab retreatment (HR = 0.11, P = 0.004).TTP of prior lapatinib therapy and the duration of double trastuzumab treatment are two predictive factors of PFS of trastuzumab retreatment. And the duration from discontinuation of lapatinib to trastuzumab retreatment is an important independent prognostic factor for trastuzumab retreatment. The patients with HER2 positive MBC should be treated continually with anti-HER2 targeted therapy.

To evaluate the efficacy and safety of 1-year adjuvant trastuzumab (herceptin) versus 1-year non-trastuzumab observation in Chinese patients with HER2-positive early breast cancer during a median follow-up of 1 year.The HERA trial was an international, multicenter, randomized, open-label, phase III trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard adjuvant chemotherapy, radiotherapy or both in patients with HER2-positive node-positive or high-risk node-negative early breast cancer. The primary endpoint was disease-free survival. Secondary end points included recurrence-free survival, distant disease-free survival, overall survival and cardiac safety. The first planned interim analysis comparing the efficacy and safety of treatment with trastuzumab for 1 year versus observation were completed in April 2005. Only the outcomes of recruited Chinese patients were reported.A total of 122 Chinese patients from 8 participating centers were included for planned interim analysis. And they were divided into trastuzumab (n = 68) and observation (n = 54) groups. Three and eight disease-free survival events were observed in the trastuzumab and observation groups respectively. Two-year disease-free survival rates were 92.9% and 81.4% respectively (P = 0.0489); 2-year recurrence-free survival and distant disease-free survivals were 98.1% vs 81.4% (P = 0.0064) and 98.1% vs 83.3% (P = 0.0117) respectively. Trastuzumab was generally well-tolerated with a decent safety profile. Severe cardiotoxicity was not observed.One-year treatment with adjuvant trastuzumab improves disease-free survival, recurrence-free survival and distant disease-free survival in Chinese patients with HER2-positive early breast cancer.

To explore the chemotherapeutic efficacies and prognostic factors of metastatic triple-negative breast cancer.The clinicopathologic data of 151 patients with metastatic triple-negative breast cancer were collected from September 1994 to November 2011 and their clinicopathologic characteristics, recurrence and survival were analyzed.Platinum plus taxol or vinorelbine was significantly higher than others for these patients (42.1% vs 23.1%, P = 0.022). The median overall survivals of those on first-line chemotherapy with partial remission, stable disease and progressive disease were 29.6, 24.7 and 13.1 months respectively. The differences were statistically significant (P = 0.045). Two or three-line chemotherapy showed no obvious statistical relationship with total overall survival. Simple factor analysis showed that the number of metastasis, visceral metastases and the efficacies of first-line chemotherapy were correlated with overall survival (all P0.05). Multivariate Cox regression showed that disease-free survival and the efficacies of first-line chemotherapy were the independent prognostic factors of metastatic triple-negative breast cancer.The combined chemotherapy of platinum may achieve better efficacies in the treatment of metastatic triple-negative breast cancer. And the efficacies of first-line chemotherapy are closely correlated with survival.

To evaluate the correlation of clinical effects and reasonable doses of docetaxel salvage therapy for patients with metastatic breast cancer.We reviewed retrospectively the clinical records of patients with metastatic breast cancer treated with docetaxel and statistically analyzed the correlation between clinical effects and reasonable doses of docetaxel.The objective response rate and clinical benefit rate of docetaxol in patients with metastatic breast cancer were 27.0% and 35.0%, respectively, and the median progression free survival (PFS) was 5.0 (3.8 - 6.3) months. In the analysis at a single dose level, the clinical benefit rate and PFS of the ≥ 90.0 mg/m(2) docetaxel group were superior to that of the90.0 mg/m(2) group (P = 0.008, P = 0.045). Multi-dose level group stratified analysis showed that the docetaxel75.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) PFS group (P = 0.018), and the ≥ 95.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) group (P = 0.048). In patients who receivedthird line treatment or previously received paclitaxel adjuvant therapy, the PFS of the ≥ 94.9 mg/m(2) docetaxel group was 6.0 months, better than the 3.0 months of the 75.0 ∼ 84.9 mg/m(2) group (P = 0.031; P = 0.021).There is a clear correlation between clinical effects and reasonable doses of docetaxel salvage therapy in patients with metastatic breast cancer.

To evaluate retrospectively the efficacy and toxicity of capecitabine-based chemotherapy in the treatment of advanced breast cancer.Three hundred and seventy-six patients with advanced breast cancer were treated with capecitabine-based chemotherapy regimens in our department from Sep 2002 to Sep 2009. They were divided into 3 groups. The group 1 was treated with capecitabine 1000 mg/m(2) orally twice daily on d1-d14, repeated every 3 weeks. The group 2 was treated with capecitabine as group 1, and combined with docetaxel 60 - 75 mg/m(2) intravenous infusion on d1, repeated every 3 weeks. The group 3 was treated with capecitabine as group 1, and combined with vinorelbine 25 mg/m(2) intravenous infusion on d1 and d8, repeated every 3 weeks. The median treatment period of treatment was 3 cycles.Among the 376 patients, 218 patients were evaluable for response. In the group 1 the objective response rate (ORR) was 12.8% and the clinical benefit rate (CBR) was 21.6%. The CBR but not ORR of first line therapy with capecitabine was 35.2%, significantly higher than that of more than first line therapy (17.1%, P0.01). The ORRs for group 2 and group 3 were 53.8% and 36.4%, respectively. In the group 2 there was no significant difference in the ORR between the first line therapy and more than first line therapy. In the group 3 the ORR of first line therapy of NX regimen was 36.4%, significantly higher than that of more than first line therapy (16.7%, P0.01).The capecitabine-based chemotherapy is effective and tolerable, and can be used not only in first line but also more than first line therapy. The single agent maintenance chemotherapy after response to combined chemotherapy can prolonge the duration of treatment for patients with metastatic breast cancer.

To assay the expression of cytidine deaminase (CDA), ribonucleotide reductase subunit 1 (RRM1), phosphatase and tensin homologue deleted from chromosome 10 (PTEN), excision repair cross-complementation group 1 (ERCC1), deoxycytidine kinase (dCK) and RRM1(-)37A/C polymorphism, which have been shown relevant to gemcitabine resistance in two human gemcitabine-resistant non-small cell lung cancer cell lines A549/Gem and NCI-H460/Gem, so as to make clear how do they vary during the course of acquiring resistance to gemcitabine.The human gemcitabine-resistant non-small cell lung cancer cell lines A549/Gem and NCI-H460/Gem were established in our Department by repeated clinical serum peak concentration and gradually increasing doses. Real-time fluorescent quantitative PCR was used to examine the expression of CDA, RRM1, PTEN, ERCC1, dCK and RRM1(-)37A/C polymorphism in those cell lines at different time points during their induction process.The resistance indexes of A549/Gem and NCI-H460/Gem cells reached 163.228 and 181.684, and then remained stable at 115.297 and 129.783, respectively. The expression of CDA, RRM1, PTEN and ERCC1 varied along with the changing gemcitabine resistance indexes, but expression of dCK did not change apparently. The wild type promoter was able to amplify the genomic DNA in different induction stages of A549/Gem and NCI-H460/Gem cells, but allelotype did not, indicating that the gene type of A549/Gem, NCI-H460/Gem and their parental cells remaining still wild type.Compared with their parental cells, the expressions of CDA, RRM1, PTEN and ERCC1 in human gemcitabine-resistant non-small cell lung cancer cell lines A549/Gem and NCI-H460/Gem rise, the expression of dCK changes inapparently, therefore, their gene type are remaining wild type.

To observe the anti-proliferation effect of bevacizumab and SN-38 (active metabolite of irinotecan), and investigate the possible mechanisms of these two agents.Human colon cancer LoVo cells were cultured under hypoxic conditions. Inhibition of cell proliferation was evaluated by MTT assay. The drug modulation on HIF-1alpha, VEGF, ERK and AKT were assessed by the following assays. The mRNA expression of HIF-1alpha and VEGF were measured by RT-PCR. The protein expression of HIF-1alpha, ERK and AKT were evaluated by Western blot analysis, and VEGF by ELISA assay.Among different combination schedules, Bevacizumab given after SN-38 show most synergistic anti-proliferation effect. Under hypoxic conditions, the expression of HIF-1alpha and VEGF increased as time accumulated, Bevacizumab combined with SN-38 almost completely inhibited the expression of HIF-1alpha and VEGF. Moreover, the MAP kinase pathway was involved in the drug modulation of HIF-1alpha and VEGF.These findings suggest the anti-proliferation effect of bevacizumab and SN-38 was schedule-dependent, and the synergistic effect of Bevacizumab and SN-38 was related to drug modulation of the HIF-1alpha and MAP kinase pathway.

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.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 (VAS50 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.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%) (Por =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.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.

To assess the polymorphism of UGT1A gene in Chinese, and to investigate the correlation between UGT1A polymorphism and irinotecan toxicity in colorectal cancer patients.70 patients with advanced colorectal cancer were treated with irinotecan and 5-fluorouracil. Polymorphism analysis was performed in all those patients and 100 healthy subjects. Genomic DNA was extracted from peripheral blood and genotyped using polymerase chain reaction and direct sequencing.14 patients exhibiting grade 3 - 4 neutropenia (20.0%), 16 patients experienced grade 2 - 4 diarrhea (22.9%), including only 4 patients with grade 3 - 4 diarrhea (5.7%). Compared with TA6/7 and TA7/7, UGT1 A1 * 28 wild genotype TA6/6 was significantly associated with reduced toxicity (42.1% vs. 15.7%, P = 0.027). There was no significant difference in the distribution of UGT1A genotypes between colorectal cancer patients and healthy subjects.Chinese patients exhibit less irinotecan-related diarrhea due to higher frequence of UGT1A A1 * 28 wild genotype TA6/6.

AIM: To evaluate the therapeutic efficiency of replicative adenovirus CNHK300 targeted in telomerase-positive hepatocellular carcinoma. METHODS: CNHK300, ONYX-015 (55 kDa protein deleted adenovirus) and wtAd5 (wild type adenovirus 5) were compared, and virus proliferation assay, cell viability assay, Western blot and fluorescence microscopy were used to evaluate the proliferation and cytolysis selectivity of CNHK300. RESULTS: The replicative multiples in Hep3B and HepGII after 48 h of CNHK300 proliferation were 40 625 and 65 326 fold, respectively, similar to that of wtAd5.. However, CNHK300 exhibited attenuated replicative ability in normal fibroblast cell line BJ. CNHK300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. CONCLUSION: CNHK300 is a cancer-selective replication-competent adenovirus which can cause oncolysis of liver cancer cells as well as wtAd5 (wild type adenovirus 5), but had severely attenuated replicative and cytolytic ability in normal cells. This novel strategy of cancer treatment offers a promising treatment platform.

To investigate the correlation between mutation in EGFR tyrosine kinase domain and tumor response as well as prognosis in advanced stage non-small cell lung cancer (NSCLC) treated with iressa.From May 2002 to Feb. 2005, iressa was orally administered at a dose of 250 mg once daily for 106 advanced stage NSCLC patients until occurrence of disease progression or intolerable toxicity. Cancer tissue was obtained from these patients, and DNA was extracted for analysis of mutation in exon 18 to 24 of EGFR. Exon 18 to 24 of EGFR were amplified by nest PCR, sequenced and analyzed from both sense and antisence directions.Primary NSCLC tissue specimens consisted of 25 frozen tissue blocks and 81 paraffin-embedded tumor tissue blocks from 106 consecutive NSCLC patients. Mutation was found to be more frequent in the adenocarcinoma than in the squamous cell carcinoma (35.9% vs 14.3%, P =0.033). Mutation was identified in 32 patients (30.2%). Response rate to iressa was 71.9% in the patients with EGFR mutation versus 13.5% in those without mutation (P0.01). Compared with the patients without EGFR mutation, those with mutation had longer overall survival (median, 13.45 vs. 5.25 months; P0.01) and median time to progression (median, 8.35 vs. 3.0 months; P0.01).EGFR mutation may be positively correlated with the response and survival in advanced stage Chinese NSCLC patient treated with iressa.

To evaluate the safety and efficacy of gefitinib as second-line or even third-line treatment for previously treated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).156 patients with locally advanced NSCLC which were about to undergo progression after previous chemotherapy were eligible for this study. The regimen was oral intake of gefitinib 250 mg once daily in the morning or afternoon until the disease progression or toxicity has become intolerable. The drug was provided by AstroZeneca Company by its Expanded Access Program.154 such patients were evaluable for response and toxicity assessment. The overall rate of objective response and disease control was 28.6% (44/154) and 89.6% (138/154). The median duration of response was 7. 5 months. The median time to disease progression (TTP) was 5. 1 months and the median overall survival time (OS) 10.0 months. The actuarial 1-year survival was 41. 0%. The response rate in adenocarcinoma was significantly higher than that in squamous carcinoma (P = 0. 026). The risk of disease progression in patients with squamous carcinoma was 1. 7 times as much as that of adenocarcinoma patients ( P = 0. 011) , and the risk of death in male was 2. 0 times as much as that in female ( P = 0. 002). At least one of these adverse events would be observed in 40.9% (63/154) of these patients, which, however was mild and reversible. Conclusion Gefitinib is effective and safe as a second-line or third-line treatment for previously treated patients with locally advanced or metastatic non-small cell lung cancer.

To investigate the predictive value of HER-2 and ER expression for chemosensitivity of taxane in the treatment of advanced breast cancer.Of 268 advanced breast cancer patients treated: 71 were by paclitaxel alone, 32 by docetaxel alone, 110 by paclitaxel combined with anthracylines or gemcitabine or platins and 55 by docetaxel-based combinations. HER-2 and ER expression of all patients treated by taxane underwent immunohistochemical (IHC) assay.Univariate analysis showed: the response rate (RR) in HER-2 overexpression group was 56.7%, and in HER-2 weak expression group 33.3% (P = 0.003). The response rate in ER positive group and ER negative group was 33.3% and 48.9%, respectively, with a significant difference (P = 0.015). The RR was 67.6% in ER negative but HER-2 overexpression group. However, in ER positive but HER-2 weak expression group and the other groups, the RR were around 35% (P0. 01). Multivariate analysis showed that overexpression of HER-2 was the only significant factor to predict the chemosensitivity of taxane (P = 0. 007), but the ER, Karnofsky performance score (KPS), anthracylines, metastatic sites were not the statistically significant chemo-sensitivity predictive factors for taxane.ER negative and/or HER-2 overexpression, especially latter, may be associated with good response in advanced breast cancers treated by taxane.

To investigate the expression of oncoprotein c-erbB2 in primary breast cancer and to analyze its relation to its prognosis.Immunohistochemical staining for c-erbB2 was performed on paraffin-embedded specimens of primary breast cancer from 284 patients, and the relation to its prognosis was statistically analyzed.Positive expression rate of c-erbB2 was 26.8% (76/284) in 284 primary breast cancer patients. Expression of c-erbB2 was positively correlated with the status of lymph node metastasis (P = 0.003). Univariate analysis indicated that c-erbB2 expression is a significant prognostic factor for the disease-free survival (DFS) (P = 0.024) and overall survival (OS) (P = 0.002), while multivariate analysis demonstrated that c-erbB2 is an independent prognostic factor for OS (P = 0.023). Moreover, tumors with c-erbB2 positive expression are more tend to metastasis to other viscera than those with c-erbB2 negative. c-erbB2 expression has different prognostic values for patients with different status of estrogen receptor (ER) and lymph node metastasis.c-erbB2 expression is an independent prognostic factor for total survival time in primary breast cancer patients, and its prognostic values are different according to the different ER status and lymph node metastasis.

To study the effects of exogenous ER beta on the growth of breast cancer MCF-7 cells under different treatment.An eukaryotic expression vector containing 1.6 kb of human entire coding sequence of ER beta (pCDNA3-ER beta) was transfected into human breast cancer MCF-7 cells using lipofectamine 2000. The biological activity of ER beta was detected with the luciferase reporter containing estrogen responsive element (ERE) and the expression of ER beta protein by Western blot. The growth properties of MCF-7, pCDNA 3-transfected MCF-7 and pCDNA 3-ER beta-transfected MCF-7 cells under different treatment, including E2 (17beta-estradiol) and 4-OHT (4-hydroxytamoxifen), were observed.A stronger activation of the reporter by ER beta in the presence of E2 was observed in the pCDNA 3-ER beta-transfected MCF-7 cells than in the pCDNA 3-transfected MCF-7 and in MCF-7 cells. Western blot analysis showed that the protein level of ER beta in the pCDNA 3-ER beta-transfected MCF-7 cells was markedly increased. Exogenous ER beta expression did not change the growth properties and the morphology of MCF-7 cells under normal condition. The pCDNA 3-ER beta-transfected MCF-7 cells proliferated at the same rate as naive cells in the presence of 4-OHT, whereas a strong inhibition of the proliferation of the pCDNA 3-ER beta-transfected MCF-7 cells in the presence of E2 was observed.Exogenous ER beta expression does not increase the resistance to 4-OHT, and a strong inhibition of the proliferation may occur in the presence of E2.

To investigate the inhibitory effect of antisense oligodeoxynucleotides targeting HER-2 mRNA on growth of breast cancer.Human breast cancer cells of the line SK-BR-3 that overexpresses HER-2 were injected subcutaneously into BALB/c nude mice. Seven to ten days after tumors were collected and made into homogenate. Antisense oligodeoxynucleotide HA6722 targeting HER-2 mRNA and its control sequence Scramble were synthesized. Forty-nine BALB/c nude mice were injected with homogenate of SK-BR-3 cells and then randomly divided into 7 equal groups: Group 1, injected intravenously with docetaxel (TXT) 7.5 mg.kg(-1).d(-1) once a week twice; Group 2, injected intravenously with TXT 15 mg.kg(-1).d(-1) once a week twice; Group 3, injected intravenously with TXT 7.5 mg.kg(-1).d(-1) once a week twice + HA6722 5 mg.kg(-1).d(-1) for 12 days; Group 4, injected intravenously with HA6722 5 mg.kg(-1).d(-1) for 12 days; Group 5, injected intravenously with TXT 7.5 mg.kg(-1).d(-1) once a week twice + Scramble6722 5 mg.kg(-1).d(-1) for 12 days; and Group 7, injected with normal saline. After the drug administration the mice were observed for additional 3-4 weeks to measure the size of tumor every other day. Then the mice were killed and the tumors were taken out to be examined. The inhibition rate was calculated.The inhibition rate of tumor in Group 3 was 88.3%, not significantly different from that in Group 2 (88.7%, P0.05). The inhibition rate in Group 4 was 76.3%. The inhibition rates of tumor of Groups 2, 3, and 4 were all significantly higher than that in Group 7. However, the inhibition rate of tumor of Group 6 was not significantly different from that in Group 7.Antisense oligodeoxynucleotides targeting HER-2 mRNA inhibits the growth of breast cancer in a sequence specific and dose-dependent manner.

To demonstrate the feasibility of breast conserving therapy (BCT) and establish a multimodality BCT model for early breast cancer in China.A prospective multicenter case control study consisting of 4461 patients was carried out by the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and nine other hospitals across China from November, 2001 to November, 2004, the result of BCT and mastectomy on early stage breast cancer were compared. Patients entry-primary tumoror = 3 cm, primary tumor in periphery quadrant, pathology showed infiltrating carcinoma and clinical absence of locoregional lymphatic or distant metastasis. Patients rejection-multiple center cancer or diffused malignant calcified spots, previous radical radiation therapy in the chest, accompanying collogenolytic vascular granuloma and simultaneous pregnancy.Of these 4461 patients, breast conserving surgery was performed in 872 (19.5%) patients who were eligible for BCT, accounting for 9.0% of all operated breast cancer patients during the same period. The rates of local recurrence, metastasis and death were 1.0% (9/872), 1.3% (11/872) and 0.1% (1/872) in BCT group, versus 0.5% (18/3589), 1.4% (49/3589) and 0.1% (4/3589) in the mastectomy group. No statistical significant difference was found between these two groups (P0.05). Cosmetic evaluation of breast in BCT group was carried out postoperatively at points of six months, one year and two years with 89.7%, 91.1% and 86.6% of the patients assessed as excellent or fine cosmetic state respectively.Breast conserving therapy for early stage breast cancer is feasible in China, with no ominous effect on the survival and recurrence rate. Breast conserving therapy is able to improve not only the quality of life but also enhance the confidence of the patients, in addition to quasi-perfect cosmetic results. Standard comprehensive BCT involving multi-centers all concentrating on combination treatment should be widely adopted in China in the future. However, breast conserving surgery should selectively be used only for early stage breast cancer, and should be combined with postoperative radiotherapy, chemotherapy and hormone therapy in order to guarantee success.

This phase II clinical trial was designed to evaluate the efficacy and toxicity of recombinant human interleukin-11 (rhIL-11) derivative manufactured in China in the prevention and treatment of chemotherapy-induced thrombocytopenia in cancer patients.A total of 100 cancer patients with chemotherapy-induced thrombocytopenia (or = 75 x 10(9)/L) were studied by self-cross control. Ninty-one of them received 2 cycles of chemotherapy. In the first cycle (control cycle) the patients received chemotherapy only, while in the second cycle (treatment cycle), the patients were given subcutaneous injection of rhIL-11 derivative (40 microg.kg(-1).d(-1)) once daily after chemotherapy for 10 consecutive days or more until platelet count reachedor = 300 x 10(9)/L.1. The patients with platelet count ofor = 75 x 10(9)/L was 89/89 in the control cycle and 44/89 in the treatment cycle (P = 0.00). The recovery time to the normal platelet count was 1-47 days (median 9 days) in the control cycle, and 1-18 days (median 5.5 days) in treatment cycle (P = 0.00). 2. Patients with platelet count ofor = 50 x 10(9)/L was 56/89 in the control cycle and 20/89 in the treatment cycle (P = 0.00). The recovery time to normal platelet count was 1-31 days (median 9 days) in the control cycle and 3-13 days (median 6 days) in the treatment cycle (P = 0.05). 3. The median nadir platelet count was 44 x 10(9)/L (range: 10 x 10(9)/L-75 x 10(9)/L) in the control cycle, and 83 x 10(9)/L (range: 10 x 10(9)/L-310 x 10(9)/L) in the treatment cycle (P = 0.00). The time of recovery to the normal platelet count was 1-31 days (median 6 days) in the control cycle, and 0-13 days (median 2 days) in the treatment cycle (P = 0.00). 4. Nine of 89 evaluable patients required platelet transfusion in the control cycle versus 1 of 89 patients in treatment cycle (P = 0.01), and the total platelet transfusion was 10 times in the control cycle versus once in the treatment cycle (P = 0.01). 5. The major adverse events associated with rhIL-11 derivative were: headache, fatigue, myalgia/arthralgia, edema and palpitation, etc.rhIL-11 derivative can be safely and effectively used for the prevention and treatment for chemotherapy-induced thrombocytopenia.

To evaluate the therapeutic efficiency of replicative adenovirus CNHK300 targeted at telomerase-positive hepatocellular carcinoma.Human liver cancer cell line HepGII and Hep3B, human embryonic kidney cell line 293, and normal human fibroblasts of the line BJ were cultured and added with adenoviruses CNHK300, ONYX-015 (55 000 protein deleted adenovirus), or wtAd5 (wild type 5) with different multiplicity of infection (MOI) for 7 days. 293 cells were used to measure the titer of the filial generation virus from different cells. The cell survival rate was calculated by MTT method 2, 4, 6, and 8 days after. Different cells were added with CNHK300 virus and then the E1A protein in the cytoplasm was measured by western blotting. Fluorescence microscopy was used to observe the CNHK300-EGFP proliferation after the cells were cultured and added with the virus for 1.5 hours.The replicative viruses CNHK300 and wtAd5 proliferated rapidly in HepGII and Hep3B cells since 24 hours after inoculation and proliferated 40625 and 65326 times respectively with a proliferation potential similar to that of the wild-type adenovirus and much higher than that of the ONYX-015 virus. CNHK300 of the MOI of 0.0002 killed half of the cancer cells, especially those of the line Hep3B, within 5 approximately 6 days, and CNHK300 virus of the MOI of 0.5 pfu/cell killed almost all the HepGII cells in the 8th day, with a killing power lower than that of the wild-type virus and higher than that of the ONYX-015 cells. The IC(50) was as low as MOI of 0.002 pfu/cell for the Hep3B cell and was as high as MOI of 100 pfu/cell for the BJ cell. CNHK300 was a less powerful killer of fibroblasts than wild-type virus. E1A expression was shown by western blotting in 293 cells and CNHK300-infected liver cancer cells, but not in the CNHK300-infected normal human fibroblasts. Fluorescence microscopy showed only isolated fluorescence-positive fibroblasts till the 10th day of infection, but obvious proliferation of CNHK300-EGFP virus since the 3rd day and fluorescence-positive cells in sheets by the 7th day, however, the fluorescent intensity was weakened since the 10th day.Tumor-selective adenovirus CNHK300 replicates in telomerase-positive liver cancer cells efficiently as well as wtAd5 and causes oncolysis, but has severely attenuated proliferation and cytolysis in normal cells.

To evaluate the relation of dose intensity and efficacy, toxicity in advanced breast cancer treated with paclitaxel as a single agent.Seventy-one patients with advanced breast cancer received paclitaxel as a single agent with different dose intensities. According to the phase I or phase II trial, the standard dose intensity of paclitaxel was defined as 58.3 mg.(m(2))(-1).week(-1). The dose of paclitaxel was 175 mg/m(2) given every three weeks, ranging 33.3 - 70.3 mg.(m(2))(-1).week(-1) [median delivered dose intensity 58.82 mg.(m(2))(-1).week(-1)]. Efficacy and toxicity was evaluated.The overall response rate in this group of advanced breast cancer was 40.8%. Responses were seen in lungs, soft tissue, bone and liver, with the response rates of 52.0%, 38.0%, 12.5%, 7.7%, respectively. When the relative dose intensity (RDI) was1.0, 0.9 - 1.0,0.9, the response rates were 44.2%, 47.6%, 0, respectively. The difference between the group (RDI/= 0.9% - 1.0%) in 7 patients and the group (RDI0.9) was significant (P0.05). Toxicity was well tolerated, with the efficacy decreased as soon as the RDI had been reduced without embarrassing the toxicity.Paclitaxel as a single agent therapy with standard dose intensity is effective and well tolerated by patients with advanced breast cancer.

Ibandronate, a third generation bisphosphonate, inhibits bone resorption in human and animal studies. This study is to evaluate the efficacy and safety of ibandronate as a single agent in patients with tumor-associated hypercalcemia.An open, multicenter, non-controlled clinical trial was conducted in 22 patients. The patients received 2 mg ibandronate intravenously if the corrected calcium was less than 3.0 mmol/L but more than 2.7 mmol/L; they received 4 mg ibandronate iv if corrected calcium was more than 3.0 mmol/L.There was 100% efficacy in these two dose groups but the calcium correcting effect was more pronounced in the 4-mg dose group than the 2-mg dose group. The most common adverse reactions were fever and skin itching with an incidence of 4.5%.Ibandronate is active in patients with tumor-associated hypercalcemia and the adverse effects are well tolerated.

To evaluate the efficacy and adverse reactions of Xeloda in the treatment of recurrent and metastatic breast cancer.This clinical study was designed to treat 69 patients with recurrent and metastatic breast cancer with Xeloda, 2500 mg/m(2)/d, twice daily for 2 weeks followed by a 1-week rest period, repeated every 3 weeks.Sixty-nine patients received Xeloda for more than 1 cycle. The overall response rate (CR + PR) was 16.0%, clinical benefit rate (CR + PR + SDor = 24 months) was 27.5%, disease control rate (CR + PR + SD) was 75.4%. The median time to failure (TTF) was 3 months (range: 0.7 - 11 months). The median time to progression (TTP) was 2 months (range: 0.7 - 11 months). The median duration of response (CR + PR) was 6 months (range: 4 - 11 months). The most common treatment-related adverse events were hand-foot syndrome (HFS) that occurred in 60.8% (42/69) patients mostly as grade I-II. Fifty-five percent (22/40) of patients who had received high dose preventive Vit B6 developed HFS without grade III; while 69% (20/29) of patients who had not received such treatment did develop HFS including 2 patients with grade III. However, there was not significant difference between the two groups.Xeloda is an effective and well tolerated treatment in patients with recurrent and metastatic breast cancer. The symptoms of HFS may be relieved by high dose Vit B6 as prevention.

To compare the efficacy of endocrine therapy with chemotherapy for bone metastasis of breast cancer.A total of 138 breast cancer patients with bone metastasis, but without visceral metastasis as retrospectively reviewed.The response rates of endocrine therapy and chemotherapy as the first-line therapy were 35.4% and 31.7% (P = 0.687), and the total response rates were 27.1% and 25.0% (P = 0.690). The clinical benefit rates of endocrine therapy and chemotherapy as first-line were 43.9% and 36.6% (P = 0.437), as second-line were 47.8% and 24.2% (P = 0.033), in total treatments were 47.5% and 27.7% (P = 0.001). The median interval to treatment failure (TTF) was 5 months and 2 months (P0.001), and that to progression (TTP) was 5 and 2.5 months (P0.001) in endocrine therapy and chemotherapy group, respectively.Endocrine therapy is superior to chemotherapy for bone metastasis of breast cancer.

In recent years,great development have been made in cancer therapeutics with replication-competent viruses (oncolytic viruses), E1B deleted adenovirus is one of promising viruses. The current study was designed to evaluate the efficacy and toxicity of intratumoral H101, a E1B-deleted adenovirus, in combination with chemotherapy on patients with cancer.A total of 50 patients with malignant tumors in multiple centers clinical trial were treated with H101, 0.5ml 5x10(11) viral particle per day for 5 consecutive days every three weeks. Routine chemotherapy was performed at the same time. And the efficacy and toxicity were recorded.Among 46 valuable cases, the overall response rate was 30.4%. The response rate was 28.0% (14/50) among ITT population, including 3 complete response (CR) and 11 partial response (PR). The overall response rate of control lesion was 13.0%, including 1 case of CR and 5 cases of PR. Thus, the response rate in injected lesion is clearly higher than that in control lesion (P0.001). Main side effects were injection site pain (26.9%) and fever (30.2%). Grade 1 hepatic dysfunction was found in 4 patients, grade 2 in 1 patients, grade 4 in 1 patients. Grade 4 hematological toxicities were found in 4 patients.The study showed that the combination of genetically modified adenovirus (H101) and chemotherapy possessed some effect for treating the patients with refractory malignant tumors, and the toxicities were lower, well tolerated.

To observe the clinical efficacy and adverse effects of herceptin for advanced Chinese breast cancer patients.Thirty-one pathologically proved advanced breast cancer women were treated by herceptin. In the first week, a loading dose 4 mg/kg was administered by intravenous infusion and from the second week, a routine dose of 2 mg/kg was given every week for at least 3 months.There were 2 CR, 6 PR, 7 SD, and 16 PD among 31 patients after treatment by herceptin, the response rate being 25.8%. In factors influencing the prognosis, age and general condition were factors favoring the results, and pathological type, site of metastasis, grade of her-2 over expression and prior treatment were irrelevant to the results. The adverse effects were mild but different from those of the common anticancer drugs.Herceptin is effective and well tolerated by the Chinese breast cancer patients.

To investigate the psychological impact of mastectomy on women with breast cancer.Questionnaires were answered by 90 patients after mastectomy for breast cancer. The data were collected and analyzed regarding the age, occupation, education, income and living place of the patients. Their psychological changes were compared and evaluated statistically using chi-square analysis.Mastectomy caused psychological impact on half of the patients, which included fear of cancer, feeling of body incompleteness, inconvenience in working and social communication, less sexual act and low spirit. 79 percent of the patients considered breast reconstruction unnecessary. 54 percent did not know that the breast could be reconstructed. The patient feelings differed with the age, occupation, income and living place.Mastectomy hurts patient psychological health.

To evaluate the response rate and adverse reactions of exemestane (a new aromatase inactivator) in the treatment of postmenopausal women with advanced breast cancer.One hundred and seventy-three patients with advanced breast cancer entered this study with two patients excluded because of postmenopausal time being less than one year. Therefore, 173 patients could be evaluated for adverse events and 171 patients could be evaluated for efficacy. Exemestane, 25 mg orally daily for 4 weeks as one cycle was given.In the 171 patients evaluated for efficacy, 4 (2.3%) experienced a complete response (CR) and 40 (23.4%) a partial response (PR), with the overall response rate of 25.7%. Ninety patients (52.6%) had stable disease (SD), with 25 having SD for at least 24 weeks. The clinical benefit (CR + PR + SDor = 24 weeks) was shown in 69 (40.4%) patients. Progressive disease (PD) was shown in 37 (21.6%) patients. The untreated patients had a higher objective response rate (33.8%) than the retreated ones (18.1%) with significant difference (P = 0.019 7). The response rates for soft-tissue, bone involvement and visceral metastasis were 32.8%, 23.9%, and 12.4% (P = 0.002). There was no significant difference in different ages, time of menopause, disease-free interval or receptor status (P0.05). Drug-related adverse events were gastric discomfort (17.9%), malaise (17.9%), nausea (13.9%), hot flushes (11.0%) and dysphoria (5.8%). Other side reactions and abnormal laboratory parameters were observed occasionally which were irrelevant.Exemestane can be used to treat postmenopausal women with advanced breast cancer giving only mild adverse reactions which are well tolerated.

To construct an ERbeta expression vector and study its expression and function in different cancer cells.Standard PCR was used to amplify the full-length coding sequence of ERbeta. The amplified ERbeta gene was cloned into the eukaryotic expression vector pCDNA3, generating pCDNA3-ERbeta. The ERbeta expression was detected by Western blot and in vitro translation. The biological activity of ERbeta was detected by transfecting the pCDNA3-ERbeta into SV40-transformed embryonic kidney cell line 293T,breast cancer cell lines MDA-MB-435, MDA-MB-436, SKBR3, and prostate cancer cell line PC-3, with reporters containing estrogen response elements.The recombinant plasmid pCDNA3-ERbeta was confirmed by restriction analysis to contain the ERbeta gene. The 63 000 ERbeta expression was shown by Western blot and further confirmed by in vitro translation. The ERbeta expression in different cancer cells was demonstrated to stimulate the expression of the reporters containing estrogen response elements, ERE and C3.ERbeta protein is successfully expressed and has biological activity, laying solid foundation for further study on its role in cancer cells.

To determine the clinical results of selected CD34(+) cell autologous transplantation in advanced malignant tumors.After pretreatment, fifteen patients aged 12 - 70 (49.5) years with various Stage III or IV malignant tumors were given the sorted CD34(+) cells collected by magnetic-activated cell sorting (Clini MACS, Milteny Biotech, Germany).Peripheral blood progenitor cells (PBPC) from the patients were mobilized by chemotherapy and G-CSF 5 micro g/kg per day. CD34(+) cells gave 2.0 - 5 log depletion after cell sorting, with a median yield of CD34(+) selected cells of 2.4 (0.15 - 12.03) x 10(6)/kg. It gave a median recovery of 64 (52 - 81.4)% and median purity of 98.2 (83.2 - 99.7)%. The median time of neutrophil recovery1.0 x 10(9)/L and platelet recovery20 x 10(9)/L post-transplantation were 14 (8 - 26) days and 13 (11 - 35) days, respectively. On follow-up of 2 - 33 (11) months, the event-free survival rate was 53.3% (8/15) and the overall survival rate was 66.7% (10/15).Transplantation of autologous selected PBPC CD34(+) cells gives prompt and stable engraftment. Selected CD34(+) cell transplantation, being a safe approach, may improve the clinical outcome even in patients with advanced malignant tumors.

To study the significance of vascular endothelial growth factor (VEGF) and microvascular density (MVD) expression in breast cancer.The expression of MVD and VEGF was studied in 81 patients with primary breast cancer by SP immunohistochemical technique.There were 49 patients with high VEGF expression (60.5%) and 35 patients with high MVD expression (43.2%). There was significant correlation between VEGF or MVD expression and TNM stage, but not age, tumor size, ER expression or lymph node status. VEGF was significantly related with MVD expression. Univariate analysis showed that patients with low expression of VEGF and MVD had longer disease free survival (DFS) and overall survival (OS). Grouping univariate analysis showed that VEGF had significant correlation with the DFS of all grouped patients and the OS of patients with LN(+) or stage III lesions. MVD had significant correlation with the DFS and OS of LN(+) patients and the DFS of stage III lesion patients. Multivariate analysis showed that MVD was a risk predictor because of its positive statistic value, the higher expression, the shorter survival time of the patients.Both VEGF and MVD are useful prognostic factors in breast cancer. MVD appears to be a strong and independent biologic marker for breast cancer prognosis.

Breast cancer is one kind of multi-gene related malignancy. Overexpression of some oncogenes such as HER-2 (c-erbB-2, Neu), bcl-2/bcl-xL, protein kinase A (PKA), and transferrin receptor gene (TfR gene), etc significantly affect the prognosis of breast cancer. It was shown that specific suppression of the overexpressed genes above resulted in the improvement of the therapy of breast cancer. Antisense interference, one of useful tools for inhibiting the overexpression of specific oncogenes, was involved in the therapy of breast cancer in recent years. Data indicated that antisense oligonucleotides (ON) could inhibit specially the expression of the target genes on mRNA or protein levels in most of cases; some ON candidates showed encouraging therapeutic effects in vitro and in vivo on breast cancer cell lines or xenografts. Furthermore, the combination use of the antisense ON and normal chemotherapeutic agents indicated synergistic antitumor effects, which was probably the best utilization of antisense ON in the treatment of breast cancer.

A randomized, selfcross-over and placebo-controlled clinical trial has been taken to evaluated the curative efficacy of rhIL-11 (Mega) for thrombocytopenia in 29 cancer patients with severe myelosuppression induced by chemotherapy. Twenty-five micro g/kg of Mega or placebo was administered subcutaneously once daily starting 24 hours after the completion of chemotherapy, and continuing for 7 to 14 days or until the platelet count reached 300 x 10(9)/L. The results from those in 118 cases performed phase II clinical trial, showed that there were 29 cases with platelet count less than 50 x 10(9)/L in placebo cycle, but there was only 1 case in Mega cycle. The percentage of the patients with platelet count less than 50 x 10(9)/L in placebo cycle of placebo + Mega group was higher than that of Mega + placebo group. The nadir and platelet counts on day 21 after chemotherapy in Mega cycle were 2.04 and 1.43 times more than those in placebo cycle, respectively. The data show that Mega had significant thrombopoietic activity with a long lasting oction for the patients experienced severe myelosuppression. It significantly increases the likelyhood of avoiding thrombocytopenia in cancer patients undergoing chemotherapy and shortens the duration of thrombocytopenia.

Patients with inoperable, locally advanced, and inflammatory breast carcinoma (LAIBC), whether with supraclavicular lymph nodes (SLN) or not (stage IIIB and IV), usually carry an overall poor prognosis. The current treatment for these patients is by means of combined modality, including preoperative chemotherapy. This strategy has led to a substantial improvement in clinical response, making some patients operable, and even making breast conservative surgery possible. However, the long-term results still are not promising. The aim of this pilot study was to determine the efficacy of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro in directing chemotherapy (including preoperative adjuvant chemotherapy and postoperative adjuvant chemotherapy) for these patients. Between June 1994 and March 1997, 10 patients with inoperable LAIBC, whether with SLN or not, were enrolled. During the period of the combined therapy modalities, the neoadjuvant chemotherapy was adopted for three cycles according to the results of chemosensitivity in vitro by MTT assay. Then a modified radical or radical mastectomy was performed, which was followed by radiotherapy and further postoperative adjuvant chemotherapy with the same regimen as that of neoadjuvant chemotherapy. All patients had been followed up from the beginning of neoadjuvant chemotherapy to the end of October 1999. Two patients had clinical complete response (CRs), with one having pathologic CR in both breast tumor and axillary lymph node, and the other having pathologic CR in axillary lymph node. The other eight patients had partial response. By the time of analysis, six patients had been dead of relapse or progression. Among the four patients who were still alive, one had local relapse, one had distant metastatic disease, and the other two had no evident disease. By retrieving from MEDLINE before 1999, the authors learned that this is the first pilot study of neoadiuvant chemotherapy for inoperable LAIBC using MTT assay to predict the chemosensitivity in vitro. Compared with conventional chemotherapy, the clinical response and long-term results seem to be more encouraging.