[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase â study].

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION: Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.

[Occupational hazard analysis of workers exposed to chromate in a steel plant].

Objective: To investigate the occupational damage to workers exposed to chromate in a steel plant. Methods: In January 2021, a retrospective analysis was used to select 850 workers exposed to chromate (observation group) and 598 workers not exposed to chromate (control group) in a steel plant in Shandong Province from 2016 to 2017 as the investigation. We collected their occupational-related information, blood routine, fasting blood sugar, nasal lesions, skin lesions, chest X-rays and other inspection results, compared the differences in the abnormal detection rate of the two groups of respondents, and analyzed the occupational hazards of chromium workers. Results: Incidence of nasal damage, skin lesion, up-regulation of ALT (Alanine aminotransferase), abnormal chest radiograph, abnormal serum biochemical index, and abnormal serum glucose level were observed higher in the exposed group than those in the control group (χ(2)=125.69, 12.25, 5.82, 10.37, 10.46, 20.66, P=0.000, 0.000, 0.016, 0.001, 0.001, 0.000). Among the symptoms, the incidence of erythra, nasal septum deviation, nasal mucosal congestion, nasal mucosal erosion and rhinitis were more frequent than those in the control group (χ(2)=101.54, 4.07, 13.20, 32.05, P=0.000, 0.044, 0.000, 0.000). There was no significant increase in the incidence of work type, age, length of work and the area of nasal mucosa erosion in the observation group compared with the control table, and the difference was not statistically significant (χ(2)=5.31、0.42、0.28, P=0.505, 0.662, 0.871) . Conclusion: Occupational hazards of long-term exposure to chromate cannot be ignored. Attention should be paid to strengthening occupational protection and health education of workers exposed to chromium, and increasing their attention.

[Influence of free nutrition lunch policy on overweight of rural adolescents: Based on China Education Panel Survey Junior High School Cohort data].

Objective: To analyze the influence of the free nutritious lunch policy on the risk of overweight in rural adolescents in China. Methods: Based on the data of China Education Panel Survey Junior High School Cohort from 2013 to 2016, this paper analyzes the influence of the policy on overweight risk in adolescents in rural China with logistic model, and a total of 3 453 rural teenagers were included. Results: Adolescents who received free lunch in the first year of junior high school had a 35.8% (P<0.05) and 31.6% (P<0.05) lower risk of being overweight in the second year and one year after junior high school graduation than those who didn't. Also, adolescents who received free lunch in the second year of junior high school had a 36.7% (P<0.05) and 29.9% (P<0.05) lower risk of being overweight in the third grade and one year after graduation than those who didn't. There was no statistically significant difference in the risk of being overweight one year after the graduation between adolescents who received free lunch in third year and those who didn't. And boys benefited more from this policy than girls. Conclusions: The free nutrition lunch policy has long term effect to reduce the likelihood of being overweight for adolescents, and the impact has a cumulative effect. This suggests that the free nutrition lunch policy is effective in promoting health of adolescents in terms of overweight.

Efficacy of utidelone plus capecitabine versus capecitabine for heavily pretreated, anthracycline- and taxane-refractory metastatic breast cancer: final analysis of overall survival in a phase III randomised controlled trial.

BACKGROUND: Primary analysis of the phase III trial BG01-1323L demonstrated that utidelone plus capecitabine significantly improved progression-free survival (PFS) and overall response rate (ORR) versus capecitabine alone in heavily-pretreated patients with metastatic breast cancer (MBC). Here, we report the final overall survival (OS) analysis and updates of other endpoints. PATIENTS AND METHODS: In total, 405 patients were randomised 2:1 to receive utidelone (30 mg/m2 IV daily, days 1-5, over 90 min) plus capecitabine (1000 mg/m2 orally b.i.d., days 1-14) or capecitabine alone (1250 mg/m2 orally b.i.d., days 1-14) every 21 days. The secondary endpoint, OS, was estimated using the Kaplan-Meier product-limit approach at a two-sided alpha level of 0.05 after the prespecified 310 death events had been reached. Exploratory analyses of the primary endpoint, PFS, and the secondary endpoint, ORR, were also done. Safety was analysed in patients who had at least one dose of study drug. RESULTS: At the final OS analysis, the median duration of follow-up was 19.6 months in the utidelone plus capecitabine group and 15.4 months in the capecitabine alone group. In the intention-to-treat population, 313 deaths had occurred at data cut-off, 203 of 270 patients in the combination group and 110 of 135 in the monotherapy group. Median OS in the combination group was 19.8 months compared with 16.0 months in the monotherapy group [hazard ratio (HR) = 0.75, 95% confidence intervals (CI) 0.59-0.94, P = 0.0142]. The updated analysis of PFS and ORR showed that the combination therapy remained superior to monotherapy. Safety results were similar to those previously reported with respect to incidence, severity and specificity. No late-emerging toxicities or new safety concerns occurred. CONCLUSIONS: For heavily-pretreated, anthracycline- and taxane-resistant MBC patients, utidelone plus capecitabine significantly improved OS versus capecitabine alone. These results support the use of utidelone plus capecitabine as a novel therapeutic regimen for patients with MBC.

[Application of SF-36 scale in the survey of quality of life of occupational disease patients].

Objective: To explore the application of the Short Form of Quality of Life (SF-36) scale in the investigation of quality of life of occupational disease patients. Methods: In May 2019, SF-36 scale was used to investigate the occupational disease patients diagnosed in Hangzhou. The reliability of the scale was evaluated by Cronbach's α coefficient, and the validity of the scale was evaluated by exploratory factor analysis. Results: The Cronbach's α coefficients of PF, RP, BP, GH, VT, SF, RE and MH were 0.937, 0.977, 0.870, 0.908, 0.815, 0.701, 0.967 and 0.863 respectively, and the half reliability coefficient α=0.905. The two factor statistics representing physiological and psychological aspects were 0.870, and the approximate chi square value was 1784.337 (P<0.01) . Compared with the national norm, the scores of each dimension of quality of life of occupational disease patients were significantly lower, and the differences were statistically significant (P<0.01) ; Compared with the scores of each dimension of quality of life of pneumoconiosis patients, the scores of PF, RP and GH of occupational disease patients were significantly higher, and the differences were statistically significant (P<0.05) . Conclusion: SF-36 scale has good reliability and validity in measuring the quality of life of patients with occupational diseases, which can be used to evaluate the quality of life of patients with occupational diseases.

[Study on quality of life and influeming factors of occupational disease patients in hangzhou].

Objective: To investigate and analyze the quality of life of occupational patients in Hangzhou and its influencing factors, so as to improve their qol. Methods: From January 2007 to June 2018, patients with diagnosed occupational diseases in Hangzhou City were randomly sampled in October 2019. The patients＇basic condition and quality of life were investigated by self-made questionnaire and SF-36, a total of 303 valid questionnaires were collected and the influencing factors were analyzed by correlation analysis and multiple linear regression. Results: The scores of physiological function, physiological function, physical pain, general health status, energy, social function, emotional function and mental health of the patients with occupational diseases in Hangzhou were lower than those of the general population in China, the differences were statistically significant (P<0.01) . The main factors affecting the score of quality of life of occupational patients are the types of occupational diseases, the level of disability and the duration of illness, the condition of suffering from other diseases, age, educational level, whether they are entitled to Work Injury Insurance, economic income, medical security and social support, the difference was statistically significant (P<0.05) . Conclusion: The quality of life of the patients with occupational diseases in Hangzhou City is poor, and the corresponding measures should be established to improve the qulity of life.

Objective response of first-line chemotherapy of triple-negative breast cancer translates into survival benefit: an analysis in an independent, prospective clinical trial and a real-world setting.

This study sought to assess whether the objective response (OR, including complete response and partial response) of first-line chemotherapy can predict overall survival (OS) for patients with metastatic triple-negative breast cancer (mTNBC) in both clinical trial and a real-world setting. The survival predictable parameters were assessed in two independent cohorts, the training cohort of 236 patients as part of a phase 3 trial (CBCSG006, Trial registration number NCT0128762) and the validation cohort of 360 patients from the real-world setting. Univariable and multivariable Cox proportional hazard models were applied to explore associations with progression-free survival and OS in the training cohort and then in the validation cohort. OR (OR vs non-OR, HR, 0.438, p<0.001) together with Eastern Cooperative Oncology Group (ECOG) performance status, disease-free survival, number of metastatic organ sites and platinum-based chemotherapy used as first-line chemotherapy were observed to be independent prognostic factors for progression-free survival (PFS), and OR (OR vs non-OR, HR, 0.602, p=0.002) together with ECOG score, disease-free survival, number of metastatic organ sites and previous anthracycline and/or taxane treatment were observed to be independent predictive factors for OS in the training cohort. These predictors were confirmed in the validation cohort. For OR and non-OR group, median OS was 23.72 and 13.83 months in the training cohort (HR, 0.637, p=0.002), and 21.95 and 13.80 months in the validation cohort (HR, 0.608, p<0.001), respectively. By adding OR in the OS predictors, the concordance index (C-index) improved from 0.622 to 0.645 in the training cohort and 0.653 to 0.675 in the validation cohort. PFS and OS of mTNBC can be predicted by OR status with any regimen of first-line chemotherapy in an independent prospective clinical trial and a real-world setting. Therefore, TNBC, not like other subtypes of breast cancer, may be in need of combination chemotherapy or intense chemotherapy to achieve a high response rate for survival.

MiR-566 protects the malignant progression of breast cancer by negatively regulating WNT6.

OBJECTIVE: To elucidate the relationship between microRNA-566 (miR-566) and prognosis in breast cancer (BC) and to clarify the influences of miR-566 and WNT6 in its locus region on BC progression. PATIENTS AND METHODS: MiR-566 and WNT6 levels in 44 pairs of BC samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The influences of miR-566 on clinical features and prognosis in BC patients were analyzed. According to the differential expressions of miR-566 in the tested BC cell lines, MDA-MB-231 and MCF-7 cells were selected for generating miR-566 knockdown and overexpression models, respectively. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and transwell assays were conducted to explore the role of miR-566 in BC cell functions. Besides, the regulatory interaction between miR-566 and its downstream gene WNT6 was assessed by performing Dual-Luciferase reporter assay. Finally, the co-regulation of miR-566 and WNT6 in BC cell functions was examined. RESULTS: MiR-566 was downregulated in BC tissues. BC patients with a low expression level of miR-566 were prone to suffering a large tumor size, advanced tumor grade, high incidence of lymphatic metastasis and poor prognosis. Overexpression of miR-566 weakened proliferative and migratory abilities in MCF-7 cells, whereas knockdown of miR-566 produced the opposite results in MDA-MB-231 cells. WNT6 was the target gene binding to miR-566, and they displayed a negative expression correlation in BC tissues. Regulatory effects of miR-566 on BC progression could be reversed by WNT6. CONCLUSIONS: MiR-566 is closely related to tumor size, tumor grade, lymphatic metastasis and prognosis in BC. It protects the malignant progression of BC by negatively regulating WNT6.

Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ib/II clinical trial NCT02915432.

BACKGROUND: High tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1. PATIENTS AND METHODS: We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/kg d1, Q2W) as a monotherapy. In cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 b.i.d., d1-d14, Q3W as first-line treatment. Primary end point was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy. RESULTS: In cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group [14.6 versus 4.0 months, HR = 0.48 (96% CI 0.24-0.96), P = 0.038], while PD-L1 overexpression did not correlate with significant survival benefit. A 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. A 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs. CONCLUSIONS: Toripalimab has demonstrated a manageable safety profile and promising antitumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent. TRIAL REGISTRATION: ClinicalTrials.gov NCT02915432.

[A comparison of fine needle nonaspiration cytology versus fine needle aspiration for thyroid nodules: a Meta-analysis].

Objective:To evaluate the differences of smear quality and diagnostic accuracy between thyroid nodules and fine needle nonaspiration cytology (FNNAC) and fine needle aspiration cytology (FNAC).Method:Databases were used to search the literature on FNNAC and FNAC. All statistical analyses were performed using Review Manager 5.3 Software.Result:A total of 10 studies were included in the study. Meta-analysis showed no significant difference in FNNAC and FNAC between low, middle and high quality smears. There was no significant difference in diagnostic accuracy.Conclusion:There were no difference in obtaining the smear quality and diagnostic accuracy, the person doing the piercing can freely choose which way according to the habit.

Biomarker assessment of the CBCSG006 trial: a randomized phase III trial of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer.

Background: CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy. Patients and methods: Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided. Results: Median progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46-9.00] months for GP arm and 6.07 (95% CI 5.32-6.83) months for GT arm (P = 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P = 0.008; 10.37 versus 4.30 months, P = 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P = 0.086; 8.90 versus 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks. Conclusions: GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients. Trial registration: ClinicalTrials.gov, NCT01287624.

[A multicenter, randomized, controlled, phase â £ clinical study of PEG-rhG-CSF for preventing chemotherapy induced neutropenia in patients with breast cancer].

Objective: To explore the efficacy and safety of polyethylene glycal recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patiens with breast cancer. Methods: There were two parts in the present phase Ⅳ clinical study. One was a randomized, controlled clinical study. Patients in this study received PEG-rhG-CSF or rhG-CSF in the first cycle and followed with both PEG-rhG-CSF in the rest of 3 cycles. The other one was a single arm study. Patients who developed Ⅲ/Ⅳ grade neutropenia in the screening cycle received PEG-rhG-CSF in the rest of 3 cycles chemotherapy. Results: In the first cycle of randomized, controlled study, the incidence of Ⅳ grade neutropenia are 31.48% and 35.58% respectively in PEG-rhG-CSF and rhG-CSF group, with no statistically significant differences (P=0.527 6). The duration of Ⅳ grade neutropenia respectively are 2.22±1.58 and 3.00±1.59 days, with a statistically significant difference (P=0.016 6). In the single arm study, the incidence of Ⅳ grade neutropenia was 57.76% in screening cycle. And the incidence decreased to 16.35%, 10%, and 8.57% in the followed 3 cycle after the use of PEG-rhG-CSF. The incidence of adverse effects was 5.06%, and the major adverse effect was bone pain which with an incidence of 2.8%. Conclusion: The fixed 6mg dose of PEG-rhG-CSF can effectively prevent neutropenia in patients with breast cancer in multicycle chemotherapy and it has a low incidence of adverse events and mild adverse reaction.

[Study of bioequiavailability of paclitaxel for Injection (Albumin Bound) and abraxane and the efficacy of extension treatments in patients with metastatic breast cancer].

Objective: To compare the bioequiavailability of paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane in the patients with metastatic breast cancer, and to investigate the safety and efficacy in the extension treatments of PAB. Methods: This study was random, two cycles, self-crossover control study in the bioequiavailability stage. PAB was the investigational drug T and Abraxane was the reference drug R. Patients were randomly assigned to two cycles therapy of either R→T or T→R(260 mg/m(2)/21d). Non-PD patients entered in the extension treatments of the investigational drug PAB(260 mg/m(2)/21d) until the disease progression or the intolerance toxicity. Results: From Mar 1, 2016 to May 24, 2016, we enrolled 40 patients. The blood concentration-time curve and the parameters of pharmacokinetics indicated the two drugs were the bioequivalent drug products in the initial two cycles crossover-therapy.The incidence of adverse drug reactions were 89.7% vs 97.4% in investigational drug vs reference drug and grade 3/4 toxicities were 20.5% vs 21.1%(P=1.000). Patients received a median of 7 treatment cycles(range 1-23) and a median of 260mg/m(2) actual drug dose (range 220-260 mg/m(2)). Seven patients (17.5%) had dose reductions because of toxicities (260 mg/m(2) reduce to 220 mg/m(2)). Twenty-two patients (55%) discontinued treatment prematurely because of toxicity.Overall response rates (ORR) were 40% (95% CI, 24.8%-55.2%). For patients who received PAB as first-line vs non-first-line therapy, the ORR were 43.8% vs 25%. For patients who taxane-naïve vs taxane-pretreated, the ORR were 45.5% vs 37.9%. Median PFS was 49 weeks(95% CI, 30weeks-NA). Conclusion: The paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane are the bioequivalent drug products.The toxicity and efficacy of the PAB are similar with abraxane.The more therapy chances for Chinese patients will come by the research and development of domestic drugs.

Histochemical distribution of four types of enzymes and mucous cells in the gastrointestinal tract of reared half-smooth tongue sole Cynoglossus semilaevis.

The histochemical distribution of acid phosphatase (ACP), alkaline phosphatase (ALP), non-specific esterase (NSE), peroxidase (POD) and mucous-cell types was evaluated in the gastrointestinal tract of the half-smooth tongue sole Cynoglossus semilaevis. The enzymes were detected in the entire stretch of the gastrointestinal tract. ACP activity was found in the supranuclear region of enterocytes and the lamina propria of the intestine, as well as the cytoplasm of epithelial cells of the stomach. The staining intensity of ACP in the anterior and posterior intestines was stronger than in the stomach. ALP activity was detected in the striated border of enterocytes and muscularis of the whole intestine, lamina propria and supranuclear cytoplasm of the enterocytes in the anterior intestine, as well as in the blood vessels of the stomach. The staining intensity for ALP in the anterior intestine was stronger than in the posterior segment and the latter was stronger than in the stomach. NSE activity was detected in the cytoplasm of the epithelial cells in the entire gastrointestinal tract, with the anterior intestine showing stronger intensity than the stomach. POD activity was located in the blood cells of the lamina propria of the gastrointestinal tract and the levels in the stomach were similar to the anterior and posterior intestines. Alcian blue (pH 2·5) periodic acid Schiff (AB-PAS) histochemical results revealed three types of mucous cells in the gastrointestinal tract. Type I cells (PAS+AB-) were observed among the gastric mucosa columnar cells in the stomach and enterocytes in the basal region of the villi and in the middle and top regions of the intestinal villi. Type II cells (PAS-AB+) and type III cells (PAS+AB+) were not detected in the stomach but were distributed ubiquitously among enterocytes in the middle and top regions of the intestinal villi.

[Prospects of hernia and abdominal wall surgery in China].

In recent 20 years, hernia and abdominal wall surgery has made great progress in China. However, what we've done still leaves much to be desired. Related guidelines of hernia disease had been conducted, but China is short of multi-center, prospective, and large-sample research evidence. These guidelines are still with low evidence level, and contents need additional modified to well meet Chinese real situation. In terms of treatment of inguinal and abdominal wall incisional hernia, some consensus has been reached from certain key issues globally, but further exploration are still needed. To stand at top of the world, we are a long distance. We should not only strengthen training and quality control but also establish patient registration system and overall management process.

Norepinephrine attenuates CXCR4 expression and the corresponding invasion of MDA-MB-231 breast cancer cells via ß2-adrenergic receptors.

OBJECTIVE: The growing evidence from laboratory and clinical studies has shown that the stress hormone, norepinephrine, and chronic stress promote tumor progression in a variety of tumor types. Chemokines and chemokine receptors have been shown to play a pivotal role in tumor progression. Recently, norepinephrine was reported to have a significant effect on macrophage migration by altering the expression of the chemokine receptor CCR2. MATERIALS AND METHODS: We investigated whether chemokines and their receptors are involved in the effects of norepinephrine on breast cancer. First, we used microarray analyses to detect the alteration of 128 chemotactically relevant genes after MDA-MB-231 cells were treated for 12 h with 100 µM norepinephrine. The CXCR4 gene demonstrated the greatest response to norepinephrine treatment, with a reduction of transcription of 95.7%, and was the focus of subsequent investigations. Real-time reverse transcription-PCR was used to determine the level of CXCR4 transcription after treatment with norepinephrine at various concentrations and for different durations. RESULTS: The results revealed that norepinephrine reduced CXCR4 transcription in a dose-dependent manner. Norepinephrine was also found to exert a negative effect on CXCR4 translational expression, as evidenced by a 44 ± 1.7% reduction in expression after a 12-h treatment with 10 µM norepinephrine. A Matrigel assay demonstrated a 51.3 ± 9.1% reduction in the number of MDA-MB-231 cells driven to migrate by CXCR4. Finally, we found the specific ß2-adrenergic antagonist, ICI 118,551, eliminated the impact of norepinephrine on CXCR4 expression. CONCLUSIONS: Norepinephrine attenuates CXCR4 expression and the corresponding invasion of MDA-MB-231 tumor cells via the ß2-adrenergic receptor. The complexity of the ß2-adrenergic receptor signaling pathway might contribute to these unexpected observations in our research, and this justifies further investigation into the intricate mechanisms involved.

Circulating tumor cells predict progression-free and overall survival in Chinese patients with metastatic breast cancer, HER2-positive or triple-negative (CBCSG004): a multicenter, double-blind, prospective trial.

BACKGROUND: The aim of this multicenter, double-blind, prospective study was to evaluate the potential utility of circulating tumor cell (CTC) measurements in predicting responses to anticancer therapies, including response to human epidermal growth factor receptor-2 (HER-2)-targeted agents, progression-free survival (PFS), and overall survival (OS) in Chinese women with metastatic breast cancer (MBC). PATIENTS AND METHODS: Three hundred MBC patients planned to complete three CTC blood draws and two imaging studies. RESULTS: A total of 294 of the 300 MBC patients enrolled from six leading Chinese cancer centers were assessable. In multivariate Cox regression analyses, the baseline CTC number remained an independent prognostic factor for PFS [hazard ratio (HR) = 1.93; 95% confidence interval (CI) = 1.39-2.69; P < 0.001) and OS (HR = 3.76; 95% CI = 2.35-6.01; P < 0.001). Similar results were observed for CTC counts at the first follow-up visit for both PFS (P = 0.049) and OS (P < 0.001). CONCLUSIONS: Enumeration of CTCs in Chinese MBC patients provides substantial prognostic information and is an independent factor associated with PFS and OS. Moreover, we demonstrated the prognostic value in the various disease subtypes, including HER-2-positive disease irrespective of therapy.

Randomized phase II trial on mitomycin-C/cisplatin +/- KLT in heavily pretreated advanced breast cancer.

A randomized phase II study using mitomycin (MMC)/cisplatin (DDP) regimen with or without Kanglaite (KLT, a traditional Chinese medicine) as salvage treatment was conducted to exploit KLT's potential effects on patients with advanced breast cancer (ABC). Triweekly regimen consisted of mitomycin (8 mg/m(2)) administered intravenously on day 1, and cisplatin (25 mg/m(2)) intravenously on days 1 to 3. KLT (100 ml) was given intravenously per day on days 1 to 14 every 3 weeks. Between April 2006 and July 2007, 60 patients with a median age of 48 years were randomized into MMC/DDP with or without KLT treatment. In all, the objective response rate (ORR) was 17.5%. There were no significant differences between experimental and control treatments in terms of ORR (14.3% vs. 20.7%, p = 0.730), clinical benefit rates (24.1% vs. 28.6%, p = 0.468), median time to progression (TTP; 3.63 vs. 4.0, p = 0.872), and overall survival (OS; 7.17 vs. not reached, p = 0.120). The median TTP for patients with complete or partial responses was 6.0 months, but only 2.1 months for patients with stable or progressive disease (SD or PD; p = 0.028). While the median OS for patients who obtained clinical benefit from chemotherapy was not reached, that of patients with SD of no more than 6 months or PD was only 7.17 months (p = 0.004). There is no additional benefit when KLT is added to the MMC/DDP doublet in the management of ABC. Patients who obtained clinical benefit from chemotherapy had a longer TTP and OS.