Comparison of the efficacy and safety of the EC-T (epirubicin/cyclophosphamide followed by docetaxel) and TCb (docetaxel/carboplatin) neoadjuvant regimens in early TOP2A-normal stage II-III breast cancer.

This study aimed to compare the efficacy and safety of the EC-T (4 cycles of epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2, followed by 4 cycles of docetaxel 75 mg/m2) and TCb (6 cycles of docetaxel 75 mg/m2, intravenous drip (ID), day 1 + carboplatin AUC 6, ID, day 1) neoadjuvant regimens in patients with TOP2A-normal stage II-III breast cancer. This study analyzed 280 patients enrolled from three studies registered with ClinicalTrials.gov (NCT03140553, NCT03154749, NCT03507465) with early TOP2A-normal stage II-III breast cancer who received neoadjuvant chemotherapy, including 100 patients who received the EC-T regimen and 180 patients who received the TCb regimen. The primary endpoint was the ratio of RCB 0/1 (residual cancer burden 0/1) after neoadjuvant chemotherapy. The secondary endpoint was the safety of the two groups. There was no significant difference in the ratio of RCB 0/1 between the two groups (23% vs. 23.9%, p=0.614). Among the triple-negative breast cancer patients, the efficacy did not differ between the two groups (40% vs. 32%, p=0.52). Among the lymph node metastasis patients, the efficacy of the EC-T group was significantly better than that of the TCb group (14% vs. 2.6%, p=0.03). Regarding the side effects, the incidence of grade 3/4 anemia was higher in the EC-T group than in the TCb group (21.0% vs. 8.33%, p=0.002), while the incidence of grade 3/4 neutropenia was higher in the EC-T group than in the TCb group (17% vs. 14.44%, p=0.570), and the incidence of grade 3/4 thrombocytopenia was low in each group (EC-T group: 6 % and TCb group: 7.22%, p=0.697). In the EC-T group, grade 3/4 nausea and vomiting occurred in 5 patients. The EC-T group showed a higher rate of grade 3/4 myalgia than the TCb group (7% and 4.44%, respectively, p=0.363). To conclude, the TCb regimen can be used as an alternative regimen for TOP2A-normal stage II-III breast cancer patients in neoadjuvant chemotherapy. However, in patients with node-positive tumors, EC-T is still recommended. Though no difference of grade 3/4 thrombocytopenia in two groups, grade 4 thrombocytopenia caused by the carboplatin-containing regimen should be taken seriously.

A phase II trial of dose-dense (biweekly) paclitaxel plus carboplatin as neoadjuvant chemotherapy for operable breast cancer.

The aim of the present study is to investigate the efficacy and safety of dose-dense (biweekly) carboplatin and paclitaxel as a neoadjuvant treatment for operable breast cancer. Patients with previously untreated breast cancer (stages Ic-III) were treated with four cycles of paclitaxel (175 mg/m(2), intravenous drip, D1) and carboplatin (area under the curve of 5, D1). Patients with HER2+ disease simultaneously received trastuzumab (6 mg/kg initial dose with subsequent doses of 4 mg/kg biweekly). The primary endpoint was a pathologically complete response (pCR). Between January 2012 and February 2014, 110 patients were enrolled. The overall pCR rate was 35.45 % (39 of 110). The pCR rates for the different cancer subtypes were as follows: 10.53 % (2 of 19) among the patients with the luminal A subtype, 12.50 % (5 of 40) among the patients with the luminal B (HER2-) subtype, 58.33 % (14 of 24) among the patients with the luminal B (HER2+) subtype, 57.14 % (8 of 14) among the patients with the triple-negative subtype, and 76.92 % (10 of 13) among the patients with the HER2+ subtype. The patients experienced the following toxicity side effects: grade 3/4 neutropenia (N = 27, 24.55 %), grade 3/4 anemia (N = 6, 5.45 %), grade 3/4 thrombocytopenia (N = 2, 1.82 %), grade 3 alanine aminotransferase (ALT) elevation (N = 1, 0.91 %), grade 3 neuropathy (N = 3, 2.73 %), grade 3 pain (N = 2, 1.82 %), and grade 3 fatigue (N = 1, 0.91 %). In total, 19.09 % of the patients experienced treatment delay or discontinuation due to hematological toxicity, and one patient discontinued treatment due to non-hematological toxicity. Neoadjuvant biweekly paclitaxel plus carboplatin is a feasible therapy that achieved high pCR rates in patients with the HER2+, triple-negative, and luminal B (HER2+) cancer subtypes (NCT0205986).

The role of heat shock proteins in oxidative stress damage induced by Se deficiency in chicken livers.

Selenium (Se) is an essential dietary trace element, which acts as an antioxidant. Heat shock proteins (HSPs) are a family of intracellular proteins whose synthesis is greatly increased upon exposure of cells to environmental stressors including oxidative metabolites, heavy metals, amino acid analogues and so on. However, little is known about the role of HSPs in oxidative stress damage induced by Se deficiency in the chicken liver. The aim of this study was to investigate the effects of Se deficiency on the expression levels of HSPs (Hsps27, 40, 60, 70, and 90) and oxidative indexes in the chicken liver. A total of 300 1-day-old sea blue white laying hens were divided into two groups (n = 150/group), and each of those groups was randomly divided into groups so that the trials were conducted in triplicate. The Se-deficient group (-Se) was fed a Se-deficient corn-soy basal diet (the Se content was 0.02 mg/kg); the Se-adequate group as control (+Se) was fed the same basal diet supplemented with Se at 0.2 mg/kg (sodium selenite). The liver tissue was collected and examined for pathological observations, oxidative indexes, mRNA and protein levels of HSPs genes at 15, 25, 35, 45, 55 and 65 days old. The histopathological analysis showed that liver tissues were injured seriously in the Se-deficient group. The oxidative indexes data showed that the malondialdehyde (MDA) level increased and the activity of L-glutathione (GSH) and glutathione peroxidase (GSH-Px) in the chicken liver decreased in Se-deficient group (p < 0.05). Additionally, the mRNA levels of HSPs (27, 40, 60, 70, and 90) increased significantly (p < 0.05) in the Se-deficient group compare to the corresponding control group. Meanwhile, the protein expression of HSPs (60, 70, and 90) also increased significantly (p < 0.05) in the Se-deficient group. These results suggested that oxidative stress and the levels of HSPs expression levels in chicken liver can be influenced by dietary Se deficiency. And HSPs played an important role in the protection of the liver after oxidative stress due to Se deficiency.

Axillary lymph node status, adjusted for pathologic complete response in breast and axilla after neoadjuvant chemotherapy, predicts differential disease-free survival in breast cancer.

BACKGROUND: Our retrospective study in breast cancer patients evaluated whether integrating subtype and pathologic complete response (pcr) information into axillary lymph node restaging after neoadjuvant chemotherapy (nac) adds significance to its prognostic values. METHODS: Patients included in the analysis had stage ii or iii disease, with post-nac axillary lymph node dissection (alnd), without sentinel lymph node biopsy before completion of nac, with definitive subtyping data and subtype-oriented adjuvant treatments. The ypN grading system was used to restage axillary lymph node status, and ypN0 was adjusted by pcr in both breast and axilla into ypN0(pcr) and ypN0(non-pcr). Univariate and multivariate survival analyses were performed. RESULTS: Among the 301 patients analyzed, 145 had tumours that were hormone receptor-positive (hr+) and negative for the human epidermal growth factor receptor (her2-), 101 had tumours that were positive for her2 (her2+), and 55 had tumours that were triple-negative. The rate of pcr in both breast and axilla was 11.7%, 43.6%, and 25.5% respectively for the 3 subtypes. Compared with the non-pcr patients, the pcr patients had better disease-free survival (dfs) and overall survival (os): p = 0.002 for dfs and p = 0.011 for os. In non-pcr patients, dfs and os were similar in the ypN0(non-pcr) and ypN1 subgroups, and in the ypN2 and ypN3 subgroups. We therefore grouped the ypN grading results into ypN0(pcr) (n = 75), ypN0- 1(non-pcr) (n = 175), and ypN2-3 (n = 51). In those groups, the 3-year dfs was 98%, 91%, and 56%, and the 3-year os was 100%, 91%, and 82% respectively. The differences in dfs and os between those three subgroups were significant (all p < 0.05 in paired comparisons). Multivariate Cox regression showed that subtype and ypN staging adjusted by pcr were the only two independent factors predicting dfs. CONCLUSIONS: Axillary lymph node status after nac, adjusted for pcr in breast and axilla, predicts differential dfs in patients without prior sentinel lymph node biopsy.

[Research progress on free radicals in human body].

Free radicals are the intermediates of metabolism, widely exist in the human bodies. Under normal circumstances, the free radicals play an important role in the metabolic process on human body, cell signal pathway, gene regulation, induction of cell proliferation and apoptosis, so as to maintain the normal growth and development of human body and to inhibit the growth of bacteria, virus and cancer. However, when organic lesion occurs affected by external factors or when equilibrium of the free radicals is tipped in the human body, the free radicals will respond integratedly with lipids, protein or nucleic acid which may jeopardize the health of human bodies. This paper summarizes the research progress of the free radicals conducted in recent years, in relations to the perspective of the types, origins, test methods of the free radicals and their relationship with human's health. In addition, the possible mechanisms of environmental pollutants (such as polycyclic aromatic hydrocarbons) mediating oxidative stress and free radicals scavenging in the body were also summarized.

[A study of measuring cardiac output in patients during mechanical ventilation with CO2 rebreathing method].

Measurement of cardiac output with CO2 rebreathing method and thermodilution method was carried out in seven COPD patients undergoing mechanical ventilation. Mixed venous PCO2 could be measured reasonably well with CO2 rebreathing method. There was a very significant positive correlation between the CO2 method and thermodilution method for measuring cardiac output (r = 0.9130, P < 0.01). The change of cardiac output before and after infusion of sodium nitroprusside could be reflected by CO2 rebreathing method. We conclude that the cardiac output in COPD patients undergoing mechanical ventilation could be measured reasonably well with CO2 rebreathing method.

[The effects of almitrine bismesylate in chronic obstructive pulmonary disease with CO2 retention].

Ten cases of chronic obstructive pulmonary disease (COPD) were examined before and 2 hours after oral administration of 150 mg of almitrine bismesylate while breathing 31% oxygen. The agent induced a rise in mouth occlusion pressure (P 0.1) from 2.67 +/- 0.64 cmH2O to 3.74 +/- 1.02 cmH2O (P less than 0.01). However the central inspiratory drive and ventilation response to hypercapnia did not change after taking almitrine. VT/Ti increased from 0.32 +/- 0.06 L/sec. to 0.40 +/- 0.08 L/sec. (P less than 0.01) and RR, Ti, Ti/Ttot were not changed, so VT and VE increased from 0.37 +/- 0.10 L to 0.42 +/- 0.16 L (P less than 0.05) and from 7.70 +/- 1.72 L to 8.85 +/- 2.28 L (P less than 0.05) respectively. VA also increased from 3.34 +/- 0.06 L to 4.14 +/- 0.86 L (P less than 0.01). Analysis of blood gases showed a marked increase in PaO2 from 88.70 +/- 16.19 mmHg to 109.10 +/- 25.57 mmHg (P less than 0.05) and a decrease in PaCO2 from 61.73 +/- 12.15 mmHg to 54.01 +/- 10.37 mmHg (P less than 0.05). Our results suggested that almitrine bismesylate could improve the blood gases in COPD patients with CO2 retention as it is a respiratory stimulant which might act through a peripheral mechanism.

[Effects of external diaphragm pacing on transdiaphragmatic pressure, ventilation and arterial blood gases in healthy volunteers].

The effects of external diaphragm pacing (EDP) were studied in seven healthy volunteers. During EDP the movement of both left and right hemidiaphragms increased on average 1.28 and 1.30 cm respectively. The transdiaphragmatic pressure also increased from 8.63 +/- 1.576 cm H2O to 15.18 +/- 1.946 cm H2O (P less than 0.01). Inductive plethysmography showed that with EDP the mean inspiratory flow rate increased from 308 +/- 28.6 ml/sec. to 454 +/- 36.6 ml/sec. (P less than 0.01), but there was no change in respiratory rate, inspiratory time and the ratio of inspiratory time to respiratory cycle. Both tidal volume and minute volume of ventilation increased from 419 +/- 33.9 ml to 691 +/- 71.5 ml (P less than 0.01) and from 7.02 +/- 0.74 l/min. to 10.14 +/- 0.73 l/min. (P less than 0.01) respectively. Accompanied with the change of ventilation, the consumption of oxygen and the production of CO2 also increased from 258 +/- 14.9 ml/min. to 310 +/- 15.0 ml/min. (P less than 0.05) and from 228 +/- 11.4 ml/min. to 299 +/- 25.9 ml/min. (P less than 0.05) respectively. Consequently PaCO2 reduced from 5.24 +/- 0.22 kPa to 4.27 +/- 0.25 kPa (P less than 0.05), whereas PaO2 increased from 12.7 +/- 0.32 kPa to 14.5 +/- 0.42 kPa (P less than 0.01).

[The changes in blood gases, hemodynamics and oxygen delivery after weaning and the treatment of sodium nitroprusside in mechanically ventilated patients with cor pulmonale].

The change of blood gases, hemodynamics and oxygen delivery after weaning and the treatment of sodium nitroprusside were respectively studied in seven and twelve patients with cor pulmonale. Weaning resulted in decrement of pulmonary vascular resistance (from 48.4 +/- 16.6 to 37.6 +/- 18.5 kPa.s-1.L-1, P < 0.01) and increment of oxygen pressure of mixed venous blood (from 5.35 +/- 0.71 to 6.00 +/- 0.89 kPa.s-1.L-1, P < 0.01). Although artery pressure of oxygen (from 12.20 +/- 4.24 to 10.07 +/- 2.83 kPa, P < 0.01) was decreased after the treatment of sodium nitroprusside, cardiac index (from 44.5 +/- 10.3 to 53.0 +/- 13.7 ml.s-1.m-2, P < 0.05) and oxygen delivery index (from 7.9 +/- 1.6 to 9.3 +/- 2.2 ml.s-1.m-2, P < 0.05) were improved. It indicates that adequate weaning and application of vasodilator is useful to mechanically ventilated patients.