Subanesthetic isoflurane reduces zymosan-induced inflammation in murine Kupffer cells by inhibiting ROS-activated p38 MAPK/NF-κB signaling.

Volatile anesthetic isoflurane (ISO) has immunomodulatory effects. The fungal component zymosan (ZY) induces inflammation through toll-like receptor 2 or dectin-1 signaling. We investigated the molecular actions of subanesthetic (0.7%) ISO against ZY-induced inflammatory activation in murine Kupffer cells (KCs), which are known as the resident macrophages within the liver. We observed that ISO reduced ZY-induced cyclooxygenase 2 upregulation and prostaglandin E2 release, as determined by western blot and radioimmunoassay, respectively. ISO also reduced the production of tumor necrosis factor-α, interleukin-1ß, IL-6, high-mobility group box-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 as assessed by enzyme-linked immunosorbent assays. ISO blocked the ZY-induced nuclear translocation and DNA-binding activity of nuclear factor- (NF)-κB p65. Moreover, ISO attenuated ZY-induced p38 mitogen-activated protein kinase (MAPK) activation partly by scavenging reactive oxygen species (ROS); the interregulation that ROS activated p38 MAPK followed by NF-κB activation was crucial for the ZY-induced inflammatory responses in KCs. An in vivo study by peritoneal injection of ZY into BALB/C mice confirmed the anti-inflammatory properties of 0.7% ISO against ZY in KCs. These results suggest that ISO ameliorates ZY-induced inflammatory responses in murine KCs by inhibiting the interconnected ROS/p38 MAPK/NF-κB signaling pathways.

A subanesthetic dose of isoflurane during postconditioning ameliorates zymosan-induced neutrophil inflammation lung injury and mortality in mice.

Anesthetic isoflurane (ISO) has immunomodulatory effects. In the present study, we investigated whether a subanesthetic dose of ISO (0.7%) protected against zymosan (ZY) induced inflammatory responses in the murine lung and isolated neutrophils. At 1 and 6 hrs after ZY administration intraperitoneally, ISO was inhaled for 1 hr, and 24 hrs later, lung inflammation and injury were assessed. We found that ISO improved the survival rate of mice and mitigated lung injury as characterized by the histopathology, wet-to-dry weight ratio, protein leakage, and lung function index. ISO significantly attenuated ZY-induced lung neutrophil recruitment and inflammation. This was suggested by the downregulation of (a) endothelial adhesion molecule expression and myeloperoxidase (MPO) activity in lung tissue and polymorphonuclear neutrophils (b) chemokines, and (c) proinflammatory cytokines in BALF. Furthermore, ZY-induced nuclear translocation and DNA-binding activity of NF- κ B p65 were also reduced by ISO. ISO treatment inhibited iNOS expression and activity, as well as subsequent nitric oxide generation. Consistent with these in vivo observations, in vitro studies confirmed that ISO blocked NF- κ B and iNOS activation in primary mouse neutrophils challenged by ZY. These results provide evidence that 0.7% ISO ameliorates inflammatory responses in ZY-treated mouse lung and primary neutrophils.

Palliative surgery for primary sarcoma in the abdominal aorta: A case report and review of the literature.

Primary sarcoma of the aorta is extremely rare and accounts for <1% of all sarcomas. The present study describes the case of a 45-year-old male who presented with lower limb and abdominal pain. Abdominal computed tomography (CT) and magnetic resonance (MR) arteriography revealed a tumor that extended from the infrarenal aorta to the aortic bifurcation. The external and internal iliac arteries were occluded by the tumor incursion. Palliative surgery was performed for the sarcoma since the patient refused a radical resection. To improve the blood supply to the lower limbs, an axillary bifemoral bypass was established. Following the surgery, the pain was significantly reduced. However, the patient succumbed due to extensive metastasis 6 months after this surgery. Aortic sarcoma is an extremely rare disease with a poor prognosis. A diagnosis at a relatively early stage is necessary for a longer survival time. Radical surgery is the most significant treatment. Patients at advanced stages should consider palliative surgery in order to improve their quality of life.

Prognostic significance of USP22 as an oncogene in papillary thyroid carcinoma.

Ubiquitin-specific protease 22 (USP22), a novel deubiquitinating enzyme, has been associated with metastasis, therapy resistance, and cell cycle progression. The purpose of this study was to investigate the expression level of USP22 in papillary thyroid carcinoma (PTC) samples and to evaluate its clinical significance in PTC patients. USP22 expression was examined in 30 fresh PTC tissues and paired adjacent noncancerous tissues by real-time quantitative RT-PCR. Immunohistochemistry for USP22 was performed on additional 156 PTC tissues. The clinical significance of USP22 expression was analyzed. We found that the expression levels of USP22 mRNA and protein in PTC tissues were both significantly higher than those in noncancerous tissues. Clinicopathological analysis showed that USP22 expression was significantly correlated with tumor size (p=0.036), extracapsular invasion (p=0.012), multifocality (p=0.014), lymph node metastasis (p=0.022), distant metastasis (p=0.005), and TNM stage (p=0.002). The Kaplan-Meier survival curves revealed that USP22 expression was associated with poor prognosis in PTC patients. USP22 expression was an independent prognostic marker of overall patient survival in a multivariate analysis. Our findings suggest that USP22 is an independent predictor of poor prognosis of PTC patients.

[Combination of recombinant human endostatin and neoadjuvant chemotherapy for breast cancer].

OBJECTIVE: Recombinant human endostatin (rh-Endostatin), a protein modified by an additional nine-amino acid sequence to the N-terminal of endostatin, is a novel antiangiogenesis drug developed in China. The preclinical data suggested that it can inhibit proliferation and migration not only in endothelial cells, but also in some types of tumor cells. Theoretically, antiangiogenesis drugs should also be effective in the therapy of other solid tumors, including breast cancer. Here a prospective, randomized, controlled, phase II trial of combining rh-Endostatin and neoadjuvant chemotherapy was performed to evaluate its efficacy and safety profiles in patients with breast cancer. METHODS: A total of 68 patients with pathologically confirmed breast cancer were randomly assigned to receive the neoadjuvant DE regimen (docetaxel: 75 mg/m(2), d1, epirubicin: 75 mg/m(2), d1) every 3 weeks with or without rh-Endostatin (7.5 mg/m(2), d1-d14). Surgical resection was performed after 3 cycles of neoadjuvant treatment. The primary end-points were objective response rate (ORR) and pathological complete response rate (PCRR) while the secondary end-points quality of life (QOL) and toxicity. RESULTS: Among all of them, 64 were assessable for efficacy and 68 for toxicity. The ORRs were 90.9% (30/33) and 67.7% (21/31) in the combination and control groups respectively (P = 0.021). The stratification analysis showed that rh-Endostatin was more effective in the treatment of pre-menopausal and Eastern Cooperative Oncology Group (ECOG) = 0 patients (P < 0.05). The PCRRs were 15.2% (5/33) and 6.5% (2/31) in the combination and control groups respectively (P = 0.428). No significant difference was identified in QOL score and side effects (P > 0.05). CONCLUSIONS: Compared with DE regimen alone, the combination of rh-Endostatin with DE chemotherapy may achieve a higher ORR with no increased toxicity in breast cancer patients. Thus it can be utilized safely and effectively in the neoadjuvant treatment of breast cancer.

[Serum level of MMP-2 in early breast cancer and its correlation with circulating tumor cells].

OBJECTIVE: To explore the serum levels of MMP-2 in early breast cancer and its clinical significance and correlation with the circulating tumor cells in the patients. METHODS: The serum levels of MMP-2 in breast fibroadenoma (n = 10) and breast cancer (n = 72) were detected by enzyme-linked immunosorbent assay (ELISA). And CK19 mRNA was measured by quantitative reverse transcription-polymerase chain reaction in blood as an index of circulating tumor cells in the patients. RESULTS: The serum level of MMP-2 in breast cancer was significantly higher than that in breast fibroadenoma (12.24 vs 2.21 µg/L, P = 0.003). Subgroup analysis showed that the serum levels of MMP-2 were higher in HER-2 positive patients than those in HER-2 negative ones (16.77 vs 10.02 µg/L, P = 0.022). CK19 mRNA was found in blood samples from 30 cases of breast cancer and the positive rate was 41.7%. However, it was not detected in the patients with breast fibroadenoma. The mean levels of serum MMP-2 were (15.48 ± 2.02) and (7.16 ± 1.55) µg/L in CK19 positive and negative patients respectively. Significant difference existed between two groups (P = 0.013). CONCLUSION: The serum level of MMP-2 in early breast cancer is closely correlated with blood micrometastasis. And its high level may be an important contributing factor for the metastasis of breast cancer.

Rectal carcinoma metastatic to the male breast after 7 years: case report.

BACKGROUND: Colorectal cancer metastasis to a mammary location is very rare. CASE REPORT: A 38-year-old male, who had undergone anterior resection of an advanced rectal carcinoma 7 years earlier, presented with a right mammary mass. Core needle biopsy of the mass indicated cytology consistent with breast adenocarcinoma. After neoadjuvant chemotherapy and modified radical mastectomy, pathology identified the mass as rectal carcinoma. CONCLUSION: The authors highlight the difficulty of making an accurate diagnosis of rectal cancer metastasis to the breast of a male.

Application of colour Doppler in encircling constriction of the superficial femoral vein in primary deep venous insufficiency of the lower limbs.

1. The aim of the present study was to evaluate the clinical value of colour Doppler application in encircling constriction of the superficial femoral vein in deep vein insufficiency. 2. A total of 87 patients with primary deep venous insufficiency (PDVI) using ascending venography were randomly divided into group A (44 patients) and group B (43 patients). All patients underwent encircling constriction of the superficial femoral vein, high ligation and ablation of the great saphenous vein and perforator vein. The duration of venous reflux at operation was monitored with colour Doppler in group A (but not group B) to evaluate the immediate effects. Clinical grading and scoring of the clinical, etiological, anatomical, pathophysiological (CEAP) classification system were used to evaluate the follow-up curative effect. 3. In four cases from group A, completely destroyed valves were identified at the time of operation and autografting of the vein segment with a valve was carried out. The intraoperative examination of colour Doppler in group A showed a much shorter duration of vein reflux after the encircling constriction procedure than the presurgery condition. According to the results of CEAP grading, the success rate of group A (95.0%, 38/40) was significantly higher than that of group B (76.7%, 33/43). Postoperative clinical scores were markedly lower than preoperative scores in both groups A and B. 4. In conclusion, our data suggest that application of colour Doppler in encircling constriction of superficial femoral vein might enhance surgical pertinence and improve surgical effect for PDVI.

T-vector and in vivo recombination as tools to construct a large antibody library of breast cancer.

The emergence of phage antibody libraries is an important advance in the field of antibody engineering. It provides a useful methodology to produce human antibodies and has the potential to replace traditional hybridoma technology. In our research, we used T-vector and in vivo recombination to construct a large antibody library from breast cancer patients. The use of T-vector considerably increased the cloning efficiency, and the diversity of the library could be increased easily using in vivo recombination. Taken together, a combination of these two techniques might be valuable in constructing a large antibody library.

Prospective study on combination of electrical impedance scanning and ultrasound in estimating risk of development of breast cancer in young women.

Based on cost-effective ratio, there has not yet been imaging methods suitable for breast cancer screening in young women. The aim of this study was to evaluate the sensitivity and specificity of the combination of electrical impedance scanning (EIS) and ultrasound in identifying breast cancer for young women, to calculate relative risks, and to determine whether there has been some more accurate imaging method used in early detection of breast cancer in young women. A prospective and multicenter clinical study was conducted in young women aged 45 years and under. The young women (583 cases) scheduled for mammary biopsy underwent EIS and ultrasound, respectively. EIS and ultrasound results were compared with final histopathology results. Study end points included sensitivities and specificities of EIS, ultrasound and the combination method, as well as relative probability of breast cancer of positive patients detected by the combination of EIS and ultrasound. Of the 583 cases, 143 were diagnosed with breast cancer. The sensitivities of EIS, ultrasound and the combination method were 86.7% (124/143), 72% (103/143), and 93.7% (134/143); the specificities were 72.9% (321/440), 82.5% (363/440), and 64.1% (282/440), and the relative possibilities of breast cancer for the positive young women detected by EIS, ultrasound, and the combination method were 8.67, 5.77, and 14.84, respectively. The combination of EIS and ultrasound is likely to become an applicable method for early detection of breast cancer in young women.

The role of survivin in diagnosis, prognosis and treatment of breast cancer.

Survivin is a cancer gene that is silenced in differentiated tissues, while overexpressed at high levels in vast majority of tumors. It has garnered great interests in recent years. Some essential properties characterizing it as an ideal target involve inhibiting apoptosis, promoting mitosis, stimulating vessel growth thus inducing chemo-resistance. These functions touch the full gamut of tumorigenesis, including proliferation, migration, and invasion, and collectively facilitate malignant behavior. In the case of breast cancer, survivin detection independent or combined in serum and/or urine has emerged as a measure for diagnosis. Moreover, many studies indicated aberrant expression of survivin is associated with poor prognosis and drug/radiation resistance. Strategies targeting survivin to treat breast cancer have got promising initial results. In this review, we summarize its role in breast cancer's diagnosis, prognosis, and treatment, with the intention to explain why this interesting molecule plays a conflicting role.

[Value of fused 18F-FDG PET/CT images in predicting efficacy of neoadjuvant chemotherapy on breast cancer].

BACKGROUND & OBJECTIVE: Previous studies confirmed that fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging relates to clinical or pathologic responses of tumors to neoadjuvant therapy. This study was to evaluate the correlation of fused 18F-FDG PET/CT images to cell apoptosis of breast cancer after neoadjuvant chemotherapy, and explore its value in predicting the efficacy of neoadjuvant chemotherapy on breast cancer. METHODS: Forty-five patients with primary breast cancer, proven by core needle biopsy, underwent 3 cycles of neoadjuvant chemotherapy. PET/CT was performed before and after treatment, and the ratio of tumor area activity to non-tumor area activity (T/N) was calculated. The apoptosis index (AI) was determined using TUNEL technique. RESULTS: Of the 45 patients, 4(8.9%) achieved complete remission (CR), 29 (64.4%) achieved partial remission (PR), 10 (22.2%) presented stable disease (SD), and 2 (4.4%) presented progressive disease (PD) after neoadjuvant chemotherapy. The mean T/N ratio was decreased from 3.23+/-0.63 before chemotherapy to 2.31+/-0.49 after chemotherapy (P=0.006) by 6.4%-50.8%. The mean AI was increased from (2.81+/-0.76)% before chemotherapy to (17.31+/-6.85)% after chemotherapy (P<0.001) by 1.9%-41.3%. The T/N ratio reduction rate was positively correlated to AI change (r(s)=0.850, P<0.001). At a threshold of 20% decrease from baseline in T/N ratio, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT in predicting clinical response were 90.9%, 83.3%, 93.8%, 76.9%, and 92.1%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy might effectively induce cell apoptosis in breast cancer and inhibit the glucose uptake. Fused PET/CT imaging is closely related to cell apoptosis status of breast cancer after neoadjuvant chemotherapy, and may be applied to predict the response of breast cancer to neoadjuvant chemotherapy.

Treatment of hepatoma with liposome-encapsulated adriamycin administered into hepatic artery of rats.

AIM: To observe the therapeutic effects of liposome-encapsulated adriamycin (LADM) on hepatoma in comparison with adriamycin solution (FADM) and adriamycin plus blank liposome (ADM + BL) administered into the hepatic artery of rats. METHODS: LADM was prepared by pH gradient-driven method. Normal saline, FADM (2 mg/kg), ADM+BL (2 mg/kg), and LADM (2 mg/kg) were injected via the hepatic artery in rats bearing liver W256 carcinosarcoma, which were divided into four groups randomly. The therapeutic effects were evaluated in terms of survival time, tumor enlargement ratio, and tumor necrosis degree. The difference was determined with ANOVA and Dunnett test and log rank test. RESULTS: Compared to FADM or ADM + BL, LADM produced a more significant tumor inhibition (tumor volume ratio: 1.243 +/- 0.523 vs 1.883 +/- 0.708, 1.847 +/- 0.661, P < 0.01), and more extensive tumor necrosis. The increased life span was prolonged significantly in rats receiving LADM compared with FADM or ADM+BL (231.48 vs 74.66, 94.70) (P < 0.05). CONCLUSION: The anticancer efficacies of adriamycin on hepatoma can be strongly improved by liposomal encapsulation through hepatic arterial administration.

[Treatment of rabbits bearing advanced VX2 tumors in the mammary gland with nano-sized liposomal adriamycin administered by various routes].

OBJECTIVE: To investigate the therapeutic effect of nano-sized liposomal adriamycin (NLADR) administered by various routes on rabbits bearing advanced breast tumors. METHODS: NLADR with a mean diameter of 120 nm was prepared by pH gradient-driven drug encapsulation method. VX(2) tumor mass suspension was injected into the breast tissues of 50 female New Zealand White rabbits. Six weeks after the inoculation 38 surviving tumor-bearing rabbits were randomly divided into 5 groups: group A (control group), receiving a sham treatment; group B, receiving subcutaneous injection of NLADR with a dose of 1 mg/kg into the areas adjacent to the implanted tumor; group C, receiving intravenous injection of NLADR with a dose of 1 mg/kg; group D, receiving NLADR with a dose of 1 mg/kg administered by subcutaneous injection combined with intravenous injection with half of the whole dose for both routes; and group E, receiving intravenous injection of free adriamycin (FADR). The treatment was repeated every 48 hours. The rabbits were killed 48 hours after the third treatment. The breast tumors, axillary lymph nodes, and all of the metastatic tumors anatomically detected in distant organs were collected. The sizes of tumors and axillary nodes before and after treatment were measured. Necrosis of tumor tissue was assessed pathologically. The mRNA expression of proliferating cell nuclear antigen (PCNA) was determined using RT-PCR. Apoptosis was identified and quantified as apoptosis index (AI) using TUNEL method. RESULTS: The average growth rate of tumor was the highest in group A (1.58) and the lowest in group C (1.33). The average growth rate of axillary lymph nodes was the highest in group A (3.70), significantly higher than in any other groups (all P = 0.00); and was the lowest in group B, significantly lower than groups A, C, and E (all P < 0.01), however without a significant difference between groups B and D (P = 0.148). The PCNA mRNA expression level of the implanted tumor in groups C was the lowest, significant lowest then those in group A and B (both P < 0.01). The sequence of PCNA mRNA in the axillary lymph nodes was group B < group D < group C < group E < group A with significant differences between group B and groups A, C, and E. The sequence of PCNA mRNA in the mediastinal lymph nodes was group B < Group E < group D < group C < group A. The PCNA mRNA expression level was the lowest in group D, significantly lower than that in group A (P = 0.011). Necrosis of implanted tumor, metastatic foci in lung and liver, and lymph nodes was obvious in groups C, D, and E. Necrosis of implanted tumor and metastatic foci in lung and liver was significantly obvious in group C than in group D (P = 0.000 and P = 0.022). Necrosis of the implanted tumor was significantly more obvious in group C than in group F (P = 0.033). Necrosis of axillary lymph nodes was significantly more obvious in group than in groups C and E (P = 0.000 and P = 0.000). The values of AI of the implanted tumor in groups C and D were 16.74% and 18.04%, both significantly higher than those in group E (P = 0.02 and P = 0.04), and those of group E were significantly higher than those in groups A and B (both P < 0.01). The AI value of the axillary lymph nodes was 21.73%, significantly than those in groups A, C, and E (all P < 0.01). The average AI values of the metastatic foci were 16.52%, 15.77%, and 14.50%, all significantly higher than that in group B (all P < 0.01), and that of group B was significantly higher than that in group A (P = 0.039). CONCLUSION: NLADR, especially intravenous administration combined with subcutaneous administration, is effective in treatment of advanced breast carcinoma with lymphatic and distant metastases.

[Drug concentration in axillary lymph nodes of patients with breast cancer after lymphatic chemotherapy].

BACKGROUND & OBJECTIVE: Lymph node status is one of the decisive prognostic factors of breast cancer. Chemotherapy targeting regional lymphatic tissues has emerged as a promising therapy for malignancies with high tendency to disseminate lymphatically. This study was to detect drug concentration in axillary lymph nodes of patients with breast cancer after lymphatic chemotherapy (LC), and to investigate effect of LC on accumulation of antitumor drugs in regional lymph nodes through comparing with the effect of intravenous chemotherapy (VC). METHODS: Sixty patients with breast cancer, confirmed by preoperative puncture biopsy, were randomized into 2 groups, 30 (LC group) were subcutaneously injected with 4 ml of carboplatin-activated carbon suspension (containing 20 mg of carboplatin) around the primary tumor, the other 30 (VC group) were intravenously injected with an equal dose of aqueous carboplatin. Every 6 patients from each group received modified radical mastectomy 1, 12, 24, 36, or 48 h after injection. Axillary lymph nodes were removed for pathologic examination. The concentration of carboplatin in nodes was detected by Zeeman atomic absorption spectrometry. RESULTS: A total of 275 axillary lymph nodes were resected, with 154 in LC group and 121 in VC group. Of the 275 lymph nodes, 136(49.5%) were from 23 patients (38.3%) had pathologically detected metastases. The concentrations of carboplatin were significantly higher in LC group than in VC group 1, 12, 24, 36, and 48 h after injection [(11.82+/-3.50) microg/g vs. (0.06+/-0.02) microg/g, (23.58+/-7.34) microg/g vs. (0.11+/-0.05) microg/g, (18.22+/-4.93) microg/g vs. (0.10+/-0.02) microg/g, (16.70+/-5.15) microg/g vs. (0.05+/-0.02) microg/g, and (14.62+/-4.29) microg/g vs. 0, respectively, P < 0.001]. Lymph node metastasis had no correlation with drug concentration (P > 0.05). CONCLUSION: Compared with VC, LC can effectively and continuously improve drug concentration in axillary lymph nodes of patients with breast cancer.

VP22 fusion protein-based dominant negative mutant can inhibit hepatitis B virus replication.

AIM: To investigate the inhibitory effect of VP22 fusion protein-based dominant negative (DN) mutant on Hepatitis Bvrus (HBV) replication. METHODS: Full-length or truncated fragment of VP22 was fused to C terminal of HBV core protein (HBc), and subcloned into pcDNA3.1 (-) vector, yielding eukaryotic expression plasmids of DN mutant. After transfection into HepG2.2.15 cells, the expression of DN mutant was identified by immunofluorescence staining. The inhibitory effect of DN mutant on HBV replication was indexed as the supernatant HBsAg concentration determined by RIA and HBV-DNA content by fluorescent quantification-PCR (FQ-PCR).Meanwhile, metabolism of HepG2.2.15 cells was evaluated by MTT colorimetry. RESULTS: VP22-based DN mutants and its truncated fragment were expressed in HepG2.2.15 cells, and had no toxic effect on host cells. DN mutants could inhibit HBV replication and the transduction ability of mutant-bearing protein had a stronger inhibitory effect on HBV replication. DN mutants with full length of VP22 had the strongest inhibitory effect on HBV replication, reducing the HBsAg concentration by 81.94%, and the HBV-DNA content by 72.30%. MTT assay suggested that there were no significant differences in cell metabolic activity between the groups. CONCLUSION: VP22-based DN mutant can inhibit HBV replication effectively.

Body distribution of nanoparticle-containing adriamycin injected into the hepatic artery of hepatoma-bearing rats.

The aim of the study was to investigate the body distribution of nanoparticle-containing adriamycin (NADR) injected into the hepatic artery of hepatoma-bearing rats. Thirty Walker-256 hepatoma-bearing rats were divided into two groups at random, with 15 rats in each. NADR and free adriamycin (FADR) were injected into the hepatic artery of animals on the seventh day after tumor implantation. At 1, 5, and 15 hr, after administration, five animals in each group were sacrificed and the ADR concentrations in the plasma, liver, heart, spleen, lungs, kidneys, and tumor were determined. The results showed that NADR substantially increased the ADR concentrations in liver, spleen, and tumor of rats compared to FADR, whereas the concentrations in plasma, heart, and lungs were significantly decreased. In conclusion, the body distribution of ADR can be modified by its encapsulation into nanoparticles and administration via the hepatic artery.

[Expression and activation of MAPK pathway signaling molecules in human breast cancer cell lines].

AIM: To detect the expression and status of extracellular regulatory kinase 1 and 2 (ERK1/2) and its upstream kinase MEK1/2 proteins in four breast cancer cell lines MCF-7, Bcap-37, SK-BR-3 and T47D and study the effects of cyclophosphamide and epirubicin on the growth of the cell lines and on the expression and status of the signaling molecules. METHODS: Western blot was used to examine the expression and status of MEK1/2 and ERK1/2 proteins in these cells and the effects of these two drugs on them. The effects of the two drugs on the proliferation of these breast cancer cell lines were detected by MTT colorimetry. RESULTS: The levels of expression and phosphorylation of MEK1/2 and ERK1/2 proteins in four breast cancer cell lines increased notably as compared with those in MCF-10 cells. Both drugs could inhibit the proliferation of breast cancer cells. And the levels of expression and phosphorylation of MEK1/2 and ERK1/2 proteins in breast cancer cell lines treated with the drugs were markedly lower than those in untreated breast cancer cells. CONCLUSION: Overexpression and phosphorylation of MEK and ERK may play an important role in the generation and development of human breast cancer. The inhibitory effect of cyclophosphamide and epirubicin on proliferation of the breast cancer cells may be by means of inhibiting expression and phosphorylation of MEK and ERK.

Enhanced antitumor efficacy on hepatoma-bearing rats with adriamycin-loaded nanoparticles administered into hepatic artery.

AIM: To investigate the antitumor activity of adriamycin (ADR) encapsulated in nanoparticles (NADR) and injected into the hepatic artery of hepatoma-bearing rats. METHODS: NADR was prepared by the interfacial polymerization method. Walker-256 carcinosarcomas were surgically implanted into the left liver lobes of 60 male Wistar rats, which were divided into 4 groups at random (15 rats per group). On the 7th day after implantation, normal saline (NS), free ADR (FADR), NADR, or ADR mixed with unloaded nanoparticles (ADR+NP) was respectively injected via the hepatic artery (i.a.) of rats in different groups. The dose of ADR in each formulation was 2.0 mg/kg body weight and the concentration was 1.0 mg/mL. Survival time, tumor enlargement ratio, and tumor necrosis degree were compared between each group. RESULTS: Compared with the rats that received NS i.a., the rats that received FADR or ADR+NP acquired apparent inhibition on tumor growth, as well as prolonged their life span. Further significant anticancer efficacy was observed in rats that received i.a. administration of NADR. Statistics indicated that NADR brought on a more significant tumor inhibition and more extensive tumor necrosis, as compared to FADR or ADR+NP. The mean tumor enlargement ratio on the 7th day after NADR i.a. was 1.106. The mean tumor-bearing survival time was 39.50 days. Prolonged life span ratio was 109.22% as compared with rats that accepted NS. CONCLUSION: Therapeutic effect of ADR on liver malignancy can be significantly enhanced by its nanopaticle formulation and administration via hepatic artery.