Apatinib is effective as third-line and more treatment of advanced metastatic non-small-cell lung cancer: A retrospective analysis in a real-world setting.

No standard methods are recommended for patients with advanced metastatic non-small-cell lung cancer (NSCLC) experiencing progression after 2 or more lines treatment now. The aim of this retrospective study was to assess the efficacy and safety of apatinib in metastatic NSCLC patients after second-line or more treatments failure in a real-world setting.A total of 52 advanced NSCLC patients who experienced progression after second-line and more treatments and received apatinib from March 2016 to February 2018 were retrospectively reviewed. Patients were treated with oral apatinib 500 mg QD (take the medicine once a day), every 4 weeks for a cycle. Responding and stable patients continued the treatment until progression or intolerable toxicity. The overall survival (OS), progression-free survival (PFS), objective remission rate (ORR) and disease control rate (DCR), and side effects of the drug were collected and reviewed.The ORR and the DCR were 6.9% and 67.4%. The median PFS and median OS of all patients were 3.8 months and 5.8 months, respectively. The Eastern Cooperative Oncology Group score was the independent influencing factor of PFS and OS for the advanced NSCLC patients who were treated with apatinib after second-line and above standard regimens (PFS: hazard ratio [HR] = 4.446, 95% confidence interval [CI]: 1.185-16.678, P = .027 and OS: HR = 8.149, 95% CI: 1.173-56.596, P = .034). The most common adverse events apatinib-related included hypertension (19.2%), hand-foot syndrome (11.5%), and mucous membrane reaction (17.3%). And treatment-related grade 3/4 toxicities were low.Apatinib showed favorable efficacy and safety and could be a treatment option in patients with advanced NSCLC experiencing progression after second-line and more treatment.

Inhibition of EGR1 inhibits glioma proliferation by targeting CCND1 promoter.

BACKGROUND: Gliomas are the most common primary tumors in central nervous system. The prognosis of the patients with glioma is poor regardless of the development of therapeutic strategies. Its aggressive behavior mainly depends on the potent ability of proliferation. The transcription factor EGR1 (early growth response 1) is a member of a zinc finger transcription factor family which plays an essential role in cell growth and proliferation. METHODS: EGR1 expression levels in 39 glioma tissues and 10 normal brain tissues were tested by RT-qPCR and Western-blotting. The effects of EGR1 on U251 cells, U251 stem-like cells (GSCs), and U87 cells proliferation were assessed using in vitro and in vivo cell proliferation assays. The specific binding between EGR1 and CCND1 promoter was confirmed by CHIP assay. EGF was used to improve EGR1 expression in this assay. RESULTS: EGR1 expression levels in human gliomas are decreased compared with normal brain tissues, however, the patients with low EGR1 expression level showed significantly enhanced patient survival in all glioma patients. EGR1 silencing inhibited proliferation and induced G1 phase arrest in glioma cells. EGR1 contributed to proliferation by directly raising CCND1. Meanwhile, EGR1 overexpression induced by EGF was able to promote the proliferation of glioma cells. CONCLUSIONS: Our results show that stable knockdown EGR1 would inhibit glioma proliferation. The results suggest EGR1 showing lower expression in cancer tissues compared with normal tissues maybe still play an important role in tumor proliferation.

A regulatory loop involving miR-29c and Sp1 elevates the TGF-ß1 mediated epithelial-to-mesenchymal transition in lung cancer.

Specificity protein1 (Sp1) is required for TGF-ß-induced epithelial-to-mesenchymal transition (EMT) which has been demonstrated to aggravate the progression of cancer including lung cancer. microRNA-29c (miR-29c) is identified to inhibit EMT, but the correlation between miR-29c and Sp1 in human lung cancer remain incompletely clarified. Here, we confirmed decreased expression of miR-29c and enhanced expression of Sp1 in lung cancer tissues (n = 20) and found that Sp1 could be targeted and inhibited by miR-29c. Besides, the expression of miR-29c was down-regulated in high-metastatic lung cancer cell lines and TGF-ß1-treated cells. The inhibition of miR-29c or overexpression of Sp1 in 95C and A549 cells dramatically enhanced the cell migration and invasion, and also induced the decrease in the expression of epithelial markers, e.g. thyroid transcription factor 1 (TTF-1) and E-cadherin, together with an increase in mesenchymal markers including vimentin, α-smooth muscle actin (α-SMA), which could be restored by overexpression of miR-29c mimics during the TGF-ß-induced EMT. Moreover, dual-luciferase reporter assay was performed and the results indicated that miR-29c/Sp1 could form an auto-regulatory loop with TGF-ß1, which impaired TGFB1 transcription. Furthermore, miR-29c overexpression could abrogate the tumor progression and inhibit the Sp1/TGF-ß expressions in vivo, indicating that miR-29c could be a tumor suppressor and repress the Sp1/TGF-ß axis-induced EMT in lung cancer.

Gastric tumor-initiating CD44+ cells and epithelial-mesenchymal transition are inhibited by γ-secretase inhibitor DAPT.

It has been proposed that the Notch signaling pathway may serve a pivotal role in cellular differentiation, proliferation and apoptosis. However, the function of Notch signaling in gastric cancer stem cells (GCSCs) is largely unknown. The present study aimed to delineate the role of the Notch1 pathway in GCSCs and during epithelial-mesenchymal transition (EMT). Flow cytometry was used to isolate CD44+ cells from the human gastric cancer cell line, MKN45. CD44+ cells displayed the characteristics of CSCs and exhibited higher Notch1 expression compared with CD44- cells. To investigate the role of the Notch1 pathway in GCSCs, CD44+ cells were treated with the γ-secretase inhibitor DAPT. DAPT treatment inhibited the expression of the Notch1 downstream target Hes1 and EMT markers, suppressed the properties of CSCs and impaired the invasion and proliferation capabilities of CD44+ cells. In addition, intraperitoneal treatment with DAPT effectively inhibited the growth of CD44+ cell xenograft tumors. The present study indicated that CD44+ GCSCs possess the characteristics of CSCs and that the Notch1 pathway serves a critical role in the maintenance of CSCs and EMT.

Silencing of RegIV by shRNA causes the loss of stemness properties of cancer stem cells in MKN45 gastric cancer cells.

Regenerating islet-derived family member 4 (RegIV) is overexpressed in several types of tumours, including pancreatic and gastric cancer (GC). However, the role it plays in gastric cancer stem cells (GCSCs) remains unknown. The present study tested the hypothesis that the silencing of RegIV by shRNA in GC cells may cause the loss of their stemness properties, indicating the inhibition of growth, proliferation and increased sensitivity to chemoradiation-induced cell death. MKN45 poorly differentiated human GC cells were propagated as mammospheres in stem cell culture conditions. Mammospheres were identified as CSCs using generally acknowledged CSC markers such as CD44. A panel of 21-nucleotide shRNAs were designed to target RegIV gene expression. Several shRNA constructs were identified that led to significant reduction in RegIV mRNA expression. Furthermore, the stemness properties of control mammospheres and RegIV knockdown mammospheres were compared by tumourigenicity assay in vivo and plate colony formation assay in vitro. Finally, we evaluated the treatment response in both mammospheres which underwent chemoradiation. The knockdown expression of RegIV by shRNA deprived CSCs of their stemness properties and increased the effectiveness of cell killing following chemoradiation. Inhibition of endogenous RegIV expression may be a new therapeutic strategy for human GC.

CD44+ gastric cancer cells with stemness properties are chemoradioresistant and highly invasive.

CD44 has been confirmed as a cancer stem cell marker in a variety of human cancer cell lines and primary tumours, but whether this marker is applicable to gastric cancer (GC) remains unknown. The responses of CD44+ GC stem-like cells to chemoradiation and the roles they play in cancer invasion are not well understood. In the present study, cell sorting was applied to the poorly differentiated human GC cells to isolate a pure concentration of the CD44+ cell populations (<1% CD44- cells). The stemness properties of the CD44+ cell population were confirmed by two 'gold standard' methods; an in vivo tumourigenicity assay and an in vitro spheroid colony formation assay. In addition, the treatment response was evaluated in CD44+ and CD44- cell fractions that underwent chemoradiation. In general, CD44+ stem-like cells tended to respond more poorly to chemoradiation than their non-stem-like counterparts. Further experimentation revealed that the CD44+ stem-like cells that recorded positive scores in the migration and invasion assay in vitro formed invasive tumours in vivo. Therefore, we hypothesized that CD44+ stem-like cells may significantly express invasion-associated genes. Consistent with this prediction, increased expression of the cancer invasion-related genes matrix metalloproteinase (MMP)-1, MMP-2, epidermal growth factor receptor (EGFR) and cyclooxygenase 2 (COX-2) were detected in the CD44+ stem-like cells. To the best of our knowledge, this is the first study that reveals the correlation between CD44+ GC cells and cancer invasion. By selectively eliminating CD44+ stem-like cells, it may be possible to treat patients with aggressive, non-resectable GCs, as well as preventing the tumours from metastasizing.

Activation of the phosphorylation of ATM contributes to radioresistance of glioma stem cells.

Ionizing radiation (IR) is currently the most efficient therapy available for malignant glioma. Unfortunately, this strategy is palliative due to the characteristics of radioresistance of malignant glioma. The aim of our study was to compare glioma stem cells (GSCs) with glioma cells (GCs) to determine whether GSCs are responsible for the radioresistance phenotype and to elucidate whether cell cycle checkpoint proteins are responsible for the radioresistance of GSCs. In this study, CD133 (a marker of brain cancer stem cells) and nestin were co-expressed in GSCs isolated from GCs. The percent of CD133+ cells in GSCs and GCs were >80 and <2%, respectively. Significantly more GSCs survived following 2, 4, 6 and 8 Gy IR than GCs. IR kills cancer cells primarily through DNA double-strand breaks (DSBs). The neutral comet assay is often used to intuitively show the level of DSBs. Significantly fewer GSCs showed DNA damage than GCs following 2 Gy IR. This demonstrated that GSCs are more resistant to in vitro radiation than GCs. Furthermore, activated ataxia telangiectasia mutated (ATM) is essential for the activation of downstream effector kinases, such as checkpoint kinase 2 (Chk2) and p53 which mainly contribute to the proper regulation of IR-induced arrest in the G1 phase. DNA damage induced by IR potently initiated activation of phosphorylation of the ATM, p53 and Chk2 checkpoint proteins. Activation of the phosphorylation of these checkpoint proteins was significantly higher in the GSCs compared to GCs. We found that inhibition of ATM activation induced cell cycle checkpoint defects and increased the rate of apoptosis of GSCs following IR. Our results suggest that GSCs were more resistant to radiation compared to GCs due to high expression of phosphorylated cell cycle checkpoint proteins, and inhibition of ATM could significantly reduce the radioresistance of GSCs and GCs. ATM may represent a source of radioresistance in GSCs and a target of improved radiosensitivity of GSCs.

Effects of berberine against radiation-induced intestinal injury in mice.

PURPOSE: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. METHODS AND MATERIALS: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-alpha, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT. The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. RESULTS: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-alpha, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonaldehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). CONCLUSION: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.

Knockdown of STAT3 expression by RNAi suppresses growth and induces apoptosis and differentiation in glioblastoma stem cells.

Glioblastoma is a highly lethal brain tumor of the human primary nervous system tumors. Previous studies demonstrated that glioblastoma stem cells were able to initiate and reform the original cancer. In this study, we found that there were expression and activation of STAT3, a key signal transduction factor and oncoprotein, in human glioblastoma stem cells (GSCs). STAT3 plays a key role in proliferation, apoptosis and differentiation in embryonic stem cells and several cancer types. To investigate the effects of STAT3 on human GSCs, the expression and activation of STAT3 were suppressed by RNAi mediated with lentivirus. We demonstrated that siRNA of STAT3 significantly suppressed STAT3 expression and activation and resulted in inhibition of cell growth in GSCs. Knockdown of STAT3 induces apoptosis and reduces significantly expression of Bcl-2 and cyclin-D in human primary GSCs, whereas no significance was achieved in BAX and caspase-3 expression. Inhibition of STAT3 expression is associated not only with decreasing of CD133+ cell proportion and increasing of GFAP and MBP expression, but also with decrease of the capacity to initiate a tumor in human primary GSCs. Together, these studies suggest that STAT3 is an important target for human GSCs in regulation of GSCs growth, apoptosis, differentiation and tumorigenic potential.

Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy.

Radiation-induced acute intestinal symptoms (RIAISs) are the most relevant complication of abdominal or pelvic radiation. Considering the negative impact of RIAIS on patients' daily activities, the preventive effects of berberine on RIAIS in patients were investigated. Thirty-six patients with seminoma or lymphomas were randomized to receive berberine oral (n = 18) or not (n = 18). Forty-two patients with cervical cancer were randomized to a trial group (n = 21) and control group (n = 21). Radiotherapy used a parallel opposed anterior and posterior. 300-mg berberine was administered orally three times daily in trial groups. Eight patients with RIAIS were treated with 300-mg berberine three times daily from the third to the fifth week. Toxicities, such as fatigue, anorexia/nausea, etc., were graded weekly according to CTC version 2.0. Patients with abdominal/pelvic radiation in the control group showed grade 1 fatigue, anorexia/nausea, colitis, vomiting, proctitis, weight loss, diarrhea and grade 2 anorexia/nausea, fatigue. Only grade 1 colitis, anorexia/nausea, and fatigue were seen in patients of abdominal radiation treated with berberine. Grade 1 fatigue, colitis, anorexia/nausea, and proctitis occurred in patients of pelvic radiotherapy treated with berberine. Pretreatment with berberine significantly decreased the incidence and severity of RIAIS in patients with abdominal/pelvic radiotherapy when compared with the patients of the control group (P < 0.05). RIAIS were reduced in patients with abdominal radiotherapy/pelvic radiation after receiving berberine treatment. Berberine significantly reduced the incidence and severity of RIAIS and postponed the occurrence of RIAIS in patients with abdominal or whole pelvic radiation.

Autocrine factors sustain glioblastoma stem cell self-renewal.

Glioblastoma stem cells are able to reform original glioblastoma and express the neural stem cell marker CD133 and Nestin. They can self-renew and proliferate in tumor sphere medium containing EGF, bFGF and LIF that is known to be permissive for stem cell proliferation. In this study, we found that neurosphere-like colonies appeared after the human primary glioblastoma cells had been switched into pure DMEM/F12 medium. We investigated whether tumor spheres formed in pure DMEM/F12 medium possess the characteristics of glioblastoma stem cells. We identified that the tumor sphere cells were cancer stem cells of glioblastoma and they can self-renew and proliferate in pure DMEM/F12 medium. Glioblastoma cells can secrete several factors that result in autocrine motility signaling and stimulate glioma invasion. We hypothesized that an essential autocrine signal promotes the self-renewal and proliferation of human glioblastoma stem cells in pure DMEM/F12 medium. Then, expression of EGF and bFGF in glioblastoma stem cells were analyzed. Both the mRNA and protein of EGF and bFGF were detected in three human glioblastoma stem cells. Our findings suggest that autocrine of EGF and bFGF may sustain the self-renewal of glioblastoma stem cells.

STAT3 silencing with lentivirus inhibits growth and induces apoptosis and differentiation of U251 cells.

Glioblastoma multiforme (GBM), the most common type of central nervous system tumor in humans, is highly proliferative and resistant to apoptosis associated with genetic mutations that deregulate cell cycle. Signal transduction and activation of transcription 3 (Stat3) is a key signal transduction protein that mediated signaling by cytokines and contributed to oncogenesis. It is constitutively activated in numerous cancers including glioblastoma. To determine the effect on proliferation and differentiation of glioblastoma U251 cells after inhibiting STAT3 expression by RNAi, STAT3 gene was silenced with lentivirus vector in U251 cells. We demonstrate that a lentivirus-based shRNA vector had highly infecting efficiency to U251 cells and lentivirus vector-mediated RNAi significantly suppressed Stat3 expression and activation in U251 cells. Knockdown of STAT3 expression by RNAi suppressed the growth and induced apoptosis of U251 cells by down-regulating expression of Bcl-2. It was found that the cell proportion of G0/G1 phase significantly increased after silencing Stat3 by down-regulating expression of cyclin D1. Knockdown of Stat3 also induces morphological changes of U251 cell. It increases significantly expression of myelin basic protein (MBP) in U251 cells. This study demonstrates that STAT3 silencing with lentivirus effectively inhibits STAT3 gene expression and activation. Stat3 is associated with the survival, growth and differentiation of U251 cells. Lentivirus vector-mediated RNAi may be serve as a novel therapeutic strategy for treatment of GBM with expression constitutively and activation of STAT3 gene.

[Expression of nuclear export factor CRM1 and p27 in glioma].

OBJECTIVE: To investigate the expression of nuclear export factor CRM1, Ser10-phosphorylated p27 and p27 in human gliomas. METHODS: The expression of CRM1, Ser10-phosphorylated p27 and p27 were investigated in 70 cases of human gliomas and 10 specimens of the normal brain tissue by immunohistochemical technique and Western blot. RESULTS: There were significant differences on the expression levels of CRM1, Ser10-phosphorylated p27 and p27 among normal brain tissue, gliomas of grades II and gliomas of grades III plus IV (P < 0.01). The expression of CRM1 in gliomas was inversely correlated with the expression of p27 (r(s) = -0.727, P < 0.01) and positively correlated with the expression of Ser10-phosphorylated p27 (r(s) = 0.954, P < 0.01) and Ki-67 (r(s) = 0.799, P < 0.01). Moreover, the expression of Ser10-phosphorylated p27 was inversely correlated with p27 (r(s) = -0.744, P < 0.01) and positively correlated with Ki-67 (r(s) = 0.785, P < 0.01). CONCLUSIONS: CRM1, through recognizing and binding with Ser10-phosphorylated p27, may promote moving of p27CRM1 from its original locating sites; act as a critical signaling component in the proliferative process of glioma cells and then, plays an important role in the development of gliomas.

[A randomized phase II trial of docetaxel and doxorubicin in treatment for patients with non-small-cell lung cancer who have failed previous platinum-based chemotherapy].

OBJECTIVE: The aim of this study was to evaluate the efficacy, toxicity and safety of doxorubicin combined with domestically produced docetaxel versus with taxotere, and to investigate whether these two regimens result in similar outcomes in the treatment for non-small-cell lung cancer (NSCLC) patients who failed previous platinum-based chemotherapy. METHODS: Eighty-eight NSCLC patients were enrolled into this clinical phase II trial. The patients randomly received either domestic docetaxel (study arm) or taxotere (control arm) at a dose of 70 mg/m2 on D2, while doxorubicin at a dose of 40 mg/m2 on D1 was administered in both groups. It was repeated every 3 weeks, totally for three cycles. No granulocyte colony-stimulating factor was used to prevent granulocytopenia. The response rate and toxicity were evaluated using World Health Organization toxicity scale and Karnofsky performance status scale. RESULTS: Of the 88 patients, 81 were evaluable in terms of efficacy. There was no complete responder in this series. The response rate (RR) was 17.1% in the study arm versus 7.5% in the control arm, and the clinical benefit rate (CBR) was 80.5% in the study group versus 72.5% in the control group. The most frequent grade 3 or 4 toxicities were neutropenia, leucopenia and gastrointestinal symptoms. Other toxicities such as alopecia and vomiting were mild and generally well tolerated. No fluid retention was noticed. CONCLUSION: The administration of doxorubicin 40 mg/m2 on D1 combined with domestic docetaxel 70 mg/m2 on D2 is proved to be as effective and tolerable as with taxotere. The domestic drug docetaxel may be considered as an alternative for patients with non-small-cell lung cancer who failed previous platinum-based chemotherapy.

Generation of rat monoclonal antibodies against murine LAIR-1.

The leukocyte-associated Ig-like receptor 1 (LAIR-1), an inhibitory receptor bearing two immunoreceptor tyrosine-based inhibitory motifs (ITIM), is expressed on the majority of peripheral leukocytes, including NK cells, T cells, B cells, monocytes, dendritic cells, granulocytes, and thymocytes and is involved in immunologic regulation and hematopoiesis. Murine LAIR-1 (mLAIR-1) is the homolog molecule of human LAIR-1. Using mLAIR-1-Fc as the immunogen and the technique of rat B lymphocyte hybridoma, we raised three hybridoma cell lines secreting monoclonal antibodies (MAb) to mLAIR-1, designated FMU-mLAIR-1.1, -1.2, and -1.3. Rat immunoglobulin class and subclass of the MAb FMU-mLAIR-1.1 approximately 3 were determined to be IgM, IgG1, and IgM, respectively. All these MAbs can bind the mLAIR-1 in immunocytochemistry and immunohistochemistry. FMU-m LAIR-1.2 worked well not only in Western blot assay but also in recognizing natural LAIR-1 molecules on the surface of P388D1, J774, and WEHI3 cells, and mLAIR-1 cDNA-transfected CHO cells detected by FCM. Thus, successful production of rat anti-murine LAIR-1 monoclonal antibodies provides a new powerful tool for investigation of murine LAIR-1 function in mouse model, both in vitro and in vivo.

[Correlation of hTERT expression to maspin and bFGF expression and their significance in glioma].

BACKGROUND & OBJECTIVE: Human telomerase reverse transcriptase (hTERT) is a determinant factor in telomerase activation and is related with tumorigenesis and the degree of malignancy. Its expression is regulated by many factors. This study was to detect the expression of hTERT, maspin, and basic fibroblast growth factor (bFGF) in glioma, and analyze their correlations and their significance in glioma. METHODS: The expression of hTERT, maspin, and bFGF in 128 specimens of human glioma and 8 specimens of normal brain tissue were detected by in situ hybridization and SP immunohistochemistry. H-score system of Gatalica was used for semi-quantitative evaluation. The positive rates between the 2 groups was compared with Chi(2) test. The correlations of hTERT, maspin, and bFGF expression to tumor grade were analyzed by Spearman rank correlation analysis. The correlations of hTERT expression to maspin and bFGF expression were analyzed by linear correlation. RESULTS: The positive rates of hTERT, maspin, bFGF were 51.6%, 46.9%, and 62.5% respectively in gliomas, and 0, 87.5%, and 0 in normal brain tissues. In the 43 specimens of grade II, 55 specimens of grade III and 30 specimens of grade IV gliomas, the positive rates of hTERT were 32.6%, 54.5%, and 73.3% (P < 0.05); the positive rates of maspin were 58.1%, 49.1%, and 26.7% (P < 0.05); the positive rates of bFGF were 39.5%, 72.7%, and 76.7% (P < 0.05).The expression of hTERT and bFGF were positively correlated to pathologic grade (rho=0.515, P < 0.01; rho=0.611, P < 0.01), while the expression of maspin was negatively correlated to pathologic grade (rho=-0.425, P < 0.05). hTERT expression was negatively correlated to maspin expression (r=-0.658, P<0.01), but positively correlated to bFGF expression (r=0.627, P < 0.01); maspin expression was negatively correlated to bFGF expression (r=-0.501, P < 0.01). The expression of hTERT showed no relationship with the age, sex, tumor size, and cell density (P > 0.05), but had obvious relationship with karyokinesis, vessel density, and necrosis (P < 0.05). CONCLUSION: The expression of hTERT, maspin and bFGF correlate to each other, and associate with the malignant degree of glioma.

[Docetaxel in the treatment of advanced breast cancer ].

OBJECTIVE: To evaluate the efficacy, toxicity and safety of an new domestic docetaxel in the treatment of pretreated advanced breast cancer. METHODS: Fourty-four breast cancer patients who had failed in first-line chemotherapy were included in this trial. They received docetaxel as the second-line chemotherapy. Docetaxel was administered alone at a dose of 70 mg/m2 every 3 weeks. The use of granulocyte colony-stimulating factor to prevent granulocytopenia was not permitted. The response rate and toxicity were evaluated by World Health Organization toxicity scale and performance status by Karnofsky scale. RESULTS: Of the 41 evaluable patients, 4 achieved complete response and 14 partial remission, with a response rate and clinical benefit rate of 43.9% and 85.4%, respectively. Grade 3 or grade 4 neutropenia developed in 42.9%, alopecia in 7.1% and vomiting in 4.8% of these patients. Fluid retention was not observed in this series. CONCLUSION: Three-week administration of docetaxel alone at a dose of 70 mg/m2 is effective and tolerable. It provides an alternative for the pretreated advanced breast cancer patients.

[Detection of proinflammatory cytokine levels in sera from patients with Kaschin-Beck disease].

AIM: To explore the role of proinflammatory cytokines (TNF, IL-1beta and IL-6) in the pathogenesis of Kaschin-Beck disease (KBD). METHODS: The levels of serum TNF, IL-1beta and IL-6 from 62 KBD patients and 60 healthy persons were detected by double antibody sandwich ELISA. RESULTS: The levels of serum IL-1beta and IL-6 in KBD patients were (238.4+/-698.5) ng/L and (164.4+/-661.4) ng/L, respectively, but they were higher than those in healthy persons, being (74.5+/-130.0) ng/L and (52.2+/-154.6) ng/L, respectively. There were no significant differences between them (P>0.05). However, the level of serum TNF in KBD patients [(109.2+/-145.3) ng/L] was significantly higher than that in healthy persons [(40.9+/-89.7) ng/L] (P<0.01). Moreover, there was no correlation between serum TNF and IL-1beta levels (r=0.0387, P>0.05) and TNF and IL-6 in KBD patients (r=0.2135, P>0.05), but there was positive correlation between serum IL-1beta and IL-6 levels (r=0.346, P<0.01). CONCLUSION: The elevated proinflammatory cytokine levels in sera may relate to the pathogenesis of Kaschin-Beck disease.

[Gene transfection of Livin isoforms into A549 cell line and its effect on cell growth and sensitivity to chemotherapy and radiotherapy].

OBJECTIVE: To express Livin alpha & beta in A549 cells by using gene transfection, and to observe its effect on cell growth and cell sensitivity to chemotherapy drugs and radiation. METHODS: Eukaryotic expression vectors of Livin alpha & beta were transfected into A549 cells and cell clones with stable expression were obtained. Livin alpha & beta expression levels in the transfected A549 cells were assessed at mRNA level and protein level, respectively. Cell growth status was assessed by biological features. MTT was performed to test effects of Livin on sensitivity of the A549 cells to chemotherapy drugs and radiation, and cell cycle analysis was performed to evaluate cell apoptosis. RESULTS: After transfection, positive cells, especially A549 cells expressing Livin, showed an increase of about 20% in colony-forming ability, a shorter doubling time (P < 0.05) and lower sensitivity to chemotherapy drugs and radiation (P < 0.01). Only 0.2% of the cells committed apoptosis with 10 Gy radiation. CONCLUSION: Livin isoforms, especially Livin alpha, are implicated in genesis and development of lung cancer, thus may be an important mechanism for drug resistance of lung cancer cells.