Nasopharyngeal carcinoma derived exosomes regulate the proliferation and migration of nasopharyngeal carcinoma cells by mediating the miR-99a-5p BAZ2A axis

Abstract Objectives Nasopharyngeal Carcinoma (NPC) is a common malignant tumor of nasopharyngeal mucosal epithelium in clinical practice. Radiotherapy and chemotherapy are the main treatment methods at present, but the therapeutic effect is still unsatisfactory. Studies have shown that exosomes and microRNAs (miRNAs) play an important role in the development of cancer. Therefore, this study aimed to investigate the effects of NPC derived exosomes on NPC and their molecular mechanisms. Methods Serum was collected from healthy subjects, Epstein-Barr Virus (EBV) infected patients and NPC patients (n = 9 group) and exosomes were extracted separately. High-throughput sequencing of exosomes was performed to screen differentially expressed miRNAs. The function of the screened miRNA was identified by treating NPC cells with exosomes. The target gene of miRNA was identified using the dual-luciferase assay. Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) was used to determine the levels of miR-99a-5p and Bromodomain Adjacent Tozinc finger domain protein 2A (BAZ2A). Cell Counting Kit-8 assay, flow cytometry, and wound healing assay were utilized to detect cell viability, cell cycle and apoptosis, and migration ability. The protein levels were evaluated by Western blot. Results MiR-99a-5p was identified as the most significant differentially expressed miRNA in exosomes (p< 0.05). The proliferation and migration of NPC cells were extremely facilitated by exosomes, accompanied by the suppressed apoptosis, upregulated BAZ2A, Monocyte Chemotactic Protein-1 (MCP1), and Vascular Endothelial Growth Factor A (VEGFA), and downregulation of Interleukin (IL)-1β and Nuclear Transcription Factor-κB (NF-κB) (p< 0.05). BAZ2A was a target gene of miR-99a-5p. Furthermore, the regulatory effect of exosomes on the proliferation, migration, and apoptosis was significantly abolished by overexpression of miR-99a-5p or downregulation of BAZ2A (p< 0.05). Conclusion NPC derived exosomes facilitated the proliferation and migration of NPC through regulating the miR-99a-5p/BAZ2A axis.

Efficacy and safety of neoadjuvant chemotherapy combined with PD-1 antibody for esophageal squamous cell carcinoma in the real world / 中华肿瘤杂志

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.

A study of the effect of changes in nasal tip prominence on the sense of anterior prominence of the upper lip / 口腔疾病防治

Objective@#The aim of this study was to investigate the effect of changes in nasal tip protrusion on the sense of upper lip protrusion in different populations and to provide a reference for the improvement of soft tissue beauty.@*Methods @# Informed consent and portrait authorization were obtained from the model. A female model whose face met the criteria was selected, and a 3D model of her was obtained using a 3D stereo camera. Based on the original model, ZBRUSH2019 software was used to simulate changes in nose tip protrusion. Then, 9 segments of facial dynamic rotation videos were produced, and an electronic questionnaire was created through a questionnaire website to evaluate the effect of different nose tip protrusions on perceived upper lip protrusion. Randomly selected orthodontic patients, orthodontics professionals and general adults completed the electronic questionnaire. In the questionnaire, a Visual Analog Scale was used to evaluate the perceived degree of protrusion of the upper lip. The higher the score, the more prominent the upper lip of the model in the image. The questionnaire data were statistically analyzed using a generalized linear mixed model. @*Results @#As the nasal tip position became progressively more retracted, the subjects' upper lip protrusion scores increased. Among male subjects, the results showed that the general population thought that the upper lip protrusion was higher than the patients did when the nasal tip protrusion was +6 mm and +4.5 mm (P = 0.023, P = 0.047). When the nasal tip protrusion was +6 mm, the scores of the general population were higher than those of the orthodontics professionals (P = 0.023). However, when the nasal tip variable was -6 mm, their score was lower than that of the patients (P = 0.003), and there was no significant difference in other retest distances between groups (P>0.05).@*Conclusion @#When the protrusion of the nasal tip decreased, the three groups experienced a visual illusion of upper lip protrusion. When the nasal tip protrusion is too large, the general population perceived the visual illusion of the upper lip protrusion as being more obvious.

Preparation of Juglone-loaded PLGA Nanoparticles and Its Anti-tumor Effect on Melanoma A375 Cells in Vitro / 中国实验方剂学杂志

Objective: To prepare Juglone-loaded poly lactic-co-glycolic acid nanoparticles (Jug-PLGA-NPs), and investigate their physicochemical properties, release characteristics in vitro and anti-tumor activities on A375 melanoma cells in vitro. Method: Jug-PLGA-NPs were prepared by emulsification-solvent evaporation method. Then the particle size, encapsulation efficiency, drug loading rate and in vitro release characteristics were investigated. Fluorescence microscopy was used to observe the uptake of PLGA-NPs in vitro. The distribution of PLGA-NPs in BALB/c nude mice after tail vein injection was observed by the small living animal imaging system. Their inhibition effect on proliferation of A375 cells was detected by thiazolyl blue tetrazolium bromide (MTT) assay. Apoptosis rate and cell cycle detection were performed by flow cytometry. Western blot was used to determine the protein kinase B (Akt), phosphorylated Akt (p-Akt) and cyclinD1. Result: The average particle size of the prepared Jug-PLGA-NPs was (149.6±21.5) nm, entrapment rate of (68.39±2.51)%, and drug-loading rate of (5.07±0.98)%, showing good sustained-release characteristics. PLGA-NPs showed good penetration and targeting properties in cellular uptake in vitro and in vivo imaging. Different concentrations of Jug-PLGA-NPs could significantly inhibit the proliferation and promote apoptosis of A375 cells in a time and concentration dependent manner (P1 expression (P0/G1 phase (PConclusion: The Jug-PLGA-NPs are easy to prepare and have good sustained-release characteristics, tumor targeting and anti-tumor ability, providing a new pharmaceutical dosage form for the future clinical application of Jug.

The application progress of tumor radiotherapy in combination with immune checkpoint blockade / 医学研究生学报

Nowadays, it has been widely reported that radiotherapy can synergize with immune checkpoint blockade to improve antitumor efficacy, which shows significant advantages in clinical practice. The value of radiotherapy combined with immune checkpoint blockade therapy mainly lies in three aspects: improved local tumor control, stimulation of systemic immune response to induce abscopal effect and the elimination of acquired immunological tolerance to fractionated radiotherapy. Further research shows that radiotherapy combined with multiple checkpoint blockade, costimulatory molecules agonist, checkpoint gene knockout will contribute to the improved antitumor effect of the combined treatment model. Thus, this article reviewed the immunoregulation characteristics of tumor radiotherapy as well as the application status and research progress of tumor radiotherapy in combination with immune checkpoint blockade.

Application of self-made fine-tuning device in distal locking process of femoral interlocking intramedullary nail / 中国骨伤

OBJECTIVE@#To evaluate the curative efficacy of self-made fine-tuning setting in the process of femoral distal implantation of intramedullary nail.@*METHODS@#From October 2015 to October 2017, 66 cases of femoral shaft fracture were treated with anterograde interlocking intramedullary nail including 45 males and 21 females with a mean age of(37.21±11.18) years old. Among them, 36 cases were treated with the manufacture's aiming device and self-made fine-tuning setting (research group), other 30 cases were treated with the manufacture's aiming device(control group). The mean operation time, the times of C-arm scan in surgery, the post-operation complications and the fracture union were observed and compared in two groups.@*RESULTS@#Sixty-two cases acquired 8 to 15 months with a mean time of 12.4 months follow-up visit. The post-operation complications and the fracture union between the two groups had no significant difference(>0.05), the mean operation time and the times of C-arm scan in surgery had statistically significant difference(<0.05).@*CONCLUSIONS@#Self-made fine-tuning setting in the process of femoral interblocking intramedullary nail could shorten operation time and reduce the the times of C-arm scan.

Changes of T Lymphocyte Subsets and Immunoglobulin in Peripheral Blood of Patients with ALL and N-ALL before and after Treatment and their Value for Monitoring of Disease and Evaluation of Prognosis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the changes of T lymphocyte subsets and immunoglobulin in peripheral blood of patients with acute lymphoblastic leukemia (ALL) and non-acute lymphocytic leukemia (N-ALL) before and after treatment and their value for monitoring of disease and evaluation of prognosis.</p><p><b>METHODS</b>One hundred and six cases of leukemia were selected in our hospital, including 48 cases of ALL (ALL group) and 58 cases of N-ALL (N-ALL group); 54 peoples of normal physical examination were selected as the normal control group in the same period. The IgA, IgG and IgM levels of peripheral blood were detected, and the absolute value of T lymphocyte subsets was determined by cell slide method. According to whether the patients' status was improved or not by treatment, the 106 patients were divided into the unimproved group (55 cases including 25 ALL, 30 N-ALL) and improved group (51 cases including 23 ALL, 28 N-ALL).</p><p><b>RESULTS</b>The levels of IgA, IgG and IgM in 106 cases of leukemia were significantly lower than those in the control group (all P<0.05), and the CD3level, CD3CD4/CD3CD8ratio and the absolute value of CD3CD4T cells in the peripheral blood were significantly lower than those in the control group(all P<0.05); the absolute value of CD3CD8T cells showed no significant difference in comparison with the control group (P >0.05). After treatment, IgA,IgG and IgM levels in the improved group were significantly higher than those before therapy (all P<0.05), while their levels were not significantly different from that in the control group (all P>0.05); the CD3level, CD3CD4/CD3CD8ratio and the absolute value of CD3CD4T cells in the peripheral blood were significantly higher than those before therapy (all P<0.05), while those were not significantly different from the control group (all P>0.05). Compared with levels before treatment, the levels of above mentioned indicators in the unimproved group after treatment were not significantly different (all P>0.05); and the CD3level, CD3CD4/CD3CD8ratio and the absolute value of CD3CD4T cells were significantly lower than those in the control group (all P<0.05), and the absolute value of CD3CD8T cells were higher than that in the control group (P<0.05).</p><p><b>CONCLUSION</b>After the treatment, the T lymphocyte subsets (CD3, CD3CD4T cells) and immunoglobulin (IgA, IgG, IgM) levels in peripheral blood of patients with ALL and N-ALL have been improved significantly, and the detection of these indexes is helpful for disease monitoring and prognosis evaluation.</p>

Percutaneous mechanical thrombectomy with subsequent iliac vein stent implantation accomplished by single-procedure for acute deep venous thrombosis of lower extremity: preliminary results in 12 cases / 介入放射学杂志

Objective To evaluate the feasibility,safety and effectiveness of percutaneous mechanical thrombectomy (PMT) and iliac vein stent implantation which are accomplished by single-procedure in treating acute deep venous thrombosis (DVT) of lower extremity.Methods During the period from December 2014 to January 2016,a total of 12 patients with acute DVT of lower extremity,including 3 males and 9 females with a mean age of (50.42±16.21) years old,were admitted to authors' hospital to receive treatment.Clinically,all patients presented with left leg swelling and pain.Central type of DVT was seen in 3 patients and mixed type of DVT was found in 9 patients.Preoperative placement of inferior vena cava filter was employed in all patients,which was retrieved after the treatment.PMT by using Angio Jet thrombus removal catheter,balloon angioplasty,and iliac vein stent implantation were successively carried out during the same procedure.When residual thrombus was identified on checkup angiography the catheter sheath would be reserved,and the thrombolytic therapy would be adopted.The patients were followed up at outpatient clinic at one,3,6 and 12 months after the treatment,and reexamination of color ultrasound and/or lower limb venography was used to assess the blood flow in the deep veins and in the stents.Results The combination of several therapies was accomplished in a single procedure,the technical success rate was 100％.The used time for the operation was 60-110 minutes,with a mean of (96.25±14.32) minutes.The used time for thrombus aspiration was 51-280 seconds,with a mean of (199.92±74.89) seconds.Thrombus clearance rate of grade Ⅲ was obtained in 10 patients,and thrombus clearance rate of grade Ⅱ was seen in 2 patients;the clinical symptoms were improved in all patients.Except some patients complained of different degrees of pain during the performance of balloon dilatation of left common iliac vein,no serious complications such as pulmonary embolism,severe hemorrhage,etc.occurred.The patients were followed up for (5.58±2.75) months;color ultrasound and/or lower limb venography performed in 11 patients showed that the blood flow in deep veins and iliac vein stents was unobstructed,and relapse of DVT was observed in one patient with cerebral astrocytoma.Conclusion For the treatment of DVT of lower extremity,PMT combined with iliac vein stent implantation that is accomplished by single-procedure is safe and feasible,its preliminary clinical results are satisfactory.

Evaluation for preparation and anticancer efficacy in vitro of drug-loaded nanoerythrosomes / 中国中药杂志

The objective of this study is to develop a new-type biodegradable, biocompatible curcumin-loaded nanoerythrosomes (Cur-RBC-NPs) by means of the sonication method. The size of Cur-RBC-NPs was optimized by varying drug loading parameters. The morphology, size distribution, stability, in vitro release pattern, cellular uptake of nanoparticles and in vitro anti-tumor effects were evaluated, respectively. The results showed the prepared Cur-RBC-NPs were nearly uniform spheres, with an average diameter of (245.7 ± 1.3) nm. Encapsulation efficiency (EE) and load efficiency (LE) of Cur-RBC-NPs were 50.65% ± 1.36% and 6.27% ± 0.29%. And the nanoparticles had a good sustained release property. According to the in vitro experiment, Cur-RBC-NPs were effectively taken in by tumor cells, and exhibited a significant anti-tumor effect. In conclusion, the method for preparing Cur-RBC-NPs is convenient, with a good sustained release behavior and anti-tumor efficacy, and so expected to be a new-type nano-drug delivery system in clinical practice.

Generation and comparison of two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To generate two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer and to compare their biological properties.</p><p><b>METHODS</b>The genetically engineered mice previously developed with mouse mammary tumor virus (MMTV) promoter driven expression of activated ErbB2/Neu and recombinant Cre (FVB/N-MMTV-NIC) were interbred with Flox-PTEN mice; and FVB/N-ErbB2KI mice, harboring endogenous promoter driven activated ErbB2/Neu expression, FVB/N-MMTV-Cre mice and the flox-PTEN mice were interbred. Neu, Cre and PTEN genes were amplified by PCR for genotyping of the offsprings. ErbB2/Neu and PTEN expression in mammary tumors were detected by immunohistochemistry. Tumor formation time, tumor number, histopathology and lung metastasis were compared between two models, Ki-67 expression was detected by immunohistochemistry, and TUNEL staining of tumor tissues was performed.</p><p><b>RESULTS</b>Two genetically engineered mouse models of ErbB2/Neu positive-PTEN homozygous deficient breast cancer were generated. The models were confirmed by genotyping and immunohistochemistry. One model with exogenous MMTV promoter driven expression of activated ErbB2/Neu and Cre coupling PTEN disruption was designated as NIC/PTEN(-/-) mice, and the other with MMTV-Cre induced endogenous promoter driven expression of activated ErbB2/Neu with PTEN disruption was designated as ErbB2KI/PTEN(-/-) mice. The tumor formation time in NIC/PTEN(-/-) mice was significantly shorter than that of ErbB2KI/PTEN(-/-) mice (30 vs 368 d, P<0.01); the number of tumor and incidence of lung metastasis was also significantly higher in NIC/PTEN(-/-) mice (10 vs 1-2 and 75.0% vs 37.5%, respectively, Ps<0.01). The Two models displayed distinct histopathological morphology. NIC/PTEN(-/-) tumor showed more Ki-67 positive cells than ErbB2KI/PTEN(-/-) tumor did (86.9%±2.8% vs 37.4%±7.2%, P<0.01), while the amount of cell apoptosis in tumors was not significantly different between two models.</p><p><b>CONCLUSION</b>Two genetically engineered mouse models of ErbB2/Neu positive-PTEN homozygous deficient breast cancer with different phenotypes have been successfully generated, which may provide useful resource for further investigation of the initiation and progression of HER2/ErbB2 breast cancer, as well as for the development of novel prevention and treatment regimens of this malignance.</p>

Correlation between the methylation of SULF2 and WRN promoter and chemosensitivity to irinotecan in gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the relationship between SULF2 and WRN promoter methylation and chemosensitivity to irinotecan, and also the clinicopathological features in patients with gastric cancer.</p><p><b>METHODS</b>The chemosensitivity to irinotecan was tested by MTT assay. The methylation of SULF2 and WRN promoter in the fresh gastric cancer tissues was detected by methylation specific PCR. The differences of chemosensitivity and clinicopathological features of the methylation group were compared with that of the non-methylation group. The tumor growth in nude mice bearing human gastric cancer xenografts treated with CPT-11was also observed.</p><p><b>RESULTS</b>The methylation rates of SULF2 and WRN were 28.4% (29/102) and 23.5% (24/102), respectively. There were no significant association between promoter methylation and clinicopathological features of patients including age, gender, histologic type, lymphatic invasion, and TNM Stage. In all the 102 cases, there were 30 cases of irrinotecan-sensitive group, and 72 cases of the irrinotecan-resistant group. The SULF2 methylation rate was 46.7% (14/30)in the sensitive group, and 20.8% (15/72) in the resistant group (P = 0.008),The WRN methylation rate was 33.3% (10/30) in the sensitive group, and 19.4% (14/72) in the resistant group (P = 0.214). Gastric cancer tissues were more sensitive to irrinotecan when both the genes were methylated. The nude mice bearing human gastric cancer xenografts with SULF2 methylation were more sensitive to irrinotecan.</p><p><b>CONCLUSIONS</b>The detection of SULF2 and WRN promoter methylation may provide evidence for screening and targeting the most sensitive gastric cancer subpopulation suitable for personalized irrinotecan chemotherapy.</p>

Clinical efficacy of electroacupuncture combined with dalitong granule for gastroesophageal reflux disease and its mechanism / 中国针灸

<p><b>OBJECTIVE</b>To observe the clinical efficacy and safety of electroacupuncture combined with Dalitong granule for gastroesophageal reflux disease and to explore the therapeutic mechanism.</p><p><b>METHODS</b>Five hundred cases diagnosed as gastroesophageal reflux disease were randomly divided into a combination group, an electroacupuncture group, a Dalitong granule group, and a western medication group, 125 cases in each group. The electroacupuncture group was treated with acupuncture at Zusanli (ST 36), Zhongwan (CV 12), Neiguan (PC 6), Tai-chong (LR 3) and Gongsun (SP 4), once daily for 6 weeks; the Dalitong granule group was treated with oral administration of Dalitong granule 6 g, three times daily; the combination group was treated with above two methods; the western medication group was treated with oral administration of Mosapride 5 mg, three times daily, Omeprazole 20 mg, twice daily and Amitriptyline 25 mg, twice daily. The total refluxing times, times of long-term reflux, percentage of upright time, percentage of supine time, percentage of total time of the 24-hour intraesophageal pH < 4 or bilirubin absorbance value (Abs) > or = 0.14, symptom score, endoscopic score, life quality score and adverse reaction were observed before treatment, at the end of treatment and 48 weeks after treatment in four groups.</p><p><b>RESULTS</b>Compared with those before treatment, esophageal acid reflux, bile reflux, endoscopic score and symptom score were decreased significantly at the end of treatment in four groups (all P < 0.01), while score of life quality was increased significantly (all P < 0.01). The improvements of above indices in the combination group were superior to other groups (all P < 0.05). Compared with the end of treatment, changes of above indices were not obvious in both of combination group and electroacupuncture group 48 weeks after treatment (all P > 0.05), but these indices all recurred significantly in other two groups (all P < 0.5). The short and long-term total effective rates in the combination group were superior to other groups (P < 0.5, P < 0.1). No serious adverse reaction occurred in four groups.</p><p><b>CONCLUSION</b>Electroacupuncture and Dalitong granule can both inhibit esophageal acid reflux and bile reflux, decrease endoscopic score, alleviate the symptom of gastroesophageal reflux and improve life quality, but the effect of combination is much better with safety and long-term efficacy, which is correlated with their acid inhibition, gastrointestinal motility and antidepressant effects.</p>

Relationship between BRCA1 mRNA expression in tumor cells from malignant effusions and chemosensitivity to cisplatin in patients with metastatic malignant effusions / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the mRNA expression of breast cancer susceptibility gene 1 (BRCA1) in tumor cells isolated from malignant pleural and peritoneal effusions, and the predictive role of BRCA1 related to the efficacy of cisplatin-based chemotherapy.</p><p><b>METHODS</b>Tumor cells were isolated from malignant pleural and peritoneal effusions of 31 cancer patients. The response of these tumor cells to cisplatin was determined by CCK8 assay. Real time quantitative RT-PCR was used to examine the BRCA1 mRNA level in the primary culture cancer cells.</p><p><b>RESULTS</b>The expression level of BRCA1 mRNA was 0.618 (0.014 - 18.063) in primary culture tumor cells. The IC(50) of DDP was 2.809 µg/ml in the primary culture tumor cells (0.118 - 19.439 µg/ml). Both BRCA1 mRNA expression and the tumor cells IC(50) of DDP were not significantly related with patient age, gender, the type of primary tumor, whether to accept the chemotherapy and effusion type (P > 0.05). The level of BRCA1 mRNA was negatively correlated with the chemosensitivity in terms of IC(50) of cisplatin (P < 0.001).</p><p><b>CONCLUSION</b>Assessment of expression level of BRCA1 mRNA may be useful in predicting the efficacy of cisplatin-based chemotherapy in patients with metastatic malignant effusions.</p>

A case of intoxication caused by aciclovir overinfusion and cured by chinese medicine / 中国结合医学杂志

ABSTRAC: The therapeutic course of an aciclovir-induced acute renal dysfunctional patients was summarized. This had been relieved through a 15-day treatment with Western medicine but with a two-week protracted low fever that was cured by the authors using Chinese medicinal herbs for supplementing qi to support essence, nourishing yin to depress fire, clearing heat, and detoxicating. For the sake of providing a reference to clinical medication, the materials used for the disease were recorded and analyzed to explore the clinical characteristics of Chinese medicine treatment and prevention of anaphylaxis responses, such as the protracted low fever after acute renal dysfunction induced by overinfused aciclovir.

Anti-angiogenic effect of vinorelbine in combination with cetuximab in vitro and in vivo / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This experiment aims to study the anti-angiogenic ability of vinorelbine combined with cetuximab in vitro and in vivo.</p><p><b>METHODS</b>Human lung adenocarcinoma A549 cells were used as control group. Proliferation of human umbilical vein endothelial cells (HUVEC) was assessed by MTT assay. Furthermore, we used Transwell chambers, capillary tube formation and flow cytometry to observe the effects of vinorelbine combined with cetuximab on HUVEC migration, tube formation and cell apoptosis, respectively. In addition, the anti-angiogenic ability of the drugs was checked using chicken chorioallantoic membrane (CAM) model.</p><p><b>RESULTS</b>The inhibitory rate of HUVEC growth was 25.8%, 39.2%, 54.0% for vinorelbine at the concentration of 0.1 ng/ml, 0.4 ng/ml, and 0.8 ng/ml, respectively; that of 0.25 microg/ml cetuximab was 19.7%, and that of 0.1 ng/ml vinorelbine + 0.25 microg/ml cetuximab, 0.4 ng/ml vinorelbine + 0.25 microg/ml cetuximab and 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 29.5%, 46.4%, 64.6%, respectively. The inhibitory rates of the drugs at the above mentioned combinations of migration and tube formation of HUVEC were 51.9%, 68.2%, 95.0%, respectively. The inhibitory rate of 0.1 ng/ml + 0.25 microg/ml cetuximab and 0.4 ng/ml vinorelbine + 0.25 microg/ml cetuximab on tube formation of HUVEC was 38.8% and 57.7%, respectively, showing a sub-additive effect, and that of combination of 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 78.9%, showing a synergistic effect. In addition, the apoptotic rate of HUVEC induced by 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 59.9%, showing a synergistic effect. The in vivo experiment also showed that the combination of the two drugs had a synergistic anti-angiogenic effect.</p><p><b>CONCLUSION</b>Both low dose vinorelbine and cetuximab have an anti-angiogenic effect in vitro and in vivo, and the combination of the two drugs has sub-additive or synergistic inhibitory effect on angiogenesis.</p>

Clinical study on the treatment of gastroesophageal reflux by acupuncture / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the clinical efficacy and safety of acupuncture in treating gastroesophageal reflux (GER).</p><p><b>METHODS</b>Sixty patients with confirmed diagnosis of GER were randomly assigned to two groups. The 30 patients in the treatment group were treated with acupuncture at acupoints Zhongwan (CV 12), bilateral Zusanli (ST36), Sanyinjiao (SP6), and Neiguan (PC6), once a day, for 1 week as a therapeutic course, with interval of 2-3 days between courses; the 30 patients in the control group were administered orally with omeprazole 20 mg twice a day and 20 mg mosapride thrice a day. The treatment in both group lasted 6 weeks. Patients' symptoms and times of reflux attacking were recorded, the 24-h intraesophageal acid/bile reflux were monitored, and the endoscopic feature of esophageal mucous membrane was graded and scored at three time points, i.e., pre-treatment (T0), immediately after ending the treatment course (T1) and 4 weeks after it (T2). Besides, the adverse reactions were also observed.</p><p><b>RESULTS</b>Compared with those detected at T0, 24-h intraesophageal pH and bile reflux, endoscopic grading score and symptom score were all decreased significantly at T1 in both groups similarly (P<0.01), showing insignificant difference between groups (P>0.05). These indices were reversed at T2 to high level in the control group (P<0.05), but the reversion did not occur in the treatment group (P>0.05). No serious adverse reaction was found during the therapeutic period.</p><p><b>CONCLUSION</b>Acupuncture can effectively inhibit the intraesophageal acid and bile reflux in GER patients to alleviate patients' symptoms with good safety and is well accepted by patients.</p>

Prognostic significance of ERCC1 mRNA expression in patients with non-small cell lung cancer receiving platinum-based chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlation of the mRNA expression level of excision repair cross-complementing group 1 (ERCC1) gene with clinicopathological parameters and clinical outcome in patients with non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy.</p><p><b>METHODS</b>The mRNA expression of ERCC1 in formalin-fixed paraffin-embedded primary tumor specimens was measured by real-time quantitative reverse transcriptase polymerase chain reaction. The association between ERCC1 expression levels and clinicopathological parameters in NSCLC patients was analyzed.</p><p><b>RESULTS</b>The median value of ERCC1 mRNA expression level compared with beta-actin in tumor specimens of 61 NSCLC patients was 0.48. There was no correlation between ERCC1 expression and clinicopathological parameters. Patients with low expression of ERCC1 mRNA (less than 0.35, 0.28, respectively) had a significantly longer median time to progression (TTP) (14.3 vs. 8.0 months, P = 0.028) and overall survival (OS) (28.4 vs. 12.9 months, P = 0.0064) than those with high expression. Multivariate analysis showed that a low ERCC1 mRNA expression was an independent factor for OS.</p><p><b>CONCLUSION</b>Our findings suggest that intratumoral ERCC1 mRNA expression level, although is uncorrelated with clinicopathological parameters, is an independent predictive marker for survival of the patients with NSCLC receiving platinum-based chemotherapy, and may provide critical information for personalized chemotherapy.</p>

Differential gene expression of the inhibitor of apoptosis proteins in docetaxel-resistant gastric cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Resistance to chemotherapy may indicate an unfavorable outcome for patients with gastric cancer. The purpose of this study was to examine whether docetaxel-resistance could be due in part to the expression of the inhibitor of apoptosis proteins (IAP).</p><p><b>METHODS</b>Docetaxel-resistant cells, BGC-823/R1, BGC-823/R2 and BGC-823/R3, were established from parent BGC-823 cells by stepwise increasing concentration of docetaxel. To characterize these cells, we examined the effects of docetaxel on cell growth and apoptosis by MTT assay and double staining with both annexin-V-FITC and PI, and analyzed the cross-resistance to various anticancer drugs. Expression of IAP compared with that in parental cells was evaluated by real-time quantitative PCR.</p><p><b>RESULTS</b>The BGC-823 resistant cells, BGC-823/R1, R2 and R3 cells, were 10.2-, 24.5-, 56.3-fold more resistant to docetaxel than parental cells, respectively, and this resistance was paralleled with reduced induction of apoptosis. BGC-823/R3 cells showed cross-resistance to paclitaxel, whereas exhibited weak or no cross-resistance against 5-fluorouracil, cisplatin and oxaliplatin. The expressions of survivin and XIAP were gradually increased with the extent of docetaxel resistance (r = 0.909, P < 0.001 and r = 0.892, P < 0.001, respectively).</p><p><b>CONCLUSION</b>IAP may make an important contribution to the resistance to the apoptotic effect of docetaxel in gastric cancer, and could be used as a potential therapeutic target.</p>

Synergistic effect of Chinese materia medica and chemotherapeutic agents / 中国中西医结合杂志

Both in vitro and in vitro studies have proved that partial of Chinese materia medica including monomer or active ingredients have synergistic action with chemotherapeutic agents, the former could enhance the effect of the latter. Its mechanism may be correlated with the actions of Chinese materia medica in enhancing immune function, directly killing tumor cells, inducing tumor cell apoptosis, regulating cell cycle and reversing chemotherapeutic drug resistance, etc. The present article summarized the synergistic effect of Chinese materia medica, monomer or active ingredients, with various chemotherapeutic agents, and tried to provide a theoretical evidence for combined application of them in the procedure of clinical tumor treatment.

Inhibitory effect of oxaliplatin in combination with hyperthermia on angiogenesis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the effect of oxaliplatin in combination with hyperthermia on angiogenesis in vitro and in vivo.</p><p><b>METHODS</b>MTT method was used to observe the influence of oxaliplatin on the proliferation of human umbilical vein endothelial cells (HUVEC) or human colon cancer cells (LOVO). The influence of oxaliplatin on HUVEC migration was evaluated by Transwell. Chick embryo chorioallantoic membrane (CAM) model was used to check whether the neovascularization of CAM could be suppressed in vivo.</p><p><b>RESULTS</b>The survival rate of HUVEC was 80.1% - 42.5% within a range of 0.5 - 16 microg/ml and was negatively correlated with the concentration (correlation coefficient was - 0. 943, P = 0.005). The survival rate of LOVO cells within those doses was more than that of HUVEC. There was a synergistic antiangiogenic effect when a combination of oxaliplatin (0.5 microg/ml, 1 microg/ml and 16 microg/ml) with hyperthermia was used while additional effect was shown by the combinatioin of oxaliplatin (2 microg/ml, 4 microg/ml and 8 microg/ml) and hyperthermia in vitro. Oxaliplatin inhibited migration of HUVEC in vitro at low doses (0.25 - 2 microg/ml), and also suppressed angiogenesis of CAM in vivo at doses of 1 -4 microg/ml.</p><p><b>CONCLUSION</b>The results of this experiment showed that low dose of oxaliplatin has anti-angiogenic effect in vitro, while in combination with hyperthermia has additional effect both in vivo and in vitro.</p>