Multicenter postmarketing clinical study on using pegylated recombinant human gran-ulocyte-colony stimulating factor to prevent chemotherapy-induced neutropenia / 中国肿瘤临床

Objective: To investigate the efficacy and safety of using pegylated recombinant human granulocyte-colonystimulating factor (PEG-rhG-CSF) in preventing neutropenia in multiple chemotherapy cycles. Methods: A multicenter, prospective, open-label, singlearmstudy was designed. Patients with malignant tumors, such as lung, ovarian, and colorectal cancers, who received multiple cycles of chemotherapy with the prophylactic use of PEG-rhG-CSF for 2-4 consecutive cycles participated in the study. Results: After the prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 4.76% (13/273) in the first cycle to 1.83% (5/273), 1.15% (2/174), and 2.08% (2/96) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 11.36% (31/ 273) in the first cycle to 6.23% (17/273), 2.87% (5/174), and 3.13% (3/96) in subsequent cycles. The incidence of febrile neutropenia (FN) during the first cycle was 0.73% (2/273). The duration of FN was 2 days in one case and 5 days in another case. FN was not observed during the second, third, or fourth cycle. After the secondary prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 25% (7/28) to 3.57% (1/28), 0% (0/28), and 6.67% (1/15) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 71.43% (20/28) to 10.71% (3/28), 14.29% (4/28), and 0% (0/15) in subsequent cycles. The proportion of patients who received antibiotic therapy during the entire chemotherapy period was 10.48% (44/420). Conclusion: The application of PEG-rhG-CSF once per chemotherapy cycle can effectively reduce the occurrence of neutropenia in patients under multiple cycles of chemotherapy treatment with good safety.

Therapeutic effects of crizotinib in lung cancer and the treatment after drug resistance / 国际肿瘤学杂志

Crizotinib is a tyrosine kinase inhibitor (TKI),which is a target for echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK).It can prolong the progression free survival (PFS)of ALK positive patients with advanced non-small cell lung cancer (NSCLC).The median PFS in the first-line and second-line mPFS is 10.9 months and 7.7 months.However,despite an initial benefit,patients inevitably experience tumor progression,due to the ALK fusion gene amplification and secondary mutations of ALK kinase domain.Clinical trials show the promising efficacy like next generation ALK inhibitors and heat shock protein 90 (HSP90)can overcome acquired resistance.

A Randomized Controlled Clinical Study on Prevention and Treatment for Acute Radiation Esophagitis by Compound Kushen Injection / 中国中医药信息杂志

Objective To investigate the prevention and treatment effects of Compound Kushen Injection on acute radiation esophagitis. Methods Eighty-two eligible patients with esophageal cancer were randomly divided into the treatment group (41 cases) and the control group (41 cases). All the patients received radiotherapy. Throughout the course of radiotherapy, patients in the treatment group received Compound Kushen Injection, and patients in the control group received Kangfuxin Liquid. Occurrence time and level of radiation esophagitis, and dosage of painkillers were observed. Results Different degrees of acute esophageal toxicity were observed in the two groups. The occurrence rate of high level (degree III and degree IV) acute radiation esophagitis was 7.3%(3/41) in the treatment group, and 31.7%(13/41) in the control group. There was significant difference between the two groups (P<0.05). The dosage of the analgesic drug (Fentanyl Transdermal System) in the treatment group was far less than the controlled group (P<0.001). Conclusion Compound Kushen Injection could decrease the incidence rate of acute radiation esophagitis, and reduce the high-level esophagitis and the dosage of the analgesic drug, which can help the completion of radiation.

c-MET gene amplification in advanced primary non-small cell lung cancer and associated lymph node-metastases / 国际肿瘤学杂志

Objective To examine the positive rate of c-MET gene amplification in primary and lymph node-metastatic non-small cell lung cancer( NSCLC),and to explore their relationships. Methods From November 2011 to November 2013,147 cases of primary NSCLC consisting of 71 cases of paired lymph node-metastatic tumors and 47 cases of normal lung specimens as the control group were collected in General Hospital of Beijing Military Region. The c-MET gene copy number was examined by RT-PCR and the positive rate of c-MET gene amplification among NSCLC population was figured out,thus the consistency of c-MET gene ampli-fication in advanced primary NSCLC and associated lymph node-metastases and the relationship between c-MET gene amplification and clinical data were analyzed. Results The positive rate of c-MET gene amplification on primary tumor was 8. 84% (13 / 147). For those 71 paired cases,the positive rate on primary tumor was 8. 45%(6 / 71),with that of lymph node-metastases 18. 31%(13 / 71). Among the 71 cases,there were 8 cases whose metastases were positive but primary tumors negative and 1 case whose primary tumor was positive but metastases negative. It was of statistical significance between the two groups(McNemar test,χ2 = 4. 274, P = 0. 039). The positive rate of primary tumors could be predicted by lymph node-metastases(κ = 0. 464, P ﹤ 0. 001). The sensitivity was 83. 3% and the specificity was 87. 7% . Positive rate of c-MET amplification was higher in male and smoking patients with lymph node-metastases above N2 . Conclusion c-MET amplifica-tion test should be one of the routine genetic testing projects. The amplification on primary tumors is higher than that on lymph node-metastases,implying that metastases test can pick out more patients with indication. Metas-tases test can predict the amplification on primary focus,and it is an alternative way to guide the treatment of c-MET target medicine. Moreover,the clinical characteristic can be served as an indicator of positive c-MET am-plification.

EML4-ALK rearrangement in cancer tissue and serum of non-small cell lung cancer patients / 国际肿瘤学杂志

Objective To observe EML4-ALK fusion gene mutation expression rate in serum and cancer tissue of patients with non-small cell lung cancer (NSCLC) in Chinese populations,and the consistency of mutation in serum and cancer tissues,and the feasibility of real-time,dynamic detection of EML4-ALK fusion gene therapy by using FQ-PCR.Methods 123 cases of serum and 98 cases of tissue of NSCLC patients were detected by fluorescence quantitative polymerase chain reaction,and 77 cases of which were matched.The clinical curative effects of ALK inhibitor (crizotinib) were analyzed.Results 13 rearrangement in 123 (10.6％) of the patients'serum samples and 11 rearrangement in 98 (11.2％) tumor tissue.EML4-ALK rearrangement were mainly discovered in adenocarcinoma (x2 =4.083,P =0.036),and non-smokers in NSCLC (x2 =5.326,P =0.019).The consistency of patients with EML4-ALK matched tumor tissue and serum reached 66.7％ (6/9,κ =0.779).The EML4-ALK fusion gene rearrangement in patients receiving ALK inhibitor (crizotinib) treatment achieved significant benefit.Conclusion The EML4-ALK rearrangement mainly exists in the serum and tumor tissue of adenocarcinoma and non-smokers in NSCLC.When tumor tissue samples are unable to be obtained,FQ-PCR can be used to detect serum EML4-ALK fusion gene mutation for selecting NSCLC patients suitable for crizotinib therapy instead of tumor tissue.

Expression of IMD, CRLR, RAMP1, RAMP2 and RAMP3 in cancer tissues of patients with non-small cell lung cancer and their clinical significance / 肿瘤研究与临床

Objective To investigate the expression and significance of intermedin (IMD) and its.receptors CRLR,RAMP1,RAMP2 and RAMP3 in cancer tissues of patients with non-small cell lung cancer.Methods The mRNA gene expressions of IMD,CRLR,RAMP1,RAMP2 and RAMP3 were detected by realtime quantitative RT-PCR in cancerous and para-cancerous tissues from 27 patients with lung cancer.Results Real-time quantitative PCR detection results showed that the expression of IMD,CRLR,RAMP1,RAMP2 and RAMP3 in cancer tissues were [(59±7.9)×10-8,(96±2.7)×10-6,(29±3.9)×10-9,(14±2.6)×10-6,(65±1.1)×10-6]which were higher than those in adjacent tissues[(40±4.7)×10-10,(21 ±3.9)×10-6,(53±7.8)×10-10,(64±1.9)×10-8,(36±1.3)×10-9] to some extent (all P ＜ 0.05); the higher expression of RAMP3 was found is higher expressions than RAMP1 and RAMP2 in cancer tissues (all P ＜ 0.05).Conclusion The expressions of IMD and its receptors in cancer tissues are higher than those in paracancerous tissues.IMD may play an important role in the development of cancer by activate RAMP3 which is the most high expressed receptor in cancer tissues.Therefore,it might be helpful for the investigation of new gene thereapy in non-small cell lung cancer.

Expression and clinical significance of urotensin Ⅱ in lung cancer tissue / 国际肿瘤学杂志

ObjectiveTo investigate the expression of urotensin Ⅱ(UⅡ) in the lung cancer tissue from surgical resection of lung cancer patients,and to detect the relationship between UⅡ expression and pathologie types and the clinical stages of lung cancer.MethodsThe expression rates of UⅡof 45 lung cancer tissues and 20 inflammatory pseudotumor were measured by immunohistochemical assay,and the relationship between UⅡ expression and the pathologic types and clinical stages of lung cancer was analyzed.ResultsUⅡwas mainly distributed in lung cancer cell cytoplasm,which was tan-yellow particles.The positive expression rate of UⅡin nonsmall cell lung cancer was 61.3％ (19/31),which was higher than that in small cell lung cancer(7.1％,1/14)and pulmonary inflammatory pseudotumor( 15.0％,3/20) (P ＜ 0.01 ).The positive expression rate of UⅡ was 100％ in adenocareinoma.The positive expression rate of UⅡin staging Ⅲ non-small cell lung cancer( 85.7％ )was higher than that of staging Ⅰ ( 16.7％ ) ( P ＜ 0.05).ConclusionUⅡ cxists in the cytoplasm of lung cancer cells,and the expression of UⅡis correlated with the pathological type and TNM staging of lung cancer.

Her-2 and targeted treatment for gastric cancer / 国际肿瘤学杂志

Her-2( human epidermal growth fact or receptor 2) is a type of 185 kD across the membrane glycoprotein with tyrosine kinase activity,play an important function in the cell divisions across a cell membrane proliferation signal transduction,and finally affect biological activities of tumor cells from multiple ways,such as a tumor cell proliferation and adhesion,transfer and differentiation and other related gene regulation.Recent studies show that Her-2 overexpression rate of gastric cancer patients is about 12％ ～ 35％,and Her-2 is a gastric cancer poor-prognostic factors,while Her-2 monoclonal antibody-Trastuzumab is expected to become a new standard gastric cancer treatment for the patients with Her-2 overexpressed.

Expression of intermedin in lung cancer patients and its clinical significance / 肿瘤研究与临床

Objective To investigate the expression of intermedin (IMD) in plasma and tissues of lung cancer patients compared with control group and to explore the relationship of IMD with the stage and pathological type of lung cancer. Methods The content of IMD in plasma of 88 lung cancer patients measured using ELISA, 36 lung cancer tissue using immunohistochemistry, compared with control groups. Results Healthy control group IMD level [(38.68±12.65) pg/ml] was lower than lung cancer group [(81.61 ± 30.78) pg/ml] (t =-5.818, P 0.05); IMD in stage Ⅳ is higher than stage Ⅰ - Ⅲ (t =-3.444, -3.093, -3.955, P <0.05); IMD with distant metastasis is significantly higher than that without distant metastasis (t =8.052, P =0.000). IMD expression in lung cancer tissues [23/36 (63.9 %)] is significantly higher than adjacent tumor tissues [5/21 (23.8 %)] (x2= 8.525, P <0.05). IMD in Stage Ⅲ[14/17(82.4 %)] is significantly higher than in stage Ⅰ [1/5 (20.0 %)] (x2 = 6.924, P =0.009). Conclusion The expression of IMD in lung cancer patients is significantly higher than control groups. Expression has correlation with stage and metastasis, which might play a vital role in the pathogenesis of lung cancer.

Epidermal growth factor receptor mutations in non-small cell lung cancer of tissue and peripheral blood by fluorescence quantitive polymerase chain reaction / 国际肿瘤学杂志

Objective To investigate gene mutations of the epidermal growth factor receptor of tumor tissue and peripheral blood in non-small-cell lung cancer, and to compare the consistency of EGFR mutations in tumor tissue and peripheral blood, fluorescence quantitive polymerase chain reaction (FQ-PCR) was performed according to standard procedure. Methods 112 peripheral blood and 87 tumor tissue of NSCLC were detected by FQ-PCR, among which 45 cases were analyzed using peripheral blood-tumor tissue matched samples. The relationship between clinical efficacy and EGFR mutations Was analyzed. Results Our results showed that there is 32 mutations in EGFR in 112(28.6%)of the patients'peripheral blood samples and 27 mutations in EGFR in 87(31.O%)tumor tissue. EGFR mutations were mainly found in adenocarcinoma and non-smokers in NSCLC (P<0.05). The consistency of EGFR mutation between tumor tissue and peripheal blood reached 71.4%. The clinical outcome of mutations Was significantly effective(P

Variety and significance of Intermedin on hypoxic pulmonary arterial hypertension in rats / 中国基层医药

Objective To observe and compare the changes of Intermedin's contents in plasma and bron-choalveolar lavage fluid (BALF) in rats with hypoxic pulmonary hypertension. Methods male Wistar rats were ran-domly divided into control group and 1,2 and 3 weeks hypoxia group. Intermedin's contents in plasma and bronchoal-veolar lavage fluid were measured by radioimmunoassay. Results Intermedin's contents in plasma and bronchoalveo-lar lavage fluid were markedly increaseded compared with control group. Meanwhile transformational trend is consist-ent between plasma and bronchoalveolar lavage. Conclusions Intermedin's contents in plasma and bronchoalveolar lavage increase ,which shows that there is protection and moderation to hypoxic pulmonary hypertension.

The expression, synthesis and release of Urotensin Ⅱ in hypoxic pulmonary hypertension and its significance / 中国医师杂志

Objective To study the release of synthetic gene expression induced by vasopressin Ⅱ (U Ⅱ ) in hypoxic pulmonary hypertension. Methods Rat model of HPH was establish. RIA was used to observe the different time points of hypoxia in plasma and the dynamic changes of U Ⅱ , ADM content in bronchoalveolar lavage fluid (BALF). The impact of the release of U Ⅱ , as well as the relation-ship among U Ⅱ , ADM and HPH were explored to reveal the role of U Ⅱ in the pathophysiology of HPH. Results Rat HPH model was successfully established. Hypoxia promoted the expression, synthesis and release of U Ⅱ in lung tissue. U Ⅱ involved in the pathogenesis of HPH. HPH took place in the development of U Ⅱand was positive correlated with ADM. Conclusion The two peptides have opposite physiological effects on blood vessel, which suggest that these two peptides play an important role in maintaining the balance between the pul-monary circulation and lung ventilation as well as the stability of pulmonary artery pressure.

Bio-artificial dura mater versus autogenous periosteum for Substituting dura mater / 中国组织工程研究

BACKGROUND:At present,autogenous periosteum and artificial dura mater are usually applied as the substitute grafts for the dural defect by neurological surgery.However they do not accord with the developing trend of modern medicine,due to the limitations of material size and shape,operational complex and additional wound.OBJECTIVE:To observe and compare the evolution of a new type bio-artificial dura and autogenous periosteum in replacing orthotopic duraDESIGN:Controlled observation and trial.SETTING:Animal Testing Center in the 157 Hospital of Guangzhou City.MATERIALS:Nine New Zealand rabbits.aged 6 months and weighed 2-3 kg,either gender was selected.Twelve hybrid healthy dogs of both genders,aged 2 years and weighed 15-20 kg.New type dura mater(No.2006.3460627).METHODS:The experiment was carried out at the Animal Testing Center in the 157 Hospital of Guangzhou City from October 2003 to October 2005.After the general anesthesia and bilateral craniotomy,the bilateral dural defect and pia mater injury were induced partly,then dural neoplasty was performed using new type artificial dura and autogenous periosteum.MAIN OUTCOME MEASURES:At months 1,6,12 of modeling,each three rabbits were selected to isolate and expose the implanted materials,while each four dogs were selected at months 6,12,24 of modeling,died of disease or prior to death.General observation and microscopic assessment of samples were compared to analyze the development of implanted materials at difference stages.RESULTS:Except one experimental dog died during the anesthesia,9 rabbits and 11 dogs were involved in the final presented the extemal surface of adherence and separation with pedcranium,grew well with surrounding orthotopic dura.For the internal surface of materials,the new type artificial dura was more likely the orthotopic dura and did no adhere to pericranium, and filament-shaped adherence appeared occasionally, while there were filament-shaped even month 12 of grafting new type artificial dura into the experimental rabbits.inflammatory cellular reactions such as neutrophil and lymphocyte were not found,additionally no capsule wall formation occurred.The internal surface of artificial dura was covered with epithelial cells,which appeared fibroplasia,fibroblast proliferation,degradation of implants and obvious reduction of total cell amount.Moreover the blood capillary was also found.CONCLUSION:New type artificial dura can achieve the dural reconstruction through producing epithelial cells and being nibbled.degraded and substituted by autogenous tissue.And no adherence to cerebral tissues is found.New type artificial dura is superior to autogenous periosteum for repairing the dural defects.

Changes of urotensinⅡ content in plasma and bronchoalveolar lavage fluid of rats with chronic hypoxic pulmonary hypertension / 第三军医大学学报

Objective To observe the dynamic changes of urotensionⅡ (U Ⅱ) content in plasma and bronchoalveolar lavage fluid (BALF) of rats with chronic hypoxic pulmonary hypertension and to investigate the effects of hypoxia on the synthesis and secretion of U Ⅱ and the correlation of U Ⅱ with the mean pulmonary artery pressure (mPAP) and the partial pressure of arterial oxygen (PaO 2). Methods Male Wistar rats were randomly divided into control group and hypoxic groups. Model of chronic hypoxic pulmonary hypertension was established by normal barometric and discontinuous hypoxia. mPAP and RVdp/dt max of each rat were measured using right cardiac catheterization. PaO 2 was detected by blood gas analysis. U Ⅱcontents in plasma and BALF were detected by radioimmunoassay. Results During hypoxia, mPAP, RVdp/dt max , U Ⅱ content in plasma, and BALF increased in rats (P

EXPERIMENTAL STUDY OF PATHOLOGICAL CHANGES IN PULMONARY VESSELS AND THEIR MECHANISMS UNDERLYING HYPOXIC PULMONARY HYPERTENSION IN RATS / 解放军医学杂志

A model of hypoxic pulmonary hypertension (HPH) was reproduced in rats by exposing them to chronic hypoxia environment corresponding to 5km level. At 10d,20d, 30d after hypoxia in hypoxia groups and control group, the pulmonary vascular structural changes were observed with optical microscope, histochemistry and electronic microscope. The changes in hypoxia groups were as follows: ①the wall of small pulmonary arteries of every calibre showed marked thickening compared with that in control group, and the main changes involved smooth muscle cells(SMC)proliferation and collagen deposition in the vessels wall; ② SMC proliferation, muscularization of non myocytic arteries and partial myocytic arteries were observed in intra acinar pulmonary arteries, so the counts of muscular arteries significantly increased compared with control group( P

Plasma adenomedullin, calcitonin gene-related peptide and c-type natriuretic peptide in rats with hypoxic pulmonary hypertension / 第三军医大学学报

Objective　To explore the effects of hypoxia on the syntheses and secretion of adrenomedullin (AM), calcitonin gene related peptide (CGRP) and c-type natriuretic peptide (CNP) and the relationship between these peptides. Methods　Rat models were established with hypoxia for 10, 20 and 30 d respectively and rats under normal altitude were served as control. Pulmonary artery pressure and the maximum increasing speed of right ventricle (RVdp/dtmax) were measured in every group. The dynamic changes of AM, CGRP and CNP concentrations in plasma were studied with radioimmunoassay. Results　During hypoxia, pulmonary artery pressure and RVdp/dtmax were enhanced. Plasma AM and CNP concentrations were increased while CGRP was decreased significantly. The plasma level of AM had positive correlation with that of CNP, but negatively correlated with that of CGRP. Conclusion　Results indicate that hypoxia may cause pulmonary artery pressure change and right ventricle has compensatory reaction to hypoxic pulmonary hypertension. Dynamic changes of plasma AM, CGRP and CNP concentrations can be regarded as indexes for condition of illness.