The Clinical Usefulness of ^(99m)Tc-Tetrofosmin Scintigraphy in the Diagnosis of Lung Neoplasmas and Mediastinal Lymphoid Node Involvement

In order to investigate the clinical significance of 99mTc-Tetrofosmin （TF） scintigraphy in the evaluation of lung cancer and mediastinal lymphoid node involvement, 33 patients with pulmo- nary neoplasmas were subjected to both 99mTc-TF scintigraphies and CT scans in one week before their operations or puncturations. All the images were judged visually and the emission images were analyzed with semi-quantitative methods in addition. The results of each group were compared. There was marked difference in target/non-target （T/N） ratio between the lung cancer group and the benign lesion group （P〈0.001）. Moreover, in the lung cancer group, T/N ratio in tomographies was signifi- cantly higher than that in planar images （P〈0.01）. The sensitivity and accuracy of semi-quantitative analysis in 99mTc-TF SPECT were significantly higher than those of CT in the diagnosis of pulmonary neoplasmas （P〈0.05 and P〈0.01 respectively）, so was the sensitivity of 99mTc-TF SPECT vs CT in the diagnosis of mediastinal lymphoid node metastasis （P〈0.05）. It was also found that epidermoid squamous cell carcinomas and adenocarcinomas had a higher T/N ratio than in small cell carcinomas （P〈0.05）, and 2 h washout rate （WR） of adenocarcinomas was higher than that of epidermoid squamous cell carcinomas （P〈0.05）. In conclusion, 99mTc-TF scintigraphy showed a favorable diag- nostic accuracy in appraising lung cancers and mediastinal lymph node metastases. Furthermore semi-quantitative technology can improve the accuracy, and is potential to offer some information about histological type of the cancer tissue. Therefore, 99mTc-TF scintigraphy will be a useful tool in the diagnosis and staging of lung cancer.

SIGNIFICANCE OF ELECTRON MICROSCOPIC EXAMINATION IN THE DIAGNOSIS OF PULMONARY NEOPLASMS

The significance of electronic microscopc examination(EM) in the diagnosis of pulmonary neoplasms was evaIuated in 40 cases of Patients with different kinds of Pulmonary neoplasms.In 27 of the 40 cases,final diagnoses were made by light microscope(LM) examination,while in the remaining 13 cases,LM faded to reach definite diagnoses which were established with the help of EM.By analyzing our data,we conclude that in the following situations,EM helps meet in the diagnosis of pulmonary neoplasm:1.diagnosis of neuroendocrinal carcinomas of the lung;2.diagnosis of some rare pulmonary neoplasm;3.documentation of the histologic origins of the matastatic pulmonary neoplasms and 4.differentiation of malignant mesothelioma with pleural metastasis of Pulmonary adenocarcinoma.

Gastric metastasis of small cell lung carcinoma:Three case reports and review of literature

BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metastasis have been reported.Therefore,SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed.CASE SUMMARY We report three cases of gastric metastasis from SCLC in this article.The first patient presented primarily with cough,hemoptysis,and epigastric fullness.The other two patients presented primarily with abdominal discomfort,epigastric distension,and pain.All patients underwent gastroscopy and imaging examinations.Meanwhile,the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma.Finally,the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis.The three patients did not receive appropriate treatment and died within a short time.CONCLUSION Here,we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians'understanding of this disease.

Deep learning model based on primary tumor to predict lymph node status in clinical stage IA lung adenocarcinoma:a multicenter study

Objective:To develop a deep learning model to predict lymph node(LN)status in clinical stage IA lung adeno-carcinoma patients.Methods:This diagnostic study included 1,009 patients with pathologically confirmed clinical stage T1N0M0 lung adenocarcinoma from two independent datasets(699 from Cancer Hospital of Chinese Academy of Medical Sciences and 310 from PLA General Hospital)between January 2005 and December 2019.The Cancer Hospital dataset was randomly split into a training cohort(559 patients)and a validation cohort(140 patients)to train and tune a deep learning model based on a deep residual network(ResNet).The PLA Hospital dataset was used as a testing cohort to evaluate the generalization ability of the model.Thoracic radiologists manually segmented tumors and interpreted high-resolution computed tomography(HRCT)features for the model.The predictive performance was assessed by area under the curves(AUCs),accuracy,precision,recall,and F1 score.Subgroup analysis was performed to evaluate the potential bias of the study population.Results:A total of 1,009 patients were included in this study;409(40.5%)were male and 600(59.5%)were female.The median age was 57.0 years(inter-quartile range,IQR:50.0-64.0).The deep learning model achieved AUCs of 0.906(95%CI:0.873-0.938)and 0.893(95%CI:0.857-0.930)for predicting pN0 disease in the testing cohort and a non-pure ground glass nodule(non-pGGN)testing cohort,respectively.No significant difference was detected between the testing cohort and the non-pGGN testing cohort(P=0.622).The precisions of this model for predicting pN0 disease were 0.979(95%CI:0.963-0.995)and 0.983(95%CI:0.967-0.998)in the testing cohort and the non-pGGN testing cohort,respectively.The deep learning model achieved AUCs of 0.848(95%CI:0.798-0.898)and 0.831(95%CI:0.776-0.887)for predicting pN2 disease in the testing cohort and the non-pGGN testing cohort,respectively.No significant difference was detected between the testing cohort and the non-pGGN testing cohort(P=0.657).The recalls of this model for predicting pN2 disease were 0.903(95%CI:0.870-0.936)and 0.931(95%CI:0.901-0.961)in the testing cohort and the non-pGGN testing cohort,respectively.Conclusions:The superior performance of the deep learning model will help to target the extension of lymph node dissection and reduce the ineffective lymph node dissection in early-stage lung adenocarcinoma patients.

Relationship between the Expression of E-cadherin and Microvessel Density in Lung Cancer and Its Significance

To study the relationship between the expression of E-cadherin andmicrovessel density (MVD) in lung cancer. Methods: The expression of E-cadherin and factor VIII wasdetected in 104 lung cancer tissues by an immunohistochemical method, and MVD was calculated by animage-analysis system. Results: The expression of E-cadherin was significantly related to thedifferentiation of lung cancers (P 【 0.05). A negative correlation was found between E-cadherinexpression and MVD in lung cancer tissues (P=0.047). Conclusion: Down-expression of E-cadherin andan increase of MVD may play an important role in the invasion and metastasis of lung cancer, and mayalso be used as a useful marker for tumor prognosis.

Clinical Course Of Patients with Small Cell Lung Cancer As Second Primary Malignancy

Objective： To evaluate the clinical course of patients with small cell lung cancer （SCLC） as second primary malignancy. Methods： Among the 355 patients diagnosed with SCLC at Helen and Harry Gray Cancer Center of Hartford Hospital Connecticut USA between 1988 and 1998, the records of 48 patients, which had been diagnosed with other malignancies before their diagnosis of SCLC, were retro- spectively reviewed. Results： Forty-eight patients （13.5%） were diagnosed with other malignancies prior to their SCLC among which 43 had documented smoking history and 93% of them （40/43） were current/former smokers. Of the 28-second primary SCLC patients who were treated with standard method, 11 （39.3%） achieved CR. 12 （42.8%） achieved PR, and the RR was 82.1%. The median survival of the 28 treated with standard method was 11.3 months （5.1-77.7 months）, while that of the rest 19 untreated patients （1 of 20 was lost to follow-up） was only 2.0 months （0.5 34.0 months）. There was no significant difference in the median survival and RR between 165 treated first primary SCLC （13.5 months and 77.6% respectively） and 28 treated secondary primary SCLC （11.3 months and 82.1% respectively） （P〉0.05）. The patients who had prostate cancer were older and subjected to less treatments than those with skin cancer, so their survival was shorter than the latter （3.5 months vs. 15 months, P〈0.05）. Conclusion： The response and survival of the treated patients with SCLC as a second malignancy showed no difference as compared to the treated ones with SCLC only. Therefore, an active medical treatment is important to relieve symptom and prolong survival of the second primary SCLC patients.

The 7th lung cancer TNM classification and staging system:Review of the changes and implications

Lung cancer is the most common cause of death from cancer in males,accounting for more than 1.4 million deaths in 2008.It is a growing concern in China,Asia and Africa as well.Accurate staging of the disease is an important part of the management as it provides estimation of patient’s prognosis and identifies treatment sterategies.It also helps to build a database for future staging projects.A major revision of lung cancer staging has been announced with effect from January 2010.The new classification is based on a larger surgical and non-surgical cohort of patients,and thus more accurate in terms of outcome prediction compared to the previous classification.There are several original papers regarding this new classification which give comprehensive description of the methodology,the changes in the staging and the statistical analysis.This overview is a simplified description of the changes in the new classification and their potential impact on patients’ treatment and prognosis.

The Inhibitory Effects of Rh-endostatin(YH-16) in Combination with Radiotherapy on Lung Adenocarcinoma A549 in Mice and the Underlying Mechanisms

In order to investigate the inhibitory effects of Endostar(rh-endostatin,YH-16)in combination with radiotherapy on lung adenocarcinoma A549 in mice and the interaction mechanisms of combined therapy,the transplantation tumor models of A549 lung adenocarcinoma were established.When the largest diameter of tumor reached 1.0cm,all nude mice were randomly divided into 4 groups:Endostar group,radiotherapy group,radiotherapy plus Endostar(combined treatment)group,and control group(n=6 in each group).The largest d...

基于CT GE Lung VCAR软件鉴别肺原位腺癌和微浸润腺癌

目的:利用GE Lung VCAR软件分析肺原位腺癌(AIS)与微浸润腺癌(MIA)的CT鉴别诊断要点。方法:收集2016年1月至2017年3月温州医科大学附属第一医院经病理证实的AIS患者50例、MIA患者55例。使用GE Lung VCAR软件对105例结节的CT图像进行三维后处理分析,比较2组结节实性成分及总体的左右径(LRD)、前后径(APD)、上下径(SID)、平均密度(DAVG)、非实性部分体积(VNS)、实性部分体积(V_S)、总体体积(V_T)、实性部分体积百分率(V_S%)以及形态学特征的差异,并与二维轴位CT图像肺窗下手动测量结节最大径的诊断效能进行比较,评估GE Lung VCAR软件的诊断价值。结果:AIS组与MIA组的二维手动测量最大径与软件分析获得结节实性部分及总体三径、V_S、V_T、V_S%、结节形态、毛刺征、结节与血管关系、累及血管根数的差异具有统计学意义(P<0.05)。GE Lung VCAR软件评估结节大小较手动测量诊断效能高;部分参数诊断效能由高到低分别为:累及血管根数、毛刺征、总体LRD、实性APD、V_T、V_S;最佳截断值分别为:累及3根血管、短毛刺征、总体LRD:14.5 mm、实性APD:8.5 mm、V_T:802 mm^3、V_S:133 mm^3。结论:GE Lung VCAR软件在肺结节CT诊断中具有较好实用价值,是鉴别AIS和MIA的一项有利工具。

Comparison of Effectiveness of Gefitinib, Erlotinib, and Afatinib in Advanced Non-small Cell Lung Cancer Patients with EGFR Mutation Positive in Indonesian Population

Background and objective EGFR-tyrosine kinase inhibitors(EGFR-TKIs) were used to treat non-small cell lung cancer(NSCLC) patients with EGFR mutation positive. This study aims to compare the effectiveness of first line TKIs;gefitinib, erlotinib, and afatinib in the treatment of advanced stage NSCLC patients with EGFR mutation positive in the Indonesian population.Methods A retrospective cohort study of 88 NSCLC patients with EGFR mutation positive treated with gefitinib(n=59), erlotinib(n=22), and afatinib(n=7) was performed in national cancer hospital in Indonesia.Inclusion criteria were stage IIIb or IV NSCLC with adenocarcinoma subtype. Subjects less than 18 years or with a history of other malignancy were excluded. Outcomes were treatment response, progression-free survival(PFS), and mortality rate. Results Complete response, partial response, and stable disease were shown in 1.1%, 35.2%, and 31.8% of subjects, respectively. There were 31.8% of subjects developed progressive disease during treatment. Regarding EGFR mutation positive profile, a total of 56.8% subjects had deletion in exon 19, 42% subjects had mutation in exon 21, and rare mutation in exon 18 was found in 3.4% of total subjects. Demography and clinical characteristics had no significant association with the risk of progressive disease. The median PFS of subjects was 11 months(95%CI: 6.8-15.2 months). There was no statistical difference of PFS between treatment groups.Conclusion Gefitinib, erlotinib, and afatinib have similar effectiveness in advanced stage NSCLC with EGFR mutation positive. Afatinib tends to be associated with longer PFS but further investigation is required.

Colonic metastasis after resection of primary squamous cell carcinoma of the lung:A case report and literature review

Lung cancer is a common malignancy in the world; however symptomatic colonic metastasis from primary lung cancer is rare. A 64-year-old man was originally found poorly differentiated squamous cell carcinoma of right lung and received right lower lobectomy and lymph node dissection. Three years later, the patient presented to our emergency room with the symptom of upper abdominal pain and weight loss. Abdominal palpation and computed tomography scan of the abdomen revealed a large mass measuring 7.6 cm &#x000d7; 8.5 cm in the ascending colon. Colonoscopy and biopsy revealed poorly differentiated squamous cell carcinoma with similar morphological pattern to that of the previous lung cancer. Chemotherapy was given and the patient died 5 mo later. Lung cancer metastatic to the colon confers a poor prognosis: overall survival ranged from 5 wk to 1 year, with a median survival of 3 mo after the diagnosis of the colonic metastasis.

Do inhaled corticosteroids increase the risk of Pneumocystis pneumonia in people with lung cancer?

Pneumocystis pneumonia(PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical history of chronic obstructive pulmonary disease treated with formoterol and a moderate daily dose of inhaled budesonide. He had also advanced stage non-small lung cancer treated with concurrent chemo-radiation with a cisplatin-etoposide containing regimen. The diagnosis of PCP was suspected based on the context of rapidly increasing dyspnea, lymphopenia and the imaging findings. Polymerase chain reaction testing on an induced sputum specimen was positive for Pneumocystis jirovecii. The patient was treated with oral trimethoprim-sulfamethoxazole and systemic corticotherapy and had showed clinical and radiological improvement. Six months after the PCP diagnosis, he developed a malignant pleural effusion and expired on hospice care. Through this case, we remind the importance of screening for PCP in lung cancer patients under chemotherapeutic regimens and with increasing dyspnea. In addition, we alert to the fact that long-term inhaled corticosteroids may be a risk factor for PCP in patients with lung cancer. Despite intensive treatment, the mortality of PCP remains high, hence the importance of chemoprophylaxis should be considered.

Serum Vascular Endothelial Growth Factor Levels in Patients with Non-small Cell Lung Cancer and Its Relations to the Micrometastasis in Peripheral Blood

To examine the relationship between the levels of the serum vascular endothelial growth factor （VEGF） and the micrometastasis of peripheral blood in patients with non-small cell lung cancer （NSCLC）, 108 NSCLC patients, including 40 patients with benign lung diseases and 30 healthy controls, were investigated. The serum VEGF levels were detected by ELISA and CK19 mRNA in peripheral blood by reverse transcriptase-polymerase chain reaction （RT-PCR）. In NSCLC group, the serum VEGF levels and the positive rate of CK19 mRNA in peripheral blood were 479.8±268.5 pg/mL and 66.7%, which were significantly higher than those of the other two groups respectively （P〈0.01）, and both of them were increased significantly with the progression of clinical stage of the tumors （P〈0.01）. Serum VEGF levels as well as the positive rate of CK19 mRNA in different pathological types of lung cancer had no significant differences （P〉0.05）. Serum VEGF levels in the patients positive for CK19 mRNA was 561.7±325.6 pg/mL. It is significantly higher than that in the negative patients （P〈0.01）. There existed a significant correlation between serum VEGF levels and expression of CK19 mRNA in peripheral blood in NSCLC patients （P〈0.001）. The detection of serum VEGF levels and CK19 mRNA in peripheral blood is helpful in judging the condition and the prognosis of NSCLC patients, and serum VEGF levels and CK19 mRNA are independent of the pathological types of lung cancer. The micrometastasis in peripheral blood of NSCLC patients is significantly associated with serum VEGF levels.

In vitro study of radiosensitization by β-Elemene in A549 cell line from adenocarcinoma of lung

Objective： To explore the effect and possible mechanism in vitro of radiosensitization by β-Elemene in A549 cell line from adenocarcinoma of lung. Methods： The A549 cell line from adenocarcinoma of lung was chosen for the study to determine the inhibition ratio by using MTT assay. Morphologic change, growth curve, cloning efficiency, divisional index were observed. Change of cell cycle and apoptosis rate were analyzed by FCM and the expressions of gene P53 and Bcl-2 were detected. Results： Reproductive activity of the group which was under irradiation and β-Elemene was significantly suppressed and its cloning efficiency and divisional index also declined. The apoptosis rate of the group which was under irradiation and β-Elemene was significantly higher at 48 h and 72 h, which was analyzed by FCM. The expression of P53 without Bcl-2 was observed in the group under irradiation and β-Elemene and the group under β-Elemene only at the 48th hour point, while the expression of Bcl-2 without p53 was observed in the group under irradiation only and the control group. Conclusion： β-Elemene is good at radiosensitization and its mechanism may be relevant to the up-regulation of P53, down-regulation of Bcl-2 and inducing apoptosis.

DIAGNOSTIC VALUE OF SERUM PROGRP31-98 IN PATIENTS WITH SMALL-CELL LUNG CANCER

Objective To explore the clinical significance of serum level of pro gastrin releasing peptide 31 98 (ProGRP31 98) for small cell lung cancer (SCLC), in comparison with neuron specific enolase (NSE). Methods Serum level of ProGRP31 98 and NSE was measured by ELISA respectively in 30 patients with SCLC, 30 with non small cell lung cancer (NSCLC), 15 with benign lung diseases and 15 normal subjects, additionally, 10 SCLC patients after having treatment with chemotherapy were included. The receiver operating characteristic (ROC) curve was used to set the cut off value and evaluate the diagnostic accuracy. Results The serum level of ProGRP31 98 was higher in patients with SCLC than that in other groups. The SCLC patients with extensive disease had a higher value than the patients with limited disease. In SCLC patients with distant metastases, it was also higher than in those without. Increase in serum ProGRP31 98 and NSE was both seen in SCLC patients, but for the former one, the increase was of much greater compared to the normal controls. Given the cut off value for ProGRP31 98 was 40ng·L -1 and for NSE 8μg·L -1 , their sensitivity of diagnosis in SCLC was 73% and 60%, respectively. The area under ROC curve of ProGRP31 98 was significantly larger than that of NSE. All patients responded to chemotherapy showed marked decrease in ProGRP31 98. Conclusion ProGRP31 98 is a more specific and sensitive marker than NSE in the diagnosis of SCLC.

Antineoplastic effects of deoxyelephantopin,a sesquiterpene lactone from Elephantopusscaber, on lung adenocarcinoma (A549) cells

OBJECTIVE： Deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber, showed inhibition of the growth of various tumor cells in vitro. In the present study, we investigated the cytotoxicity and apoptosis-inducing capacity of deoxyelephantopin on lung adenocarcinoma （A549） cells. METHODS： The cytotoxic effect of deoxyelephantopin on A549 cells and normal lymphocytes was evaluated using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay and 50% inhibitory concentration （IC50） value was determined. The self-renewal and proliferating potential of A549 cells after treatment with deoxyelephantopin were examined by colony formation assay. Cellular morphology of deoxyelephantopin-treated cells was observed using phase- contrast microscopy. The induction of apoptosis was evaluated using acddine orange and ethidium bromide staining, Hoechst 33342 staining, terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling （TUNEL） assay, DNA fragmentation analysis and Annexin V-fluorescein isothiocyanate staining by flow cytometry. Activation of caspases was detected using fluorogenic substrate specific to caspases 2, 3, 8 and 9 and flow cytometric analysis. The total cellular DNA content and expression of cleaved poly （ADP-ribose） polymerase was also analyzed. RESULTS： Deoxyelephantopin exhibited cytotoxicity to A549 cells （IC50 = 12.287 μg/mL）, however, there was no toxicity towards normal human lymphocytes. Deoxyelephantopin suppressed the colony-forming ability of A549 cells in a dose-dependent manner. Acridine orange, ethidium bromide and Hoechst 33342 staining showed cell shrinkage, chromosomal condensation and nuclear fragmentation, indicating induction of apoptosis. Deoxyelephantopin increased apoptosis of A549 cells, as evidenced by more TUNEL-positive cells. DNA fragmentation and Annexin V staining revealed late-stage apoptotic cell population. Deoxyelephantopin inhibited A549 cell growth by cell cycle arrest at G2/M phase and induced apoptosis through both extrinsic and intrinsic pathways. CONCLUSION： These results suggest that deoxyelephantopin has great potential as a new chemotherapeutic agent to be developed further for the treatment of lung cancer.

Risk prediction models for lung cancer:Perspectives and dissemination

Objective: The objective was to systematically assess lung cancer risk prediction models by critical evaluation of methodology, transparency and validation in order to provide a direction for future model development.Methods: Electronic searches(including PubMed, EMbase, the Cochrane Library, Web of Science, the China National Knowledge Infrastructure, Wanfang, the Chinese BioMedical Literature Database, and other official cancer websites) were completed with English and Chinese databases until April 30 th, 2018. Main reported sources were input data, assumptions and sensitivity analysis. Model validation was based on statements in the publications regarding internal validation, external validation and/or cross-validation.Results: Twenty-two studies(containing 11 multiple-use and 11 single-use models) were included. Original models were developed between 2003 and 2016. Most of these were from the United States. Multivariate logistic regression was widely used to identify a model. The minimum area under the curve for each model was 0.57 and the largest was 0.87. The smallest C statistic was 0.59 and the largest 0.85. Six studies were validated by external validation and three were cross-validated. In total, 2 models had a high risk of bias, 6 models reported the most used variables were age and smoking duration, and 5 models included family history of lung cancer.Conclusions: The prediction accuracy of the models was high overall, indicating that it is feasible to use models for high-risk population prediction. However, the process of model development and reporting is not optimal with a high risk of bias. This risk affects prediction accuracy, influencing the promotion and further development of the model. In view of this, model developers need to be more attentive to bias risk control and validity verification in the development of models.

H pylori seroprevalence in patients with lung cancer

AIM: To assess H pylori seroprevalence in lung cancer and determine whether there is a potential association between lung cancer and H pylori infection. METHODS: The study was conducted on forty consecutive patients with lung cancer, confirmed by pathology (32 men, 8 women; mean age 55.50 ± 11.91 years, range 16-77 years). Forty healthy subjects (25 men, 15 women; mean age 43.08 ± 12.60 years, range 20-79 years) from the patients’ family members were matched to each case subject on the basis of age and socioeconomic status. H pylori infection was detected with a commercially available immunoglobulin G (IgG) enzyme-linked immunosorbent assay (Trinity kit, Biotech co., USA), previously validated in adults (86% sensitivity, 96% specificity) against a gold standard of culture and histology. RESULTS: H pylori seropositivity was present in 52.5% of patients with lung cancer in comparison to 45.0% of healthy control subjects. Although H pylori seropositivity was more frequent in lung cancer patients than in controls, the difference did not reach statistical significance (OR = 1.35, 95% CI = 0.56-3.25; P = 0.65). In addition, there was no significant difference between cases and controls in terms of gastrointestinal symptoms. CONCLUSION: The earlier described association between H pylori infection and lung cancer was not supported in this study. Further studies with larger sample sizes should be undertaken to assess the frequency of H pylori infection in patients with lung cancer and their potential association.

Up-Regulation of the Gap Junction Intercellular Communication by Tea Polyphenol in the Human Metastatie Lung Carcinoma Cell Line

Our previous study has proven that tea polyphenol has a role in lung neoplasms. The present communication was to investage the anti-proliferation effect of tea polyphenol on the PG cells, which was a high metastatic human lung carcinoma cell line, by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide (MTT) cell viability assay, and to study the change of intracellular calcium concentration, connexin43 (Cx43) expression, gap junctional intercellular communication (GJIC) and cell cycle distribution after the tea polyphenol treatment by laser scanning confocal microscopy and flow cytometry. The results showed that 1) tea polyphenol could kill the PG cells in a dose-depent manner via inhibiting the PG cell proliferation and blocking the PG cell cycle progression staying in G0/G1 phase and not transfering in S and G2/M phases to reduce the PG cell proliferation index;2) the increases of intracellular calcium concentration, GJIC and Cx43 expression were related with the tea polyphenol doses. The data suggested that tea polyphenol could inhibit the growth of PG cells, which mechanism was associated with the up-regulation of GJIC.

Phase Ⅰ/Ⅱ study of gemcitabine and oxaliplatin chemotherapy in combination with concurrent 3-D conformal radiotherapy for locally advanced non-small cell lung cancer

Background and objective Recent studies have showed that combination of chemotherapy and radiotherapy might result in better outcome for locally advanced non-small cell lung cancer (NSCLC). The aim of this study is to determine the maximal tolerance dose (MTD) and efficacy of full-dose gemcitabine and oxaliplatin when given concurrently with 3-dimentional radiation therapy (3D-RT) for locally advanced NSCLC. Methods Oxaliplatin was administered at a fixed dose of 130mg/m^2, and gemcitabine was administered at a starting dose of 800mg/m^2 with an incremental dose gradient of 200mg/m^2 for 3 dose levels. MTD was defined as the immediate dose level lower than the dose at which dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered at 3-week cycle. The RT was given as 3-D conformal manner at a single daily dose of 2Gy for 5 days per week. Results Twenty-two patients were evaluable and distributed to three different dose levels: 6 at level 1, 8 at level 2 and 8 at level 3. Pulmonary toxicity, esophageal and hematologic toxicity were the main DLT. Grade Ⅲ acute pulmonary toxicity occurred in one patient each at level 2 and level 3, both with V20>20%, and grade Ⅲ esophagitis in two patients at level 3. The MTD of gemcitabine in this study was 1000mg/m^2. The overall response rate was 75.0% (9/12). The 1- and 2-year survival rate was 70.0% and 30.5% respectively. The median time to progression was 8.7 months (range 5--11.8 months). Conclusion With reduced radiation volume, gemcitabine of 1000mg/m^2 in combination with oxaliplatin of 130mg/m^2 was effective and could be safely administered for NSCLC.