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.

Prognostic factors in patients with stage IV non-small cell lung cancer

Objective： To investigate the prognostic factors for stage Ⅳ non-small cell lung cancer （NSCLC） with distant metastasis and establish a reliable model of clinical prognostic index. Methods： From January 1990 to April 2005, 313 primary NSCLC patients with metastasis, who had been treated in Shanghai Chest Hospital, were reviewed. Survival time was estimated according to the Kaplan-Meier method. Cox proportional hazard regression model was used for multivariate analysis. Results：Among the 313 cases of non-small cell lung cancer （NSCLC） at stage Ⅳ, there were 218 and 95 patients with metastasis to single and different organs, respectively. The overall median survival time for all 313 cases of NSCLC patients was 10.8 （9.00, 12.30） months and the overall 1-, 2-, 3-, 4- and 5-year survival rate was 45%, 18%, 12%, 4% and 0%. There were 63, 174, 127, 36, 18, 11 and 5 patients with metastasis to brain （20.13%）, bone （55.59%）, lung （40.58%）, liver （11.50%）, adrenal gland （5.75%）, subcutaneous （3.51%） and others, respectively. The survival time was shortest in subcutaneous metastasis （4.6 months）, and liver 7.0 months, brain 8.0 months, adrenal gland 8.6 months, bone 10.6 months, lung 11.8 months. Kaplan-Meier estimation showed that patients anatomic typing, KPS, numbers of organ with metastasis, appetite, liver, adrenal gland and subcutaneous metastasis, body weight loss, smoking, index of smoking, chemotherapy, cycles of chemotherapy were the predictors of survival. Multivariate analysis showed survival statistically significant correlation with anatomic typing, KPS, appetite, liver and subcutaneous metastasis, body weight loss, cycles of chemotherapy. The relative risk （RR） was 1.51, 1.97, 1.55, 1.67, 2.56, and 2.56 respectively. Conclusion： Survival time decreases distinctly in patients who had distant metastasis to more than two different organs （P〈0.01）. Bone is the commonest organ for distant metastasis in lung cancer. The prognosis is poor when lung cancer appears subcutaneous metastasis and liver metastasis. Independent prognostic factors in patient with stage Ⅳ non-small cell lung cancer were liver and subcutaneous metastasis, anatomic typing, KPS, appetite, body weight loss, cycles of chemotherapy.

Expression of Thyroid Transcription Factor-1(TTF-1)in Lung Carcinomas and Its Correlations with Apoptosis and Angiogenesis

OBJECTIVE To investigate the correlations between the expression of thyroid transcription factor-1 （TTF-1） and apoptosis and angiogenesis in lung carcinomas. METHODS A 829 microarray of the paraffin tissue chips was constructed, which contained 196 lung carcinomas, 10 normal lung tissues, and 1 muscular tissue. Terminal deoxynucleotidyl transferase mediated nick end labeling （TUNEL） and immunohistochemical SP method were used to detect apoptosis and expression of TTF-1 and CD34 in different types of lung carcinomas. A Leica Q500 MC image analysis system was used to measure and calculate TTF-1 positive unit （PU）, apoptotic index （AI） and microvessel density （MVD）. RESULTS AI of lung small cell carcinoma and large cell carcinoma were smaller than those of lung adenocarcinoma and squamous cell carcinoma （P = 0.000）. AI of lung carcinomas with lymph node metastases was smaller than that of those without （P = 0.039）. AI of lung carcinomas in TNM stage I-IV was smaller than that in stage I （P = 0.008）. The PU of the TTF-1 was negatively correlated with AI in small cell lung carcinoma （r = -0.752, P = 0.000）. MVD of lung carcinomas without lymph node metastases was smaller than that of those with lymph node metastasis （P = 0.031）. MVD of lung carcinomas in TNM stage I was smaller than that in stage I-IV （P = 0.040）. The PU of TTF-1 was positively correlated with MVD in lung adenocarcinoma （r = 0.708, P = 0.000）. CONCLUSION There is a negative correlation between TTF-1 PU and AI in small cell lung carcinoma. TTF-1 PU and AI may be correlated with each other. There is a positive correlation between TTF-1 PU and MVD in lung adenocarcinoma. TTF-1 may induce the development of lung adenocarcinoma by inducing tumor angiogenesis.

Anti-angiogenesis therapy for lung cancer: the shore and the other shore

Angiogenesis is known to be an important event in tumor growth. In preclinical and clinical researches, anti-angiogenesis therapy has made great progress, but there are still many problems for future anti-angiogenesis therapy. Here, we review recently completed clinical trials of emerging antiangiogenic agents in patients with non-small cell lung cancer(NSCLC) and discuss the challenges of anti-angiogenic therapy.

HRCT Scans of Peripheral Non-Small Cell Lung Cancers and their Relationship with Cyclin D1 Expression:a Longitudinal Study

OBJECTIVE To investigate cyclin D1 expression in peripheral lung cancers and its relationship with CT signs and prognosis. METHODS Cyclin D1 expression in peripheral lung cancers and its relationship with the CT imaging and prognosis were analyzed retrospectively by means of SP immunohistochemistry and spiral CT scanning in 92 patients with peripheral lung cancer verified by pathology. RESULTS Cyclin D1 expression was related to deep lobulation,spiculate protuberance,short thin spinules sign and mediastina lymph node metastasis.Cyclin D1 expression was not related to tumor size,cavity,pleural indentation,histological type,differentiation,tumor TNM stage,age or sex.Cyclin D1 was a negative prognostic factor whose over-expression indicated a poor prognosis. CONCLUSION Cyclin D1 expression may play an important role in the occurrence,progress and CT scan results of lung cancers.Cyclin D1 was a negative factor whose over-expression implied a poor prognosis.Detection of the cyclin D1 and observation of the CT scan can be considered as indexes of clinical diagnosis and prognostic evaluation.

Multi-Targeted Therapies in Non-Small Cell Lung Cancer

Current treatment modalities provide limited improvement in the natural course of lung cancer, and prognosis remains poor. Lung cancer is a malignancy with great molecular heterogeneity. The complexity of the signaling process leading to cancer cell proliferation and to the neoplastic phenotype supports the necessity of interfering at different stages to avoid cancer cell resistance to therapy. For this reason, new strategies for the simultaneous inhibition of multiple molecular targets are being pursued.

The short-term efficacy of icotinib on the treatment of advanced non-small-cell lung cancer

Objective： The aim of the study was, （1） to observe the short-term efficacy and adverse reactions of icotinib hydrochloride on the treatment of advanced non-small cell lung cancer （NSCLC）; （2） to explore whether there is difference in the efficacy of icotinib hydrochloride among the subgroups of sex, age, smoking history, classification of CEA, histological type, multi-line treatment and PS score. Methods： The study was conducted to collect 138 patients taking icotinib hydrochloride with advanced non-small cell lung cancer in hospitals of Dalian （China） from September 1st 2011 to June 14th 2012. All patients had taken icotinib hydrochloride （125 mg three times a day） until the disease was progressed or the adverse reactions could not be tolerated. During the period of taking it, other anti-tumor treatments were forbidden. We observed the symptoms, such as cough, short breath, hemoptysis, pain. The objective efficacy was evaluated by RECIST criteria, and the adverse reactions related to the treatment was assessed on the basis of NCl-CTC 3.0. Results： Of all patients, CR was 1 （0.7%）, PR was 59 （42.8%）, SD was 37 （26.8%）, PD was 41 （29.7%）. And ORR was 43.5% （60/138）, DCR 70.3% （97/138）. The DCR of females was 83.5% （71/85） versus 49.1% （26/53） of males. The difference of ORR and DCR between the two subgroups had statistical significance （X2 = 8.065, P = 0.05; X2 = 18.577, P = 0.000）. The difference of ORR and DCR between the subgroups of patients after or before 70 years old had no statistical significance. The difference of ORR and DCR between the subgroups of smoking and non-smoking had statistical significance （X2 = 8.492; X2 = 13.602）. The difference of ORR and DCR between the CEA subgroups had statistical significance （X2 = 14.141; X2 = 14.160）, showed 81 patients with abnormal CEA before the treatment with ORR 56.8.0% （46/81）, DCR 81.5% （66/81）; 57 patients of normal CEA before the treatment with ORR 24.6% （14/57）, DCR 52.6% （30/57）. The 36 patients （26.1%） using icotinib hydrochloride as the first-line treatment, 78 patients （56.5%） using icotinib hydrochloride as the second-line, 20 patients （14.5%） using icotinib hydrochloride as the third-line, and 4 patients （2.9%） with tyrosine kinase inhibitor （TKI） resistance, there was statistical difference of DCR among the multi-groups above （~2 = 11.734, P = 0.008）. ORR was 31.1% （14/45） versus DCR 53.3% （24/45） in 45 patients with PS 3-4 points, and ORR was 49.4% （46/93） versus DCR 78.5% （73/93） in 93 patients with PS 0-2 points, and there was statistical difference （X2 = 4.156; X2 = 9.149）. The main adverse reactions were rash （26.8%）, diarrhea （13.8%）, mild liver function abnormal （10.9%）. Conclusion： The short-term efficacy of icotinib hydrochloride on the treatment of advanced NSCLC is positive, and the relevant adverse reactions are mild. The efficacy is better when the patient is female, non-smoker, treated as first-line, with higher CEA before treatment and lower PS scores.

The effect of low dose radiation on cytokine correlated to injury of lungs induced by Bleomycin A5

Objective： The aim of this study was to explore the effect of low dose radiation on cytokine excreted by mice inbreathing of atomization of PYM. Methods： Kunming male mice were randomly divided into three groups： blank group, PYM group （P group）, low dose radiation ＋ PYM group （P ＋ L group）. Mice of P ＋ L group were given whole body low dose radiation 75 mGY, dose rate were 12.5 mGY/min. After 6 h, mice in both P ＋ L group and P group were given inbreathe of atomization of PYM, concentration was 2 mg/mL. Mice were sacrificed after the dl, d7, d14, d21 and d28, IL-6 were detected in alveolar irrigating solution. The tissue samples of mice lung were fixed in 10% formalin, TNF-α and TGF-β were analyzed by immuno- histochemistry. Results： Compared with P group, IL-6 in low dose radiation ＋ PYM group were lower, near to blank group, the difference had notable statistical significance on the dl and the d7, while on the d14, d21, d28, the difference had not statisti- cal significance. It suggested that low dose radiation could reduce the resection of IL-6 at the begin of lung injure induced by low dose radiation. The expression of TGF-β and TNF-α in P ＋ L group were lower than that in P group, but the difference in the two groups had statistical significance by gray analysis P 〈 0.05. Conclusion： In the early stage of lung injure caused by PYM in mice, low dose radiation of 75 mGY can reduce the secretion of IL-6, decrease the production of TGF-β and TNF-α.

Screening study on new tumor marker periplakin for lung cancer

Objective: The aim of this study was to use lung cancer targeting binding polypeptide ZS-9 to screen cDNA library of human lung cancer and obtain ZS-9 specific ligand to confirm tumor marker of non small-cell lung cancer. Methods: Artificially synthesize biotin labeled peptide ZS-9, anchored ZS-9 in the enzyme label plate coupled by avidin, used ZS-9 as probe to screen cDNA library of human lung cancer, after screening, obtained bacteriophage clone specifically binding with anchored polypeptide ZS-9. Extracted plasmid of bacteriophage and performed sequencing after amplified by PCR. Results: It was demonstrated by bioinformatic analysis on the sequence of ligand binded by lung cancer specific peptide ZS-9 that the ligand was the cytoskeletal protein periplakin on the surface of lung cancer cells, suggesting that periplakin might be a new marker for non-small-cell lung cancer in lung cancer. Conclusion: Use specific lung cancer binding peptide to screen new tumor marker periplakin in lung cancer and further studies on its biologic functions in genesis and development of lung cancer are still needed.

Clinical significance of Smac expression on non-small cell lung cancers

Objective:The aim of our study was to investigate the clinical significance of Smac(second mitochondria-derived activator of caspase) expression on non-small cell lung cancer(NSCLC).Methods:The expression of Smac was evaluated on RNA and protein level in tumor tissues.The expression of Smac mRNA was examined by RT-PCR in 59 samples of tumor tissues and matched normal lung tissues.The expression of Smac protein was examined by IHC in 213 cancer tissues.Results:The positive rate of Smac mRNA was found in 59.3% of cancer tissues,but only in 30.5% of matched normal tissues(P<0.05).The positive rate of Smac protein was 76.5%.The expression of Smac in stage II disease was significantly higher than that in stage I disease(P=0.001).The survival of patients with Smac overexpression was significantly shorter than those who were negative.Conclusion:Smac might be involved in the progression of NSCLC,the biologic significance of Smac in primary lung cancer needs further study.

Vasculogenic mimicry in non-small cell lung cancer and its relationship with tumor stage

Objective： The purpose of the study was to study the mechanism of vasculogenic mimicry （VM） and its relationship with tumor stage in non-small cell lung cancer （NSCLC）. Methods： Forty-two patients with NSCLC were collected, 19 belonged to the early stage （stages Ⅰ ＋Ⅱ） while 23 were late stage （stages Ⅲ ＋ Ⅳ）. Moreover, 20 patients got surgical treat ment and 22 got chemotherapy. We studied the relationship of VM with stage, chemotherapeutic effect, HIF-la, microves sel density （MVD） and clinicopathologic features. Results： VM in patients of early stages were significantly more than late stages （68.4% vs 26.1%, P = 0.006）, and the positive rate of VM was proportional to HIF-la （P = 0.034）. But no correlation was found between VM and chemotherapeutic effect （14.3% vs 26.7%, P = 1.00） or MVD （P 〉 0.05）. Furthermore, we found VM also showed a negative correlation with distant metastases and lymph nodes metastases （P 〈 0.05） while no correlation was found with other clinicopathologic. Conclusion： VM was generated during the early stage in NSCLC and correlated with lymph nodes metastases. As the disease progressed, VM may be replaced by vascular endothelial cells, so the late-stage patients especially people with distant metastases had fewer VM. As the main factor produced by hypoxia, HIF-la may make a difference in VM formation. Thus we inferred VM might be a new target for targeted therapy, and could provide help for clinical staging and treatment.