Oncogenic ras results in increased cell kill due to defective thermoprotection in lung cancer cells

Background. The survival response of normal cells to heat stress is an upregulation of heat shock proteins and ras protein activation. We hypothesized that in lung cancer cells the presence of oncogenic ras interferes with thermoprotective mechanisms resulting in cell death.

Methods. An equal number of lung tissue culture cells (normal and cancerous) were subjected to either heat stress and then recovery (43°C for 180 minutes, 37°C for 180 minutes) or recovery alone (37°C for 360 minutes). End points were surviving number of cells, cell-death time course, heat shock protein (HSP70, HSC70, HSP27) expression before and after heat stress, and time course for HSP70 expression during heat stress and recovery. Heated cells were compared with unheated control cells, then this difference was compared between cell types.

Results. Heat stress in normal cells caused an 8% decrease in cell number versus a 78% ± 5% decrease in cancer cells (p < 0.05). In normal cells, heat stress caused a 4.4-fold increase in HSP70, no change in HSC70, and a 1.7-fold increase in HSP27. In contrast, cancer cells initially contained significantly less HSP70 (p < 0.05), and there was a 27-fold increase in HSP70 and a 2-fold increase in HSC70 with no HSP27 detected (comparison significant, p < 0.05). HSP70 time course in normal cells showed that HSP70 increased 100-fold, reaching a vertex at 2 hours and remaining elevated for 24 hours; in cancer cells, HSP70 maximum expression (100-fold) peaked at 5 hours, then decreased to slightly elevated at 24 hours.

Conclusions. Cancer cells with oncogenic ras have defective thermoprotective mechanism(s) causing increased in vitro cell death, which provides an opportunity for thermal treatment of lung cancer.     

Oncogenic emergencies: appropriate treatment in lung cancer

Several critical situations in patients with lung cancer are considered oncogenic emergencies. For example. massive hemoptysis, severe airway stenosis, retention of large amounts of pleural and pericardial effusion, and superior vena cava syndrome are situations requiring immediate care. For uncontrollable massive hemoptysis, embolization of the bronchial artery is a useful treatment method. For airway stenosis, rapid widening of the airway by endoscopic surgery is necessary. Since massive retention of pleural or pericardial effusion is life-threatening prompt drainage is required. For brain metastasis with increased intracranial pressure, decompression surgery is useful to prevent brain herniation. Spinal cord compression by epidural metastasis is considered to be an indication for emergency decompressive laminectomy in selected patients. Since the severity of emergent situations varies individually, the appropriate treatment should be determined based on the clinical condition of individual patients.     

转bak基因协同阿霉素杀伤膀胱癌耐药细胞

目的：研究转bak基因与阿霉素（ADM）联合杀伤膀胱癌耐药细胞的效果,并探讨其机制。方法：利用脂质体将基因bak导入膀胱癌耐药细胞,通过原位杂交法检测bak mRNA的表达,同时加入ADM,利用MTT法算出细胞生存率,进而推算半数抑制浓度（IC50）和抗药指数。用荧光分光光度计检测细胞内ADM的聚集量。结果：转基因后,细胞内bak mRNA阳性表达、细胞生存率较单用ADM明显降低（P＜0．05）,细胞内ADM聚集量无明显增加（P＞0．05）。结论：转bak基因可以协同ADM更有效杀伤膀胱癌耐药细胞,但并非通过帮助ADM进入细胞起作用。     

Exploring exposure to Agent Orange and increased mortality due to bladder cancer

Background

During the Vietnam War, many veterans were exposed to Agent Orange (AO), a chemical defoliant containing varying levels of the carcinogen dioxin. The health effects of AO exposure have been widely studied in the VA population. Here we review and interpret data regarding the association between AO exposure and bladder cancer (BC) mortality.

Long-term results of operation for non-small cell lung cancer in the elderly

We surgically treated 185 patients with non-small cell lung cancer who were 70 years old or older. The operative mortality rate was 3%, and the 5-year survival rate was 48%. The mortality and prognosis were similar to those in younger patients. The number of elderly patients who smoked heavily or who had ventilatory defects was high, but the incidence of pneumonectomy was low. There were no differences based on age in regard to histological type, TNM classification, and curability. Pulmonary complications occurred in 21% of the elderly patients and were correlated with preoperative pulmonary function and smoking habits. When the elderly are to undergo elective pulmonary resection for lung cancer, the preoperative evaluation of pulmonary function should be thorough, and both preoperative and postoperative physical therapy should be given. If postoperative pulmonary function is predicted to be less than 0.8 L/m2 of vital capacity and 0.6 L/m2 of forced expiratory volume in 1 second, a limited resection or nonsurgical therapy should be considered.     

Inhibition of NF-kappaB sensitizes non-small cell lung cancer cells to chemotherapy-induced apoptosis

BACKGROUND: Most non-small cell lung cancers (NSCLC) are chemoresistant. Identification and modulation of chemoresistance cell-signaling pathways may sensitize NSCLC to chemotherapy and improve patient outcome. The purpose of this study was to determine if chemotherapy induces nuclear factor-kappa B (NF-kappaB) activation in NSCLC in vitro and whether inhibition of NF-kappaB would sensitize tumor cells to undergo chemotherapy-induced apoptosis. METHODS: Non-small cell lung cancer cells were treated with gemcitabine, harvested, and nuclear extracts analyzed for NF-kappaB DNA binding by electrophoretic mobility shift assays. Additionally, NSCLC cells that stably expressed a plasmid encoding the superrepressor IkappaBalpha protein (H157I) or a vector control (H157V) were generated. These cells were then treated with gemcitabine and apoptosis determined by terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay. RESULTS: Chemotherapy induced NF-kappaB nuclear translocation and DNA binding in all NSCLC cell lines. H157I cells had enhanced cell death compared with H157V cells, suggesting that NF-kappaB is required for cell survival after chemotherapy. The observed cell death following the loss of NF-kappaB occurred by apoptosis. CONCLUSIONS: Inhibition of chemotherapy-induced NF-kappaB activation sensitizes NSCLC to chemotherapy-induced apoptosis in vitro. Novel treatment strategies for patients with advanced NSCLC may involve chemotherapy combined with inhibition of NF-kappaB-dependent cell-survival pathways.     

Adhesion or organization during surgery due to mediastinoscopy before induction therapy for non-small cell lung cancer

We conducted a retrospective study to investigate amounts of adhesion or organization during surgery due to mediastinoscopy before induction therapy for non-small cell lung cancer (NSCLC). A case series of 13 patients (c-stage IIIA in 11 and IIIB in 2) with right-side NSCLC who underwent induction therapy were assessed. They were between 39 and 71 years old and 8 males and 5 females. Induction therapy was chemotherapy alone in 4 cases and chemo-radiotherapy in 9 cases. The mediastinocopy was used in 4 cases. Mediastinal lymph node resection was incomplete in 3 of the 4 (75%) cases among the mediastinoscopy group but the no-mediastioscopy group had no incomplete resection (p = 0.01), though 2 of the 9 (22%) cases among the chemo-radiation group and 1 of the 4 (25%) among the chemo alone group (p > 0.9). Severe adhesion or organization can occur after the mediastinoscopy and induction therapy, which might be a course of incomplete mediastinal lymph node resection.     

Long-term results after pulmonary resection in elderly patients with non-small cell lung cancer

BACKGROUND: The number of elder by patients with lung cancer is expected to increase. But, there was no report that 10 years completely passed in surgically treated elderly patients (E-pts). This study assesses late results of surgery. METHODS: From 1981 to 1987, 160 patients with non-small cell lung cancer underwent lobectomy or pneumonectomy with mediastinal lymph node dissection. Of these, 37 (23%) were 70 years of age or older. The outcome of this group was compared with that of 123 non-elderly patients (NE-pts). RESULTS: There were no significant differences in the background between E-pts and NE-pts. Five- and 10-year survivals in the E-pts were 35.1%, and 24.3%, respectively. In outcome more than 5 years from operation, E-pts had a significantly poorer prognosis than NE-pts (p=0.04) by any causes of death, but a similar prognosis by primary death. E-pts died of nontumor-related death significantly more than NE-pts (p=0.6). CONCLUSIONS: This study showed that E-pts could consummate their lives completely. Additionally, when long-term prognosis of the postoperative E-pts was discussed, we should contemplate that E-pts had more deaths from nontumor-related causes.     

Short-term results of radical surgeries for non-small cell cancer of the lung

The results of radical surgical treatment of 358 patients with NSCCL were analyzed. Majority of patients were men (84.6%) and persons older 60 years -- 239 (66.8%) patients. Central cancer was diagnosed in 164 (45,8%) patients, peripheral -- in 194 (54.2%). There were 137 (38.3%) pneumonectomies, 184 (51.4%) lobectomies; 149 (41.6%) surgeries were combined. Complications after radical surgeries were seen in 92 (25.7%) of 358 patients, including 18 (5.0%) patients with complications and 74 (21%) patients with ones. Complications were seen more often in patients over 60 years and occurred less frequently after segmentectomy (7 patients). Lethality was 5.0% (18 patients). Respiratory complications (7 cases) and pulmonary embolism (5 patients) were the main causes of lethal outcome.     

Progress in lung cancer: Non-oat cell (non-small cell lung cancer)

Lung cancer remains the greatest killing cancer in the United States with 149,000 new cases expected in 1987. The present expected mortality rate is 87 per cent. More women in the United States died of lung cancer than breast cancer in 1986. Asymptomatic, early and curable lung cancer in high risk individuals is usually found by routine chest X-ray. So-called Stage I lung cancer was reported to have a 83 per cent survival rate at three years by Martini and Beattie in 1977 and 70 per cent five year survival rate subsequently. When the more than 30,000 volunteer males were enrolled in the National Cancer Institute, national lung program for screening, 223 unsuspected lung cancers were found. 47 per cent were Stage I with a survival rate at five years of over 76 per cent. The PMI-Strang/Memorial Sloan Kettering Cancer Center study found 53 cancers in its first screen and 235 lung cancers over the next eight years of the study. Forty per cent were Stage I with a five year survival rate of 70 per cent. Sputum cytology as compared to chest X-ray was of little additional value. Studies (Martini) of N1 lung cancer was found to have a 49 per cent survival rate following resection. The N2 group of lung cancers where the mediastinal tumor was surgically removable and followed by external radiation therapy had a 27 per cent survival rate at five years. Those tumors with solitary brain metastases where the solitary brain metastasis could be resected and the primary tumor controlled, gave a 27 per cent survival rate at six years. The group of advanced N2 disease where the mediastinum could not be completely cleared were a serious group of cancers. A study of 100 patients treated from 1977 to 1980 with surgery plus internal radiotherapy followed by external radiotherapy had an overall 22 per cent survival rate for four to eight years with most of the deaths occurring because of metastases outside the chest. More recently chemotherapy has been used pre-operatively for those individuals with advanced lung cancer in the chest then followed by a combination of surgery, internal radiotherapy, external radiotherapy and more chemotherapy, if chemotherapy sensitive. This is the so-called multidisciplinary approach. In our present early studies it seems that those so treated who are chemotherapy sensitive have a 44 per cent, two year survival rate in a group of patients considered to have extremely poor prognosis. Director Kriser Lung Cancer Center, Chief Thoracic Surgery, Director Clinical Cancer Programs, Beth Israel Medical Center Chief Medical Officer Emeritus, Attending Surgeon, Member of Board of Overseers, Memorial-Sloan-Kettering Cancer Center This report is the gist of a paper read by E.J.B. at the 87th Annual Congress of the Japanese Surgical Society, Tokyo, Japan, 1987.     

Spontaneous splenic rupture due to splenic metastasis of lung cancer

We report the case of a patient who underwent splenectomy for spontaneous rupture of the spleen due to splenic metastasis. Pathologic examination revealed diffuse infiltration by carcinoma. Chest X-ray revealed a right lung superior lobe tumor, related to poorly differentiated carcinoma. Total splenectomy is a good option for diagnosis and treatment of splenic metastases.     

胚胎干细胞抗Lewis非小细胞肺癌作用的体内研究

目的 研究胚胎干细胞动物体内抗Lewis非小细胞肺癌的作用及初步机制.方法 以小鼠Lewis肺癌模型为基础,检测实验组和对照组小鼠的肿瘤生长情况和免疫指标,探讨胚胎干细胞在体内的抗肿瘤作用及其初步分子免疫机制.结果 肿瘤生长曲线显示,与对照组小鼠相比,实验组小鼠肿瘤的生长速度明显减慢,从实验的第5天开始两组小鼠的肿瘤体积相比差异均有统计学意义(P＜0.05).小鼠外周血T、B淋巴细胞亚群检测结果,与对照组小鼠相比,实验组小鼠外周血CD4+、CD8+淋巴细胞比例增加,差异有统计学意义,分别为P＜0.05、P＜0.01,CD19+淋巴细胞比例下降(P＜0.05).血清细胞因子(IL-2、IL-4和IFN-γ)检测结果,与对照组相比,实验组小鼠外周血中IL-2和IFN-γ细胞因子水平增高,差异有统计学意义(P＜0.05),IL-4略有增高但无统计学意义.结论 胚胎干细胞不仅在体外具有明显的抗肿瘤作用,在动物体内胚胎干细胞也能通过激活免疫系统从而产生有效的抗肿瘤作用,抑制或延缓肿瘤的形成和发展.

Abstract：

Objective To investigate the function and mechanism of embryonic stem cells against Lewis non-small cell lung cancer in vivo. Methods Based on the mouse Lewis non-small cell lung cancer model, we have tested some tumor growth indexes and investigated the immune response of embryonic stem cells against cancer cells. Results Compared with the mice in control group, mice in experimental group received obvious antitumor immunity, which means more activated lymphocytes and antitumor cytokines, resulted in the effective control and inhibition of tumor development. Conclusion Besides the antitumor effect in vitro, embryonic stem cells can also generates immune response in vivo, which could effectively inhibit and/or delay the development of cancer.     

Role of fiberscopic transbronchial needle aspiration in the staging of N2 disease due to non-small cell lung cancer

BACKGROUND: Transbronchoscopic needle aspiration (TBNA) can offer a unique opportunity to identify surgically unresectable lung cancer and to avoid surgical mediastinal exploration in many patients with mediastinal lymph node extension of the tumor. The aim of this study was to assess the yield of TBNA performed with either histology or cytology needles in mediastinal staging of N2 disease due to non-small cell lung cancer (NSCLC). METHODS: Retrospective chart review was carried out on 194 TBNA procedures performed between January 1997 and September 2000 at a single institution. Inclusion criteria were pathologic evidence of NSCLC; contrast enhancement computed tomography scan of the chest suggesting N2 disease; and negative bronchoscopic examination for possible neoplastic lesions at the site of RESULTS: Overall sensitivity and diagnostic accuracy were 71% and 73%, respectively, with no significant differences between 19-gauge and 22-gauge cytology needles. Procedures performed for right paratracheal and subcarinal lymph node stations had a significantly higher yield than those for the left paratracheal station. CONCLUSIONS: TBNA mediastinal staging, performed during the initial diagnostic evaluation of NSCLC, can spare costs and risks of more invasive procedures in patients with inoperable tumors, in patients who are not candidates for operation because of coexistent significant comorbidities, and in patients with N2 disease.     

Surgery after neo-adjuvant therapy of non-small cell lung cancer. Preliminary results]

The Authors report their personal experience of surgical treatment following neo-adjuvant therapy in NSCLC (III a N2) in order to assess: 1) the feasibility and safety of surgical treatment following major responses to neoadjuvant chemotherapy; 2) the sectile rate; and 3) the survival rate. Preliminary results show that: 1) chemotherapy using cisplatin and VP-16 gives a high rate of major responses in these patients; 2) surgery is feasible; 3) there is high radical sectile rate; 4) further research is needed to obtain statistical significance.