Background: Lung cancer is one of the most common types of cancer causing high morbidity and mortality worldwide. An increasing incidence of lung cancer has been observed in India. Objectives:To evaluate the clinicpathological profile and haematological abnormalities associated with lung cancer in Bangalore, India. Materials and Methods: This prospective study was carried out over a period of 2 years. A total of 96 newly diagnosed and histopathologically confirmed cases of lung cancer were included in the study. Results: Our lung cancer cases had a male to female ratio of 3:1. Distribution of age varied from 40 to 90 years, with a major contribution in the age group between 61 and 80 years (55.2%). Smoking was the commonest risk factor found in 69.7% of patients. The most frequent symptom was cough (86.4%) followed by loss of weight and appetite (65.6%) and dyspnea (64.5%). The most common radiological presentation was a mass lesion (55%). The most common histopathological type was squamous cell carcinoma (47.9%), followed by adenocarcinoma (28.1%) and small cell carcinoma (12.5%). Distant metastasis at presentation was seen in 53.1% patients. Among the haematological abnormalities, anaemia was seen in 61.4% of patients, leucocytosis in 36.4%, thrombocytosis in 14.5% and eosinophilia in 19.7% of patients. Haematological abnormalities were more commonly seen in non small cell lung cancer. Conclusions: Squamous cell carcinoma was found to be the most common histopathological type and smoking still remains the major risk factor for lung cancer. Haematological abnormalities are frequently observed in lung cancer patients, anaemia being the commonest of all.
The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anti-cancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.
Cichello, Simon Angelo;Yao, Qian;Dowell, Ashley;Leury, Brian;He, Xiao-Qiong
Asian Pacific Journal of Cancer Prevention
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v.16
no.11
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pp.4781-4786
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2015
Siberian ginseng (Eleutherococcus senticosus) is used primarily as an adaptogen herb and also for its immune stimulant properties in Western herbal medicine. Another closely related species used in East Asian medicine systems i.e. Kampo, TCM (Manchuria, Korea, Japan and Ainu of Hokkaido) and also called Siberian ginseng (Acanthopanax senticosus) also displays immune-stimulant and anti-cancer properties. These may affect tumour growth and also provide an anti-fatigue effect for cancer patients, in particular for those suffering from lung cancer. There is some evidence that a carbohydrate in Siberian ginseng may possess not only immune stimulatory but also anti-tumour effects and also display other various anti-cancer properties. Our study aimed to determine the inhibitory and also proliferative effects of a methanol plant extract of Siberan ginseng (E. senticosus) on various cancer and normal cell lines including: A-549 (small cell lung cancer), XWLC-05 (Yunnan lung cancer cell line), CNE (human nasopharyngeal carcinoma cell line), HCT-116 (human colon cancer) and Beas-2b (human lung epithelial). These cell lines were treated with an extract from E. senticosus that was evaporated and reconstituted in DMSO. Treatment of A-549 (small cell lung cancer) cells with E. senticosus methanolic extract showed a concentration-dependent inhibitory trend from $12.5-50{\mu}g/mL$, and then a plateau, whereas at 12.5 and $25{\mu}g/mL$, there is a slight growth suppression in QBC-939 cells, but then a steady suppression from 50, 100 and $200{\mu}g/mL$. Further, in XWLC-05 (Yunnan lung cancer cell line), E. senticosus methanolic extract displayed an inhibitory effect which plateaued with increasing dosage. Next, in CNE (human nasopharyngeal carcinoma cell line) there was a dose dependent proliferative response, whereas in Beas-2 (human lung epithelial cell line), an inhibitory effect. Finally in colon cancer cell line (HCT-116) we observed an initially weak inhibitory effect and then plateau.
Background: The anti-tumor therapeutic effect of autologous tumor cell lysate pulseddendritic cells (DCs) was studied for non-immunogenic and immune suppressive lung cancer model. To test the possibility as an adjuvant therapy, minimal residual disease model was considered in mouse in vivo experiments. Methods: Syngeneic 3LL lung cancer cells were inoculated intravenously into the C57BL/6 mouse. Autologous tumor cell (3LL) or allogeneic leukemia cell (WEHI-3) lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, tumor formation in the lung and the tumor-specific systemic immunity were observed. Tumor-specific lymphocyte proliferation and the IFN-${\gamma}$ secretion were analyzed for the immune monitoring. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with tumor cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor formation was suppressed in 3LL tumor cell lysate pulsed-DC treated group, while 3LL-specific immune stimulation was minimum. WEHI-3-specific immune stimulation occurred in WEHI-3 lysate-pulsed DC treated group, which had no correlation with tumor regression. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs as an adjuvant therapy for minimal residual disease state of lung cancer. The significance of immune modulation in DC therapy including the possible involvement of NK cell as well as antigen-specific cytotoxic T cell activity induction was discussed.
Purpose: This analysis was conducted to evaluate the efficacy and safety of irinotecan based regimens as second-line chemotherapy in treating patients with small cell lung cancer. Methods: Clinical studies evaluating the efficacy and safety of irinotecan based regimens as second-line chemotherapy for patients with small cell lung cancer were identified using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In irinotecan based regimens as second-line chemotherapy, 4 clinical studies which including 155 patients with small cell lung cancer were considered eligible for inclusion. In all chemotherapy consisted of irinotecan with or without nedaplatin. Pooled analysis suggested that, in all patients, the pooled RR was 27.1% (42/155) in irinotecan based regimens. Nausea, vomiting, diarrhea and myelosuppression were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related death occurred with the irinotecan based treatments. Conclusion: This systemic analysis suggests that irinotecan based regimens as second-line chemotherapy are associated with mild response rate and acceptable toxicity for patients with small cell lung cancer.
The synchronous primary lung cancer is very rare cancer, proportion of synchronous lung cancer is about 1∼2% of total lung cancer, When pathologic type is same, preoperative diagnosis is very difficult and it may be misdiagnosed as lung to lung metastasis. We have experienced synchronous primary lung cancer of heterogenous squamous cell carcinoma.
A major obstacles to evaluation of newly-developed treatment strategy for human lung cancer has been the lack of appropriate experimental animal models. We describe a new experimental model of orthotopically-developed non-small cell lung cancer in nude rat, involving inoculation of tumor cell suspension by thoracotomy. Over 40 direct implantation to the periphery of the lung has been performed to date, each requiring less than'1 hour for completion. This model has been used to perform a series of experiments to investigate whether the rat lung and surrounding structures trapped tumor cells with 2 different non-small cell lung cancer cell lines(NCI-H46O and NCI-H1299). Every animal showed development of tumor masses, which were loculated at the periphery of the lung karenchyma and identified also by radiography. After 3 weetu of the inoculation, tumor develop meat at the mediastinal strutures were identified. The life expectancies of the victims were different between the cell lines, but were approximately 5 weeks when NCI-H46O cell line was used. This new orthotopic lung cancer model may be facilitate future studies of the new therapeutics of localized non-small cell lung cancer .
Oguz, Arzu;Unal, Dilek;Kurtul, Neslihan;Aykas, Fatma;Mutlu, Hasan;Karagoz, Hatice;Cetinkaya, Ali
Asian Pacific Journal of Cancer Prevention
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v.14
no.7
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pp.4325-4328
/
2013
Introduction: The influence of season at diagnosis on cancer survival has been an intriguing issue for many years. Most studies have shown a possible correlation in between the seasonality and some cancer type survival. With short expected survival, lung cancer is an arena that still is in need of new prognostic factors and models. We aimed to investigate the effect of season of diagnosis on 3 months, 1 and 2 years survival rates and overall survival of non small cell lung cancer patients. Materials and Methods: The files of non small cell lung cancer patients that were stages IIIB and IV at diagnosis were reviewed retrospectively. According to diagnosis date, the patients were grouped into 4 season groups, autumn, winter, spring and summer. Results: A total of 279 advanced non small cell lung cancer patients' files were reviewed. Median overall survival was 15 months in the entire population. Overall 3 months, 1 and 2 years survival rates were 91.0%, 58.2% and 31.2% respectively. The season of diagnosis was significantly correlated with 3 months survival rates, being diagnosed in spring being associated with better survival. Also the season was significantly correlated with T stage of the disease. For 1 and 2 years survival rates and overall survival, the season of diagnosis was not significantly correlated. There was no correlation detected between season and overall survivals according to histological subtypes of non small cell lung cancer. Conclusion: As a new finding in advanced non small cell lung cancer patients, it can be concluded that being diagnosed in spring can be a favorable prognostic factor for short term survival.
The lung adenocarcinoma is considered more aggressive than other types of non-small cell lung cancer. As metabolites of tryptophan degradation along the kynurenine pathway, including kynurenic acid, have been shown to induce immunosuppression and facilitate escape of tumor cells from immune surveillance, a hypothesis was set up that differences in biological behavior between types of lung cancer may be associated with altered activity of the kynurenine metabolic pathway. The aim of the study was to determine kynurenic acid levels in the serum of patients with bronchial adenocarcinoma for comparison with other types of non-small cell lung cancer. A total of 227 patients with non-small cell lung cancer were enrolled in the study, including 71 with adenocarcinoma and 96 with squamous cell carcinoma. Serum kynurenic acid concentration was determined with use of high performance liquid chromatography and fluorometry. The level of kynurenic acid in the serum of patients with adenocarcinoma was significantly higher than in those with squamous cell lung cancer ($107.1{\pm}62.8$ pmol/ml; 95%CI: 92.4 to 132.3 pmol/ml versus $82.1{\pm}47.6$ pmol/ml; 95%CI: 78.5 to 91.2 pmol/ml, respectively; p = 0.027). Differences between other histological types of lung cancer were insignificant. We conclude that increased activity of kynurenine metabolic pathway manifested by elevated serum kynurenic acid level may be one of the factors associated with clinically distinct biological behavior of adenocarcinoma, in particular high invasiveness and rapid progression.
Background: Lung cancer and chronic obstructive lung disease often coexist in the same person who are elderly and cigarette smoking. There are several reports that the presence of chronic obstructive pulmonary disease constitutes an independent risk factor for the development of lung cancer. Moreover, the association between mucus hypersecrtion and lung cacer has been reported. Method: In 72 cases with primary lung cancer which were confirmed histopathologically at Chonbuk University Hospital from August 1986 to July 1991, We evaluated the relationship between spirometry and lung cancer characteristics. Results: Six cases(8.3%) showed normal lung function, 16(22.2%) cases showed pure restrictive lung disease, 46(63.9%) cases showed moderated obstructive lung disease and 4(5.6%) cases showed severe obstructive lung disease. $FEV_1$(%) was lower in central type than in peripheral type, lower in advanced non-small cell cancer and lower in subjects with phlegm. $FEV_1$/FVC(%) was higher in small cell cancer than in squamous cell cancer and higher in patients without previous pulmonary disease than with previous pulmonary disease. But there was no statistically significant difference in lung function according to histologic types and smoking history. Lung cancers with $FEV_1$/FVC less than 75% consisted of 35 cases of squamous cell cancer, 7 of small cell cancer(14%), 5 of adenocarcinoma(10%), 2 of large-cell carcinoma and 1 of unclassified carcinoma. Squamous cell carcinoma occured more in patients with $FEV_1$/FVC<75% than with $FEV_1$/FVC$\geq$75%(p<0.05). Conclusion: It was suggest that low $FEV_1$/FVC, as reflection of obstructive lung disease, may be at greater risk for squamous cell carcinoma in cigarette smoker.
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