Tag Archives: Lung cancer

Chemoprevention of Lung Cancer in Transgenic Mice: Use of Transgenic Mouse Model in Chemoprevention Studies

Chemoprevention of Lung Cancer in Transgenic Mice: Use of Transgenic Mouse Model in Chemoprevention StudiesWe examined the effects of two potential agents on the development of adenomas/adenocarcinomas in these mice. The two classes of agents examined were budes-onide’ and the FTI inhibitor L778,123. The former is a glucocorticoid that presumably interacts with the glucocorticoid receptor, and has been shown to be a profoundly effective agent in the A/J mouse model. L778,123 inhibits the farnesyltransferase enzyme that transfers farnesyl onto proteins and allows their transport to and activation in the cell membrane. FTI inhibitors were initially produced because they should block the farnesylation of the mutant Ras oncogenes (H-ras, N-ras, and K-ras). Although they effectively block H-ras and N-ras farnesylation and activation, they do not block farnesylation of K-ras due apparently to the high affinity of this protein for the farnesyltransferase enzyme. We examined the abilities of these agents to inhibit tumor formation either in a prevention setting in which budes-onide was administered beginning prior to benzo(a)pyrene and throughout the study or in a delayed experiment, which we feel may be closer to that achieved in former or current smokers. http://www.patanol-eyedrops.com/

Chemoprevention of Lung Cancer in Transgenic Mice: Lung tumors

The incidence of lung tumors in all four groups of treated mice was 100%. p53+/-Ink4a/Arf+/+, and p53+/-Ink4a/ Arf+/- mice carrying a mutant p53 transgene (Val135) with or without Ink4a/Arf heterozygous deletion had a higher number of lung tumors (an average of 25 tumors per mouse) after treatment with benzo(a)pyrene than wild-type and p53+/+Ink4a/Arf+/- mice (an average of 12.0 tumors per mouse). More interestingly, mice with p53-dominant negative mutation and Ink4A/Arf heterozygous deficiency (p53+/-Ink4a/Arf+/-) exhibited a striking increase in tumor volume (approximately 23-fold) compared to a ninefold increase in tumor volume in mice with only the p53-dominant negative mutation (p53+/-Ink4a/Arf+/+). There was also an approximate 50% and an approximate fourfold increase in tumor volume in Ink4a/Arf heterozygous-deficient mice (p53+/+Ink4a/Arf+/-), indicating that the effect of Ink4A/Arf heterozygous deficiency is mostly on late-stage lung tumor progression. In addition, most of the lung tumors (approximately 60%) from mice with a p53 mutation and deletion of Ink4A/Arf (p53+/-Ink4a/ Arf+/-) were lung adenocarcinomas. In contrast, lung adenocarcinomas were seen in < 10% of the lung tumors from the wild-type mice, and approximately 50% of the lung tumors from either p53 transgenic mice or Ink4a/Arf heterozygous-deficient mice. These results clearly indicate a significant synergistic interaction between the presence of a mutant p53 transgene and the Ink4A/Arf deletion during lung tumor progression. http://life-without-allergy.com/

Chemoprevention of Lung Cancer in Transgenic Mice: Transgenic Mouse Model for Lung Adenocarcinomas

Chemoprevention of Lung Cancer in Transgenic Mice: Transgenic Mouse Model for Lung AdenocarcinomasAlthough the A/J mouse lung adenoma model is valuable because of similar histology to a subtype of human adenocarcinoma, there are some features yet to be desired in order to make this model better. For example, the progression of lung adenomas to adenocarcinomas is rare in A/J mice. The most common genetic alteration associated with these tumors being carcinogen-specific mutations is K-ras. The limited number of large adenocarcinomas produced in this model has been shown to produce characteristic LOH changes. However, even most of these larger adenocarcinomas do not show mutations or loss of the p53 tumor suppressor gene or lost expression of the cyclin D1/cyclin D kinase inhibitor p16 gene, although these or closely related genes are routinely altered in human lung cancer. In order to incorporate these specific alterations into the A/J tumor model, we placed two different transgenes onto the A/J background. canadian pharmacy

Chemoprevention of Lung Cancer in Transgenic Mice: Use of A/J Mice in Chemoprevention Studies

The A/J mouse lung model of chemical carcinogenesis has been the most frequently employed murine model both for testing for potential chemical carcinogens and to screen for agents that prevent carcinogenesis (chemopre-ventive agents). The model has been shown to respond to a wide variety of potential chemical carcinogens, including the tobacco-related carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(a)pyrene, yielding multiple peripheral adenomas. Among the agents tested in A/J mice, several groups of chemicals have shown significant efficacy against mouse lung tumor development.

Chemoprevention of Lung Cancer in Transgenic Mice

Chemoprevention of Lung Cancer in Transgenic MiceLung cancer is the leading cause of cancer deaths in men and women in the United States. Epidemiologic and laboratory animal model studies have demonstrated that smoking and environmental exposure to carcinogens are closely linked to increased lung cancer risk. Tobacco exposure has been implicated in 90% of lung carcinomas, and smokers have a 20-fold greater risk of acquiring lung cancer compared with persons who have never smoked. Although approximately one half of all people who had ever smoked are now former smokers, many people are unable or unwilling to stop smoking. For these reasons, chemoprevention is a potentially important approach to reduce the large number of tobacco-caused cancer deaths, especially for former smokers. Chemoprevention is the use of pharmacologic or natural agents to inhibit the development of cancer.

Staging lung cancer: CONCLUSION


Because resection of lung cancer is the best current treatment for localized lung cancer, a very aggressive approach should be considered, including a variety of invasive techniques, before accepting ‘indeterminate’ radiographical findings that imply unresectability. Even if staging rules out curative resection, it may allow entry into induction protocols, with later resection being possible. A systematic approach to staging allows coordination among pulmonologists, radiologists, oncologists and surgeons, and is the basis of a ‘rational’ approach to the management of lung cancer. It’s time to pay less money – just get discount Cialis Professional at the best online pharmacy.

Staging lung cancer: SUMMARY


Staging lung cancer requires a physiological as well as pathological assessment. It is laborious, and many patients are unsuitable for resection. There are some ‘grey’ areas where definite recommendations cannot be made, and each centre needs to review its own results. Lymphadenopathy can be assessed by mediastinoscopy, bronchoscopy, CT-guided needle biopsy and/or thoracoscopy. There is evidence for ‘selective’ mediastinoscopy, but there is also strong support for ‘routine’ mediastinoscopy. Thoracoscopy can be viewed in the same fashion. The definition of what constitutes a ‘physiological’ high risk patient also varies between centres. Despite all of these issues, there are three basic ‘guidelines’.


Carcinoid tumours have been considered a tumour type in a spectrum of Kulchitsky cell or neuroendocrine neoplasms, which range from typical carcinoid through atypical carcinoid and, finally, SCLC . Typical carcinoids have low malignant potential, with less than 5% incidence of lymph node metastases and greater than 80% cure rates with surgery . Atypical carcinoids have an incidence of lymphatic me-tastases in up to 70%, with a 10-year survival of less than 50% . Clinical evidence of carcinoid syndrome implies atypical features, a large lesion or metastases, with rare exceptions . The most recent authoritative classification of neuroendocrine neoplasms adds a tumour type called large cell neuroendocrine carcinoma . This is ahigh grade carcinoma that fits in the spectrum somewhere between atypical carcinoid and SCLC, with a prognosis approaching that of SCLC.

Staging lung cancer: STAGING SCLC (2)

Lung cancer

Approach to diagnosis of adenocarcinoma: Diagnosis of adenocarcinoma, unlike other cell types that commonly arise in the lung, does not necessarily imply primary lung cancer, and on pathological examination alone it may be difficult to impossible to confirm a lung origin. One therefore needs to consider the possibility of metastatic disease, even when the lesion appears to be solitary.

Staging lung cancer: STAGING SCLC (1)

The role of surgery in SCLC is limited because chemotherapy is considered the primary treatment. Staging is mainly used for prognosis and to determine eligibility for treatment protocols . However, application of TNM staging reveals that stage I SCLC can be resected with 25% five-year survival or higher, assuming chemotherapy is also given. Frequently, stage I SCLC is diagnosed after resecting a solitary pulmonary nodule when this diagnosis was not anticipated preoperatively. Extensive staging is still required.

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