Squamous lung carcinoma

Figure 40. SOX2 Gene amplification and protein overexpression foretell more favorable clinical course of squamous cell lung cancer. Strong nuclear immuno-histochemistry in squamous lung carcinoma cells in a sample (a). Lung squamous carcinoma cells with amplified and non-amplified Sox2 (b). No SOX2 amplification in tumor cells (c). Normal bronchial epithelial cells show limited confined SOX2 expression (d) (Wilbertz T et al. Mod Pathol 2011 24 944—953).

Weber et al. (1982) treated 46 patients with squamous lung carcinoma in a randomized trial of bleomycin and CCNU (cyclohexyl chlorethyl nitrosourea) with or without etretinate. No statistical difference in response rate or duration of remission was noted between the two groups. Other clinical trials that utilize etretinate as adjuvant therapy after primay surgical or radiation treatment are ongoing in patients with carcinomas of the bladder, esophagus, and lung. Data from these European studies are very preliminary. 

LRP1B Loss-of-function (sporadic) Esophageal squamous cell carcinoma, nonsmall-cell lung cancer... 

Hypercalcemia occurs in 10% to 30% of patients with cancer during the course of their disease. The most common tumor types associated with hypercalcemia are breast cancer squamous cell carcinomas of the head, neck, and lung and renal cancer. 

Mouse inhalation AM AD 1.4 pm o,2.0 luCeO (MO wks 378 life span radiation fibrosis of lung, squamous metaplasia of bronchi, thickening of arteries, radiation pneumonitis, squamous cell carcinoma 5/14 No No No (1972) Lundgren et ai. 

Inhalation studies at the U.S. Air Force Aerospace Medical Research Laboratory showed an increased tumor response (hemangiosarcomas and Kupffer cell sarcomas) in mice exposed at 5 ppm, 6 h/d, 5 d/w for 6 mon (MacEwen and Vernot 1977, and Flaun 1977, reviewed in Trochimowicz 1994). Rats similarly exposed at 5 ppm exhibited increased incidences of squamous cell carcinomas of the lung and hepatocellular carcinomas. Hamsters subjected to a similar experimental protocol failed to show an increased incidence of tumors (MacEwen and Vernot 1975). It must be noted that the 1,1-dimethylhydrazine used in these studies contained 0.12% dimethylnitrosamine, which could be a significant confounder. 

The major cell types are SCLC (-15% of all lung cancers), adenocarcinoma (-50%), squamous cell carcinoma (less than 30%), and large cell carcinoma. The last three types are grouped together and referred to as NSCLC. 

Ichinose, Y. et al., Randomized double-blind placebo-controlled trial of bestatin in patients with resected stage I squamous-cell lung carcinoma, J Natl Cancer Inst, 95, 605, 2003. 

Other studies have seemed to implicate blood groupings (including Rh factors in one case) in toxemia of pregnancy, bronchopneumonia, fertility, abortions, oat cell lung tumors, and squamous cell carcinomas of the lung. 10,11... 

Table 5.2 Lung Squamous Cell Carcinoma Differential Gene Expression... 

Squamous cell carcinomas of the skin were produced in three studies after skin application of benzotrichloride to mice. Lung carcinomas, pulmonary adenomas, and lymphomas were also observed, ftitraperitoneal injection of benzotrichloride produced a significant increase in the lung tumor response in strain A/f mice within 24 weeks. Administration by gastric intubation of doses ranging from 2.0 to... 

J,l/mouse, twice a week for 25 weeks, to female ICR mice produced forestomach tumors (squamous cell carcinoma and papilloma), lung tumors (adenocarcinoma and adenoma), and tumors of the hematopoietic system (thymic lymphosarcoma and lymphatic leukemia), with dose-related response by 18 months. It was concluded that the target organ of benzotrichloride carcinogenesis in mice is the local tissue that is primarily exposed and the lung and hematopoietic tissue when administered systemically. 

Chromite ore roast mixed with sheep fat implanted intrapleurally in rats produced sarcomas coexisting with squamous cell carcinomas of the lungs the same material implanted in the thigh of rats produced fibrosarcomas/ However, the lARC concluded that these studies were inadequate to fully evaluate the carcinogenicity of this compound/ Other animal studies have found no increase in the incidence of tumors with chromium metal and chromite ore/ The lARC has determined that there is inadequate evidence in humans and animals for the carcinogenicity of metallic chromium and chromium(III) compounds. 

In a carcinogenic study, male and female rats were given DMHP by gavage 5 days/week for 103 weeks. At 200mg/kg, there were increases in alveolar/bronchiolar carcinomas, squamous cell carcinomas of the lung, and carcinomas of the stomach in male rats. Neoplastic lesions did not occur in mice after similar treatments. Species-dependent differences in the metabolism of DMPH were limited to more rapid metabolism and elimination by mice compared with rats. Therefore, the... 

In animal studies, significant increases in adenocarcinomas and squamous cell carcinomas of the lung have occurred in rats after inhalation or intratracheal instillation in rats, but not in hamsters. Increasing in vitro and in vivo evidence suggests that the rat lung tumor response to crystalline silica exposure is a result of marked and persistent inflammation and epithelial proliferation. However, other pathways such as a role for crystalline silica surfacegenerated oxidants or a direct genotoxic effect cannot be ruled out. 

In addition to in vivo studies in models of CML, BMS-354825 has also been studied in models of solid tumors. BMS-354825 was efficacious in head and neck squamous cell carcinoma and non-small cell lung cancer animal models [151]. Based on this activity, BMS-354825 has been advanced into clinical trials for the treatment of solid tumors. 

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