Recent experimental studies revealing new biological effects of tamoxifen on tumor cells both expressing and not expressing different types of estrogen receptors (ERα and ERβ) show new aspects of a seemingly well known agent. This review describes tamoxifen targets, the blocking of which leads to inhibition of tumor cell growth and angiogenesis, stimulation of programmed cell death (apoptosis, autophagia and necrosis), inhibition of multidrug resistance, invasion and metastasis. Since outcomes of tamoxifen action on cells are prognostically good from the point of view of both tumor growth/metastasis inhibition and tumor response to drug therapy, the authors believe this is an extremely important addition to tamoxifen antiestrogenic effect. Arguments are provided to consider the strategy of long-term tamoxifen treatment proposed by Professor Craig V. Jordan in the 1970s that is also applicable to the treatment of other tumors. This is, first of all, the fact that expression of estrogen receptor-beta that can also be targeted by tamoxifen therapy in solid tumors of practically all known sites and histologies. The authors believe that molecular biological screening of patients with respect to expression of tamoxifen cellular targets other than ERα and ERβ is needed to use to the full all tamoxifen biological activities other than modulation of estrogen receptors during long-term adjuvant therapy for cancers of various sites.
This review considers data on expression of different types of estrogen receptors (ERα and ERβ) in in vitro cultured cells of non-small cell lung cancer and also in human and animal lung tumors. Estrogens are shown to play an important role in genesis and development of non-small cell lung cancer because the estrogen-stimulated cell proliferation as well as antiestrogen-caused inhibition of proliferation occurred only in the cells expressing different types of estrogen receptors. In general, the situation is similar to that observed in breast cancer, but in the cells of non-small cell lung cancer not ERα are expressed in more than half of cases but ERβ. Just estrogen receptors β play the crucial role in inducing cell proliferation in response to estrogens, and ERβ is a prognostic marker of a favorable course of non-small cell lung cancer. Data on the interactions between ER and EGFR signaling pathways, as well as on the additive antitumor effect of antiestrogens (tamoxifen and fulvestrant) combined with tyrosine kinase inhibitors (gefitinib, erlotinib, and vandetanib) are considered. The review also includes data on the influence of estrogens on genesis and development of lung cancer in humans and animals and the frequency of ERα and ERβ expression in non-small cell lung cancer in tissues from patients of the two sexes. Problems of quantitative determination of α and β estrogen receptors in the tumor cells are also discussed.
Simultaneous operations increase resectability, radicality and functional operability and therefore promise improvement of follow-up results in the most serious category of cancer patients in question.
We performed a parallel evaluation of the status of epidermal growth factor receptors EGFR and HER-2 in tumor samples from 31 patients with squamous cell carcinoma of the esophagus. Hyperexpression of proteins was detected by immunohistochemical methods and gene amplification and other chromosome abnormalities were studied using FISH reaction. Evaluation of EGFR status showed that amplification of EGFR gene was present in 25% cases and chromosome 7 polysomy was detected in 29.2% cases positive by protein expression (2+/3+). Immunohistochemically positive EGFR status was confirmed by the results of FISH reaction for gene amplification and chromosome 7 polysomy in 54.2% cases (p=0.002). During evaluation of HER-2 status in the tumor, hyperexpression of the protein detected histochemically was not confirmed by FISH reaction for detection of amplification of the corresponding gene in 16.1% cases. In 22.6% patients, chromosome 7 polysomy was detected; it was not accompanied by amplification of HER-2 gene, but was related to immunohistochemically positive status of the tumor. Hyperexpression of EGFR protein significantly correlated with the presence of intravascular invasion (p=0.006) and increased depth of invasion (p=0.044), while amplification of EGFR gene (≥2.2) correlated with low differentiation degree of the tumor (p=0.006). The outcome of the disease was not associated with EGFR status at the gene and protein levels, whereas clinical course of the disease in patients with immunohistochemically negative expression of HER-2 protein was more favorable than in patients with positive expression (p=0.004). The results of this study suggest that hyperexpression/amplification of EGFR and hyperexpression of HER-2 are important clinical markers for evaluation of disease prognosis and development of new regimens of targeted therapy for patients with squamous cells carcinoma of the esophagus.
Renal angiomyolipomas (AMLs) are benign renal tumors that may possess the features of a malignant neoplasm, such as local and vascular invasion. We describe the diagnosis and management of a rare case of AML associated with tumor thrombus extending into the right atrium.
The content of matrix metalloproteinases (MMP) -2, -7, and -9 was significantly higher in tumors in comparison with the adjacent histologically intact gastric mucosa in 80, 70, and 72% patients with gastric cancer, respectively, the increase in the level of MMP tissue inhibitor-2 (TIMP-2) detected in 61% tumors was insignificant. Only plasma level of MMP-7 was elevated in primary patients in comparison with the control and positively correlated with the expression of this protein in the tumor. The concentration of MMP-7 was maximum in the blood of patients with tumor invasion in lymph vessels. These data suggest MMP-7 as a possible serological marker of gastric cancer.
The efficiency of treatment of diffuse stomach cancer can be improved by using a complex phytoadaptogen. In groups receiving phytoadaptogen, the level of tumor marker CA 19-9 decreased and the mean life span of patients increased by 2.5 times. The drug exhibited immunomodulating (including interferonogenic and adhesiogenic), antioxidant, and hormone-modulating effects.
A method for decellularization of the trachea for subsequent repopulation with allogenic MSC was optimized. Tracheas from C57BL/6 mice were devitalized and repopulated with MSC from BALB/c mice. The tracheal matrix with devitalized mucosa and intact cartilaginous structure, fit for repopulation with allogenic MSC, was obtained by chemical treatment with NaClO4. This approach seemed to be promising for transplantation of allogenic trachea.
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