The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients

Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen

Therapeutic fascism: re-educating Communists in Nazi-occupied Serbia, 1942-44

This article probes the relationship between psychoanalysis and right-wing authoritarianism, and analyses a unique psychotherapeutic institution established by Serbia’s World War II collaborationist regime. The extraordinary Institute for compulsory re-education of high-school and university students affiliated with the Communist resistance movement emerged in the context of a brutal civil war and violent retaliations against Communist activists, but its openly psychoanalytic orientation was even more astonishing. In order to stem the rapid spread of Communism, the collaborationist state, led by its most extreme fascistic elements, officially embraced psychotherapy, the ‘talking cure’ and Freudianism, and conjured up its own theory of mental pathology and trauma – one that directly contradicted the Nazi concepts of society and the individual. In the course of the experiment, Serbia’s collaborationists moved away from the hitherto prevailing organicist, biomedical model of mental illness, and critiqued traditional psychiatry’s therapeutic pessimism