Mutational analysis of BRCA1/2 in a group of 134 consecutive ovarian cancer patients. Novel and recurrent BRCA1/2 alterations detected by next generation sequencing

The importance of proper mutational analysis of BRCA1/2 in individuals at risk for hereditary breast and ovarian cancer syndrome is widely accepted. Standard genetic screening includes targeted analysis of recurrent, population-specific mutations. The purpose of the study was to establish the frequency of germline BRCA1/2 mutations in a group of 134 unrelated patients with primary ovarian cancer. Next generation sequencing analysis revealed a presence of 20 (14.9 %) mutations, where 65 % (n = 13) were recurrent BRCA1 alterations included in the standard diagnostic panel in northern Poland. However, the remaining seven BRCA1/2 mutations (35 %) would be missed by the standard approach and were detected in unique patients. A substantial proportion (n = 5/12; 41 %) of mutation-positive individuals with complete family history reported no incidence of breast or ovarian cancer in their relatives. This observation, together with the raising perspectives for personalized therapy targeting BRCA1/2 signaling pathways indicates the necessity of comprehensive genetic screening in all ovarian cancer patients. However, due to the limited sensitivity of the standard genetic screening presented in this study (65 %) an application of next generation sequencing in molecular diagnostics of BRCA1/2 genes should be considered

Diagnostic accuracy of liquid biopsy in endometrial cancer

Background: Liquid biopsy is a minimally invasive collection of a patient body fluid sample. In oncology, they offer several advantages compared to traditional tissue biopsies. However, the potential of this method in endometrial cancer (EC) remains poorly explored. We studied the utility of tumor educated platelets (TEPs) and circulating tumor DNA (ctDNA) for preoperative EC diagnosis, including histology determination. Methods: TEPs from 295 subjects (53 EC patients, 38 patients with benign gynecologic conditions, and 204 healthy women) were RNA-sequenced. DNA sequencing data were obtained for 519 primary tumor tissues and 16 plasma samples. Artificial intelligence was applied to sample classification. Results: Platelet-dedicated classifier yielded AUC of 97.5% in the test set when discriminating between healthy subjects and cancer patients. However, the discrimination between endometrial cancer and benign gynecologic conditions was more challenging, with AUC of 84.1%. ctDNA-dedicated classifier discriminated primary tumor tissue samples with AUC of 96% and ctDNA blood samples with AUC of 69.8%. Conclusions: Liquid biopsies show potential in EC diagnosis. Both TEPs and ctDNA profiles coupled with artificial intelligence constitute a source of useful information. Further work involving more cases is warranted.publishedVersio

Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo

Photodynamic therapy (PDT) exerts direct cytotoxic effects on tumor cells, destroys tumor blood and lymphatic vessels and induces local inflammation. Although PDT triggers the release of immunogenic antigens from tumor cells, the degree of immune stimulation is regimen-dependent. The highest immunogenicity is achieved at sub-lethal doses, which at the same time trigger cytoprotective responses, that include increased expression of glucose-regulated protein 78 (GRP78). To mitigate the cytoprotective effects of GRP78 and preserve the immunoregulatory activity of PDT, we investigated the in vivo efficacy of PDT in combination with EGF-SubA cytotoxin that was shown to potentiate in vitro PDT cytotoxicity by inactivating GRP78. Treatment of immunocompetent BALB/c mice with EGF-SubA improved the efficacy of PDT but only when mice were treated with a dose of EGF-SubA that exerted less pronounced effects on the number of T and B lymphocytes as well as dendritic cells in mouse spleens. The observed antitumor effects were critically dependent on CD8(+) T cells and were completely abrogated in immunodeficient SCID mice. All these results suggest that GRP78 targeting improves in vivo PDT efficacy provided intact T-cell immune system

The oncogene AAMDC links PI3K-AKT-mTOR signaling with metabolic reprograming in estrogen receptor-positive breast cancer

Adipogenesis associated Mth938 domain containing (AAMDC) represents an uncharacterized oncogene amplified in aggressive estrogen receptor-positive breast cancers. We uncover that AAMDC regulates the expression of several metabolic enzymes involved in the one-carbon folate and methionine cycles, and lipid metabolism. We show that AAMDC controls PI3K-AKT-mTOR signaling, regulating the translation of ATF4 and MYC and modulating the transcriptional activity of AAMDC-dependent promoters. High AAMDC expression is associated with sensitization to dactolisib and everolimus, and these PI3K-mTOR inhibitors exhibit synergistic interactions with anti-estrogens in IntClust2 models. Ectopic AAMDC expression is sufficient to activate AKT signaling, resulting in estrogen-independent tumor growth. Thus, AAMDC-overexpressing tumors may be sensitive to PI3K-mTORC1 blockers in combination with anti-estrogens. Lastly, we provide evidence that AAMDC can interact with the RabGTPase-activating protein RabGAP1L, and that AAMDC, RabGAP1L, and Rab7a colocalize in endolysosomes. The discovery of the RabGAP1L-AAMDC assembly platform provides insights for the design of selective blockers to target malignancies having the AAMDC amplification

Level of self-care in heart transplant and chronic heart disease patients

The aim of the research paper was to identify the relationship between a chronic cardiac disease and heart transplantation, and the level of patients’ selfcare. The notion of self-care and its levels has been defined, and the circumstances in which it becomes activate specified. Research findings showed that there is no difference in the level of self-care between the group of patients with a chronic heart condition and the group of patients with a heart transplant, and between cardiac patients and healthy individuals. The difference showed in the higher global level of self-care in patients after heart transplantation compared to healthy individuals. The research revealed that a heart transplantation treatment has a direct effect on the scope of self-care in patients. It can therefore be concluded that in the context of changes following a cardiac transplantation, self-care is activated as a buffering mechanism, facilitating a better adaptation of a patient. Yet, it cannot be stated that self-care is a rational mechanism consciously used in order to cope with the situation

Kształcenie umiejętności komunikowania się z pacjentami na poziomie podyplomowym, ze szczególnym uwzględnieniem medycyny paliatywnej

Clinical communication skills have been taught and researched for more than 40 years. This set of processes and communication skills with patients and/or their family, and other healthcare professionals, improves the quality of healthcare services, increases patient involvement in the treatment process and improves job satisfaction. It seems particularly important for physicians working in palliative care to have these skills. The process of pre-graduate and post-graduate training was analysed in terms of teaching clinical communication and the expectations of healthcare professionals, with a particular focus on palliative medicine. The results were compared with those of a survey of 123 physicians who identified their training needs in clinical communication. The results show that there is a significant gap between physicians' expectations of their clinical communication skills training and the requirements of the curricula. It is therefore reasonable to modify the existing clinical communication curricula.Komunikacja kliniczna to dziedzina, której naucza się i którą bada się od ponad 40 lat. Ten zbiór procesów i umiejętności, które stosowane są podczas komunikowania się lekarza z pacjentem i/lub jego rodziną, w trakcie pracy w zespole interdyscyplinarnym czy podczas komunikowania się pracowników ochrony zdrowia między sobą, poprawia jakość świadczonych usług medycznych, zwiększa zaangażowanie pacjenta w proces leczenia oraz poprawia satysfakcję z wykonywanej pracy. Szczególnie ważne wydaje się posiadanie tych umiejętności przez lekarzy pracujących w opiece paliatywnej. Przeanalizowano proces szkolenia przeddyplomowego oraz podyplomowego pod kątem nauczania oraz oczekiwań wobec pracowników ochrony zdrowia, ze szczególnym uwzględnieniem medycyny paliatywnej. Uzyskane wyniki porównano z wynikami badania przeprowadzonego na próbie 123 lekarzy, którzy określali swoje potrzeby kształcenia w zakresie komunikacji klinicznej. Uzyskane wyniki wskazują na istnienie znaczącej różnicy pomiędzy oczekiwaniami lekarzy dotyczącymi ich kształcenia w tej dziecinie a wymaganiami programów nauczania. W pełni zasadne jest zatem wprowadzenie modyfikacji dotychczasowych programów nauczania komunikacji klinicznej