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ER stress protection in cancer cells: the multifaceted role of the heat shock protein TRAP1

100%

Swann Matassa D., Arzeni D., Landriscina M., Esposito F.

Endoplasmic Reticulum Stress in Diseases

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2014

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vol. 1

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issue 1

EN

TRAP1 is an HSP90 chaperone, upregulated in human cancers and involved in organelles’ homeostasis and tumor cell metabolism. Indeed, TRAP1 is a key regulator of adaptive responses used by highly proliferative tumors to face the metabolic stress induced by increased demand of protein synthesis and hostile environments. Besides well-characterized roles in prevention of mitochondrial permeability transition pore opening and in regulating mitochondrial respiration, TRAP1 is involved in novel regulatory mechanisms: i) the attenuation of global protein synthesis, ii) the co-translational regulation of protein synthesis and ubiquitination of specific client proteins, and iii) the protection from Endoplasmic Reticulum stress. This provides a crucial role to TRAP1 in maintaining cellular homeostasis through protein quality control, by avoiding the accumulation of damaged or misfolded proteins and, likely, facilitating the synthesis of selective cancer-related proteins. Herein, we summarize how these regulatory mechanisms are part of an integrated network, which enables cancer cells to modulate their metabolism and to face, at the same time, oxidative and metabolic stress, oxygen and nutrient deprivation, increased demand of energy production and macromolecule biosynthesis. The possibility to undertake a new strategy to disrupt such networks of integrated control in cancer cells holds great promise for treatment of human malignancies.

2

TGF beta signalling and its role in tumour pathogenesis.

75%

Kaminska B., Wesolowska A., Danilkiewicz M.

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2005

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vol. 52

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issue 2

329-337

EN

Transforming growth factor beta (TGF-β) is a multifunctional cytokine involved in the regulation of cell proliferation, differentiation and survival/or apoptosis of many cells. Knock-out experiments in mice for the three isoforms of TGF-β have demonstrated their importance in regulating inflammation and tissue repair. TGF-β is implicated in the pathogenesis of human diseases, including tissue fibrosis and carcinogenesis. TGF-β receptors act through multiple intracellular pathways. Upon binding of TGF-β with its receptor, receptor-regulated Smad2/3 proteins become phosphorylated and associate with Smad4. Such complex translocates to the nucleus, binds to DNA and regulates transcription of specific genes. Negative regulation of TGF-β/Smad signalling may occur through the inhibitory Smad6/7. Furthermore, TGF-β-activated kinase-1 (TAK1) is a component of TGF-β signalling and activates stress-activated kinases: p38 through MKK6 or MKK3 and c-Jun N-terminal kinases (JNKs) via MKK4. In the brain TGF-β, normally expressed at the very low level, increases dramatically after injury. Increased mRNA levels of the three TGF-β isoforms correlate with the degree of malignancy of human gliomas. TGF-βs are secreted as latent precursors requiring activation into the mature form. TGF-β may contribute to tumour pathogenesis by direct support of tumour growth and influence on local microenvironment, resulting in immunosuppression, induction of angiogenesis, and modification of the extracellular matrix. TGF-β1,2 may stimulate production of vascular endothelial growth factor (VEGF) as well as plasminogen activator inhibitor (PAI-I), that are involved in vascular remodelling occurring during angiogenesis. Blocking of TGF-β action inhibits tumour viability, migration, metastases in mammary cancer, melanoma and prostate cancer model. Reduction of TGF-β production and activity may be a promising target of therapeutic strategies to control tumour growth.

3

Poly(adP-ribose) polymerase inhibitor olaparib in the treatment of ovarian cancer: a comprehensive review of current literature

75%

Poboży K., Domańska J., Domański P.

OncoReview

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2023

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vol. 13

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issue 2

39-47

EN

Purpose of the review: This comprehensive review aims to provide a summary of current research on the utilization of olaparib, a poly(ADP-ribose) polymerase (PArP) inhibitor, in the treatment of ovarian cancer. The review aims to highlight the key findings from recent clinical trials and assess the potential of olaparib as a targeted therapy for improving the prognosis of ovarian cancer patients. recent findings: Ovarian cancer remains a significant global health concern with high mortality rates. While optimal debulking surgery and platinum-based chemotherapy are the standard treatments, the recurrence rates remain substantial. The emergence of PArP inhibitors, particularly olaparib, has intro duced a novel therapeutic approach that targets the genomic instability and DnA repair mechanisms in cancer cells. notable clinical trials, such as SOl O1, SOl O2, and PAOlA-1, have demonstrated the effectiveness of olaparib in significantly improving progression-free survival, particularly in patients with Br CA mutations or homologous recombination deficiency. Additionally, combination therapies involving olaparib, such as those with bevacizumab or entinostat, have shown promising results. Summary: The utilization of olaparib has brought about a paradigm shift in the treatment of ovarian cancer. notably, it has shown significant improvements in progression-free survival and overall survival, particularly in patients with Br CA mutations or homologous recombination deficiency. The exploration of olaparib through various clinical trials and combination therapies continues to provide valuable insights and offer new prospects for ovarian cancer patients. Moreover, the growing understanding of PArP inhibitors holds the potential for further advancements in the prognosis of patients with this formidable condition.

4

Psychoneurocybernetyczna etiopatogeneza raków

51%

Klimek R., Czajkowski K., Kojs Z., Szymański W., Śpiewankiewicz B.

Current Gynecologic Oncology

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2013

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vol. 11

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issue 3

202-209

EN

Multicellular organisms are composed of cells which psychoneurocybernetically match each other in terms of morphology (genetics), information and energy. The most incomprehensible disease, which has been a source of fear for centuries, took its name from crab-like (the word cancer is Latin for crab) or crayfish-like, as in some countries crabs are not found, growths that destroy human body. Cancers develop as a result of a natural and common phenomenon involving the self-organization of so-called dissipative structures from systems (cells) which are to be destroyed due to their thermodynamic insufficiency, referred to as the emergence of negative entropy source. The distinction between physiological and pathological cell metabolism has allowed to separate etiology from the analysis of morphologically and/or biochemically identifiable pathogenic changes underlying disease symptoms and ailments. The thermodynamic etiology of cancerogenesis, which provided new treatment alternatives in the case of standard management insufficiency or failure, is supported by the positive effects of hyperthermia therapy. The development of cybernetics makes it possible to distinguish between precancerous conditions and cancers, and thus enables conscious cancer prevention as well as initiation of causative instead of just symptomatic treatment. Although the existence of societies dependent on legislative, executive and judiciary power is naturally regulated by information, the norms established by people cannot ignore the real natural rights, according to which the public interest is a priority. Life, which is not human-made but passed from generation to generation for the maintenance of the species, is the highest good of a man. This transfer is guaranteed, among other things, by cancers, whose cellular life form is more secure than the affected person. Cancers are only rarely genetically predeterminated, and the self-organization of a cell’s genetic code is an effect, and not the cause of cancerogenesis.

PL

Wielokomórkowe organizmy współtworzą komórki wzajemnie dopasowane psychoneurocybernetycznie pod względem morfologicznym (genetycznym), informacyjnym i energetycznym. Najbardziej niezrozumiała i od wieków przerażająca choroba wzięła nazwę od niszczących ciało człowieka narostów, przypominających wyglądem kraba, a w krajach, w których kraby nie żyją – raka. Przyczyną powstawania nowotworów jest naturalne i powszechne zjawisko samoorganizacji tzw. struktur dysypatywnych z układów (komórek) skazanych na zagładę z powodu ich termodynamicznej niewydolności, określanej jako pojawienie się ujemnego źródła entropii. Rozdzielenie fizjologicznego i patologicznego metabolizmu komórek umożliwiło oddzielenie etiologii od analizy uchwytnych morfologicznie i/lub biochemicznie patogenetycznych zmian odpowiedzialnych za objawy i dolegliwości chorobowe. Pozytywne efekty hipertermicznej terapii nowotworów potwierdziły słuszność termodynamicznej etiologii karcinogenezy, stwarzając nowe możliwości terapii w przypadku niewydolności lub niepowodzenia klasycznego postępowania. Dzięki postępowi cybernetyki można u człowieka odróżniać stany przednowotworowe od nowotworów, co pozwala na świadome zapobieganie chorobom nowotworowym i rozpoczęcie ich przyczynowego, a nie dopiero objawowego leczenia. Informacja jest naturalnym regulatorem istnienia społeczeństw podległych władzy ustawodawczej, wykonawczej i sądowniczej, jednak normy stanowione przez ludzi nie mogą pomijać rzeczywistych praw naturalnych, w których dobro ogółu jest nadrzędne. Najwyższym dobrem człowieka jest życie, którego sam nie tworzy, a tylko je przekazuje między pokoleniami dla utrzymania gatunku. Przekaz ten jest zagwarantowany między innymi przez nowotwory, których komórkowa forma życia jest bardziej zabezpieczona niż dotknięty chorobą człowiek. Nowotwory tylko wyjątkowo mają uwarunkowania genetyczne, a samoorganizacja kodu genetycznego komórki jest skutkiem, a nie przyczyną karcinogenezy

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1 Acta Biochimica Polonica

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1 Endoplasmic Reticulum Stress in Diseases

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1 Czajkowski K.

1 Danilkiewicz M.

1 Domańska J.

1 Domański P.

1 Esposito F.

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1 Klimek R.

1 Kojs Z.

1 Landriscina M.

1 Poboży K.

1 Swann Matassa D.

1 Szymański W.

1 Wesolowska A.

1 Śpiewankiewicz B.

ER stress protection in cancer cells: the multifaceted role of the heat shock protein TRAP1

TGF beta signalling and its role in tumour pathogenesis.

Poly(adP-ribose) polymerase inhibitor olaparib in the treatment of ovarian cancer: a comprehensive review of current literature

Psychoneurocybernetyczna etiopatogeneza raków