Using an active targeting approach of chemotherapeutics-loaded nanocarriers (NCs) with monoclonal antibodies is a potential strategy to improve the specificity of the delivery systems and reduce adverse reactions of chemotherapeutic drugs. Specific targeting of the human epidermal growth factor receptor-2 (HER-2), expressed excessively in HER-2-positive breast cancer cells, can be achieved by conjugating NCs with an anti-HER-2 monoclonal antibody. We constructed trastuzumab-conjugated chitosan iodoacetamide-coated NCs containing doxorubicin (Tras-Dox-CHI-IA-NCs) as a tumor-targeted drug delivery system, during the study. Chitosan-iodoacetamide (CHI-IA) was synthesized and utilized to prepare trastuzumab-conjugated NCs (Tras-NCs). The morphology, physicochemical properties, drug loading, drug release, and biological activities of the NCs were elucidated. The Tras-NCs were spherical, with a particle size of approximately 76 nm, and had a positive zeta potential; after incorporating the drug, the size of the Tras-NC increased. A prolonged, 24-h drug release from the NCs was achieved. The Tras-NCs exhibited high cellular accumulation and significantly higher antitumor activity against HER-2-positive breast cancer cells than the unconjugated NCs and the drug solution. Therefore, Tras-Dox-CHI-IA-NCs could be a promising nanocarrier for HER-2-positive breast cancer.

• MeSH
• chitosan * chemie   MeSH
• doxorubicin chemie   MeSH
• jodacetamid MeSH
• lidé MeSH
• monoklonální protilátky chemie   MeSH
• nádory prsu * farmakoterapie   MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• systémy cílené aplikace léků MeSH
• trastuzumab MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• Mediately,
• MeSH
• digitální zdraví * MeSH
• lidé MeSH
• mobilní aplikace MeSH
• nádory prsu diagnóza   MeSH
• nádory terapie   MeSH
• protinádorové látky imunologicky aktivní aplikace a dávkování   škodlivé účinky   MeSH
• telemedicína MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• rozhovory MeSH

Case studies that focused on methods of genetic testing for breast cancer. Intended for professional public.

• MeSH
• genetické testování MeSH
• genomika MeSH
• nádory prsu genetika   MeSH
• Publikační typ
• kazuistiky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• onkologie
• genetika, lékařská genetika

Breast cancer is the most frequently diagnosed cancer in women worldwide. Although dramatically increased survival rates of early diagnosed cases have been observed, late diagnosed patients and metastatic cancer may still be considered fatal. The present study's main focus was on cancer‐associated fibroblasts (CAFs) which is an active component of the tumor microenvironment (TME) regulating the breast cancer ecosystem. Transcriptomic profiling and analysis of CAFs isolated from breast cancer skin metastasis, cutaneous basal cell carcinoma, and squamous cell carcinoma unravelled major gene candidates such as IL6, VEGFA and MFGE8 that induced co‐expression of keratins‐8/‐14 in the EM‐G3 cell line derived from infiltrating ductal breast carcinoma. Western blot analysis of selected keratins (keratin‐8, ‐14, ‐18, ‐19) and epithelial‐mesenchymal transition‐associated markers (SLUG, SNAIL, ZEB1, E‐/N‐cadherin, vimentin) revealed specific responses pointing to certain heterogeneity of the studied CAF populations. Experimental in vitro treatment using neutralizing antibodies against IL-6, VEGF‐A and MFGE8 attenuated the modulatory effect of CAFs on EM‐G3 cells. The present study provided novel data in characterizing and understanding the interactions between CAFs and EM‐G3 cells in vitro. CAFs of different origins support the pro‐inflammatory microenvironment and influence the biology of breast cancer cells. This observation potentially holds significant interest for the development of novel, clinically relevant approaches targeting the TME in breast cancer. Furthermore, its implications extend beyond breast cancer and have the potential to impact a wide range of other cancer types.

• MeSH
• antigeny povrchové MeSH
• fibroblasty asociované s nádorem * metabolismus   MeSH
• fibroblasty metabolismus   MeSH
• keratiny genetika   metabolismus   MeSH
• lidé MeSH
• maligní melanom kůže MeSH
• MFC-7 buňky MeSH
• mléčné bílkoviny genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorové mikroprostředí genetika   MeSH
• nádory prsu * farmakoterapie   genetika   metabolismus   MeSH
• prognóza MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Interactions between living cells and nanoparticles are extensively studied to enhance the delivery of therapeutics. Nanoparticles size, shape, stiffness, and surface charge are regarded as the main features able to control the fate of cell-nanoparticle interactions. However, the clinical translation of nanotherapies has so far been limited, and there is a need to better understand the biology of cell-nanoparticle interactions. This study investigates the role of cellular mechanosensitive components in cell-nanoparticle interactions. It is demonstrated that the genetic and pharmacologic inhibition of yes-associated protein (YAP), a key component of cancer cell mechanosensing apparatus and Hippo pathway effector, improves nanoparticle internalization in triple-negative breast cancer cells regardless of nanoparticle properties or substrate characteristics. This process occurs through YAP-dependent regulation of endocytic pathways, cell mechanics, and membrane organization. Hence, the study proposes targeting YAP may sensitize triple-negative breast cancer cells to chemotherapy and increase the selectivity of nanotherapy.

• MeSH
• lidé MeSH
• nanočástice * MeSH
• signální proteiny YAP MeSH
• signální transdukce fyziologie   MeSH
• triple-negativní karcinom prsu * farmakoterapie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Breast cancer is a prevalent and aggressive disease characterized by high metastasis, recurrence, and mortality rates. While cisplatin is an effective chemotherapy drug, its use is limited by its toxic effects on the body. Despite advancements in therapeutic strategies, the therapeutic response is often unsatisfactory due to drug resistance, leading to poor prognosis. Recent studies have shown that cisplatin interacts with long non-coding RNAs (lncRNAs) and accelerates the development of resistance in tumor cells to therapy. This interaction highlights the complex mechanisms involved in the response of cancer cells to chemotherapy. Several lncRNAs have been identified as key players in mediating cisplatin resistance in breast cancer. These lncRNAs include SNHG15, HULC, HCP5, MT1JP, LncMat2B, DLX6-ASL, Linc00665, CARMN, and Lnc-EinRP44-3:6. These lncRNAs have been shown to target microRNAs and mRNAs and modulate the expression of genes involved in cisplatin resistance, which is important in treating breast cancer.

• MeSH
• antitumorózní látky * terapeutické užití   farmakologie   MeSH
• chemorezistence * genetika   MeSH
• cisplatina * terapeutické užití   farmakologie   MeSH
• lidé MeSH
• nádory prsu * farmakoterapie   genetika   patologie   metabolismus   MeSH
• regulace genové exprese u nádorů * účinky léků   MeSH
• RNA dlouhá nekódující * genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Východiská: Vývoj vysoko účinných protinádorových terapií za posledných niekoľko desaťročí zásadným spôsobom zmenil situáciu pacientov so zhubným nádorovým ochorením, ktorí v súčasnosti dosahujú vysokú mieru vyliečenia v skorých štádiách ochorenia. Napriek obrovskému pokroku chemoterapia naďalej zostáva základnou liečebnou modalitou včasného karcinómu prsníka. Komplikácie súvisiace s chemoterapiou majú však zásadný vplyv na kardiovaskulárnu morbiditu a mortalitu tejto skupiny pacientov. Takmer 80 % žien s diagnostikovanou rakovinou prsníka má viac ako 50 rokov a má prítomné rizikové faktory pre kardiovaskulárne ochorenie, ako je vek, rodinná anamnéza, hypertenzia, zvýšený cholesterol, fajčenie, cukrovka a zvýšený index telesnej hmotnosti. Väčšina pacientok na rakovinu prsníka nezomrie a v súlade s celkovou populáciou zostávajú kardiovaskulárne ochorenia najčastejšou príčinou úmrtia. Preklinický výskum, retrospektívne analýzy a zopár prospektívných prác popisujú dyslipidemický účinok cytostatík, ktorý môže predisponovať k vzniku aterosklerotických kardiovaskulárnych ochorení. Podanie neoadjuvantnej alebo adjuvantnej chemoterapie na báze antracyklínov a taxánov môže viesť k zvýšeniu celkového cholesterolu, triacylglyceridov, LDL cholesterolu a poklesu HDL cholesterolu. Abnormálne vysoké koncentrácie lipidov v krvi predstavujú jeden z hlavných rizikových faktorov pre rozvoj a progresiu kardiovaskulárnych ochorení. Práce naznačujú i koreláciu medzi hladinami sérových lipidov a mierou dosiahnutia patologickej kompletnej remisie po podaní neoadjuvantnej chemoterapie. Dyslipidémia je u pacientiek s rakovinou prsníka liečených neoadjuvantnou chemoterapiou asociovaná s horšou prognózou. Cieľ: Cieľom práce je poukázať na dyslipidemické účinky cytostatík a riziká vzniku aterosklerotických kardiovaskulárnych ochorení u pacientok s karcinómom prsníka, ktoré absolvovali adjuvantnú alebo neoadjuvantnú chemoterapiu pre včasný karcinóm prsníka. Identifikácia kardiovaskulárnych rizikových faktorov na začiatku onkologickej liečby, monitorácia lipidového spektra a včasná intervencia liečby dyslipidémie unikajú v súčasnosti pozornosti.

Backround: The development of highly effective anti-cancer therapies over the past several decades has dramatically changed the situation of patients with malignant tumor disease, who currently achieve a high rate of cure in the early stages of the disease. Despite tremendous progress, chemotherapy remains the primary treatment modality for early breast cancer. However, chemotherapy-related complications have a major impact on cardiovascular morbidity and mortality in this group of patients. Almost 80% of women diagnosed with breast cancer are over 50 years of age and already have risk factors for cardiovascular disease, such as age, family history, hypertension, elevated cholesterol, smoking, diabetes, and elevated body mass index. Most breast cancer patients do not die and, in line with the general population, cardiovascular disease remains the most common cause of death. Clinical research, extensive retrospective analyzes and prospective works describe the dyslipidemic effect of cytostatics, which may predispose to the development of atherosclerotic cardiovascular diseases. The administration of neoadjuvant or adjuvant chemotherapy based on anthracyclines and taxanes can lead to an increase in total cholesterol, triacylglycerides, LDL cholesterol and a decrease in HDL cholesterol. Abnormally high concentrations of lipids in the blood represent one of the main risk factors for the development and progression of cardiovascular diseases. The works also indicate a correlation between serum lipid levels and the rate of achieving pathological complete remission after the administration of neoadjuvant chemotherapy. Dyslipidemia is associated with a worse prognosis in breast cancer patients treated with neoadjuvant chemotherapy. Purpose: The aim of the thesis is to point out the dyslipidemic effects of cytostatics and the risks of atherosclerotic cardiovascular diseases in breast cancer patients who have undergone adjuvant or neoadjuvant chemotherapy for early breast cancer. The identification of cardiovascular risk factors at the beginning of oncological treatment, the monitoring of the lipid spectrum during the treatment and the timely intervention of dyslipidemia treatment escape attention at present.

• MeSH
• antracykliny farmakologie   terapeutické užití   MeSH
• cytostatické látky * farmakologie   škodlivé účinky   terapeutické užití   MeSH
• dyslipidemie * chemicky indukované   etiologie   krev   MeSH
• farmakoterapie klasifikace   metody   MeSH
• kardiovaskulární nemoci chemicky indukované   etiologie   MeSH
• lidé MeSH
• nádory prsu diagnóza   epidemiologie   farmakoterapie   MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

The human body is regularly exposed to simple catechols and small phenols originating from our diet or as a consequence of exposure to various industrial products. Several biological properties have been associated with these compounds such as antioxidant, anti-inflammatory, or antiplatelet activity. Less explored is their potential impact on the endocrine system, in particular through interaction with the alpha isoform of the estrogen receptor (ERα). In this study, human breast cancer cell line MCF-7/S0.5 was employed to investigate the effects on ERα of 22 closely chemically related compounds (15 catechols and 7 phenols and their methoxy derivatives), to which humans are widely exposed. ERα targets genes ESR1 (ERα) and TFF1, both on mRNA and protein level, were chosen to study the effect of the tested compounds on the mentioned receptor. A total of 7 compounds seemed to impact mRNA and protein expression similarly to estradiol (E2). The direct interaction of the most active compounds with the ERα ligand binding domain (LBD) was further tested in cell-free experiments using the recombinant form of the LBD, and 4-chloropyrocatechol was shown to behave like E2 with about 1/3 of the potency of E2. Our results provide evidence that some of these compounds can be considered potential endocrine disruptors interacting with ERα.

• MeSH
• alfa receptor estrogenů * metabolismus   genetika   MeSH
• endokrinní disruptory * farmakologie   toxicita   MeSH
• faktor TFF1 metabolismus   genetika   MeSH
• fenoly * farmakologie   chemie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nádory prsu metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Trastuzumab deruxtecan (T-DXd) is a human epidermal growth factor 2 (HER2)-directed antibody-drug conjugate approved in HER2-expressing breast and gastric cancers and HER2-mutant non-small-cell lung cancer. Treatments are limited for other HER2-expressing solid tumors. METHODS: This open-label phase II study evaluated T-DXd (5.4 mg/kg once every 3 weeks) for HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local or central testing) locally advanced or metastatic disease after ≥1 systemic treatment or without alternative treatments. The primary end point was investigator-assessed confirmed objective response rate (ORR). Secondary end points included safety, duration of response, progression-free survival (PFS), and overall survival (OS). RESULTS: At primary analysis, 267 patients received treatment across seven tumor cohorts: endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, and other. The median follow-up was 12.75 months. In all patients, the ORR was 37.1% (n = 99; [95% CI, 31.3 to 43.2]), with responses in all cohorts; the median DOR was 11.3 months (95% CI, 9.6 to 17.8); the median PFS was 6.9 months (95% CI, 5.6 to 8.0); and the median OS was 13.4 months (95% CI, 11.9 to 15.5). In patients with central HER2 IHC 3+ expression (n = 75), the ORR was 61.3% (95% CI, 49.4 to 72.4), the median DOR was 22.1 months (95% CI, 9.6 to not reached), the median PFS was 11.9 months (95% CI, 8.2 to 13.0), and the median OS was 21.1 months (95% CI, 15.3 to 29.6). Grade ≥3 drug-related adverse events were observed in 40.8% of patients; 10.5% experienced adjudicated drug-related interstitial lung disease (ILD), with three deaths. CONCLUSION: Our study demonstrates durable clinical benefit, meaningful survival outcomes, and safety consistent with the known profile (including ILD) in pretreated patients with HER2-expressing tumors receiving T-DXd. Greatest benefit was observed for the IHC 3+ population. These data support the potential role of T-DXd as a tumor-agnostic therapy for patients with HER2-expressing solid tumors.

• MeSH
• humanizované monoklonální protilátky škodlivé účinky   MeSH
• imunokonjugáty * škodlivé účinky   MeSH
• intersticiální plicní nemoci * chemicky indukované   farmakoterapie   MeSH
• lidé MeSH
• nádory plic * farmakoterapie   MeSH
• nádory prsu * farmakoterapie   MeSH
• nemalobuněčný karcinom plic * farmakoterapie   MeSH
• receptor erbB-2 metabolismus   MeSH
• trastuzumab škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH

Background: Antiresorptive drugs are widely used to reduce bone mineral loss in patients with osteoporosis and to prevent skeletal-related events in patients with metastatic cancers and multiple myeloma (MM). Both the bisphosphonates (BP) and denosumab typically used in this indication were shown to be effective and relatively safe. Obviously, this medication could have some adverse effects; one of them is osteonecrosis of the external auditory canal. Only sporadic cases of external auditory canal osteonecrosis have been published yet. Here, we provide a case of denosumab-related osteonecrosis of the external auditory canal successfully treated surgically in the early stage of the disease. Case report: A 68-year-old patient with breast cancer underwent comprehensive oncological treatment, including denosumab administration. She was diagnosed with osteonecroses in the jaw and ear canal. The necrotic bones in both regions were resected with primary wound closure. Both affected sites healed well with no signs of necrosis recurrence. Conclusions: Osteonecrosis of the external auditory canal is a rare but probably underdiagnosed complication of antiresorptive medication. It has a negative impact on patient quality of life if left untreated. Early surgical treatment appears to be effective. The authors highlight several similarities with medication-related osteonecrosis of the jaw. Therefore, an analogous disease staging and treatment rationale is suggested.

• MeSH
• bisfosfonátová osteonekróza čelistí chirurgie   etiologie   MeSH
• denosumab * škodlivé účinky   terapeutické užití   MeSH
• inhibitory kostní resorpce * škodlivé účinky   MeSH
• lidé MeSH
• nádory prsu * farmakoterapie   chirurgie   MeSH
• nemoci ucha chemicky indukované   chirurgie   MeSH
• osteonekróza * chemicky indukované   chirurgie   MeSH
• senioři MeSH
• zvukovod * chirurgie   patologie   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH