MicroRNAs (miRNAs) have emerged as important regulators of gene expression in various biological processes, including cancer. miR-182-5p has gained attention for its potential implications in gynecologic cancers, including breast, ovarian, endometrial, and cervical cancers. miR-182-5p dysregulation has been associated with multiple facets of tumor biology in gynecologic cancers, including tumor initiation, progression, metastasis, and therapeutic response. Studies have highlighted its involvement in key signaling pathways and cellular processes that contribute to cancer development and progression. In addition, miR-182-5p has shown potential as a diagnostic and prognostic biomarker, with studies demonstrating its correlation with clinicopathological features and patient outcomes. Furthermore, the therapeutic potential of miR-182-5p is being explored in gynecologic cancers. Strategies such as miRNA mimics or inhibitors targeting miR-182-5p have shown promise in preclinical and early clinical studies. These approaches aim to modulate miR-182-5p expression, restoring normal cellular functions and potentially enhancing treatment responses. Understanding the biologic and clinical implications of miR-182-5p in gynecologic cancers is crucial for the development of targeted therapeutic strategies and personalized medicine approaches. Further investigations are needed to unravel the specific target genes and pathways regulated by miR-182-5p. It is important to consider the emerging biologic and clinical implications of miR-182-5p in gynecologic cancers.
- MeSH
- Humans MeSH
- MicroRNAs * genetics MeSH
- Biomarkers, Tumor genetics MeSH
- Genital Neoplasms, Female * genetics therapy MeSH
- Prognosis MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Karcinomy prsu s pozitivitou receptoru 2 pro lidský epidermální růstový faktor (human epidermal growth factor receptor 2, HER2) jsou neodmyslitelně spojeny s horšími výsledky přežití ve srovnání s případy, u nichž jsou detekovány pozitivní estrogenové a progesteronové receptory a status HER2 negativní. V posledních třech desetiletích však díky soustavnému výzkumu a vývoji anti-HER2 terapie došlo k významně lepším prognostickým výsledkům pro pacienty s diagnostikovaným jak časným, tak pokročilým stadiem HER2 pozitivního karcinomu prsu. Konjugáty protilátky proti HER2 a cytostatika jsou velmi žádaným tématem pro budoucí výzkum a účinnou součástí péče o pacienty s nádory v oblasti prsu s rostoucí rolí v léčebných paradigmatech.
HER2 (human epidermal growth factor receptor 2)-positive breast cancers are inherently associated with poorer survival outcomes compared with estrogen and progesterone receptor-positive and HER2-negative cases. There has been consistent research and development of anti-HER2 therapy, which has led to significantly better prognostic outcomes for patients with both early and newly diagnosed HER2-positive breast cancer in the past thirty years. Conjugates anti-HER2 antibody and cytostatics are a highly desirable topic for future research and an effective part of the care of breast cancer patients with increasing roles in treatment paradigms.
Cíl: 18 F-fluorestradiol je nové radiofarmakum, které lze použít při zobrazování karcinomu prsu, indikace v klinických postupech ještě nemají své pevné místo, proto je cílem studie posoudit klinický význam zobrazení karcinomu prsu estrogen-pozitivních receptorů (ER+) pomocí 18 F-fluorestradiolu (18 F-FES) PET/CT nebo PET/MR z hlediska využití při rozhodnutí o léčbě. Studie se zabývá také volbou využití PET/CT nebo PET/MR ve stagingu a restagingu karcinomu prsu. Metodika: U 40 pacientek s estrogen pozitivním karcinomem prsu bylo provedeno hybridní zobrazení s intravenózní aplikací 18 F-FES, ve 25 případech bylo použito PET/CT, v 15 případech PET/MR. Radiofarmakum bylo injekčně aplikováno v aktivitě 2,5 MBq/kg. U deseti pacientek byla jako restagingová metoda použito PET/ MR, v pěti případech stagingu před operací bylo provedeno PET/MR s cíleným plným diagnostickým MR zobrazením prsu v pronační poloze s následným zobrazením trupu v poloze na zádech. Všechna vyšetření PET/MR byla provedena po aplikaci gadoliniové kontrastní látky, zobrazení zahrnovalo zobrazení mozku v T1 STARVIBE. PET/CT bylo provedeno kontinuální PET akvizicí následně po akvizici CT s intravenózním podáním jodované kontrastní látky, v pěti případech bylo provedeno ve stagingu, ve 20 případech v restagingu. Výsledky: Nejdůležitějším výsledkem byla detekce ER+ metastáz při negativním výsledku 18 F-FDG-PET (12krát) – včetně mozkových a jaterních metastáz, perzistující ER+ metastáz (7krát), staging onemocnění (10krát), ztráta ER (4krát) a negativní nález pro metastázy (2), při pěti vyšetřeních nebyly nalezeny žádné přidané informace. Závěr: 18 F-FES-PET poskytuje klinicky vý- znamné informace pro volbu léčebné strategie, 18 F-FES-PET/MR je výhodné vyšetření při zaměření na zobrazení mozku a jater s možnos- tí prokázat anebo vyloučit metastázy v těchto orgánech.
Aim. 18 F-fluoroestradiol is a novel radiopharmaceutical useful in the imaging of breast carcinoma, the indications in clinical scenarios are under development. The purpose of the study is to assess the clinical impact of the imaging of the breast carcinoma with estrogenpositive receptors (ER+) using 18 F-fluoroestra- diol ( 18 F-FES) PET/CT or PET/MRI according to the treatment decision making. The study is concerned in the different preference of PET/CT and PET/MRI in the staging and restaging. Methods. 40 patients with estrogen positive breast carcinoma underwent the hybrid imaging after intravenous application of 18 F-FES, in 25 cases it was used PET/CT, in 15 cases PET/ MRI. The radiopharmaceutical was injected with the activity of 2,5 MBq/kg. In 10 patient, PET/MRI was used as restaging method, PET/ MRI was performed in the 5 cases of the staging before surgery with targeted full diagnostic MRI imaging of the breast in prone position, followed by the trunk imaging in supine position. All PET/MRI were performed after application of the gadolinium contrast material, the imaging included brain imaging in T1 STARVIBE. PET/CT was performed using the continuous PET acquisition after CT with the intravenous administration of the iodinated contrast material, in 5 cases was performed in staging, in 20 cases in restaging Results. The most important informa- tion was detection of ER+ metastases when 18 F-FDG-PET was negative (12×) – including brain and liver metastases, the persistent ER+ of the metastases (7×), staging of the disease (10×), the loss of the ER (4x) and the negative finding for metastases (2), no added information was found in 5 examinations. Conclusion. 18 F-FES-PET provided the impor- tant clinical information to treatment strategy, 18 F-FES-PET/MRI improves the imaging of metastases in brain and liver.
Střevní mikrobiom je právem označovaný jako neviditelný orgán, který významně ovlivňuje lidský organismus po celý jeho život. Procesů, na kterých se podílí, je mnoho. Kromě dobře známé role v oblasti trávení dále ovlivňuje maturaci imunitního systému, metabolické programování a propojuje i poměrně vzdálené orgány (např. osa střevo–mozek). Vývoj střevního mikrobiomu začíná záhy po narození a působící faktory můžeme rozdělit na modifikovatelné (výživa, antibiotická léčba, prostředí) a neovlivnitelné (gestační stáří, způsob porodu). Alterace střevního mikrobiomu těmito faktory je spojována jak s krátkodobou, tak dlouhodobou morbiditou. Cílem současného výzkumu je porozumět nejen vývoji samotnému, ale i všem činitelům, které mohou do tohoto přirozeného procesu zasahovat. Poznání a pochopení komplexity střevního mikrobiomu nám umožní činit taková medicínská rozhodnutí, která budou mít pro novorozence značné benefity. Tento přehledový článek přináší vhled do problematiky vzniku a vývoje střevního mikrobiomu a s tím spojené možné klinické aspekty u donošeného i nedonošeného novorozence. Součástí našeho sdělení jsou i doporučení, která vycházejí ze současného poznání, k ovlivnění negativních následků alterace střevního mikrobiomu v tomto křehkém období.
Gut microbiome is regarded as an invisible organ influencing the human organism throughout the entire lifespan. Microbiome determines various physiological processes including immune system maturation, metabolic programming and furthermore, facilitates connections even between relatively distant organs (e.g. gut-brain axis). Its development begins shortly after birth and is modified by various aspects. We can categorize them into modifiable (antibiotic treatment, diet) and non-modifiable factors (gestational age, delivery mode). Intestinal alteration caused by these influencing factors might contribute to short-term and long-term morbidity. Our objective is to comprehend the microbiome development itself and its modifying factors. Understanding the microbiome complexity could help us make such medical decisions to outweigh negative sequelae of an early gut alteration. This review presents topics concerning microbiome origin and its development along with potential clinical aspects in term and preterm newborn. We also include recommendations for parents and health care professionals regarding possible attitudes, based on current scientific knowledge, to diminish early gut microbiome alterations.
- MeSH
- Anti-Bacterial Agents adverse effects MeSH
- Immune System microbiology growth & development MeSH
- Breast Feeding MeSH
- Humans MeSH
- Infant, Premature immunology MeSH
- Infant, Newborn MeSH
- Brain-Gut Axis physiology immunology MeSH
- Risk Factors MeSH
- Gastrointestinal Microbiome * physiology drug effects MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Publication type
- Review MeSH
Aim: To examine the level of social support of cancer patients and those undergoing surgery, and to investigate whether there are differences in social support of cancer patients according to the type of cancer. Design: A cross-sectional study. Methods: The study included 81 participants with colon, breast and lung cancer, of whom 49 (60%) were women and 32 (40%) were men, divided into three groups according to the type of cancer, one month after surgery and oncological treatment. The Multidimensional Scale of Perceived Social Support and data from medical records were used. Results: Lung cancer patients rated their health as moderate or poor, whereas those with breast cancer reported their health as very good or good (χ2 test, p = 0.003). Participants with colon cancer rated social support from family (Kruskal-Wallis test, p = 0.02) and social support from friends (Kruskal-Wallis test, p = 0.005) significantly better than patients with lung or breast cancer. Conclusion: Overall social support was rated significantly better by colon cancer patients compared to those with lung or breast cancer. Social support plays an important role in the treatment of cancer patients, and the study findings could help to develop personalized interventions and support programs for these individuals.
Breast milk, as the optimal food for infants and young children, contains all the components necessary for proper growth and development. It is a rich source of both essential nutrients and biologically active factors, making breast milk a unique food with scientifically proven health-promoting properties. Among the entire range of biologically active factors, breast milk microorganisms and prebiotic factors, in the form of breast milk oligosaccharides, occupy an important place. The aim of our research was to determine the occurrence of bacteria with probiotic potential, belonging to the Lactobacillaceae family, in the environment of breast milk and breast milk oligosaccharides. The study included 63 human milk samples from breastfeeding women at various stages of lactation. Microorganism identification based on culture tests and MALDI TOF/MS, macronutrient analysis using the MIRIS human milk analyser, as well as analysis of human milk oligosaccharides using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry were performed. The results have shown that breast milk from different breastfeeding women is characterized by great diversity in terms of the presence of Lacto-bacillaceae bacteria in its microbiological composition. These bacteria were present in 22.2 % of the tested breast milk samples. Analysis of the human milk oligosaccharide profile revealed a slightly higher content of prebiotic factors in breast milk samples containing Lactobacillaceae, including 2'-fucosyllactose, oligosaccharide occurring in the highest amount in breast milk.
BACKGROUND: Hormone receptor-positive (HR+) breast cancer responds poorly to immune checkpoint inhibitors (ICIs). In some settings, radiation therapy (RT) has been shown to mediate immunostimulatory effects and promote ICI sensitivity. METHODS: We investigated whether hypofractionated RT may be successfully combined with ICIs in a mouse model of multifocal, metachronous HR+ mammary carcinogenesis. We hypothesized that focal RT targeting the first detectable (primary) tumor combined with ICIs may generate effective immunity, delaying the development of new lesions. RESULTS: Focal RT in various doses and fractionations limited primary tumor growth, with an optimum for a 20-Gy × 2 regimen (ablative in approximately 90% of mice). The degree of primary disease control, however, did not necessarily correlate with overall survival extension because of changes in the development of new neoplastic lesions contributing to global tumor burden. Adding a PD-1 blocker to focal RT delivered in a 10-Gy × 3, 20-Gy × 2, or 8-Gy × 6 regimen failed to alter overall survival extension enabled by RT alone. Similar results were obtained with a CTLA4 blocker, an IL-1β inhibitor, and a PD-1 blocker plus recombinant FLT3LG when combined with the 10-Gy × 3 regimen. CONCLUSIONS: In this model of HR+ mammary carcinogenesis, RT to the primary tumor ameliorates overall survival (to an extent based on dose and fractionation). Increasing local control through RT alone or RT plus immunotherapy beyond a hitherto undefined threshold, however, does not necessarily inhibit the development of subsequent nonirradiated neoplasms and hence does not necessarily provide extra overall survival benefits.
- MeSH
- Programmed Cell Death 1 Receptor antagonists & inhibitors MeSH
- Mammary Neoplasms, Experimental * therapy MeSH
- Dose Fractionation, Radiation MeSH
- Radiation Dose Hypofractionation MeSH
- Immunotherapy * methods MeSH
- Immune Checkpoint Inhibitors * pharmacology therapeutic use MeSH
- Combined Modality Therapy MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Breast Neoplasms * pathology therapy MeSH
- Receptors, Estrogen metabolism MeSH
- Receptors, Progesterone metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Ecto-5'-nucleotidase (CD73) is a novel target in cancer (immuno)therapy. Its blockade prevents the formation of immunosuppressive and cancer-promoting adenosine from AMP. Here, we report on the development of a series of small molecules that mimic adenine nucleotides, in which the ribose moiety was replaced by an alkyl chain. Its length was found to be crucial for potency. A crystal structure of the N6-disubstituted acyclic ADP analog 26 (N6-benzyl,N6-methyladenine-9-yl)pentyloxydiphosphonate) in complex with human CD73 revealed that the flexible pentyl linker adopts to interdomain rotation angles differing by up to 18.5°. The most potent CD73 inhibitor of the present series was analog 27 (N6-benzyl,N6-methyladenine-9-yl)hexyloxydiphosphonate, PSB-24000) which exhibited submicromolar potency at human CD73 (Ki 563 nM at soluble CD73; Ki 481 nM at membrane-bound CD73 of triple-negative breast cancer cells). Acyclic nucleotide analogs may be advantageous compared to the previously reported nucleotidic CD73 inhibitors due to their high chemical stability, and because less off-target effects are to be expected. The structure-activity relationships discovered in this study provide valuable insights which will be useful for the development of CD73 inhibitors as immunotherapeutic drugs.
- MeSH
- 5'-Nucleotidase * antagonists & inhibitors metabolism MeSH
- Cisplatin chemistry pharmacology MeSH
- GPI-Linked Proteins antagonists & inhibitors metabolism MeSH
- Enzyme Inhibitors * pharmacology chemistry chemical synthesis MeSH
- Humans MeSH
- Models, Molecular MeSH
- Molecular Structure MeSH
- Purine Nucleotides * chemistry pharmacology chemical synthesis MeSH
- Pyrimidine Nucleotides * chemistry pharmacology chemical synthesis MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Prader-Willi syndrome (PWS) is primarily caused by a paternal microdeletion of the 15q11-q13 region, maternal uniparental disomy (mUPD) or unbalanced translocations. The MKRN3 gene, located within 15q11-q13, is a master regulator of pubertal initiation. We aimed to compare variant pubertal onset and progression with recent normative data and to correlate it with abnormal MKRN3 gene status. METHODS: Age at pubarche, gonadarche, subsequent pubertal progression and bone age (BA) at gonadarche were investigated in 37 PWS patients (18 females) who already entered pubarche and/or gonadarche with median age 11.1 (95% CI: 6.4 - 18.8) years. All patients were re-tested to confirm genetic subtypes of PWS. The MKRN3 gene was analyzed using single gene sequencing. RESULTS: Out of 37 subjects, 22 had microdeletion and 15 mUPD. Regardless of genetic subtypes and MKRN3 gene status, no correlation between genotypes and the pubertal pattern was found. They initiated pubarche early - girls at 7.4 (95%CI:6.4-8.4), and boys at 9.2 (8.2-10.2) years. The subsequent progression from PH2 to PH4 (pubic hair development) was prolonged to 3.7 years in girls (1.5-5.9;p<0.05), and 2.9 in boys (2.2-3.6;p<0.001). The age at gonadarche was adequate - 10.0 years in girls (8.8-11.2), and 11.0 in boys (9.8-12.1). Progression rate of breast development from B2 to B4 was 3.9 (0.2-7.5) years in girls and of testicular volume from 4 ml to 15ml was 3.8 (0.0-8.1) years in boys. The BA at gonadarche is advanced by 0.6 ± 1.1 years (p<0.001). CONCLUSIONS: Children with PWS, regardless of the genetic subtype and/or MKRN3 status, had an early pubarche and normally timed gonadarche. Pubarche progression was slower. Advanced BA was significantly correlated with gonadarche.
- MeSH
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Prader-Willi Syndrome * genetics physiopathology MeSH
- Disease Progression MeSH
- Puberty * physiology genetics MeSH
- Ribonucleoproteins genetics MeSH
- Ubiquitin-Protein Ligases genetics MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND AND AIMS: Janus kinase (JAK) inhibitors, such as tofacitinib, are potent anti-inflammatory agents used in the treatment of ulcerative colitis (UC). Current guidelines recommend avoiding their use during pregnancy due to safety concerns, as well as during breastfeeding due to the potential excretion into breast milk. METHODS: This case report describes the impact of in utero exposure to tofacitinib during pregnancy and subsequent exposure via breastfeeding on the immune development of the exposed infant. RESULTS: A 37-year-old woman with UC, who was being treated with tofacitinib and vedolizumab, became pregnant and continued both medications, with the tofacitinib dosage reduced from 10 to 5 mg BID at gestational week 28. The infant was born healthy, with normal growth and development, and received all scheduled non-live vaccinations. At 15 months, immune parameters-including response to vaccination-were evaluated. The results showed normal immunoglobulin levels and an adequate serologic response to vaccination, with no signs of immune dysfunction. CONCLUSIONS: This case suggests that prolonged prenatal and postnatal exposure to tofacitinib may not adversely affect infant immune development. However, caution is advised due to the limited number of documented cases. Further research is needed to fully understand the long-term implications of JAK inhibitor exposure during pregnancy and breastfeeding.
- MeSH
- Adult MeSH
- Antibodies, Monoclonal, Humanized therapeutic use MeSH
- Janus Kinase Inhibitors * adverse effects MeSH
- Protein Kinase Inhibitors adverse effects therapeutic use MeSH
- Infant MeSH
- Breast Feeding * MeSH
- Pregnancy Complications drug therapy MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Piperidines * adverse effects therapeutic use MeSH
- Pyrimidines * adverse effects therapeutic use MeSH
- Pyrroles adverse effects therapeutic use MeSH
- Pregnancy MeSH
- Colitis, Ulcerative * drug therapy MeSH
- Prenatal Exposure Delayed Effects * immunology chemically induced MeSH
- Check Tag
- Adult MeSH
- Infant MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
