Colorectal cancer (CRC) is one of the most deaths causing diseases worldwide. Several risk factors including hormones like insulin and insulin like growth factors (e.g., IGF-1) have been considered responsible for growth and progression of colon cancer. Though there is a huge advancement in the available screening as well as treatment techniques for CRC. There is no significant decrease in the mortality of cancer patients. Moreover, the current treatment approaches for CRC are associated with serious challenges like drug resistance and cancer re-growth. Given the severity of the disease, there is an urgent need for novel therapeutic agents with ideal characteristics. Several pieces of evidence suggested that natural products, specifically medicinal plants, and derived phytochemicals may serve as potential sources for novel drug discovery for various diseases including cancer. On the other hand, cancer cells like colon cancer require a high basal level of reactive oxygen species (ROS) to maintain its own cellular functions. However, excess production of intracellular ROS leads to cancer cell death via disturbing cellular redox homeostasis. Therefore, medicinal plants and derived phytocompounds that can enhance the intracellular ROS and induce apoptotic cell death in cancer cells via modulating various molecular targets including IGF-1 could be potential therapeutic agents. Alkaloids form a major class of such phytoconstituents that can play a key role in cancer prevention. Moreover, several preclinical and clinical studies have also evidenced that these compounds show potent anti-colon cancer effects and exhibit negligible toxicity towards the normal cells. Hence, the present evidence-based study aimed to provide an update on various alkaloids that have been reported to induce ROS-mediated apoptosis in colon cancer cells via targeting various cellular components including hormones and growth factors, which play a role in metastasis, angiogenesis, proliferation, and invasion. This study also provides an individual account on each such alkaloid that underwent clinical trials either alone or in combination with other clinical drugs. In addition, various classes of phytochemicals that induce ROS-mediated cell death in different kinds of cancers including colon cancer are discussed.

• Klíčová slova
• HIF-1α, IGF-1, IGFBP-3, alkaloids, apoptosis, colon cancer progression, mutation, oxidative stress,
• MeSH
• alkaloidy * terapeutické užití   MeSH
• hormony terapeutické užití   MeSH
• insulinu podobný růstový faktor I MeSH
• lidé MeSH
• nádory tračníku * farmakoterapie   metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• alkaloidy * MeSH
• hormony MeSH
• insulinu podobný růstový faktor I MeSH
• reaktivní formy kyslíku MeSH

PURPOSE: We aimed to assess the oncologic efficacy of combining docetaxel (DOC) versus abiraterone (ABI) with androgen deprivation therapy (ADT) in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC), with a focus on the efficacy of sequential therapy, in a real-world clinical practice setting. METHODS: The records of 336 patients who harbored de novo high-risk mHSPC, based on the LATITUDE criteria, and had received ADT with either DOC (n = 109) or ABI (n = 227) were retrospectively analyzed. Overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), including time to castration-resistant prostate cancer (CRPC), time to 2nd-line progression (PFS2), and 2nd- and 3rd-line PFS, were compared. We used one-to-two propensity score matching to minimize the confounders. The differential efficacy of 2nd-line therapy based on agents in each arm was evaluated using the unmatched cohort as an additional interest. RESULTS: After propensity score matching, 86 patients treated with DOC + ADT and 172 with ABI + ADT were available for analyses. The 3-year OS and CSS for DOC versus ABI were 76.2% versus 75.1% (p = 0.8) and 78.2% versus 78.6% (p = 1), respectively. There was no difference in the median PFS2 (49 vs. 43 months, p = 0.39), while the median time to CRPC in patients treated with ABI was significantly longer compared to those treated with DOC (42 vs. 22 months; p = 0.006). The median 2nd-line PFS (14 vs. 4 months, p < 0.001) and 3rd-line PFS (4 vs. 2 months, p = 0.012) were significantly better in the DOC group than in the ABI group. Among the unmatched cohort, after ABI for mHSPC, the median 2nd-line PFS did not differ between the patients treated with DOC and those treated with enzalutamide as 2nd-line therapy (both 3 months, p = 0.8). CONCLUSIONS: ADT with DOC or ABI has comparable oncologic outcomes in terms of OS, CSS, and PFS2 in patients with de novo high-risk mHSPC. Compared to DOC, ABI resulted in longer time to CRPC but worse 2nd and 3rd-line PFS. Further studies are needed to clarify the optimal sequence of therapy in the upfront intensive treatment era.

• Klíčová slova
• abiraterone, docetaxel, high-risk, metastatic hormone-sensitive prostate cancer, sequential therapy,
• MeSH
• antagonisté androgenů terapeutické užití   MeSH
• docetaxel terapeutické užití   MeSH
• hormony terapeutické užití   MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * patologie   MeSH
• nádory prostaty * patologie   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• abiraterone MeSH Prohlížeč
• antagonisté androgenů MeSH
• docetaxel MeSH
• hormony MeSH

BACKGROUND: Combination systemic therapies have become the standard for metastatic hormone-sensitive prostate cancer (mHSPC). However, the effect of age on oncologic outcomes remains unknown. Our aim was to perform a systematic review, meta-analysis, and network meta-analysis (NMA) on the effect of chronological age on overall survival (OS) in patients treated with combination therapies for mHSPC. METHODS: We searched the PubMed®, Web of ScienceTM, and Scopus® databases to identify randomized controlled trials (RCTs) that analyzed the efficacy of combination systemic therapies using ADT plus docetaxel and/or androgen receptor signaling inhibitor (ARSI) in patients with mHSPC. We included studies, which provided separate hazard ratios (HRs) for younger vs. older patients. The selected age cut-off was 70 years (±5 years). Our outcome of interest was OS. RESULTS: We included nine RCTs with a total of 9183 patients. Younger and older men constituted 51% and 49% of included patients, respectively. Docetaxel plus ADT significantly improved OS among both older (HR 0.79, 95% CI 0.63-0.99, p = 0.04) and younger patients (HR 0.79, 95% CI 0.69-0.90, p < 0.001) with no differences according to age. ARSI plus ADT improved OS in older (HR 0.72, 95% CI 0.64-0.80, p < 0.001) and younger (HR 0.58, 95% CI 0.51-0.66, p < 0.001) patients; younger patients did benefit more (p = 0.02). On NMA treatment ranking, triplet therapy showed the highest probability of OS benefit irrespective of age group; in older patients, the benefit of triplet therapy compared to doublet was less expressed. CONCLUSIONS: Patients with mHSPC benefit from combination systemic therapies irrespective of age; the effect is, however, more evident in younger patients. Chronological age alone seems not to be a selection criteria for the administration of combination systemic therapies.

• MeSH
• antagonisté androgenů terapeutické užití   MeSH
• docetaxel MeSH
• hormony terapeutické užití   MeSH
• lidé MeSH
• nádory prostaty * patologie   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH
• Názvy látek
• antagonisté androgenů MeSH
• docetaxel MeSH
• hormony MeSH

PURPOSE: This study aimed to evaluate the efficacy of long-term neoadjuvant androgen-deprivation therapy (ADT) before radical prostatectomy (RP). METHODS: We conducted meta-analyses and network meta-analyses, which included randomized controlled trials that assessed patients with prostate cancer (PC) who received either short-term (<6 months) or long-term (≥6 months) neoadjuvant ADT before RP. RESULTS: Thirteen articles with 2778 patients were eligible for analysis. Short-term neoadjuvant ADT was neither associated with biochemical recurrence (OR 1.19, 95% CI, 0.93-1.51, p = 0.17), metastasis (OR 0.73, 95% CI, 0.45-1.19, p = 0.21), nor overall mortality (OR 0.72, 95% CI 0.43-1.21, p = 0.22); no study investigated survival outcomes in patients on long-term neoadjuvant ADT. In terms of pathologic outcomes, long-term neoadjuvant ADT was significantly associated with a reduced risk of positive surgical margin (SM) and an increased rate of organ-confined disease (OCD) compared to short-term neoadjuvant ADT (OR 0.56, 95% CI 0.39-0.80, p = 0.001, and OR 1.48, 95% CI 1.10-1.99, p = 0.009, respectively). These findings were confirmed in the network meta-analyses. Meanwhile, only a non-significant trend favoring long-term neoadjuvant ADT was observed for pathologic complete response (OR 1.98, 95% Crl 1.00-3.93). CONCLUSION: Long-term neoadjuvant ADT was associated with more favorable pathologic outcomes, but whether these findings translate into favorable survival outcomes still remains unproven due to very limited evidence. Since there are no reliable survival data, long-term neoadjuvant ADT before RP should not be used in clinical practice until more robust evidence arises from ongoing trials.

• Klíčová slova
• ADT, duration, long-term, meta-analysis, neoadjuvant, radical prostatectomy,
• MeSH
• antagonisté androgenů * terapeutické užití   MeSH
• hormony terapeutické užití   MeSH
• lidé MeSH
• nádory prostaty * farmakoterapie   patologie   chirurgie   MeSH
• neoadjuvantní terapie MeSH
• prostatektomie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• antagonisté androgenů * MeSH
• hormony MeSH

CONTEXT: Novel prospective randomized controlled observations addressing combination therapy in metastatic hormone-sensitive prostate cancer (mHSPC) have demonstrated promising overall survival (OS) outcomes. OBJECTIVE: To compare these novel findings and systematically review and address them within formal network meta-analyses (NMAs) that include observations from other prospective randomized controlled trials (RCTs). EVIDENCE ACQUISITION: First, we focused on abiraterone, enzalutamide, apalutamide, and docetaxel effects on OS in mHSPC using the PRISMA methodology. PubMed and abstracts identified prospective RCTs in first-line mHSPC. Second, we focused on mature studies that reached median OS and tested OS between abiraterone and docetaxel with tumor burden stratification. EVIDENCE SYNTHESIS: The first part included seven studies (n = 6639) and the second part, five studies (n = 4462). In the first part, abiraterone ranked first for high-volume mHSPC. Conversely, enzalutamide ranked first for low-volume mHSPC. In the second part, abiraterone treatment in high-volume mHSPC resulted in median OS of 50.1 mo and exceeded that with docetaxel (45.9 mo) and ADT alone (34.0 mo). Docetaxel treatment in low volume mHSPC resulted in median OS of 69.5 mo versus 67.7 mo with ADT alone. CONCLUSIONS: In conventional NMA that relied on conventional hazard ratios, differences were identified with respect to the relative efficacy of the combination therapies examined; abiraterone dominated the alternatives in high-volume mHSPC. In part two, which relied on trials for which median OS is available, comparison of abiraterone versus docetaxel revealed a 4-mo difference in OS in high-volume mHSPC. Conventional NMA may have overestimated the importance of treatment efficacy instead of focusing on median OS duration, which might represent a more important clinical endpoint. PATIENT SUMMARY: We reviewed studies on hormonal treatments and chemotherapy used for prostate cancer that has spread outside the prostate gland (metastatic prostate cancer, mPC). We found that the best overall survival was with the hormone agents abiraterone in high-volume mPC and enzalutamide in low-volume mPC. In comparison to the chemotherapy drug docetaxel, median overall survival with abiraterone was 4 months longer among patients with mPC.

• Klíčová slova
• Abiraterone, Androgen deprivation therapy, Apalutamide, Docetaxel, Enzalutamide, High volume, Low volume, Metastatic burden,
• MeSH
• antagonisté androgenů terapeutické užití   MeSH
• docetaxel terapeutické užití   MeSH
• hormony terapeutické užití   MeSH
• lidé MeSH
• nádory prostaty * patologie   MeSH
• síťová metaanalýza MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• antagonisté androgenů MeSH
• docetaxel MeSH
• hormony MeSH

BACKGROUND: Prostate cancer is one of the most common malignancies in men. Chemotherapy has an important role in the management of prostate cancer, especially for the treatment of castrate resistant prostate cancer (mCRPC). According to recently published studies, chemotherapy can also be used to treat advanced hormone sensitive disease. AIM: The aim of this report is to review the currently available options for chemotherapy of prostate cancer. RESULTS: Docetaxel is a chemotherapeutic agent used for standard treatment of mCRPC as 1st line therapy. In TAX 327 and SWOG 9916 studies reported in 2004, docetaxel, the first cytostatic agent indicated for this disease, prolonged overall survival. As a 2nd line mCRPC treatment, kabazitaxel resulted in longer overall survival than mitoxantrone, according to the results of the TROPIC study. Targeted hormone treatment, radium-223 irradiation, and immunotherapy are other treatment options for patients with mCRPC. Currently, the main focus is to develop an optimal sequence of treatments. Standard androgen deprivation therapy (ADT) is the standard option for patients with advanced hormone sensitive prostate cancer. According to recently published studies (CHAARTED, STAMPEDE), docetaxel with ADT increases overall survival in this group of patients. In the Czech Republic, this option is still off-label. Chemotherapy is not indicated in patients with early prostate cancer after radical prostatectomy or radiotherapy.Key words: prostate cancer - metastasis - chemotherapy - docetaxel - cabazitaxelThe authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 9. 5. 2016Accepted: 6. 6. 2016.

• MeSH
• antagonisté androgenů terapeutické užití   MeSH
• antitumorózní látky terapeutické užití   MeSH
• docetaxel MeSH
• hormony terapeutické užití   MeSH
• lidé MeSH
• mitoxantron terapeutické užití   MeSH
• nádory prostaty rezistentní na kastraci farmakoterapie   MeSH
• taxoidy terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antagonisté androgenů MeSH
• antitumorózní látky MeSH
• cabazitaxel MeSH Prohlížeč
• docetaxel MeSH
• hormony MeSH
• mitoxantron MeSH
• taxoidy MeSH

Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disorder characterized by progressive thyroid failure. Th1 and Treg subset of CD4(+) cells have been implicated in the pathogenesis; however, less is known about their respective roles across the spectrum of HT clinical presentations. To shed more light on CD4(+) subsets role in HT, we investigated the mRNA expression levels of several Th1/Treg-associated transcription factors (T-bet/ETS1, HIF1α/BLIMP1/FOXP3) in peripheral blood T cells of 10 hypothyroid, untreated HT patients, 10 hypothyroid patients undergoing hormone replacement therapy, 12 euthyroid HT subjects, and 11 healthy controls by the qRT-PCR. Compared to euthyroid HT patients and controls, both hypothyroid (2.34-fold difference versus controls, P < 0.01) and thyroxine-supplemented patients (2.5-fold, P < 0.001) showed an increased FOXP3 mRNA expression in T cells. Similarly, mRNA expression levels of T-bet were upregulated in severely affected but not in euthyroid HT subjects (2.37-fold and 3.2-fold, hypothyroid and thyroxine-supplemented HT patients versus controls, resp., P < 0.01). By contrast, no differences in mRNA expression levels of ETS1, BLIMP1, and HIF1α were observed across the study groups. In summary, severe but not euthyroid HT was associated with robust upregulation of T-bet and FOXP3 mRNA in peripheral T cells, independent of the thyroid hormone status but proportional to disease activity.

• MeSH
• autoimunitní nemoci metabolismus   MeSH
• CD4-pozitivní T-lymfocyty cytologie   metabolismus   MeSH
• dospělí MeSH
• forkhead transkripční faktory metabolismus   MeSH
• Hashimotova nemoc imunologie   metabolismus   MeSH
• hormony terapeutické užití   MeSH
• hypotyreóza imunologie   metabolismus   MeSH
• kohortové studie MeSH
• leukocyty mononukleární cytologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• proteiny T-boxu metabolismus   MeSH
• regulace genové exprese MeSH
• studie případů a kontrol MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• forkhead transkripční faktory MeSH
• FOXP3 protein, human MeSH Prohlížeč
• hormony MeSH
• messenger RNA MeSH
• proteiny T-boxu MeSH
• T-box transcription factor TBX21 MeSH Prohlížeč

Hormonal therapy in transsexual patients (TS) includes sexagens administration: androgens in female-to-male transsexual patients (FtM) and oestrogens and antiandrogens in male-to-female transsexual patients (MtF). Duration of hormonal therapy should continue at least 1 year before gender reassignment surgery. Hormonal therapy supresses former gender and induces partially new gender changes. Hormonal therapy continues subsequently after surgery during life. Hormonal therapy in MtF TS includes oestrogens and antiandrogens application. In very young persons in both groups blocking gonadoliberin analogues can be used. In FtM TS testosterone oneself is given (orally and/or parenterally). Authors describe their own experiences with hormonal treatment in 282 TS (163 FtM and 119 MtF). During hormonal therapy statistically significant weight increasing was found in both groups. Total cholesterol increased in FtM. In MtF during hormonal therapy average prolactin level increased from 350.1 to 570.5 mU/l without clinical significance. Total average hormonal therapy duration was 6.73 years in FtM and 4.64 years in MtF and so overall therapy safety assessment is not possible. Any endocrinopathy occurence in the beginning of surveillance was found in 35 persons (12.4 %): simple goiter, autoimmune thyreoiditis, hypothyroidism, hyperthyroidism, gynecomastia, DM type 1, congenital adrenal hyperplasia (CAH), Klinefelter syndrome and nonfunctional pituitary adenoma. It is appropriate as well as in other rare medicine conditions to manage diagnosing and therapy in centers with experience with these issues.

• Klíčová slova
• antiandrogens - female-to-male - hormonal therapy - male-to-female - oestradiol - prolactin - testosterone - transsexualism.,
• MeSH
• hormony terapeutické užití   MeSH
• lidé MeSH
• pohlavní dimorfismus MeSH
• postupy změny pohlaví * MeSH
• rozvrh dávkování léků MeSH
• transsexualismus * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hormony MeSH

• MeSH
• hormony terapeutické užití   MeSH
• lidé MeSH
• postupy změny pohlaví * MeSH
• transsexualismus * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• komentáře MeSH
• úvodníky MeSH
• Názvy látek
• hormony MeSH

For more than 200 years, cardiotonic glycosides have been used for the treatment of congestive heart failure. Ouabain is a well-known arrow poison obtained from different Acokanthera or Strophanthus species. Much information has now accumulated that this plant toxin and its congeners are mammalian steroid hormones involved in the pathophysiology of cardiovascular diseases. There is an interesting fact that 50% patients with essential hypertension have elevated levels of endogenous ouabain. A better knowledge of the interactions of these compounds with the hormones of salt and water metabolism might help to improve the diagnosis and therapy of hypertension.

• MeSH
• fytoterapie * MeSH
• hormony farmakologie   fyziologie   terapeutické užití   MeSH
• lidé MeSH
• ouabain farmakologie   terapeutické užití   MeSH
• rostlinné extrakty terapeutické užití   MeSH
• srdeční glykosidy farmakologie   terapeutické užití   MeSH
• steroidy farmakologie   fyziologie   MeSH
• Strophanthus MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• hormony MeSH
• ouabain MeSH
• rostlinné extrakty MeSH
• srdeční glykosidy MeSH
• steroidy MeSH