Straightforward access to enantiomerically pure 3,4-diamino-3,4-dideoxyphytosphingosines, as novel analogues of natural d-ribo-phytosphingosine was accomplished, starting from two available chirons: dimethyl l-tartrate and d-isoascorbic acid. A sequential Overman rearrangement followed by late-stage introduction of the alkyl side chain moiety via olefin cross-metathesis is the cornerstone of this approach. The preliminary evaluation study of the synthesised sphingomimetics, based on their ability to inhibit a proliferation of human cancer cells, showed promising cytotoxicity against Jurkat and HeLa cells for (2R,3R,4S)-2,3,4-triaminooctadecan-1-ol trihydrochloride.

• Klíčová slova
• Cytotoxic activity, OCM, Sequential rearrangement, Sphingoid bases, d-ribo-phytosphingosine,
• MeSH
• antitumorózní látky farmakologie   chemie   chemická syntéza   MeSH
• HeLa buňky MeSH
• Jurkat buňky MeSH
• lidé MeSH
• proliferace buněk * účinky léků   MeSH
• sfingosin * analogy a deriváty   chemie   farmakologie   chemická syntéza   MeSH
• stereoizomerie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• phytosphingosine MeSH Prohlížeč
• sfingosin * MeSH

OBJECTIVE: An increased number of NK cells is associated with autoimmune disorder and is known to play a role in infertility. The aim of our research was to monitor the density of NK cells CD56+ and CD16+ in ovulatory cervical mucus (OCM) and in endometrium in infertile women as well as in connection with the actual status of antibodies against phospholipids, sperm and HHV-6 antibodies. TYPE OF STUDY: Original aticle. SETTING: Genetika - Plzeň. METHODS: Seventy-two randomly selected women aged 20-39 (mean age: 32.3) years old resulted in fifty-seven patients with repeated unexplained miscarriages, and fifteen fertile healthy women. The hormonal status was studied including ovulation, the humoral autoimmune responses to eight phospholipids, trombophilia, karyotyping, hysteroscopy, and endometrium immunohistology. Patients were without any clinical and laboratory symptoms of vaginitis at the time of OCM sampling and endometrium study. In one patient antiphospholipid syndrome was present, and in one woman diabetes mellitus was identified. Uterine NK cells CD56+ , CD16+ and NK cells in OCM were identified by immunocytochemistry, antiphospholipid antiboides by ELISA. We used indirect MAR-test for study of local spermagglutinating antibodies in OCM. Indirect immunofluorescent method was used for detection of serum and OCM IgM, IgG antibodies against HHV-6 levels at the time of ovulation. RESULTS: We found both high density of NK cells CD56+ and CD16+ in OCM and in endometrium in only two infertile women with repeated abortions. NK cells in OCM were missing in other samples of patients. The prevalence of high density of NK cells CD56+ in the endometrium was seen in twenty three (40%), NK cells CD16+ in eleven (19%), NK cells 56+ and NK cells 16+ together in eight (14%). Levels of serum and OCM IgG against HHV-6 in all examined patients were not elevated, no cervical sperm antibodies were found. CONCLUSION: We compared density of NK cells CD56+ and CD16+ in OCM and secretory endometrium in all infertile patients. Our results show that cell mucosal activity in the cervical area at the time of ovulation in two infertile patients was evident. We excluded the abnormal number of NK cells owing to local and general viral infection (HHV-6). But our question still remains - are cervical NK cells fixed or still migrating from endometrium into OCM? New research is planned.

• Klíčová slova
• HHV-6, NK cells, endometrium, infertility, ovulatory cervical mucus,
• MeSH
• antigeny CD56 imunologie   MeSH
• buňky NK imunologie   metabolismus   MeSH
• CD antigeny krev   MeSH
• cervikální hlen fyziologie   MeSH
• dospělí MeSH
• endometrium imunologie   metabolismus   patologie   MeSH
• fertilita imunologie   MeSH
• habituální potrat krev   imunologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• ženská infertilita krev   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD56 MeSH
• CD antigeny MeSH

OBJECTIVE: The aim of our preliminary study was to compare the levels of total local sIgA and IgG with activity of detected sperm antibodies in ovulatory cervical mucus (OCM). SETTING: Department of Gyneacology and Obstetrics, Medical School and Faculty Hospital, Charles University, Plzen. METHODS: We screened samples of OCM from 12 pacients aged 26-31 (29,6 years on average) by radial immunodifusion (RID) to determine s IgA and IgG. Indirect MAR test was used for detection of spermagglutinationg antibodies. RESULTS: We found out by RID the average concentration of sIgA in OCM 567,84 mg/l (0 -1250,47) and the average concentration of IgG in OCM 23,57 mg/l (8,74-47,99). Antibody activity against sperm cells dominates in IgA with 6 pacients, in IgA with 1 patient, in IgA and IgG together with 1 infertile woman and in IgA and IgM isotypes together with 1 patient. No local sperm antibodies were determined with 3 patients. CONCLUSION: We proved the hypothesis, that the levels of spermagglutinating antibodies do not correlate with findings of total sIgA and IgG in OCM with our patients.

• MeSH
• aglutinace spermií imunologie   MeSH
• cervikální hlen imunologie   MeSH
• dospělí MeSH
• imunoglobulin A sekreční analýza   MeSH
• imunoglobulin G analýza   MeSH
• lidé MeSH
• mladý dospělý MeSH
• ovulace * MeSH
• protilátky analýza   MeSH
• spermie imunologie   MeSH
• ženská infertilita imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• imunoglobulin A sekreční MeSH
• imunoglobulin G MeSH
• protilátky MeSH

PURPOSE: To assess the effect of race/ethnicity in cancer-specific mortality (CSM) adjusted for other-cause mortality (OCM) in metastatic prostate cancer patients (mPCa) treated with external beam radiotherapy (EBRT) to the prostate. METHODS: We relied on the Surveillance, Epidemiology, and End Results (SEER) database to identify Caucasian, African-American, Hispanic/Latino and Asian mPCa patients treated by EBRT between 2004 and 2016. Cumulative incidence plots displayed CSM after adjustment for OCM according to race/ethnicity. Propensity score matching accounted for patient age, prostate-specific antigen, clinical T and N stages, Gleason Grade Groups and M1 substages. OCM adjusted multivariable analyses tested for differences in CSM in African-Americans, Hispanic/Latinos and Asians relative to Cauacasians. RESULTS: After 3:1 propensity score matching and OCM adjustment, Asians exhibited lower CSM at 60 and 120 months (48.2 and 60.0%, respectively) compared to Caucasians (66.7 and 79.4%, respectively, p < 0.001). In OCM adjusted multivariable analyses, Asian race/ethnicity was associated with lower CSM (HR 0.66, CI 0.52-0.83, p < 0.001). Conversely, African-American and Hispanic/Latino race/ethnicity did not affect CSM. OCM rates were comparable between examined races/ethnicities. CONCLUSION: In the setting of mPCa treated with EBRT, Asians exhibit lower CSM than Caucasians, African-Americans and Hispanic/Latinos. This observation may warrant consideration in prognostic stratification schemes for newly diagnosed mPCa patients.

• Klíčová slova
• Cancer-specific mortality, External beam radiotherapy, Metastatic prostate cancer, Other-cause mortality, Race/ethnicity,
• MeSH
• Američané asijského původu statistika a číselné údaje   MeSH
• běloši statistika a číselné údaje   MeSH
• černoši nebo Afroameričané statistika a číselné údaje   MeSH
• Hispánci a Latinoameričané statistika a číselné údaje   MeSH
• karcinom etnologie   mortalita   radioterapie   sekundární   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mortalita etnologie   MeSH
• nádory kostí etnologie   mortalita   sekundární   MeSH
• nádory prostaty etnologie   mortalita   patologie   radioterapie   MeSH
• program SEER MeSH
• radioterapie * MeSH
• senioři MeSH
• tendenční skóre MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: To test the association between external beam radiotherapy (EBRT) after radical prostatectomy (RP) vs RP only on rates of other-cause mortality (OCM) in men with prostate cancer (PCa). PATIENTS AND METHODS: Within the 2004-2016 Surveillance, Epidemiology, and End Results database, we identified 181,849 localized PCa patients, of whom 168,041 received RP only vs 13,808 who received RP + EBRT. Cumulative incidence plots displayed OCM between RP vs RP + EBRT after propensity score matching for age, PSA, clinical T- and N-stages, and biopsy Gleason scores. Multivariable competing risks regression models addressed OCM, accounting prostate cancer-specific mortality (CSM) as a competing event. Stratifications were made according to low- vs intermediate- vs high-risk groups and additionally according to age groups of ≤ 60, 61-70, and ≥ 71 years, within each risk group. RESULTS: In low-, intermediate-, and high-risk patients, RP + EBRT rates were 2.7, 5.4 and 17.0%, respectively. After matching, 10-year OCM rates between RP and RP + EBRT were 7.7 vs 16.2% in low-, 9.4 vs 13.6% in intermediate-, and 11.4 vs 13.5% in high-risk patients (all p < 0.001), which, respectively, resulted in multivariable HR of 2.1, 1.3, and 1.2 (all p < 0.001). In subgroup analyses, excess OCM was recorded in low-risk RP + EBRT patients of all age groups (all p ≤ 0.03), but only in the older age group in intermediate-risk patients (61-70 years, p = 0.03) and finally, only in the oldest age group in high-risk patients (≥ 71 years, p = 0.02). CONCLUSION: Excess OCM was recorded in patients exposed to RT after RP. Its extent was most pronounced in low-risk patients, decreased in intermediate-risk patients, and was lowest in high-risk patients.

• Klíčová slova
• Adjuvant therapy, External beam radiotherapy, Overtreatment, Radiation, Radical prostatectomy, Salvage therapy, Survival,
• MeSH
• lidé MeSH
• nádory prostaty * radioterapie   chirurgie   MeSH
• prostata MeSH
• prostatektomie * metody   MeSH
• senioři MeSH
• stupeň nádoru MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

AIM: To compare overall mortality (OM), cancer-specific mortality (CSM), and other cause mortality (OCM) rates between radical prostatectomy (RP) versus radiotherapy (RT) in clinical node-positive (cN1) prostate cancer (PCa). MATERIALS AND METHODS: Within Surveillance, Epidemiology, End Results (SEER) (2004-2016), we identified 4685 cN1 PCa patients, of whom 3589 (76.6%) versus 1096 (24.4%) were treated with RP versus RT. After 1:1 propensity score matching (PSM), Kaplan-Meier plots and Cox regression models tested the effect of RP versus RT on OM, while cumulative incidence plots and competing-risks regression (CRR) models addressed CSM and OCM between RP and RT patients. All analyses were repeated after the inverse probability of treatment weighting (IPTW). For CSM and OCM analyses, the propensity score was used as a covariate in the regression model. RESULTS: Overall, RT patients were older, harbored higher prostate-specific antigen values, higher clinical T and higher Gleason grade groups. PSM resulted in two equally sized groups of 894 RP versus 894 RT patients. After PSM, 5-year OM, CSM, and OCM rates were, respectively, 15.4% versus 25%, 9.3% versus 17%, and 6.1% versus 8% for RP versus RT (all p < 0.001) and yielded respective multivariate hazard ratios (HRs) of 0.63 (0.52-0.78, p < 0.001), 0.66 (0.52-0.86, p < 0.001), 0.71 (0.5-1.0, p = 0.05), all favoring RP. After IPTW, Cox regression models yielded HR of 0.55 (95% confidence interval [CI] = 0.46-0.66) for OM, and CRR yielded HRs of 0.49 (0.34-0.70) and 0.54 (0.36-0.79) for, respectively, CSM and OCM, all favoring RP (all p < 0.001). CONCLUSIONS: RP may hold a CSM advantage over RT in cN1 PCa patients.

• Klíčová slova
• clinical node positive, external beam radiotherapy, prostate cancer, radical prostatectomy,
• MeSH
• lidé MeSH
• nádory prostaty * radioterapie   chirurgie   MeSH
• program SEER MeSH
• prostatektomie * metody   MeSH
• rizikové faktory MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: To test for rates of other cause mortality (OCM) and cancer-specific mortality (CSM) in elderly prostate cancer (PCa) patients treated with the combination of radical prostatectomy (RP) and external beam radiation therapy (EBRT) versus RP alone, since elderly PCa patients may be over-treated. METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2016), cumulative incidence plots, after propensity score matching for cT-stage, cN-stage, prostate specific antigen, age and biopsy Gleason score, and multivariable competing risks regression models (socioeconomic status, pathological Gleason score) addressed OCM and CSM in patients (70-79, 70-74, and 75-79 years) treated with RP and EBRT versus RP alone. RESULTS: Of 18,126 eligible patients aged 70-79 years, 2520 (13.9%) underwent RP and EBRT versus 15,606 (86.1%) RP alone. After propensity score matching, 10-year OCM rates were respectively 27.9 versus 20.3% for RP and EBRT versus RP alone (p < .001), which resulted in a multivariable HR of 1.4 (p < .001). Moreover, 10-year CSM rates were respectively 13.4 versus 5.5% for RP and EBRT versus RP alone. In subgroup analyses separately addressing 70-74 year old and 75-79 years old PCa patients, 10-year OCM rates were 22.8 versus 16.2% and 39.5 versus 24.0% for respectively RP and EBRT versus RP alone patients (all p < .001). CONCLUSION: Elderly patients treated with RP and EBRT exhibited worrisome rates of OCM. These higher than expected OCM rates question the need for combination therapy (RP and EBRT) in elderly PCa patients and indicate the need for better patient selection, when combination therapy is contemplated.

• Klíčová slova
• other cause mortality, overtreatment, radiation, radical prostatectomy, survival,
• MeSH
• kombinovaná terapie škodlivé účinky   MeSH
• lidé MeSH
• nadbytečná léčba statistika a číselné údaje   MeSH
• nádory prostaty mortalita   radioterapie   chirurgie   MeSH
• příčina smrti MeSH
• program SEER MeSH
• prostatektomie * MeSH
• prostatický specifický antigen krev   MeSH
• rizikové faktory MeSH
• senioři MeSH
• stupeň nádoru MeSH
• věkové faktory MeSH
• výsledek terapie MeSH
• záchranná terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• prostatický specifický antigen MeSH

BACKGROUND: We tested for other-cause mortality (OCM) differences according to race/ethnicity in metastatic renal cell carcinoma (mRCC). Such differences may affect treatment considerations. METHODS: Within the Surveillance, Epidemiology, and End Results Research Plus repository (2000-2018), we identified clear cell (ccmRCC) and non-clear cell (non-ccmRCC) mRCC patients and stratified according to race/ethnicity: Caucasian vs. Hispanic vs. African American vs. Asian. Poisson smoothed cumulative incidence plots and competing risks regression (CRR) models addressing OCM, after adjustment for cancer-specific mortality , were fitted. Subsequently, multivariable logistic regression models tested access to cytoreductive nephrectomy (CNT) and systemic therapy (ST). RESULTS: Of 10,958 ccmRCC patients, 7,892 (72%), 1,743 (16%), 688 (6%), and 635 (6%) were Caucasian, Hispanic, African American, and Asian, respectively. Of 1,239 non-ccmRCC patients, 799 (64%), 106 (9%), 278 (22%), and 56 (5%) were Caucasian, Hispanic, African American, and Asian, respectively. In multivariable CRR models, OCM was higher in African Americans vs. Caucasians in ccmRCC (HR:1.55; CI:1.19-2.01; P < 0.001) and in non-ccmRCC (HR:1.54; CI:1.01-2.35; P = 0.04). In multivariable logistic regression models, African Americans with ccmRCC were less likely to undergo CNT (OR:0.72, CI:0.60-0.86; P < 0.001), but more likely to undergo ST (OR:1.34, CI:1.11-1.61; P = 0.002). CONCLUSIONS: In this retrospective analysis, African Americans with ccmRCC and non-ccmRCC exhibited higher OCM than Caucasians. Based on higher OCM, African Americans were less likely to undergo CNT, but more likely to benefit from ST.

• Klíčová slova
• Cytoreductive nephrectomy, Kidney, Race/ethnicity minorities, Targeted therapy,
• MeSH
• dostupnost zdravotnických služeb MeSH
• etnicita MeSH
• karcinom z renálních buněk * patologie   MeSH
• lidé MeSH
• nádory ledvin * patologie   MeSH
• program SEER MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: To evaluate the presence and activity of local sperm antibodies and electrophoretic analysis of ovulatory cervical mucus (OCM) to prove the correlation of results of Kremer mucus sperm capillary penetration test and i-MAR (mixed antiimmunoglobulin reaction) test with SDS-PAGE. DESIGN: Retrospective study. SETTING: Department of Obstetrics and Gynecology, Medical Faculty of Charles University, Pilsen. METHODS: 94 patients aged 22-40 (average age 32.3 years) were chosen for our study. Ovulatory cervical mucus was taken from uterine cervical canal in Consultation for Reproductive Immunology. Kremer test and indirect mixed antiglobulin reaction test for IgG, IgA, IgM and IgE were used for detection of sperm antibodies. For the SDS-PAGE analysis, OCM was incubated with sodium dodecyl sulfate. We studied separated protein fractions from OCM. RESULTS: Sperm-capillary ovulatory mucus penetration test (Kremer) was 0-10 cm/hour in our group (average value in patiens without sperm antibodies was 2.43 cm/hour, with sperm agglutinating antibodies 1.4 cm/hour), significant levels (> 45%) of spermagglutinating antibodies were detected in IgA in 6 patients (6.38%), IgG in 5 (5.32%) patients, sperm-cytotoxic levels (IgA and/or IgG) in 5 patients (5.32%); levels of IgE less than 30% in 3 patients (3.19%). Individual immunological factors gained by SDS-PAGE showed the spectrum of various molecular weights with range of 14.4- 350 kDa. The presence of IgG and/or IgA was in 53 cases (56.38%), with 13 ASA positivities (24.53% correlation with i-MAR test) and no ASA activity in 40 cases (75.47%); 6 ASA positive patiens (31.58%) were not detected by SDS-PAGE. CONCLUSIONS: Analysis of 94 OCM by SDS-PAGE showed several significant correlates, but their specifications will be based on further immunoblot research.

• MeSH
• aglutinace spermií MeSH
• cervikální hlen imunologie   MeSH
• dospělí MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• fertilizace in vitro * MeSH
• imunoglobuliny analýza   MeSH
• lidé MeSH
• ovulace * MeSH
• protilátky analýza   MeSH
• spermie imunologie   MeSH
• terapie neúspěšná MeSH
• ženská infertilita imunologie   terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• imunoglobuliny MeSH
• protilátky MeSH

BACKGROUND: In the era of standardized outcome reporting, it remains unclear if widely used comorbidity and health status indices can enhance predictive accuracy for morbidity and long-term survival outcomes after radical cystectomy (RC). PATIENTS AND METHODS: In this monocentric study, we included 468 patients undergoing open RC with pelvic lymph node dissection for bladder cancer between January 2009 and December 2017. Postoperative complications were meticulously assessed according to the EAU guideline criteria for standardized outcome reporting. Multivariable regression models were fitted to evaluate the ability of ASA physical status (ASA PS), Charlson comorbidity index (± age-adjustment) and the combination of both to improve prediction of (A) 30-day morbidity key estimates (major complications, readmission, and cumulative morbidity as measured by the Comprehensive Complication index [CCI]) and (B) secondary mortality endpoints (overall [OM], cancer-specific [CSM], and other-cause mortality [OCM]). RESULTS: Overall, 465 (99%) and 52 (11%) patients experienced 30-day complications and major complications (Clavien-Dindo grade ≥IIIb), respectively. Thirty-seven (7.9%) were readmitted within 30 days after discharge. Comorbidity and health status indices did not improve the predictive accuracy for 30-day major complications and 30-day readmission of a reference model but were associated with 30-day CCI (all P < .05). When ASA PS and age-adjusted Charlson index were combined, ASA PS was no longer associated with 30-day CCI (P = .1). At a median follow-up of 56 months (IQR 37-86), OM, CSM, and 90-day mortality were 37%, 24%, and 2.9%, respectively. Both Charlson and age-adjusted Charlson index accurately predicted OCM (all P < .001) and OM (all P ≤ .002) but not CSM (all P ≥ .4) and 90-day mortality (all P > .05). ASA PS was not associated with oncologic outcomes (all P ≥ .05). CONCLUSION: While comorbidity and health status indices have a role in predicting OCM and OM after RC, their importance in predicting postoperative morbidity is limited. Especially ASA PS performed poorly. This highlights the need for procedure-specific comorbidity assessment rather than generic indices.

• Klíčová slova
• ASA physical status, Charlson Comorbidity index, Comorbidity indices, Mortality, Urinary Bladder Neoplasms,
• MeSH
• cystektomie * škodlivé účinky   MeSH
• komorbidita MeSH
• lidé MeSH
• morbidita MeSH
• nádory močového měchýře * patologie   MeSH
• pooperační komplikace etiologie   MeSH
• retrospektivní studie MeSH
• ukazatele zdravotního stavu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH