Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets.

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension.

Biotechnological Potential of the Stress Response and Plant Cell Death Regulators Proteins in the Biofuel Industry.

Production of biofuel from lignocellulosic biomass is relatively low due to the limited knowledge about natural cell wall loosening and cellulolytic processes in plants. Industrial separation of cellulose fiber mass from lignin, its saccharification and alcoholic fermentation is still cost-ineffective and environmentally unfriendly. Assuming that the green transformation is inevitable and that new sources of raw materials for biofuels are needed, we decided to study cell death-a natural process occurring in plants in the context of reducing the recalcitrance of lignocellulose for the production of second-generation bioethanol. "Members of the enzyme families responsible for lysigenous aerenchyma formation were identified during the root hypoxia stress in Arabidopsis thaliana cell death mutants. The cell death regulatory genes, LESION SIMULATING DISEASE 1 (LSD1), PHYTOALEXIN DEFICIENT 4 (PAD4) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) conditionally regulate the cell wall when suppressed in transgenic aspen. During four years of growth in the field, the following effects were observed: lignin content was reduced, the cellulose fiber polymerization degree increased and the growth itself was unaffected. The wood of transgenic trees was more efficient as a substrate for saccharification, alcoholic fermentation and bioethanol production. The presented results may trigger the development of novel biotechnologies in the biofuel industry.

Baseline CTC Count as a Predictor of Long-Term Outcomes in High-Risk Prostate Cancer.

The aim of the present study was to verify whether the baseline circulating tumor cell (CTC) count might serve as a predictor of overall survival (OS) and metastasis-free survival (MFS) in patients with high-risk prostate cancer (PCa) during a follow-up period of at least 5 years. CTCs were enumerated using three different assay formats in 104 patients: the CellSearch® system, EPISPOT assay and GILUPI CellCollector. A total of 57 (55%) patients survived until the end of the follow-up period, with a 5 year OS of 66% (95% CI: 56-74%). The analysis of univariate Cox proportional hazard models identified a baseline CTC count ≥ 1, which was determined with the CellSearch® system, a Gleason sum ≥ 8, cT ≥ 2c and metastases at initial diagnosis as significant predictors of a worse OS in the entire cohort. The CTC count ≥ 1 was also the only significant predictor of a worse OS in a subset of 85 patients who presented with localized PCa at the baseline. The baseline CTC number did not affect the MFS. In conclusion, the baseline CTC count can be considered a determinant of survival in high-risk PCa and also in patients with a localized disease. However, determining the prognostic value of the CTC count in patients with localized PCa would optimally require longitudinal monitoring of this parameter.

Reasons behind the Delayed Diagnosis of Testicular Cancer: A Retrospective Analysis.

The aim of the present study was to identify the reasons behind the delayed diagnosis of testicular cancer in a group of Polish males diagnosed with this malignancy in 2015-2016. The study included data from 72 patients aged between 18 and 69 years. Based on the median time elapsed to the testicular cancer diagnosis, the study patients were divided into the timely diagnosis group (diagnosis within 10 weeks from initial manifestation, n = 40) and the delayed diagnosis group (diagnosis > 10 weeks from initial manifestation, n = 32). Diagnosis of testicular cancer > 10 weeks after its initial manifestation was associated with less favorable survival (5-year overall survival: 78.1% [95% CI: 59.5-88.9%] vs. 92.5% [95% CI: 78.5-97.5%], p = 0.087). Multivariate logistic regression analysis identified two independent predictors of the delayed diagnosis, age > 33 years (OR = 6.65, p = 0.020) and residence in the countryside (OR = 7.21, p = 0.012), with another two parameters, the lack of a regular intimate partner (OR = 3.32, p = 0.098) and the feeling of shame (OR = 8.13, p = 0.056), being at the verge of statistical significance. All the factors mentioned above should be considered during planning social campaigns aimed at the early detection of testicular malignancies, along with improving the quality and trustfulness of Internet-based information resources.

The role of cytoreductive nephrectomy in the treatment of patients with metastatic kidney cancer - review article.

The role of cytoreductive nephrectomy (CN), i.e. the removal of a kidney involved by cancer in patients with advanced kidney cancer with distant metastases, is the subject of intense debate among urologists and oncologists. For many years, CN has been considered the gold standard in the treatment of patients at this stage of the disease, especially in patients in good general health with no significant contraindications to surgical treatment. The starting point for questioning the validity of CN was the publication of the results of the cancer du rein metastatique nephrectomie et antiangiogéniques and SURTIME clinical trials (2018 and 2019, respectively), which questioned the validity of surgery in some patients with late-stage cancer. Given the complexity of the disease, the role of removing the involved kidney is the subject of much controversy. In recent years, several studies have been conducted to evaluate the efficacy and safety of nephrectomy in patients with metastatic kidney cancer, resulting in conflicting information regarding the eligibility criteria for patients in different risk groups. The aim of this article is to analyse the available data, provide an up-to-date review of the literature, and discuss the controversies and challenges related to CN in patients with metastatic kidney cancer. The present literature review aims to organize and systematize the current state of knowledge, which may help in making clinical decisions regarding qualification for CN in patients with advanced kidney cancer.

Preoperative cell-free DNA concentration in plasma as a diagnostic and prognostic biomarker of clear cell renal cell carcinoma.

Introduction: Assessment of renal tumour masses is based on conventional imaging studies (computer tomography or magnetic resonance), which does not allow characterisation of the histopathological type. Moreover, the prediction of prognosis in localised and metastatic renal cell carcinoma requires improvement as well. Analysis of circulating free DNA (cfDNA) in blood is one of the variants of liquid biopsy that may improve diagnostics and prognosis issues of patients with renal tumour masses suspected to be renal cell carcinoma. The aim of the study was to assess the diagnostic and prognostic role of preoperative cfDNA concentration in the plasma samples of clear cell renal cell carcinoma (ccRCC) patients. Material and methods: The preoperative plasma cfDNA concentration was assessed in ccRCC patients (n = 46) and healthy individuals (control group) (n = 17). The circulating free DNA concentration was reflected by the 90 bp DNA fragments determined by real-time polymerase chain reaction. Results: The median cfDNA concentration was significantly higher in ccRCC patients (n = 46) compared to the control g roup (n = 17) (2588 ±2554 copies/ml vs. 960 ±490 copies/ml, p < 0.01). In multivariate analysis, the preoperative plasma cfDNA concentration was the significant factor increasing the probability of ccRCC detection (OR: 1.003; 95% CI: 1.001-1.005). The median cfDNA concentration depended on the stage of ccRCC; it was higher in metastatic ccRCC patients (n = 11) compared to non-metastatic ccRCC patients (n = 35) (3619 ±4059 copies/ml vs. 2473 ±1378 copies/ml, p < 0.03). Kaplan-Meier survival analysis demon-strated that patients with high cfDNA values (above 2913 copies/ml) had significantly worse cancer-specific survival (HR: 4.5; 95% CI: 1.3-16.9, log-rank Mantel-Cox test p = 0.015). Conclusions: Preoperative plasma cfDNA concentration has diagnostic and prognostic potential in ccRCC pa-tients.

Evaluation of the Hydrolysis Efficiency of Bacterial Cellulose Gel Film after the Liquid Hot Water and Steam Explosion Pretreatments.

The influence of bacterial cellulose gel film pretreatment methods on the efficiency of enzymatic hydrolysis was investigated. An increase in the efficiency of enzymatic hydrolysis due to liquid hot water pretreatment or steam explosion was shown. The glucose yield of 88% was obtained from raw, non-purified, bacterial cellulose treated at 130 °C. The results confirm the potential of bacterial cellulose gel film as a source for liquid biofuel production.

Clinical Relevance of Circulating Tumor Cells in Prostate Cancer Management.

Given the low specificity of the routinely used biomarker prostate-specific antigen, circulating tumor cell (CTC) enumeration seems to be particularly useful in the monitoring of prostate cancer. In this review, we focused on a few aspects of CTC enumeration in prostate malignancies: prognostic value in metastatic and non-metastatic tumors, role in the monitoring of treatment outcomes, use as a surrogate marker for survival, and other applications, mostly for research purposes. CTC enumeration, without a doubt, offers an attractive perspective in the management of prostate cancer. However, the vast majority of available data about the role of CTC in this malignancy originate from randomized studies of anticancer agents and do not necessarily translate into real-world clinical practice. Further, most studies on the application of CTC in prostate cancer patients were limited to advanced stages of this malignancy. Meanwhile, the role of CTC in the early stages of prostate cancer, in which some patients may present with occult disseminated disease, is still relatively poorly understood, and should thus be studied extensively. Other obstacles in the widespread application of CTC enumeration in routine clinical practice include considerable discrepancies in the number of cells determined with various commercially available systems.

Polish Medical Students' Knowledge Regarding Human Papillomavirus's Ways of Transmission, Risk of Cancer Development and Vaccination, and Their Intention to Recommend Vaccination.

INTRODUCTION: Human papillomavirus (HPV) is associated with six types of cancer in men and women. A vaccine against HPV, preferably administered before initial sexual intercourse, has been proven to be highly effective in preventing these cancers. An effective healthcare provider recommendation has significant influence on HPV vaccine uptake; therefore, it is critical that medical students receive comprehensive training in this area. AIM: The aim of the study was to assess the knowledge of medical students regarding Human Papillomavirus's (HPV) ways of transmission, risk of cancer development, and vaccination against HPV. This study also investigated factors among medical students that would affect their intention to recommend HPV vaccination to others. MATERIALS AND METHODS: The study was conducted among 1061 (678 women and 383 men) medical students who filled in our questionnaire. The medical students were divided into two subgroups: (1) pre-clinical medical students (MS pre-clinical; first-to third-year students; n = 683) and (2) clinical medical students (MS clinical; fourth-to six-year students; n = 378). RESULTS: A total259 (24.41%) of the 1061 medical students were vaccinated against HPV. We found a significant improvement in the general level of knowledge in the later years of education (4-6) compared to the early years of education (1-3). However, it was demonstrated that, despite medical education advancements, there are still significant gaps of knowledge about the relationship between HPV infection and cancers other than cervical cancer, as well as in relation to the routes by which HPV is transmitted. Medical students' intentions to recommend HPV vaccine to others were related to their own HPV-related knowledge and their own vaccination status. CONCLUSION: Medical students have gaps of knowledge regarding particular issues and aspects of HPV. It is necessary to further educate medical students in the field of prevention and in the treatment of lesions caused by HPV infection. Medical students' intention to recommend the HPV vaccine can be improved by including them and members of their families in the HPV vaccination program.

Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney.

The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension.

Attitudes about Testicular Self-Examination among Polish Males.

INTRODUCTION: Epidemiological data indicate an increased incidence of testicular cancer (TC), making it the most common malignant tumor in men from aged 15-45. Oncological and urological associations recommend that men with specific TC risk factors should regularly perform a testicular self-exam (TSE). The aim of the study was to discover the attitudes among Polish males regarding TSE and factors (environmental, social, educational) that affect intention to perform TSE. METHODS: An original survey containing 21 questions was used to conduct a study among the Polish branch of VW (Volkswagen Poland) employees. RESULTS: A total of 522 fully completed questionnaires were collected. The mean age of the surveyed respondents was 32 years. Information about TC and how to perform TSE was obtained by 34.4% (n = 185) of the men. It was shown that the following factors increase men's intention to perform TSE: TC in their family member (p < 0.05; HR = 5.9; 95% CI: 1.5-23.0), GP's(General Practitioner) recommendations (p < 0.001; HR = 6.8; 95% CI: 3.2-14.3), concern expressed by their partner (p < 0.001; HR = 3.3; 95% CI: 2.1-5.3), and social campaigns (p < 0.001; HR = 2.6; 95% CI: 1.5-4.6). CONCLUSIONS: Approximately half of young polish males do not perform TSE. Access to information on TC prevention is limited. Further action is needed to improve men's awareness of TC and TSE.

Hypertension and renin-angiotensin system blockers are not associated with expression of angiotensin-converting enzyme 2 (ACE2) in the kidney.

AIMS: Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)-the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. METHODS AND RESULTS: We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. CONCLUSION: Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.

Circulating Tumor Cells as a Marker of Disseminated Disease in Patients with Newly Diagnosed High-Risk Prostate Cancer.

The aim of this study was to investigate whether the enumeration of circulating tumor cells (CTCs) in blood can differentiate between true localized and metastatic prostate cancer. A cross-sectional study of 104 prostate cancer patients with newly diagnosed high-risk prostate cancer was conducted. In total, 19 patients presented metastatic disease and 85 were diagnosed with localized disease. Analyses included intergroup comparison of CTC counts, determined using the CellSearch® system, EPISPOT assay and GILUPI CellCollector®, and ROC analysis verifying the accuracy of CTC count as a maker of disseminated prostate cancer. The vast majority (94.7%) of patients with advanced-stage cancer tested positively for CTCs in at least one of the assays. However, significantly higher CTC counts were determined with the CellSearch® system compared to EPISPOT assay and GILUPI CellCollector®. Identification of ≥4 CTCs with the CellSearch® system was the most accurate predictor of metastatic disease (sensitivity 0.500; specificity 0.900; AUC (95% CI) 0.760 (0.613-0.908). Furthermore, we tried to create a model to enhance the specificity and sensitivity of metastatic prediction with CTC counts by incorporating patient's clinical data, including PSA serum levels, Gleason score and clinical stage. The composite biomarker panel achieved the following performance: sensitivity, 0.611; specificity, 0.971; AUC (95% CI), 0.901 (0.810-0.993). Thus, although the sensitivity of CTC detection needs to be further increased, our findings suggest that high CTC counts might contribute to the identification of high-risk prostate cancer patients with occult metastases at the time of diagnosis.

Urology resident training in laparoscopic surgery - results of the first national survey in Poland.

INTRODUCTION: For many urological procedures the open approach is being replaced by the laparoscopic approach. Laparoscopy technique requires special training conditions. A well-designed, step-by step training program is significantly important for shortening the learning curve. AIM: The purpose of the study was to evaluate urology residents' (UR) experience in laparoscopic procedures, training patterns and facilities available in departments of urology in Poland. MATERIAL AND METHODS: The survey developed by the authors included 18 questions concerning laparoscopy training and was distributed among UR who participated in 2 courses in laparoscopic surgery for UR in Poland in 2017. The survey consisted of questions regarding the number of laparoscopic procedures, acquired laparoscopic experience, laparoscopic simulation training and motivation for further learning. RESULTS: Of the 2017 invited UR in Poland, 108 (34%) completed the survey. Seventy-two (78%) UR from the study group have access to laparoscopic surgery in their department. Only 20 (25%) of urology departments are equipped with a laparoscopy box and a small number of UR perform regular training. As a primary operator basic (varicocele repair) and advanced (e.g. radical nephrectomy, radical prostatectomy, nephron-sparing surgery) laparoscopic procedures are performed respectively by 55 (71%) UR and 8 (10%) UR. Most residents evaluated their laparoscopic skills as poor (15, 19%), very poor (31, 40%) or absent (10, 13%), while only 22 (28%) evaluated them as at least satisfactory. CONCLUSIONS: Laparoscopic technique is available in most Polish training centers. However, the majority of UR consider their skills unsatisfactory. Additionally, a large number of Polish UR do not have access to intensive training. UR considered that their availability of training courses and fellowships is low. Surgical exposure among Polish UR comprises mainly minor laparoscopic procedures.

Analysis of Circulating Tumor Cells in Patients with Non-Metastatic High-Risk Prostate Cancer before and after Radiotherapy Using Three Different Enumeration Assays.

The characterization of circulating tumor cells (CTCs) can lead to a promising strategy for monitoring residual or relapsing prostate cancer (PCa) after local therapy. The aim of this study was to compare three innovative technologies for CTC enumeration in 131 high-risk patients with PCa, before and after radiotherapy, combined with androgen deprivation. The CTC number was tested using the FDA-cleared CellSearch® system, the dual fluoro-EPISPOT assay that only detects functional CTCs, and the in vivo CellCollector® technology. The highest percentage of CTC-positive patients was detected with the CellCollector® (48%) and dual fluoro-EPISPOT (42%) assays, while the CellSearch® system presented the lowest rate (14%). Although the concordance among methods was only 23%, the cumulative positivity rate was 79%. A matched-pair analysis of the samples before, and after, treatment suggested a trend toward a decrease in CTC count after treatment with all methods. CTC tended to be positivity correlated with age for the fluoro-EPISPOT assay and with PSA level from the data of three assays. Combining different CTC assays improved CTC detection rates in patients with non-metastatic high-risk PCa before and after treatment. Our findings do not support the hypothesis that radiotherapy leads to cancer cell release in the circulation.

Uncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics.

Nephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys. The initial discovery analysis of 260 kidney transcriptomes from the TRANScriptome of renaL humAn TissuE Study (TRANSLATE) and the Cancer Genome Atlas identified 37 age-associated genes. For 19 of those genes, the association with age was replicated in 303 kidney transcriptomes from the Nephroseq resource. Surveying 42 nonrenal tissues from the Genotype-Tissue Expression project revealed that, for approximately a fifth of the replicated genes, the association with age was kidney-specific. Seventy-three percent of the replicated genes were associated with functional or histological parameters of age-related decline in kidney health, including glomerular filtration rate, glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arterial narrowing. Common genetic variants in four of the age-related genes, namely LYG1, PPP1R3C, LTF and TSPYL5, correlated with the trajectory of age-related changes in their renal expression. Integrative analysis of genomic, epigenomic, and transcriptomic information revealed that the observed age-related decline in renal TSPYL5 expression was determined both genetically and epigenetically. Thus, this study revealed robust molecular signatures of the aging kidney and new regulatory mechanisms of age-related change in the kidney transcriptome.

Molecular insights into genome-wide association studies of chronic kidney disease-defining traits.

Genome-wide association studies (GWAS) have identified >100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt.

Inosine monophosphate dehydrogenase 2 as a marker of aggressive and advanced prostate cancer.

INTRODUCTION: There is a need for a new biochemical marker of aggressive prostate cancer (PCa). Inosine monophosphate dehydrogenase 2 (IMPDH2) is a candidate for such a marker - its activity is increased in certain tumors and neoplastic cell lines, including PCa, and may correlate with cancer aggressiveness. MATERIAL AND METHODS: IMPDH2 levels were measured in blood samples from 34 PCa patients. The results were analyzed and correlated with prostate-specific antigen (PSA), digital rectal examination (DRE), Gleason score, risk groups according to d'Amico and metastatic disease. Twenty healthy (non-PCa) patients served as the control group. RESULTS: There was no significant difference in IMPDH2 level between the PCa and control group, and no significant correlation between PSA and IMPDH2. IMPDH2 levels were significantly higher in the DRE (+) patients (148.5 ±174.8 vs. 33.4 ±46.4, p <0.05), in patients with metastatic disease (100.1 ±139.0 vs. 25.3 ±25.9, p <0.05) and in the high-risk group according to d'Amico (93.4 ±129.2 vs. 18.8 ±10.4, p <0.05). There was a significant correlation between the Gleason score and IMPDH2. CONCLUSIONS: These results suggest that IMPDH2 is a promising candidate as a biomarker for those with advanced PCa and those at high risk of progression towards advanced PCa.

Re-thinking the Migration of Cariban-Speakers from the Middle Orinoco River to North-Central Venezuela (AD 800).

Moving back in time from the early colonial to the late pre-colonial period we evaluate the hypothesis asserting the migratory movement of Cariban-speaking groups from the Middle Orinoco River area towards north-central Venezuela. The explanation in vogue maintains that the migration followed fluvial routes and occurred between 1350 and 1150 BP (AD 600-800). We examine archaeological, linguistic, ethnohistorical, genetic, and ecological data seeking similarities between the Orinoco emigrants and their north-central Venezuelan descendants. As a result, we propose an alternative terrestrial/fluvial route and suggest these events occurred between 1150 and 1050 BP (AD 800-900). The route first proceeded upstream along rivers of the central llanos and later followed a natural terrestrial geomorphological corridor into the Lake Valencia Basin. We argue that, while future interdisciplinary (especially archaeo-linguistic and bioarchaeological) research is needed to further assess the results of these analyses, the Orinocan descendants in north-central Venezuela emerge as one of the most dynamic sociopolitical Cariban-speaking entities in all northeastern South America and the insular Caribbean on the eve of the European Conquest.

Hormone therapy in combination with radiotherapy in the treatment of prostate cancer: why and in which group of patients?

In recent years, significant development in the treatment of prostate cancer has taken place. One of the most documented methods of treatment in patients characterised by a high risk of progression is a combination of radiotherapy (RT) with long-term hormone therapy (HT). In this group of patients, neither RT alone nor HT alone allows satisfactory outcomes to be achieved, and therefore as monotherapy they are not recommended as optimal methods of treatment. In this review, we summarise arguments for combining radiotherapy with hormonal therapy in high-risk prostate cancer, with an emphasis on the results of phase III trials.