Development and validation of a clinical nomogram to predict prostatic inflammation in men with lower urinary tract symptoms.

BACKGROUND: Prostatic inflammation is an important etiological component of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). The Prostatic Inflammation Nomogram Study (PINS) aimed to develop and validate a nomogram for predicting the presence of prostatic inflammation in men with LUTS. METHODS: This non-interventional, cross-sectional, prospective study was conducted in six secondary/tertiary centers across Cyprus, Greece, Italy, Portugal, and Spain. Men (≥40 years) with BPH/LUTS scheduled to undergo prostatic surgery or transrectal ultrasound-guided (TRUS) prostate biopsy were included. Fifteen demographic and clinical participant characteristics were selected as possible predictors of prostatic inflammation. The presence of inflammation (according to Irani score) in the prostatic tissue samples obtained from surgery/TRUS biopsy was determined. The effect of each characteristic on the likelihood a prostate specimen demonstrated inflammation (classified by Irani score into two categories, 0-2 [no/minimal inflammation] or 3-6 [moderate/severe inflammation]) was assessed using multiple logistic regression. A nomogram was developed and its discriminatory ability and validity were assessed. RESULTS: In total, 423 patients (mean age 68.9 years) were recruited. Prostate volume ultrasound (PVUS) > 50 mL, history of urinary tract infection (UTI) treatment, presence of diabetes, and International Prostate Symptom Score (IPPS) Storage score were statistically significant predictors of Irani classification. Logistic regression demonstrated a statistically significant effect for leucocytes detected via urine dipstick, presence of diabetes, PVUS > 50 mL, history of UTIs, and higher IPSS Storage score for the odds of an inflammatory score category of 3-6 versus 0-2. The nomogram had a concordance index of 0.71, and good internal validity. CONCLUSIONS: The nomogram developed from PINS had good predictive ability and identified various characteristics to be predictors of prostatic inflammation. Use of the nomogram may aid in individualizing treatment for LUTS, by identifying individuals who are candidates for therapies targeting prostatic inflammation.

The loss of antioxidant activities impairs intestinal epithelium homeostasis by altering lipid metabolism.

Reactive oxygens species (ROS) are common byproducts of metabolic reactions and could be at the origin of many diseases of the elderly. Here we investigated the role of ROS in the renewal of the intestinal epithelium in mice lacking catalase (CAT) and/or nicotinamide nucleotide transhydrogenase (NNT) activities. Cat-/- mice have delayed intestinal epithelium renewal and were prone to develop necrotizing enterocolitis upon starvation. Interestingly, crypts lacking CAT showed fewer intestinal stem cells (ISC) and lower stem cell activity than wild-type. In contrast, crypts lacking NNT showed a similar number of ISCs as wild-type but increased stem cell activity, which was also impaired by the loss of CAT. No alteration in the number of Paneth cells (PCs) was observed in crypts of either Cat-/- or Nnt-/- mice, but they showed an evident decline in the amount of lysozyme. Cat deficiency caused fat accumulation in crypts, and a fall in the remarkable high amount of adipose triglyceride lipase (ATGL) in PCs. Notably, the low levels of ATGL in the intestine of Cat -/- mice increased after a treatment with the antioxidant N-acetyl-L-cysteine. Supporting a role of ATGL in the regulation of ISC activity, its inhibition halt intestinal organoid development. These data suggest that the reduction in the renewal capacity of intestine originates from fatty acid metabolic alterations caused by peroxisomal ROS.

MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, enhancing the viral infection of Burkitt lymphoma cells.

MYC is an oncogenic transcription factor dysregulated in about half of total human tumors. While transcriptomic studies reveal more than 1000 genes regulated by MYC, a much smaller fraction of genes is directly transactivated by MYC. Virtually all Burkitt lymphoma (BL) carry chromosomal translocations involving MYC oncogene. Most endemic BL and a fraction of sporadic BL are associated with Epstein-Barr virus (EBV) infection. The currently accepted mechanism is that EBV is the BL-causing agent inducing MYC translocation. Herein we show that the EBV receptor, CR2 (also called CD21), is a direct MYC target gene. This is based on several pieces of evidence: MYC induces CR2 expression in both proliferating and arrested cells and in the absence of protein synthesis, binds the CR2 promoter and transactivates CR2 in an E-box-dependent manner. Moreover, using mice with conditional MYC ablation we show that MYC induces CR2 in primary B cells. Importantly, modulation of MYC levels directly correlates with EBV's ability of infection in BL cells. Altogether, in contrast to the widely accepted hypothesis for the correlation between EBV and BL, we propose an alternative hypothesis in which MYC dysregulation could be the first event leading to the subsequent EBV infection.

Analysis of prognostic factors of failure in perineal urethrostomy.

PURPOSE: To identify prognostic factors of failure in patients undergoing perineal urethrostomy (PU) with Blandy technique, with inverted U-shaped perineal flap. METHODS: This is a retrospective study of PU of non-oncological causes (2001-2017). Data of age, BMI, history of diabetes mellitus, etiology of urethral stricture, type of stricture, previous surgeries, dilatation and suprapubic catheter were collected. Failure was defined as the need for any instrumentation after surgery. Variables were analyzed by Cox regression and Kaplan-Meier curves were used for survival analysis. RESULTS: A total of 115 PU were performed. Median age was 61 years (IQR 53-68) and BMI 27.9 (IQR 25-30.9). The most frequent etiologies were: lichen sclerosus (30.4%), iatrogenic (27%), and idiopathic (25.7%). 62.6% had panurethral stricture. There were no complications in 73%. Clavien I complications occurred in 25.2%, Clavien II in 0.9% and Clavien IVa in 0.9%. The overall success rate was 51.3% with a median follow-up of 71 months. In the last 8 years, it was 75%. In the multivariate analysis, we found that age (p = 0.01), BMI (p = 0.01), date of surgery (p = 0.01), and suprapubic catheter (p = 0.003) were predictive variables. The voiding satisfaction rate was 88.7%. CONCLUSIONS: PU with Blandy technique is a surgery with low morbidity. During the entire study period, it had a failure rate of 48.7% but the failure rate decreased to 25% over the last 8 years. Age, BMI, date of surgery and suprapubic catheter are the most important prognostic factor of failure.

A cross-sectional serosurvey of SARS-CoV-2 and co-infections in stray cats from the second wave to the sixth wave of COVID-19 outbreaks in Spain.

Severe Acute Respiratory Syndrome Coronavirus 2 is the causative agent of Coronavirus Disease 2019 in humans. Among domestic animals, cats are more susceptible to SARS-CoV-2 than dogs. The detection of anti-SARS-CoV-2 antibodies in seemingly healthy cats and/or infected cats which are in close contact with infected humans has been described. The presence of animals that tested positive by serology or molecular techniques could represent a potential transmission pathway of SARS-CoV-2 that can spill over into urban wildlife. This study analyses the seroprevalence variation of SARS-CoV-2 in stray cats from different waves of outbreaks in a geographical area where previous seroepidemiological information of SARS-CoV-2 was available and investigate if SARS-CoV-2-seropositive cats were exposed to other co-infections causing an immunosuppressive status and/or a chronic disease that could lead to a SARS-CoV-2 susceptibility. For this purpose, a total of 254 stray cats from Zaragoza (Spain) were included. This analysis was carried out by the enzyme-linked immunosorbent assay using the receptor binding domain of Spike antigen and confirmed by serum virus neutralization assay. The presence of co-infections including Toxoplasma gondii, Leishmania infantum, Dirofilaria immitis, feline calicivirus, feline herpesvirus type 1, feline leukemia virus and feline immunodeficiency virus, was evaluated using different serological methods. A seropositivity of 1.57% was observed for SARS-CoV-2 including the presence of neutralizing antibodies in three cats. None of the seropositive to SARS-CoV-2 cats were positive to feline coronavirus, however, four SARS-CoV-2-seropositive cats were also seropositive to other pathogens such as L. infantum, D. immitis and FIV (n = 1), L. infantum and D. immitis (n = 1) and L. infantum alone (n = 1).Considering other pathogens, a seroprevalence of 16.54% was detected for L. infantum, 30.31% for D. immitis, 13.78%, for T. gondii, 83.86% for feline calicivirus, 42.52% for feline herpesvirus type 1, 3.15% for FeLV and 7.87% for FIV.Our findings suggest that the epidemiological role of stray cats in SARS-CoV-2 transmission is scarce, and there is no increase in seropositivity during the different waves of COVID-19 outbreaks in this group of animals. Further epidemiological surveillances are necessary to determine the risk that other animals might possess even though stray cats do not seem to play a role in transmission.

Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study.

To compare the effectiveness at ten years of follow-up of radical prostatectomy, brachytherapy and external radiotherapy, in terms of overall survival, prostate cancer-specific mortality and biochemical recurrence. Cohort of men diagnosed with localized prostate cancer (T1/T2 and low/intermediate risk) from ten Spanish hospitals, followed for 10 years. The treatment selection was decided jointly by patients and physicians. Of 704 participants, 192 were treated with open radical retropubic prostatectomy, 317 with 125I brachytherapy alone, and 195 with 3D external beam radiation. We evaluated overall survival, prostate cancer-specific mortality, and biochemical recurrence. Kaplan-Meier estimators were plotted, and Cox proportional-hazards regression models were constructed to estimate hazard ratios (HR), adjusted by propensity scores. Of the 704 participants, 542 patients were alive ten years after treatment, and a total of 13 patients have been lost during follow-up. After adjusting by propensity score and Gleason score, brachytherapy and external radiotherapy were not associated with decreased 10-year overall survival (aHR = 1.36, p = 0.292 and aHR = 1.44, p = 0.222), but presented higher biochemical recurrence (aHR = 1.93, p = 0.004 and aHR = 2.56, p < 0.001) than radical prostatectomy at ten years of follow-up. Higher prostate cancer-specific mortality was also observed in external radiotherapy (aHR = 9.37, p = 0.015). Novel long-term results are provided on the effectiveness of brachytherapy to control localized prostate cancer ten years after treatment, compared to radical prostatectomy and external radiotherapy, presenting high overall survival, similarly to radical prostatectomy, but higher risk of biochemical progression. These findings provide valuable information to facilitate shared clinical decision-making.Study identifier at ClinicalTrials.gov: NCT01492751.

Preclinical Studies of Granulysin-Based Anti-MUC1-Tn Immunotoxins as a New Antitumoral Treatment.

Two granulysin (GRNLY) based immunotoxins were generated, one containing the scFv of the SM3 mAb (SM3GRNLY) and the other the scFv of the AR20.5 mAb (AR20.5GRNLY). These mAb recognize different amino acid sequences of aberrantly O-glycosylated MUC1, also known as the Tn antigen, expressed in a variety of tumor cell types. We first demonstrated the affinity of these immunotoxins for their antigen using surface plasmon resonance for the purified antigen and flow cytometry for the antigen expressed on the surface of living tumor cells. The induction of cell death of tumor cell lines of different origin positive for Tn antigen expression was stronger in the cases of the immunotoxins than that induced by GRNLY alone. The mechanism of cell death induced by the immunotoxins was studied, showing that the apoptotic component demonstrated previously for GRNLY was also present, but that cell death induced by the immunotoxins included also necroptotic and necrotic components. Finally, we demonstrated the in vivo tumor targeting by the immunotoxins after systemic injection using a xenograft model of the human pancreatic adenocarcinoma CAPAN-2 in athymic mice. While GRNLY alone did not have a therapeutic effect, SM3GRNLY and AR20.5GRNLY reduced tumor volume by 42 and 60%, respectively, compared with untreated tumor-bearing mice, although the results were not statistically significant in the case of AR20.5GRNLY. Histological studies of tumors obtained from treated mice demonstrated reduced cellularity, nuclear morphology compatible with apoptosis induction and active caspase-3 detection by immunohistochemistry. Overall, our results exemplify that these immunotoxins are potential drugs to treat Tn-expressing cancers.

The state of the art of marine natural products in Colombia / El estado del arte de los productos naturales marinos en Colombia / O estado da arte dos produtos naturais marinhos na Colômbia

Abstract Marine Natural Products (MNPs) isolated from samples collected in Colombia have been an object of study since the early 1980's; however, this information is neither integrated nor compiled. This systematic review describes the articles published in scientific journals up to December 2019. 173 papers met the inclusion criteria of focusing on MNPs obtained from specimens collected from Colombian seas; all original papers written in English, Portuguese or Spanish. The selected papers were mostly authored by researchers from Colombian groups, with low interaction amongst themselves. 99.4% of the papers studied samples collected from the Caribbean Sea; 183 species were studied, mainly sponges and octocorals. In this study, 1,690 compounds (238 new ones) were reviewed, mainly diterpenes and sterol derivatives. Of the selected papers, 76.8% measured various biological activities, including antibiotic (34%) and anticancer (30%). These papers were published in 51 journals (74.6% were international). In conclusion, scientific work on natural marine products of Colombian origin has incremented over time. The most relevant opportunities to address and fill existing gaps comprise: exploring Pacific Ocean organisms and several of the misrepresented taxa; promoting strong interactions amongst the MNPs research groups, and accordingly with other areas of knowledge; and having the productive sector participate in MNPs research.

Resumen Los productos naturales marinos (PNM) aislados de muestras recolectadas en Colombia han sido estudiados desde principios de los años 1980, mas esta información no está integrada, ni recopilada. Esta revisión sistemática describe los artículos publicados hasta diciembre de 2019. 173 artículos cumplieron los criterios de inclusión de enfoque en PNM obtenidos de especímenes recolectados en mares colombianos; trabajos originales escritos en inglés, portugués o español. La mayoría de los artículos fueron escritos por investigadores de grupos colombianos, con poca interacción entre ellos. El 99,4% de los artículos estudiaban muestras recolectadas del mar Caribe. Se estudiaron 183 especies, especialmente esponjas y octocorales. Se identificaron 1690 compuestos (238 nuevos), principalmente diterpenos y derivados de esteroles. En el 76,8% de los artículos se midió alguna actividad biológica, principalmente antibiótica (34%) y anticancerígena (30%). Los artículos se publicaron en 51 revistas (74,6% internacionales). En conclusión, la investigación sobre los PNM de origen colombiano ha crecido con el tiempo. Algunas oportunidades para abordar las lagunas encontradas comprenden: explorar los organismos del océano Pacífico y los taxa poco estudiados; promover interacciones entre los grupos de investigación de los PNM y de otras áreas del conocimiento; e involucrar al sector productivo en la investigación de los PMN.

Resumo Os Produtos Naturais Marinhos (PNMs) isolados de amostras coletadas na Colômbia têm sido objeto de estudo desde a década de 1980; porém, esta informação não está integrada nem compilada. Esta revisão sistemática descreve os artigos publicados em revistas científicas até dezembro de 2019. 173 artigos atenderam aos critérios de inclusão de foco em PNMs obtidos de espécimes coletados em mares colombianos; artigos originais escritos em inglês, português ou espanhol. A maioria dos autores dos artigos eram pesquisadores de grupos colombianos, com baixa interação entre eles. 99,4% dos artigos estudavam amostras coletadas no Mar do Caribe. Foram estudadas 183 espécies, especialmente esponjas e octocorais. Nesta revisão, identificaram-se 1690 compostos (238 novos), principalmente diterpenos e derivados de esterol. 76,8% dos artigos mediram algumas atividades biológicas, incluindo antibiótica (34%) e anticancerígena (30%). Os artigos analisados foram publicados em 51 periódicos (74,6% internacionais). Em conclusão, o trabalho científico sobre PNM de origem colombiana cresceu ao longo do tempo. As oportunidades mais relevantes para preencher as lacunas existentes incluem: explorar organismos do Oceano Pacífico e os taxa pouco estudados; promover interação entre os grupos de pesquisa de PNMs e com grupos de outras áreas do conhecimento; e envolver o setor produtivo na pesquisa de PNMs.

Serological evidence of SARS-CoV-2 and co-infections in stray cats in Spain.

A new coronavirus known as SARS-CoV-2 emerged in Wuhan in 2019 and spread rapidly to the rest of the world causing the pandemic disease named coronavirus disease of 2019 (COVID-19). Little information is known about the impact this virus can cause upon domestic and stray animals. The potential impact of SARS-CoV-2 has become of great interest in cats due to transmission among domestic cats and the severe phenotypes described recently in a domestic cat. In this context, there is a public health warning that needs to be investigated in relation with the epidemiological role of this virus in stray cats. Consequently, in order to know the impact of the possible transmission chain, blood samples were obtained from 114 stray cats in the city of Zaragoza (Spain) and tested for SARS-CoV-2 and other selected pathogens susceptible to immunosuppression including Toxoplasma gondii, Leishmania infantum, feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) from January to October 2020. Four cats (3.51%), based on enzyme-linked immunosorbent assay (ELISA) using the receptor binding domain (RBD) of Spike antigen, were seroreactive to SARS-CoV-2. T. gondii, L. infantum, FeLV and FIV seroprevalence was 12.28%, 16.67%, 4.39% and 19.30%, respectively. Among seropositive cats to SARS-CoV-2, three cats were also seropositive to other pathogens including antibodies detected against T. gondii and FIV (n = 1); T. gondii (n = 1); and FIV and L. infantum (n = 1). The subjects giving positive for SARS-CoV-2 were captured in urban areas of the city in different months: January 2020 (2/4), February 2020 (1/4) and July 2020 (1/4). This study revealed, for the first time, the exposure of stray cats to SARS-CoV-2 in Spain and the existence of concomitant infections with other pathogens including T. gondii, L. infantum and FIV, suggesting that immunosuppressed animals might be especially susceptible to SARS-CoV-2 infection.

JKST6, a novel multikinase modulator of the BCR-ABL1/STAT5 signaling pathway that potentiates direct BCR-ABL1 inhibition and overcomes imatinib resistance in chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is a hematological malignancy that highly depends on the BCR-ABL1/STAT5 signaling pathway for cell survival. First-line treatments for CML consist of tyrosine kinase inhibitors that efficiently target BCR-ABL1 activity. However, drug resistance and intolerance are still therapeutic limitations in Ph+ cells. Therefore, the development of new anti-CML drugs that exhibit alternative mechanisms to overcome these limitations is a desirable goal. In this work, the antitumoral activity of JKST6, a naphthoquinone-pyrone hybrid, was assessed in imatinib-sensitive and imatinib-resistant human CML cells. Live-cell imaging analysis revealed JKST6 potent antiproliferative activity in 2D and 3D CML cultures. JKST6 provoked cell increase in the subG1 phase along with a reduction in the G0/G1 phase and altered the expression of key proteins involved in the control of mitosis and DNA damage. Rapid increases in Annexin V staining and activation/cleavage of caspases 8, 9 and 3 were observed after JKST6 treatment in CML cells. Of interest, JKST6 inhibited BCR-ABL1/STAT5 signaling through oncokinase downregulation that was preceded by rapid polyubiquitination. In addition, JKST6 caused a transient increase in JNK and AKT phosphorylation, whereas the phosphorylation of P38-MAPK and Src was reduced. Combinatory treatment unveiled synergistic effects between imatinib and JKST6. Notably, JKST6 maintained its antitumor efficacy in BCR-ABL1-T315I-positive cells and CML cells that overexpress BCR-ABL and even restored imatinib efficacy after a short exposure time. These findings, together with the observed low toxicity of JKST6, reveal a novel multikinase modulator that might overcome the limitations of BCR-ABL1 inhibitors in CML therapy.

The Multiple Faces of MNT and Its Role as a MYC Modulator.

MNT is a crucial modulator of MYC, controls several cellular functions, and is activated in most human cancers. It is the largest, most divergent, and most ubiquitously expressed protein of the MXD family. MNT was first described as a MYC antagonist and tumor suppressor. Indeed, 10% of human tumors present deletions of one MNT allele. However, some reports show that MNT functions in cooperation with MYC by maintaining cell proliferation, promoting tumor cell survival, and supporting MYC-driven tumorigenesis in cellular and animal models. Although MAX was originally considered MNT's obligate partner, our recent findings demonstrate that MNT also works independently. MNT forms homodimers and interacts with proteins both outside and inside of the proximal MYC network. These complexes are involved in a wide array of cellular processes, from transcriptional repression via SIN3 to the modulation of metabolism through MLX as well as immunity and apoptosis via REL. In this review, we discuss the present knowledge of MNT with a special focus on its interactome, which sheds light on the complex and essential role of MNT in cell biology.

High ulcerative colitis and Crohn's disease ratio in a population-based registry from Córdoba, Argentina.

BACKGROUND: Few studies have described the epidemiology and clinical behavior of inflammatory bowel disease (IBD) in South America. The aim of this study was to report on the prevalence, phenotype, and treatment of patients with IBD diagnosis in Capital Department of the Province of Córdoba, Argentina. METHODS: Data from adult patients (≥ 18 years-old) with IBD diagnosis that attended 12 public or private centers between 05/2014 and 05/2019 were included in a common registry. RESULTS: A total of 655 patients were included (females: 53.4%). The ratio of ulcerative colitis (UC) (n = 561) to Crohn's disease (CD) (n = 88) was 6.38, with age-adjusted IBD prevalence being 70.1 (95% confidence interval 70.08-70.12) cases/100,000 habitants. Extraintestinal manifestations were diagnosed in 22.8% of patients, and left-side colitis (46%) was the most frequent extension in UC patients. In CD patients, colonic involvement (55.7%) and non-stricturing/non-penetrating behavior (74%) were the most frequent presentations. Biologic therapy was used in 36.4% of CD patients and 9.1% of UC patients (P<0.001). CONCLUSION: In this population registry study, IBD prevalence was similar to that reported in other series in the region. A higher UC/CD ratio was observed due to the lower prevalence of CD compared to similar studies in South America.

A novel role of MNT as a negative regulator of REL and the NF-κB pathway.

MNT, a transcription factor of the MXD family, is an important modulator of the oncoprotein MYC. Both MNT and MYC are basic-helix-loop-helix proteins that heterodimerize with MAX in a mutually exclusive manner, and bind to E-boxes within regulatory regions of their target genes. While MYC generally activates transcription, MNT represses it. However, the molecular interactions involving MNT as a transcriptional regulator beyond the binding to MAX remain unexplored. Here we demonstrate a novel MAX-independent protein interaction between MNT and REL, the oncogenic member of the NF-κB family. REL participates in important biological processes and it is altered in a variety of tumors. REL is a transcription factor that remains inactive in the cytoplasm in an inhibitory complex with IκB and translocates to the nucleus when the NF-κB pathway is activated. In the present manuscript, we show that MNT knockdown triggers REL translocation into the nucleus and thus the activation of the NF-κB pathway. Meanwhile, MNT overexpression results in the repression of IκBα, a bona fide REL target. Both MNT and REL bind to the IκBα gene on the first exon, suggesting its regulation as an MNT-REL complex. Altogether our data indicate that MNT acts as a repressor of the NF-κB pathway by two mechanisms: (1) retention of REL in the cytoplasm by MNT interaction, and (2) MNT-driven repression of REL-target genes through an MNT-REL complex. These results widen our knowledge about MNT biological roles and reveal a novel connection between the MYC/MXD and NF-κB pathways, two of the most prominent pathways in cancer.

Comparative Effectiveness Research in Localized Prostate Cancer: A 10-Year Follow-up Cohort Study.

PURPOSE: Long-term comparative effectiveness research on localized prostate cancer treatments is scarce, and evidence is lacking especially for brachytherapy. The aim of this study was to assess the long-term impact of the side effects of radical prostatectomy, brachytherapy, and external radiation therapy on patients with localized prostate cancer at 10 years, using propensity score analyses. METHODS AND MATERIALS: This was a prospective observational study of a cohort of men who received a diagnosis of clinically localized prostate cancer (clinical stage T1 or T2, low and intermediate risk group) and were treated with radical prostatectomy (n = 139), brachytherapy (n = 317), or external radiation therapy (n = 194). Treatment decisions were jointly made by patients and physicians. Patient-reported outcome (PRO) evaluation included the Expanded Prostate Cancer Index Composite and Short Form-36, administered centrally by telephone interviews before and annually after treatment. The Expanded Prostate Cancer Index Composite covers urinary, bowel, sexual, and hormonal domains. To assess PRO changes over time, while accounting for correlation among repeated measures, generalized estimating equation models adjusted by propensity scores were constructed. RESULTS: The PRO completion rate at 10 years was 85.8%. Generalized estimating equation models showed that the pattern of radical prostatectomy side effects, with substantial urinary incontinence and sexual dysfunction, remained until 10 years after treatment (standard deviation [SD], -1.1 and -1.3, respectively). Brachytherapy produced late deterioration in urinary continence (SD, -0.4) and sexual function (SD, -0.9) that appeared midterm, but the differences from radical prostatectomy remained statistically significant at 10 years (P < .001 after adjusting by propensity score). External radiation therapy showed similar results to brachytherapy, but with bowel bother (SD, -0.3). CONCLUSIONS: Although late deterioration in radiation therapy groups attenuated differences from radical prostatectomy, relevant PRO differences still remained after 10 years. Our findings support that brachytherapy is the treatment option that causes the least impact on PROs; it is therefore an alternative to be considered when making evidence-based decisions on localized prostate cancer treatment.

Ameloblastoma Acantomatoso: Reporte de caso y revisión de la literatura / Acantomatous ameloblastoma: Case report and review of the literature

Introducción. El ameloblastoma es un tumor benigno raro, ocasionalmente con comportamiento agresivo, proveniente de las células productoras de esmalte. Localizado con mayor frecuencia en la mandíbula, teniendo su mayor incidencia entre la 4ta 5ta década de la vida, generalmente asintomático, siendo los estudios de imágenes la prueba diagnóstica fundamental. Reporte del caso: Presentamos el caso de una mujer de 43 años con una tumoración en maxilar inferior izquierda de crecimiento progresivo, sin limitación funcional. La TAC de mandíbula muestra una lesión osteolítica y expansiva de bordes definidos, que rompe la cortical anterior infiltrando partes blandas; es sometida a extracción tumoral asociado a curetaje; conjuntamente en la anatomopatológica se identidica Ameloblastoma Acantomatoso. Conclusión: El ameloblastoma Acantomatoso tiene larga sobrevida libre de recurrencia si su diagnóstico es oportuno y su tratamiento es multidisciplinario, incluyendo cirugía y radioterapia, aunque su rareza ocasiona dificultad en encontrar el mejor tratamiento disponible.

Introduction. Ameloblastoma is a rare benign tumor, occasionally with aggressive behavior, originating from enamel-producing cells. Located most frequently in the mandible, having its highest incidence between the 4th 5th decade of life, generally asymptomatic, imaging studies being the fundamental diagnostic test. Case report: We present the case of a 43-year-old woman with a progressively growing tumor in the left lower jaw, without functional limitation. The CT of the mandible shows an osteolytic and expansive lesion with defined edges, which breaks the anterior cortex, infiltrating soft tissues; she is subjected to tumor extraction associated with curettage; jointly in the pathology, Acantomatous Ameloblastoma is identified. Conclusion: Acantomatous ameloblastoma has a long recurrence-free survival if its diagnosis is timely and its treatment is multidisciplinary, including surgery and radiotherapy, although its rarity causes difficulty in finding the best available treatment.

Structural characterization of an unprecedented lectin-like antitumoral anti-MUC1 antibody.

The molecular basis of antibody 5E5, which recognizes the entire GalNAc unit as a primary epitope is disclosed. The antibody's contacts with the peptide are mostly limited to two residues, allowing it to show some degree of promiscuity. These findings open the door to the chemical design of peptide-mimetics for developing efficient anti-cancer vaccines and diagnostic tools.

Production of a Granulysin-Based, Tn-Targeted Cytolytic Immunotoxin Using Pulsed Electric Field Technology.

Granulysin is a protein present in the granules of human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, with cytolytic activity against microbes and tumors. Previous work demonstrated the therapeutic effect of the intratumoral injection of recombinant granulysin and of the systemic injection of an immunotoxin between granulysin and the anti-carcinoembryonic antigen single-chain Fv antibody fragment MFE23, which were produced in the yeast Pichia pastoris. In the present work, we developed a second immunotoxin combining granulysin and the anti-Tn antigen single-chain Fv antibody fragment SM3, that could have a broader application in tumor treatment than our previous immunotoxin. In addition, we optimized a method based on electroporation by pulsed electric field (PEF) to extract the remaining intracellular protein from yeast, augmenting the production and purificiation yield. The immunotoxin specifically recognized the Tn antigen on the cell surface. We also compared the thermal stability and the cytotoxic potential of the extracellular and intracellular immunotoxins on Tn-expressing human cell lines, showing that they were similar. Moreover, the bioactivity of both immunotoxins against several Tn+ cell lines was higher than that of granulysin alone.

The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells.

The MAX network transcriptional repressor (MNT) is an MXD family transcription factor of the basic helix-loop-helix (bHLH) family. MNT dimerizes with another transcriptional regulator, MYC-associated factor X (MAX), and down-regulates genes by binding to E-boxes. MAX also dimerizes with MYC, an oncogenic bHLH transcription factor. Upon E-box binding, the MYC-MAX dimer activates gene expression. MNT also binds to the MAX dimerization protein MLX (MLX), and MNT-MLX and MNT-MAX dimers co-exist. However, all MNT functions have been attributed to MNT-MAX dimers, and no functions of the MNT-MLX dimer have been described. MNT's biological role has been linked to its function as a MYC oncogene modulator, but little is known about its regulation. We show here that MNT localizes to the nucleus of MAX-expressing cells and that MNT-MAX dimers bind and repress the MNT promoter, an effect that depends on one of the two E-boxes on this promoter. In MAX-deficient cells, MNT was overexpressed and redistributed to the cytoplasm. Interestingly, MNT was required for cell proliferation even in the absence of MAX. We show that in MAX-deficient cells, MNT binds to MLX, but also forms homodimers. RNA-sequencing experiments revealed that MNT regulates the expression of several genes even in the absence of MAX, with many of these genes being involved in cell cycle regulation and DNA repair. Of note, MNT-MNT homodimers regulated the transcription of some genes involved in cell proliferation. The tight regulation of MNT and its functionality even without MAX suggest a major role for MNT in cell proliferation.

Carcinoma renal con translocación xp11. 2 en una infante / Xp11. 2 Translocation Renal Carcinoma In A Child

El carcinoma de células renales con translocación (CRT) es un subtipo de carcinoma de células renales (CCR). El presente caso trata de una niña de 11 años con dolor en fosa ilíaca derecha de dos semanas de evolución. Se evidenció tumoración de 2,2 x 1,9 x 2,8 cm en el polo superior del riñón derecho, por ecografía. Luego, fue sometida a nefrectomía radical derecha y a disección ganglionar regional, tras lo cual se diagnosticó CRT subtipo Xp 11.2. Posteriormente, se inició tratamiento de primera línea con pazopanib y quimioterapia concomitante. Esta enfermedad es más frecuente entre los 10 y 15 años. Su pronóstico suele ser mejor comparado al de los adultos. El manejo multidisciplinario asociado a la disponibilidad de medicamentos de primera línea, mejora la sobrevida libre de progresión.

Translocation renal cell carcinoma (t-RCC) is a subtype of renal cell carcinoma (RCC). This case is about an 11-year-old with pain in right iliac fossa for two weeks. Tumor of 2.2 x 1.9 x 2.8 cm was evidenced in the upper pole of the right kidney, by ultrasound. Then, she underwent to a right radical nephrectomy and regional lymph node dissection, after which CRT subtype Xp 11.2 was diagnosed. Subsequently, first-line treatment with pazopanib and concomitant chemotherapy was initiated. This disease is more frequent between 10 and 15 years. Their prognosis is usually better compared to adults. The multidisciplinary management associated with the availability of first-line medications improves progression-free survival.