To study those factors that influence the occurrence of surgical complications and local relapse in patients intervened for breast cancer and receiving intraoperative radiotherapy.
Observational ...study on patients intervened for breast cancer with conservative surgery and intraoperative radiotherapy with low-voltage X-ray energy source (INTRABEAM), from 2015 to 2017 with 24 months minimum follow-up. Variables possibly associated to the occurrence of postoperative complications were analyzed with the Student t-test and the Fisher exact test; P < 0.05 considered significant. Subsequently, the construction of multiple multivariate analysis models began, thus building a logistic regression analysis using the IBM SPSS Statistics ver. 23 software. Local relapse was described.
The study included 102 patients, mean age of 61.2 years; mean global size of tumor, 12.2 mm. Complications occurred in 29.4%. Fibrosis was the most frequently observed complication, followed by postoperative seroma. Using a 45 mm or larger applicator were significantly associated with the occurrence of complications. Tumor size 2 cm or larger and reintervention showed borderline significant association. Only one case of local relapse was observed.
Certain factors may increase the risk of complication after the use of intraoperative radiotherapy. Using external complementary radiotherapy does not seem to increase the rate of complications. Select patients and the involvement of a multidisciplinary team are essential for achieving good results.
17β-estradiol (E2) may interfere with endocrine, metabolic, and gender-differentiated functions in liver in both females and males. Indirect mechanisms play a crucial role because of the E2 influence ...on the pituitary GH secretion and the GHR-JAK2-STAT5 signaling pathway in the target tissues. E2, through its interaction with the estrogen receptor, exerts direct effects on liver. Hypothyroidism also affects endocrine and metabolic functions of the liver, rendering a metabolic phenotype with features that mimic deficiencies in E2 or GH. In this work, we combined the lipid and transcriptomic analysis to obtain comprehensive information on the molecular mechanisms of E2 effects, alone and in combination with GH, to regulate liver functions in males. We used the adult hypothyroid-orchidectomized rat model to minimize the influence of internal hormones on E2 treatment and to explore its role in male-differentiated functions. E2 influenced genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, immune, and male-specific responses. E2 induced a female-pattern of gene expression and inhibited GH-regulated STAT5b targeted genes. E2 did not prevent the inhibitory effects of GH on urea and amino acid metabolism-related genes. The combination of E2 and GH decreased transcriptional immune responses. E2 decreased the hepatic content of saturated fatty acids and induced a transcriptional program that seems to be mediated by the activation of PPARα. In contrast, GH inhibited fatty acid oxidation. Both E2 and GH replacements reduced hepatic CHO levels and increased the formation of cholesterol esters and triacylglycerols. Notably, the hepatic lipid profiles were endowed with singular fingerprints that may be used to segregate the effects of different hormonal replacements. In summary, we provide in vivo evidence that E2 has a significant impact on lipid content and transcriptome in male liver and that E2 exerts a marked influence on GH physiology, with implications in human therapy.
Triple-negative breast cancer (TNBC) is difficult to treat; therefore, the development of drugs directed against its oncogenic vulnerabilities is a desirable goal. Herein, we report the antitumor ...effects of CM728, a novel quinone-fused oxazepine, against this malignancy. CM728 potently inhibited TNBC cell viability and decreased the growth of MDA-MB-231-induced orthotopic tumors. Furthermore, CM728 exerted a strong synergistic antiproliferative effect with docetaxel
and this combination was more effective than the individual treatments
. Chemical proteomic approaches revealed that CM728 bound to peroxiredoxin-1 (Prdx1), thereby inducing its oxidation. Molecular docking corroborated these findings. CM728 induced oxidative stress and a multi-signal response, including JNK/p38 MAPK activation and STAT3 inhibition. Interestingly, Prdx1 downregulation mimicked these effects. Finally, CM728 led to DNA damage, cell cycle blockage at the S and G
/M phases, and the activation of caspase-dependent apoptosis. Taken together, our results identify a novel compound with antitumoral properties against TNBC. In addition, we describe the mechanism of action of this drug and provide a rationale for the use of Prdx1 inhibitors, such as CM728, alone or in combination with other drugs, for the treatment of TNBC.
Background
Impulse control disorders (ICDs) have an increased frequency in patients with Parkinson's disease (PD), mainly because of treatment with dopamine agonists (DA). Factors related with the ...country of origin (culture, economy, healthcare politics) may impact phenomenology.
Objectives
To explore phenomenology of ICDs depending on the country.
Methods
A systematic review following PRISMA guidelines was performed using Pubmed database. Articles published up to 2018 in which the prevalence of ICDs was analyzed were selected.
Results
Thirty‐two studies from 22 countries worldwide were included. The highest prevalence of ICDs in each continent was found in UK (59%), USA (39.1%) and India (31.6%). Frequency of ICDs was higher in those studies with lower mean age, higher proportion of males, whenever a screening instrument was used and whenever prescription of DAs was more common. Prevalence of ICDs was higher in Western countries compared to Asian countries (20.8% vs. 12.8%, P < 0.001) as it was the proportion of patients treated with DAs (66% vs. 48.2%, P < 0.001). Hypersexuality was the most common ICD overall (up to 23.8%). The highest frequencies of compulsive buying and eating were found in Western countries. Gambling was less commonly diagnosed, but prevalence was relevant Japan (14%).
Conclusion
We observed a tendency towards a different ICD profile in different geographical areas, which may be attributable to socio‐economical, cultural or political influences in the phenomenology of these disorders. Acknowledging these differences could help their early detection, which is critical for prognosis.
Assessment of local relapse in patients treated with surgery for breast cancer.
This observational study included 673 patients treated with surgery for breast cancer between 2005 and 2010, who were ...monitored for a 7-year minimum follow-up period. The study was concluded on 2017 and yielded a total of 31 cases of local relapse.
4.6% of patients presented local relapse, most of them during the first 3 years of follow-up; 45% of patients with local relapse subsequently presented the disease at distant points. The association between the occurrence of local relapse and later onset of the disease at distant points was significant. The Kaplan–Meier survival analysis revealed that negative results for the presence of progesterone receptors, the use of neoadjuvant chemotherapy and the presence of the disease at distant points were factors that significantly influenced patient survival.
Almost half of the patients suffering relapse subsequently present the disease at distant points. Certain factors increase the aggressiveness of the disease, predict higher risk of relapse and determine its prognosis.
Desde el inicio de la pandemia de la COVID-19 en marzo de 2020, el uso de la mascarilla ha constituido un pilar fundamental para el control de la transmisión del SARS-CoV-2 en diferentes ámbitos. Su ...obligatoriedad ha sido regulada por diferentes normativas, y la efectividad de la misma para la reducción de la transmisión del SARS-CoV-2 y de otros virus respiratorios ha sido fuertemente probada. Al respecto, destaca el impacto beneficioso en los centros sanitarios en los que ha demostrado reducir la transmisión de las infecciones respiratorias, tanto en pacientes como en profesionales sanitarios. Este documento plantea una propuesta de recomendaciones para el uso de la mascarilla en los centros sanitarios en el momento actual en el que nos encontramos con un cese de la obligatoriedad de su uso en España. Están dirigidas a profesionales sanitarios, pacientes y acompañantes/visitantes y pretenden protegerles de adquirir infecciones respiratorias agudas como consecuencia de las complejas relaciones establecidas en el ámbito sanitario.
Human Chronic Myelogenous Leukemia (CML) is a hematological stem cell disorder which is associated with activation of Bcr-Abl-Stat5 oncogenic pathway. Direct Bcr-Abl inhibitors are initially ...successful for the treatment of CML but over time many patients develop drug resistance. In the present study, the effects of CM363, a novel naphthoquinone (NPQ) derivative, were evaluated on human CML-derived K562 cells. CM363 revealed an effective cell growth inhibition (IC50 = 0.7 ± 0.5 μM) by inducing cancer cells to undergo cell cycle arrest and apoptosis. CM363 caused a dose- and time-dependent reduction of cells in G0/G1 and G2/M phases. This cell cycle arrest was associated with increased levels of cyclin E, pChk1 and pChk2 whereas CM363 downregulated cyclin B, cyclin D3, p27, pRB, Wee1, and BUBR1. CM363 increased the double-strand DNA break marker γH2AX. CM363 caused a time-dependent increase of annexin V-positive cells, DNA fragmentation and increased number of apoptotic nuclei. CM363 triggered the mitochondrial apoptotic pathway as reflected by a release of cytochrome C from mitochondria and induction of the cleavage of caspase-3 and -9, and PARP. CM363 showed multikinase modulatory effects through an early increased JNK phosphorylation followed by inhibition of pY-Bcrl-Abl and pY-Stat5. CM363 worked synergistically with imatinib to inhibit cell viability and maintained its activity in imatinib-resistant cells. Finally, CM363 (10 mg/Kg) suppressed the growth of K562 xenograft tumors in athymic mice. In summary, CM363 is a novel multikinase modulator that offers advantages to circumvent imanitib resistance and might be therapeutically effective in Bcrl-Abl-Stat5 related malignancies.
To elucidate whether microsatellite instability (MSI) predicts clinical outcome in radiation-treated endometrioid endometrial cancer (EEC).
A consecutive series of 93 patients with EEC treated with ...extrafascial hysterectomy and postoperative radiotherapy was studied. The median clinical follow-up of patients was 138 months, with a maximum of 232 months. Five quasimonomorphic mononucleotide markers (BAT-25, BAT-26, NR21, NR24, and NR27) were used for MSI classification.
Twenty-five patients (22%) were classified as MSI. Both in the whole series and in early stages (I and II), univariate analysis showed a significant association between MSI and poorer 10-year local disease-free survival, disease-free survival, and cancer-specific survival. In multivariate analysis, MSI was excluded from the final regression model in the whole series, but in early stages MSI provided additional significant predictive information independent of traditional prognostic and predictive factors (age, stage, grade, and vascular invasion) for disease-free survival (hazard ratio HR 3.25, 95% confidence interval CI 1.01-10.49; p = 0.048) and cancer-specific survival (HR 4.20, 95% CI 1.23-14.35; p = 0.022) and was marginally significant for local disease-free survival (HR 3.54, 95% CI 0.93-13.46; p = 0.064).
These results suggest that MSI may predict radiotherapy response in early-stage EEC.
Abstract Aim DNA double strand break (DSB) repair is a central cellular mechanism of the DNA damage response to maintain genomic stability. DSB components are frequently mutated in colorectal cancer ...with microsatellite instability (MSI). We investigated whether DSB repair is involved in endometrial cancer (EC) with MSI. Methods Mononucleotide microsatellite tracts of 14 genes of the DSB repair system were analysed in a series of 41 EC with MSI. Among these genes, the microcephalin 1 ( MCPH1 / BRIT1 ) has never been tested as target of MSI in tumour series. Results The most frequently mutated gene was DNAPKcs ( n = 14, 34%) followed by RAD50 ( n = 7, 17%), MRE11 , ATR and BRCA1 ( n = 6, 15%), and by CtIP and MCPH1 ( n = 5, 12%). While DSB biallelic mutations were infrequent, a high proportion of tumours ( n = 30, 73%) presented mutations at some component of the DSB repair pathway, and almost half of them showed alterations at two or more components. Tumours with mutations in two or more genes were significantly associated with advanced grade ( p = 0.03) and vascular invasion ( p = 0.02) and marginally associated with advanced stage ( p = 0.07). Conclusions Our results suggest that in EC, the DSB repair is a relatively common mutational target of MSI and might contribute to tumour progression, and also that MCHP1 may be a novel target gene of MSI.
Even after two years of pandemic, there are still uncertainties on how to proceed when we schedule endoscopic procedures. During the COVID-19 pandemic, some scientific societies recommended universal ...preprocedural testing for all patients. However, other societies recommended against and considered enough to maintain strict infection control strategies. Our aim was to evaluate this approach in order to see if it was safe for both patients and healthcare workers to proceed with the endoscopies without performing a systematic PCR on all patients.
Retrospective chart review of all patients undergoing endoscopy without preprocedural COVID testing at our center from March 2020 to May 2021. PCR tests performed in the patients receiving an endoscopic procedure were analyzed, and patients who tested positive between 14 days before and after the endoscopic procedure were selected. The registry of the endoscopy unit members participating in these procedures was also analyzed.
A total of 10,132 procedures were performed in the unit with 26 patients infected with SARS-CoV-2. Nineteen of these procedures were performed in patients with unknown SARS-CoV-2 carrier status. In 23 (88.5%) cases, transmission occurred through social or familial contact, and in 3 (11.5%), transmission occurred in the hospital. Four health care workers became infected during this period and none of them were related to the endoscopic procedures performed in patients with COVID-19.
SARS-CoV-2 positive testing in asymptomatic ambulatory patients is rare and the adequate use of individual protective measures emerges as the main way to control the spread of COVID-19 infection in endoscopy centers.
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