Face-Fusion of Icosahedral Boron Hydride Increases Affinity to γ-Cyclodextrin: closo,closo-[B21 H18 ]- as an Anion with Very Low Free Energy of Dehydration.

The supramolecular recognition of closo,closo-[B21 H18 ]- by cyclodextrins (CDs) has been studied in aqueous solution by isothermal titration calorimetry and nuclear magnetic resonance spectroscopy. These solution studies follow up on previous mass-spectrometric measurements and computations, which indicated the formation and stability of CD ⋅ B21 H18- complexes in the gas phase. The thermodynamic signature of solution-phase binding is exceptional, the association constant for the γ-CD complex with B21 H18- reaches 1.8×106  M-1 , which is on the same order of magnitude as the so far highest observed value for the complex between γ-CD and a metallacarborane. The nature of the intermolecular interaction is also examined by quantum-mechanical computational protocols. These suggest that the desolvation penalty, which is particularly low for the B21 H18- anion, is the decisive factor for its high binding strength. The results further suggest that the elliptical macropolyhedral boron hydride is another example of a CD binder, whose extraordinary binding affinity is driven by the chaotropic effect, which describes the intrinsic affinity of large polarizable and weakly solvated chaotropic anions to hydrophobic cavities and surfaces in aqueous solution.

Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.

BACKGROUND: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. METHODS: We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). RESULTS: In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P < 0.001 and HR 3.81; 95% CI 2.28-6.37; P < 0.001, respectively], PFS (HR 2.18; 95% CI 1.08-4.39; P = 0.03, and HR 1.95; 95% CI 1.23-3.11; P = 0.01, respectively) and rate of PSA decline ≥50% [odds ratio (OR), 4.7; 95% CI 1.17-19.17; P = 0.035 and OR, 5.0; 95% CI 1.70-14.91; P = 0.003, respectively]. AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. CONCLUSION: Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required. CLINICAL TRIAL NUMBER: NCT02288936 (PREMIERE trial).

Stroke-related mortality in a tertiary care hospital in Andalusia: Analysis and reflections. / Mortalidad asociada al ictus en un hospital andaluz de tercer nivel. Análisis y reflexiones.

OBJECTIVES: Stroke is a very common cause of death, especially in southern Spain. The present study analyses in-hospital mortality associated with stroke in an Andalusian tertiary care hospital. METHODS: We gathered the files of all patients who had died at Hospital Universitario Virgen de las Nieves in Granada in 2013 and whose death certificates indicated stroke as the cause of death. We also gathered stroke patients discharge data and compared them to that of patients with acute coronary syndrome (ACS). RESULTS: A total of 825 patients had a diagnosis of stroke (96 deaths, 11.6%); of these, 562 had ischaemic stroke (44 deaths, 7.8%) and 263 haemorrhagic stroke (52 deaths, 19.7%). Patients with haemorrhagic stroke therefore showed greater mortality rate (OR=2.9). Patients in this group died after a shorter time in hospital (median, 4 vs 7 days; mean, 6 days). However, patients with ischaemic stroke were older and presented with more comorbidities. On the other hand, 617 patients had a diagnosis of ACS (36 deaths, 5.8%). The mortality odds ratio (MOR) was 2.1 (stroke/SCA). Around 23% of the patients who died from stroke were taking anticoagulants. 60% of the deceased patients with ischaemic stroke and 20% of those with haemorrhagic stroke had atrial fibrillation (AF); 35% of the patients with ischaemic stroke and AF were taking anticoagulants. CONCLUSIONS: Stroke is associated with higher admission and in-hospital mortality rates than SCA. Likewise, patients with haemorrhagic stroke showed higher mortality rates than those with ischaemic stroke. Patients with fatal stroke usually had a history of long-term treatment with anticoagulants; 2 thirds of the patients with fatal ischaemic stroke and atrial fibrillation were not receiving anticoagulants. According to our results, optimising prevention in patients with AF may have a positive impact on stroke-related in-hospital mortality.

[Clinical and radiological effectiveness of natalizumab extended dosage interval in patients with relapsing multiple sclerosis]. / Efectividad clínica y radiológica del intervalo extendido de dosis con natalizumab en pacientes con esclerosis múltiple recurrente.

INTRODUCTION: Natalizumab (NTZ) is a very effective treatment approved for highly active multiple sclerosis. The main risk of treatment with NTZ is the possibility of developing progressive multifocal leukoencephalopathy, which is related to JC virus positivity and the number of NTZ infusions. This risk decreases with the extended dosage interval (EDI), which involves 9 or fewer infusions/year. However, it is a matter of controversy as to whether EDI remains effective in reducing recurrences and the presence of new lesions in magnetic resonance imaging (MRI). PATIENTS AND METHODS: A prospective observational study was conducted from 1 April 2019 to 30 June 2021, following up patients on NTZ treatment who switched to EDI. Patients should have at least one MRI six months after the start of EDI. The presence of attacks or MRI activity (new lesions in T2) during the EDI was recorded. RESULTS: Twenty-three patients with a mean age of 43.5 ± 9.4 years were included. The median number of NTZ infusions was 68 (minimum, 25; maximum, 127). The median interval between the start of the EDI and the last MRI was 14 months (minimum, 6; maximum, 25), and 23 months from the last medical follow-up visit (minimum, 7; maximum, 28). Two patients (8.7%) presented with attacks and two others (8.7%) showed MRI activity. CONCLUSIONS: EDI with NTZ maintains high clinical and activity effectiveness in MRI.

TITLE: Efectividad clínica y radiológica del intervalo extendido de dosis con natalizumab en pacientes con esclerosis múltiple recurrente.Introducción. El natalizumab (NTZ) es un tratamiento de alta eficacia aprobado para la esclerosis múltiple de alta actividad. El principal riesgo del tratamiento con NTZ es la posibilidad de desarrollar una leucoencefalopatía multifocal progresiva, que está en relación con la positividad al virus JC y el número de infusiones del NTZ. Este riesgo disminuye con el intervalo extendido de dosis (IED), lo que supone 9 infusiones/año o menos. Sin embargo, es materia de controversia si el IED mantiene la efectividad sobre la reducción de las recurrencias y la presencia de nuevas lesiones en la resonancia magnética (RM). Pacientes y métodos. Se ha realizado un estudio observacional prospectivo desde el 1 de abril de 2019 hasta el 30 de junio de 2021, siguiendo a los pacientes en tratamiento con NTZ que se pasaron al IED. Los pacientes deberían tener al menos una RM a los seis meses del inicio del IED. Se registró la presencia de brotes o de actividad en la RM (nuevas lesiones en T2) durante el IED. Resultados. Se incluyó a 23 pacientes con una media de edad de 43,5 ± 9,4 años. La mediana de infusiones de NTZ fue de 68 (mínimo, 25; máximo, 127). La mediana del intervalo entre el inicio del IED y la última RM fue de 14 meses (mínimo, 6; máximo, 25), y de 23 meses respecto a la última visita de seguimiento médico (mínimo, 7; máximo, 28). Dos pacientes (8,7%) presentaron brotes y otros dos pacientes (8,7%) presentaron actividad en la RM. Conclusiones. El IED de NTZ mantiene una alta efectividad clínica y de actividad en la RM.

Spontaneus subscapular abscess. A clinical case.

Infections of the subscapular space are very infrequent entities, which is why their diagnosis (for which it is crucial to carry out magnetic resonance imaging or, failing that, computerized tomography) can prove complicated. This difficulty in making the diagnosis conditions the speed of treatment (surgical draining that can be accompanied by antibiotherapy), which is crucial for the medium and long-term prognosis. We present the case of a patient who developed a spontaneous subscapular abscess that was drained using a delto-pectoral approach, with the subscapular space accessed via a medial route to the coracoids. The relevance of this case lies in its singular character and in the description of an approach that has only been used in two prior cases in the literature.

Ischaemic stroke and SARS-CoV-2 infection: A causal or incidental association? / Ictus isquémico e infección por SARS-CoV-2, ¿asociación casual o causal?

INTRODUCTION: Ischaemic stroke has been reported in patients with COVID-19, particularly in more severe cases. However, it is unclear to what extent this is linked to systemic inflammation and hypercoagulability secondary to the infection. METHODS: We describe the cases of 4 patients with ischaemic stroke and COVID-19 who were attended at our hospital. Patients are classified according to the likelihood of a causal relationship between the hypercoagulable state and ischaemic stroke. We also conducted a review of studies addressing the possible mechanisms involved in the aetiopathogenesis of ischaemic stroke in these patients. RESULTS: The association between COVID-19 and stroke was probably causal in 2 patients, who presented cortical infarcts and had no relevant arterial or cardioembolic disease, but did show signs of hypercoagulability and systemic inflammation in laboratory analyses. The other 2 patients were of advanced age and presented cardioembolic ischaemic stroke; the association in these patients was probably incidental. CONCLUSIONS: Systemic inflammation and the potential direct action of the virus may cause endothelial dysfunction, resulting in a hypercoagulable state that could be considered a potential cause of ischaemic stroke. However, stroke involves multiple pathophysiological mechanisms; studies with larger samples are therefore needed to confirm our hypothesis. The management protocol for patients with stroke and COVID-19 should include a complete aetiological study, with the appropriate safety precautions always being observed.

Lignin and ethylcellulose in controlled release formulations to reduce leaching of chloridazon and metribuzin in light-textured soils.

In this research, controlled release formulations (CRFs) of the herbicides chloridazon and metribuzin, identified as potential leachers, have been evaluated in soils with different texture. To prepare the CRFs, ethylcellulose (EC) and dibutylsebacate (DBS) have been used as coating agents in lignin-polyethylene glycol based formulations. Mobility experiments have been carried out in two light textured soils (sandy and sandy-loam). Breakthrough curves have shown that the use of CRFs reduces the presence of chloridazon and metribuzin in the leachate compared to technical and commercial products, being the lignin CRF coated with EC and DBS the most efficient to diminish the herbicide leaching. Mass balance study has shown a higher amount of chloridazon and metribuzin recovered in soils when these herbicides were tested as CRFs compared to technical and commercial products. The gradual release of herbicides from the CRFs resulting in a rather available levels of chloridazon and metribuzin in soil for a longer time. A good correlation between percentages of herbicide recovered in leachates and T50 values (time corresponding to 50% release of herbicide in water) was obtained, which allows to select the most appropriate CRF in each agro-environmental practice to reduce the potential pollution of groundwater by chloridazon and metribuzin.

Modifying sorbents in controlled release formulations to prevent herbicides pollution.

The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in alginate-based granules to obtain controlled release properties. In this research the effect of incorporation of sorbents such as bentonite, anthracite and activated carbon in alginate basic formulation were not only studied on encapsulation efficiency but also on the release rate of herbicides which was studied using water release kinetic tests. In addition, sorption studies of herbicides with bentonite, anthracite and activated carbon were made. The kinetic experiments of chloridazon and metribuzin release in water have shown that the release rate is higher in metribuzin systems than in those prepared with chloridazon, which has lower water solubility. Besides, it can be deduced that the use of sorbents reduces the release rate of the chloridazon and metribuzin in comparison to the technical product and to the alginate formulation without sorbents. The highest decrease in release rate corresponds to the formulations prepared with activated carbon as a sorbent. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T(50), were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the herbicide release data, the release of chloridazon and metribuzin from the various formulations into water is controlled by a diffusion mechanism. Sorption capacity of the sorbents for chloridazon and metribuzin, ranging from 0.53mgkg(-1) for the metribuzin sorption on bentonite to 2.03x10(5)mgkg(-1) for the sorption of chloridazon on the activated carbon, was the most important factor modulating the herbicide release.

[Impact of warning against procrastination of thrombolysis in ischemic stroke]. / Impacto de las advertencias contra la procrastinación sobre las demoras en la trombólisis del ictus.

INTRODUCTION: Fibrinolysis in stroke should be carried out as soon as possible, but delays occur for various reasons. In the first 17 ischemic infarcts treated in our center we confirmed a tendency to exhaust the therapeutic window. We look now at whether warnings against this tendency, without other logistical or organizational modifications, have had an impact on delays. PATIENTS AND METHODS: Neurologists were encouraged to avoid procrastination. When we reached 51 treated patients, we compared features and delay times between the first 17 (February, 2002 to June, 2004) and the 17 most recent cases (October, 2005 to April, 2006). Non-parametric tests were used (significant if p < 0.05). RESULTS: Both groups were similar clinically and demographically. The onset-arrival time lengthened (46 min vs. 75 min; p = 0.01) and scattered. The CT-treatment time halved (57 min vs. 30 min; p = 0.001), with consequent shortening of the 'door-to-needle' period (121 min vs. 90 min; p = 0.002). The arrival-CT time had remained constant (50 min vs. 53 min; p = 0.9), thus the total delay from onset did not change significantly (165 min vs. 170 min; p = 0.7), and the inverse linear correlation between the onset-CT time and the CT-treatment time weakened. CONCLUSIONS: Warnings against procrastination appear to be important in terms of shortening the delays. The time used for clinical-radiologic evaluation (arrival through CT)--about which there had been no action taken--had not been modified, but the time employed in the decision to treat (CT-treatment) and the 'door-to-needle' time had decreased appreciably. This effective compensatory reduction permitted treatment of late-arriving patients, such that although the overall time from onset to treatment apparently was not modified, the actual treatment rate increased.

Efectividad clínica y radiológica del intervalo extendido de dosis con natalizumab en pacientes con esclerosis múltiple recurrente / Clinical and radiological effectiveness of natalizumab extended dosage interval in patients with relapsing multiple sclerosis

Introducción: El natalizumab (NTZ) es un tratamiento de alta eficacia aprobado para la esclerosis múltiple de alta actividad. El principal riesgo del tratamiento con NTZ es la posibilidad de desarrollar una leucoencefalopatía multifocal progresiva, que está en relación con la positividad al virus JC y el número de infusiones del NTZ. Este riesgo disminuye con el intervalo extendido de dosis (IED), lo que supone 9 infusiones/año o menos. Sin embargo, es materia de controversia si el IED mantiene la efectividad sobre la reducción de las recurrencias y la presencia de nuevas lesiones en la resonancia magnética (RM). Pacientes y métodos: Se ha realizado un estudio observacional prospectivo desde el 1 de abril de 2019 hasta el 30 de junio de 2021, siguiendo a los pacientes en tratamiento con NTZ que se pasaron al IED. Los pacientes deberían tener al menos una RM a los seis meses del inicio del IED. Se registró la presencia de brotes o de actividad en la RM (nuevas lesiones en T2) durante el IED. Resultados: Se incluyó a 23 pacientes con una media de edad de 43,5 ± 9,4 años. La mediana de infusiones de NTZ fue de 68 (mínimo, 25; máximo, 127). La mediana del intervalo entre el inicio del IED y la última RM fue de 14 meses (mínimo, 6; máximo, 25), y de 23 meses respecto a la última visita de seguimiento médico (mínimo, 7; máximo, 28). Dos pacientes (8,7%) presentaron brotes y otros dos pacientes (8,7%) presentaron actividad en la RM. Conclusiones: El IED de NTZ mantiene una alta efectividad clínica y de actividad en la RM.(AU)

Introduction: Natalizumab (NTZ) is a very effective treatment approved for highly active multiple sclerosis. The main risk of treatment with NTZ is the possibility of developing progressive multifocal leukoencephalopathy, which is related to JC virus positivity and the number of NTZ infusions. This risk decreases with the extended dosage interval (EDI), which involves 9 or fewer infusions/year. However, it is a matter of controversy as to whether EDI remains effective in reducing recurrences and the presence of new lesions in magnetic resonance imaging (MRI). Patients and methods: A prospective observational study was conducted from 1 April 2019 to 30 June 2021, following up patients on NTZ treatment who switched to EDI. Patients should have at least one MRI six months after the start of EDI. The presence of attacks or MRI activity (new lesions in T2) during the EDI was recorded. Results: Twenty-three patients with a mean age of 43.5 ± 9.4 years were included. The median number of NTZ infusions was 68 (minimum, 25; maximum, 127). The median interval between the start of the EDI and the last MRI was 14 months (minimum, 6; maximum, 25), and 23 months from the last medical follow-up visit (minimum, 7; maximum, 28). Two patients (8.7%) presented with attacks and two others (8.7%) showed MRI activity. Conclusions: EDI with NTZ maintains high clinical and activity effectiveness in MRI.(AU)

Controlled release of isoproturon, imidacloprid, and cyromazine from alginate-bentonite-activated carbon formulations.

Different alginate-based systems of isoproturon, imidacloprid, and cyromazine have been investigated in order to obtain controlled release (CR) properties. The basic formulation [sodium alginate (1.50%), pesticide (0.30%), and water] was modified using different amounts of bentonite and activated carbon. The higher values of encapsulation efficiency corresponded to those formulations prepared with higher percentages of activated carbon, showing higher encapsulation efficiency values for isoproturon and imidacloprid than for cyromazine, which has a higher water solubility. The kinetic experiments of imidacloprid/isoproturon release in water have shown us that the release rate is higher in imidacloprid systems than in those prepared with isoproturon. Moreover, it can be deduced that the use of bentonite and/or activated carbon sorbents reduces the release rate of the isoproturon and imidacloprid in comparison with the technical product and with alginate formulation without modifying agents. The highest decrease in release rate corresponds to the formulations prepared with the highest percentage of activated carbon. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T50, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the pesticide release data, the release of isoproturon and imidacloprid from the various formulations into water is controlled by a diffusion mechanism. The sorption capacity of the sorbents and the permeability of the formulations were the most important factors modulating pesticide release. Finally, a linear correlation of the T50 values and the content of activated carbon in formulations were obtained.

Cosorption study of organic pollutants and dissolved organic matter in a soil.

In this study we have evaluated the effects of dissolved organic matter (DOM) on sorption of imidacloprid, 3,4-dichloroaniline (3,4-DCA) and 4-bromoaniline (4-BA) on a typical calcareous soil (Luvic Xerosol) from south-eastern Spain. Two different types of DOM were used, that is to say, dissolved natural organic matter extracts from a commercial peat (DNOM) and a high-purity tannic acid (TA) solution. The experiments were carried out in a 0.01 M CaCl2 aqueous medium at 25 degrees C. The results indicated that the presence of both DNOM and TA, over a concentration range of 15-100 mg L(-1), produced an increase in the amount of 3,4-DCA and 4-BA sorbed and a decrease in the amount of imidacloprid retained on the soil studied. A modified distribution coefficient, K(doc), has been proposed as a safer parameter for soil sorption predictions of organic pollutants and it could be of help to model the fate of these in the environment.

Use of bentonite and activated carbon in controlled release formulations of carbofuran.

Controlled release systems (CRS), unlike the conventional formulations, facilitate a gradual and controlled discharge of the pesticides, reducing the losses by evaporation and leaching and minimizing pesticide pollution. In this study, carbofuran-an insecticide-nematicide identified as a groundwater pollutant-was incorporated in alginate-based granules to obtain controlled release properties. The effect on carbofuran release rate caused by the incorporation of bentonite, activated carbon, and different mixtures of both sorbents in alginate basic formulation was studied by immersion of the granules in water. The water uptake, sorption capacity of the sorbent, permeability, and time taken for 50% of the active ingredient to be released into water, T(50), were calculated by the comparison of the preparations. T(50) values were higher for those formulations containing bentonite and/or activated carbon (T(50) values range from 14.76 h for the alginate formulation containing only bentonite as the sorbent to 29.5 weeks for the alginate formulation containing only activated carbon as the sorbent) than for the preparation without these sorbents (11.72 h). On the basis of a parameter of an empirical equation used to fit the insecticide-nematicide release data, it appears that the release of carbofuran from the various formulations into water is controlled by a diffusion mechanism. The sorption capacity of the sorbents for carbofuran was the most important factor modulating carbofuran release. In addition, it was observed that there is a linear correlation of the T(50) values and the content of activated carbon in dry granules.

Effects of dissolved organic carbon on sorption of 3,4-dichloroaniline and 4-bromoaniline in a calcareous soil.

To evaluate the effects of dissolved organic carbon on sorption of 3,4-dichloroaniline (3,4-DCA) and 4-bromoaniline (4-BA) on soils, batch sorption experiments were carried out. The soil used was a typical calcareous soil from south-eastern Spain. Two different types of dissolved organic carbon were used, that is, dissolved organic carbon extracts from a commercial peat (DOC-PE) and high-purity tannic acid (DOC-TA). The experiments were carried out in a 0.01 M CaCl2 aqueous medium at 25 degrees C. The results obtained from the sorption experiments show that the presence of both DOC-PE and DOC-TA, over a concentration range of 15-100 mg l-1, produced in all cases, an increase in the amount of 3,4-DCA and 4-BA adsorbed on the soil studied.

[Thrombolysis in stroke: inappropriate consideration of the 'window period' as the time available]. / Trombólisis en el ictus: consideración inapropiada del 'período de ventana' como tiempo disponible.

AIMS: The earlier r-TPA is administered in ischaemic strokes, the more effective it is. The aim of this study is to analyse the delay times in health care afforded in a consecutive series of cases that had received treatment, with a view to shortening them. PATIENTS AND METHODS: We analysed the medical records of the first patients to be treated in our centre. The paper describes several variables involving demographic and clinical factors, as well as the delay in entering the Emergency department, performing a CAT scan and especially the time elapsed between the CAT scan and starting treatment. We have examined the existence of an inappropriate correlation between delays that should be independent of one another. RESULTS: The mean age of the 17 patients treated was 68 years and they had a stroke severity score of 17 points on the NIHSS. The mean time of delay until arrival, arrival-CAT, and CAT-treatment were slightly under 1 hour each, and onset-treatment delay was 165 minutes, which is very close to the limit of the therapeutic window period. We found a strong inverse linear association between the time elapsed between onset and the CAT scan, and from the latter to the beginning of treatment (Spearman's r: -0.664, p = 0.004). CONCLUSIONS: Findings indicate that in our hospital, as in other centres in the initial phases of implementation, the therapeutic time window for intravenous thrombolysis in ischaemic stroke tends to run out. It must be highlighted that the resolve of the physician who indicates the treatment exerts a decisive effect on the delay.

Targeting the epigenetic machinery of cancer cells.

Cancer is characterized by uncontrolled cell growth and the acquisition of metastatic properties. In most cases, the activation of oncogenes and/or deactivation of tumour suppressor genes lead to uncontrolled cell cycle progression and inactivation of apoptotic mechanisms. Although the underlying mechanisms of carcinogenesis remain unknown, increasing evidence links aberrant regulation of methylation to tumourigenesis. In addition to the methylation of DNA and histones, methylation of nonhistone proteins, such as transcription factors, is also implicated in the biology and development of cancer. Because the metabolic cycling of methionine is a key pathway for many of these methylating reactions, strategies to target the epigenetic machinery of cancer cells could result in novel and efficient anticancer therapies. The application of these new epigenetic therapies could be of utility in the promotion of E2F1-dependent apoptosis in cancer cells, in avoiding metastatic pathways and/or in sensitizing tumour cells to radiotherapy.

Metaplastic Breast Carcinoma with Unusual Presentation: Review of Three Cases.

BACKGROUND: Metaplastic breast carcinoma is an uncommon type of breast cancer that usually appears as a large, fast growing breast lump. CASE REPORT: We report 3 cases of metaplastic breast carcinoma presented at our clinic in 2014. The mean age at diagnosis was 67.3 years. 1 patient presented with a fast growing, large mass detected by herself. However, in the other 2 patients, the nodule was approximately 1.5 cm in size, not fast growing, and was detected on mammography. All 3 patients were treated surgically (2 lumpectomies and 1 mastectomy), with the final pathology of metaplastic carcinoma with chondroid mesenchymal differentiation in 2 cases and metaplastic carcinoma with myoepithelial differentiation in the 3rd case. The patients are still under adjuvant therapy. CONCLUSIONS: Metaplastic breast carcinoma may present unusually as a non-palpable lump. This entity must be considered in any breast lump.