Cytogenetic and comparative genomic hybridization findings in four cases of breast cancer after neoadjuvant chemotherapy

To assess a potential common pattern of genetic alterations in chemotherapy-resistant tumors we analyzed four tumors from breast cancer patients (patients 1-4) after neoadjuvant chemotherapy, by comparative genome hybridization (CGH) and conventional chromosome banding analysis. All patients showed structural aberrations involving chromosomes 1, 5, 11, 16, and 17. In CGH analysis, the patients showed typical imbalances for ductal breast cancer: gains of 1q (3 patients), 5q (2 patients), 8q (3 patients), and X (4 patients) and losses of 1p33 approximately p36 (3 patients), 16q (3 patients), 17p (3 patients), 19 (4 patients), and 22q (4 patients). Other recurrent imbalances of atypical pattern for ductal breast cancer were gain of 4q21 approximately q32 (2 patients), 20q21 approximately q22 (2 patients), and 21 (2 patients) and loss of 20p (3 patients). Three patients showed involvement of several regions bearing genes of drug resistance (MDR1 [HUGO symbol: ABCB1], BCRP [HUGO symbol: ABCG2], MRP1 [HUGO symbol: ABCC1], RFC1); the fourth patient displayed an amplification in the region of MYC (alias c-myc), thus providing--at the level of the light microscope--an explanatory background for the ability of their tumors to survive anthracycline-, taxane- and cyclophosphamide-based chemotherapy. Conventional cytogenetic analysis and CGH displayed highly coincidental findings in the tumors of four patients after neoadjuvant chemotherapy for breast cancer.     

Evaluating the efficacy and safety of vascular IPL for treatment of acute cutaneous leishmaniasis: a randomized controlled trial

Lasers in Medical Science - Treatment of cutaneous leishmaniasis (CL) continues to be a health concern, and alternative therapies with fewer side effects are substantially needed. This study aimed...     

Mitigation of Methimazole-Induced Hepatic Injury by Taurine in Mice

Methimazole is the most widely prescribed antithyroid medication in humans. However, hepatotoxicity is a deleterious adverse effect associated with methimazole administration. No specific protective agent has been developed against this complication yet. This study was designed to investigate the role of taurine as a hepatoprotective agent against methimazole-induced liver injury in mice. Different reactive metabolites were proposed to be responsible for methimazole hepatotoxicity. Hence, methimazole-induced liver injury was investigated in intact and/or enzyme-induced animals in the current investigation. Animals were treated with methimazole (200 mg/kg, by gavage), and hepatic injury induced by this drug was investigated in intact and/or enzyme-induced groups. Markers such as lipid peroxidation, hepatic glutathione content, alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in plasma, and histopathological changes in the liver of animals were monitored after drug administration. Methimazole caused liver injury as revealed by increased plasma ALT. Furthermore, a significant amount of lipid peroxidation was detected in the drug-treated animals, and hepatic glutathione reservoirs were depleted. Methimazole-induced hepatotoxicity was more severe in enzyme-induced mice. The above-mentioned alterations in hepatotoxicity markers were endorsed by significant histopathological changes in the liver. Taurine administration (1 g/kg, i.p.) effectively alleviated methimazole-induced liver injury in both intact and/or enzyme-induced animals.     

Disrupted amygdala-prefrontal functional connectivity in civilian women with posttraumatic stress disorder

Many features of posttraumatic stress disorder (PTSD) can be linked to exaggerated and dysregulated emotional responses. Central to the neurocircuitry regulating emotion are functional interactions between the amygdala and the ventromedial prefrontal cortex (vmPFC). Findings from human and animal studies suggest that disruption of this circuit predicts individual differences in emotion regulation. However, only a few studies have examined amygdala-vmPFC connectivity in the context of emotional processing in PTSD. The aim of the present research was to investigate the hypothesis that PTSD is associated with disrupted functional connectivity of the amygdala and vmPFC in response to emotional stimuli, extending previous findings by demonstrating such links in an understudied, highly traumatized, civilian population. 40 African-American women with civilian trauma (20 with PTSD and 20 non-PTSD controls) were recruited from a large urban hospital. Participants viewed fearful and neutral face stimuli during functional magnetic resonance imaging (fMRI). Relative to controls, participants with PTSD showed an increased right amygdala response to fearful stimuli (p_corr < .05). Right amygdala activation correlated positively with the severity of hyperarousal symptoms in the PTSD group. Participants with PTSD showed decreased functional connectivity between the right amygdala and left vmPFC (p_corr < .05). The findings are consistent with previous findings showing PTSD is associated with an exaggerated response of amygdala-mediated emotional arousal systems. This is the first study to show that the amygdala response may be accompanied by disruption of an amygdala-vmPFC functional circuit that is hypothesized to be involved in prefrontal cortical regulation of amygdala responsivity.     

Genome expression analysis by suppression subtractive hybridization identified overexpression of Humanin, a target gene in gastric cancer chemoresistance

Background

In cancer cells, apoptosis is an important mechanism that influences the outcome of chemotherapy and the development of chemoresistance. To find the genes involved in chemoresistance and the development of gastric cancer, we used the suppression subtractive hybridization method to identify the genes that are overexpressed in gastric cancer tissues compared to normal gastric tissues.

Results

In the suppression subtractive hybridization library we constructed, the most highly overexpressed genes were humanin isoforms. Humanin is a recently identified endogenous peptide that has anti-apoptotic activity and has been selected for further study due to its potential role in the chemoresistance of gastric cancer. Upregulation of humanin isoforms was also observed in clinical samples by using quantitative real-time PCR. Among the studied isoforms, humanin isoform 3, with an expression level of 4.166 ± 1.44 fold, was the most overexpressed isoform in GC.

Conclusions

The overexpression of humanin in gastric cancer suggests a role for chemoresistance and provides new insight into the biology of gastric cancer. We propose that humanin isoforms are novel targets for combating chemoresistance in gastric cancer.     

Epicardial Versus Endocardial Pacemakers in the Pediatric Population: A Comparative Inquiry

Background: Most children in need of cardiac pacemakers remain dependent on the function of the permanent from childhood to adulthood. We sought to evaluate and compare the function between epicardial and endocardial pacemakers in pediatric groups with different conditions. Methods: Between 2012 and 2018, this single-canter study evaluated 44 pediatric patients with indications for epicardial or endocardial pacemakers. Results: The 2 groups, at a median age of 5 (0.1–16) years, were compared concerning the characteristics of the leads used (n = 80: bipolar, unipolar, steroid-eluting, and non–steroid-eluting), survival data, and complications. The reason for pacemaker implantation was congenital complete heart block in 11 (25%) cases and postoperative heart block in 33 (75%) cases. The commonest congenital heart disease accompanied by postoperative block was the ventricular septal defect. In the endocardial lead group, the mean ventricular pacing threshold immediately after the implantation and during the follow-up was less than that in the epicardial lead group (0.75 vs. 0.81 V; P = 0.01 and 0.8 vs. 2.4 V; P = 0.001). During the follow-up, the mean battery longevity was better in the endocardial group (last visit: 6.7 endocardial vs. 3.3 years epicardial). Lead failure was commoner in the epicardial pacemaker, and chronic high-pacing threshold pattern was seen in 14 patients in this group. After 3 years, freedom from lead failure was 94% and 63% in the endocardial and epicardial leads. Conclusions: Pacemakers with endocardial bipolar steroid-eluting leads showed better lead characteristics regarding survival and battery longevity than epicardial pacemakers without these lead characteristics. An appropriate pacemaker type should be selected based on the patient’s condition.     

Cyproterone acetate-loaded nanostructured lipid carriers: effect of particle size on skin penetration and follicular targeting

Cyproterone acetate (CPA) is used to treat various skin disorders such as acne, hirsutism, and alopecia. Due to the limited skin penetration of CPA, nanostructured lipid carriers (NLCs) with different size ranges were considered in this study in order to enhance skin penetration and to target hair follicles. Drug loading, drug release and morphological assessment were evaluated for each targeted size (100, 300, and 600?nm). Ex vivo skin penetration was also investigated using Franz diffusion cells. Finally, in vivo follicular targeting was evaluated using rhodamine B-loaded micro and nanoparticles. Results revealed that 60–85% of drug was slowly released from lipid nanoparticles within 72?h. CPA-NLC with average diameter of 600?nm had better penetration and deposition in dermis-epidermis layer, also CPA-NLC 100 and 300?nm significantly increased drug penetration in dermis-epidermis in comparison to free CPA. Follicular targeting results revealed that NLC 300?nm had the best accumulation capacity in hair follicles. CPA-NLC with average diameter of 300?nm could be a promising topical novel drug delivery system for specific targeting of hair follicles and sebaceous glands to treat androgenic skin disorders such as acne, hirsutism, and alopecia.