Declining estrogen receptor-beta expression defines malignant progression of human breast neoplasia

It has been shown that the risk of breast cancer developing in certain morphologically identifiable benign breast lesions correlates with expression of estrogen receptor alpha (ER-alpha). Although ER-alpha and ER-beta genes share a large degree of homology, it is generally thought that their distribution and functions are substantially different in many tissues. Recent development of reliable antibodies to ER-beta has provided this first opportunity to test the hypothesis that the likelihood of malignant transformation in morphologically benign breast lesions can be accurately defined by the distribution and level of ER-beta expression relative to that of ER-alpha. Using a monoclonal antibody, ER-beta protein expression has been analyzed in 53 normal breasts and compared with a cohort of histologically distinct breast lesions of different prognostic risk (54 hyperplasia of usual type, 35 ductal carcinoma in situ, and 141 invasive cancers). All of these tissues were also assessed for ER-alpha. Expression of ER-beta protein was also analyzed in an additional spectrum of benign breast lesions with low or negligible risk of progression to malignancy. The median proportion of cells expressing ER-beta was highest in normal breast lobules (median 94.33%, interquartile range 78.25-99.00) but declined significantly through usual ductal hyperplasia (median 76.67, interquartile range 49.17-95.00, P = 0.002) and ductal carcinoma in situ (median 70.00, interquartile range 59.00-85.00, P = 0.009) to invasive cancer (median 60.00, interquartile range 50.00-80.00, P < 0.001). An appreciable proportion (33.81%) of ER-alpha-negative invasive cancers expressed ER-beta. A high but variable level of ER-beta expression occurred in the benign lesions. The data from the intact histologic tissues were evaluated with respect to the relative expression of ER-alpha and ER-beta in five mammary cell lines of different behavioral phenotype (MCF7, ZR-75, T47D, MDAMB231, HUMA121). The highly significant differences in expression and distinct tissue distributions of ER-alpha and ER-beta within the histologic lesions of defined risk, together with the data from the cell lines, support the original hypothesis that the tissue concentration, relative occurrence, and/or interaction of these two types of estrogen receptor may play an important role in modulating mammary tumorigenesis.     

Synthesis and biological investigations of new thiazolidinone and oxadiazoline coumarin derivatives

Ethyl (coumarin-4-oxy)acetate 1 was prepared through the reaction of 4-hydroxycoumarin with ethyl bromoacetate. Compound 1 was allowed to react with hydrazine hydrate to produce coumarin-4-oxyacetic hydrazide 2. The synthesis of N-(arylidene and alkylidene)-coumarin-4-oxyacetic hydrazones 3-20 was performed. The preparation of 2-substituted-3-[(coumarin-4-oxy) acetamido]thiazolidinones 21-26 and 2-[(coumarin-4-oxy)methyl]-4-acetyl-5-substituted-delta2-1,3,4-oxadiazolines 27-33 was performed by the reaction of the hydrazones 3, 4, 7, 9, 12, 14 with mercaptoacetic acid and the hydrazones 3, 4, 5, 7, 12, 15, 16 with acetic anhydride, respectively. The antiviral activities, cytotoxicities and structure-activity relationship (SAR) towards different microorganisms of the prepared compounds were studied.     

Correlation between p53 mutations and HPV in bilharzial bladder cancer

Alterations of the p53 tumor suppressor gene are the most common genetic changes detected in human cancers as well as in papillary and invasive bladder cancer. Several studies have demonstrated an association between HPV infection and urological malignancies. In the present work, the p53 gene status was studied together with the frequency of HPV in 99 cases of Bilharzial bladder cancer [BBC] in Egypt and both were correlated to the clinicopathological features of the patients. SSCP and sequencing were used to screen the p53 gene for mutations at exons 4-10 and IHC was performed to detect protein overexpression. PCR was used for detection and typing of HPV-DNA in tumor samples. p53 mutations were detected in 33.3% of the studied cases whereas protein overexpression was detected in 35.6% of the cases. The highest concordance rate was observed in cases harboring mutations at exon 4 [87.5%]. Bilharzial infestation was obvious in 72.2% of the cases that showed mutations. Exon 8 showed the highest rate of mutation [32%] followed by exons 4 and 5 [22% each]. The commonest mutational event was G:C transversion [15/50] especially at CpG dinucleotides. A mutational hot spot was detected at exon 4, codons 72-73. HPV-DNA was detected in 48.97% of the cases the majority of which [64.6%] were of type 16. Significant correlation was found between p53 mutation and the pathological stage as well as p53 overexpression and tumor grade. Our results demonstrate that the mutational spectrum in BBC is different from that of bladder cancer in Western countries in many aspects and suggest an etiological role of HPV in this type of neoplasm. However, both HPV infection and p53 gene abnormalities may contribute to Bilharzial bladder carcinogenesis in an independent way.     

The insecticidal activity of four medicinal plants against the blowfly Lucilia sericata (Diptera: Calliphoridae)

Background  The larvae of Lucilia sericata induce myiasis and transmit mycobacterial infections to humans and animals. Consequently, the blowfly should be controlled for human welfare and economic reasons.
Methods  The insecticidal effect of fenugreek ( Trigonella foenum-graecum ), celery ( Apium graveolens ), radish ( Raphanus sativus ), and mustard ( Brassica compestris ) against the third larval instars of L. sericata was evaluated, for the first time, through ingestion assays. The effect of sublethal concentrations on certain biological aspects, such as the pupation rates and adult emergence, was revealed.
Results  The LC₅₀ values were 2.81, 4.60, 6.93, and 7.92% for fenugreek, celery, radish, and mustard, respectively. The adverse effects on larval treatment also included the survival of pupae and adults. The pupation rate was strongly decreased after treatment with 16% fenugreek and celery. Moreover, adult emergence was suppressed after treatment of larvae with 8% mustard, 12% radish, and 16% fenugreek and celery oils. The number of emerged males exceeded the number of females, which could lead to population decline. Morphologic abnormalities of larvae, pupae, and adults were recorded after treatment with all tested oils.
Conclusion  The results suggest that oils may represent new and safe potential insecticides for the control of blowflies.     

Effect of cyproterone acetate in comparison to flutamide and megestrol acetate on the ventral prostate, seminal vesicle, and adrenal glands of adult male rats

Cyproterone acetate (CPA) has a stronger inhibitory effect than megestrol acetate (MGA) and flutamide (FL) on the prostate and seminal vesicle of intact adult rats. Only in the clinically irrelevant regimen of castration and simultaneous androgen substitution is FL as a competitive androgen antagonist more potent than CPA and MGA. The latter inhibit complete involution of the ventral prostate but not of the seminal vesicle of castrated adult rats. This effect is very small in magnitude, cannot be increased by the use of higher doses, and is only reduced but not blocked by simultaneous treatment with high doses of FL. Further, CPA is unable to stimulate proliferation or restore the function of the involuted rat prostate. CPA and MGA inhibit adrenal weight in rats, thus indicating a glucocorticoidlike activity in this species. A critical review of all available data on the antiandrogenic, glucocorticoidlike, and possible paradoxical androgenlike activities of CPA in different animal experiments has no important bearing on the clinical effectiveness of CPA in the treatment of prostatic cancer.     

Hepatitis E virus coinfection with hepatotropic viruses in Egyptian children

BACKGROUND AND PURPOSE: Major hepatotropic viruses continue to be important causes of acute viral hepatitis in developing countries. This work was carried out to detect the seroprevalence of hepatitis E virus (HEV) markers in children with acute viral hepatitis due to hepatotropic viruses (A, B and C) and non-A, non-B, non-C acute hepatitis, and to ascertain the influence of HEV superinfection in individuals infected with hepatitis viruses (A, B and C). METHODS: We studied prospectively 162 children with sporadic acute hepatitis who reported to our hospital. Thirteen healthy controls were also included in the study. Laboratory investigations were performed, including complete liver function tests. Complete serological profiles for hepatitis viruses A, B, C and E were evaluated. RESULTS: HEV immunoglobulin G was detected with highest percentage among patients with hepatitis B (56.7%), followed by patients with hepatitis C virus (52.0%), hepatitis A virus (34.1%) and combined hepatitis B and C viruses (30.0%). The detection rate among patients with non-A, non-B, non-C hepatitis was 7.1%. HEV immunoglobulin M was found in 4.5% of hepatitis A virus patients and in 3.3% of hepatitis B patients. The prevalence of HEV immunoglobulin G and immunoglobulin M correlated with the levels of hepatic aspartate aminotransferase and alanine aminotransferase in patients with dual markers of infection with hepatitis E and other viruses compared to patients with acute hepatitis due to A and C viruses. CONCLUSIONS: HEV serological markers are common among children with acute viral hepatitis, especially from hepatitis C and B viruses. There may be increased sensitivity to HEV coinfection in association with hepatitis B and C infections. Dual infection with HEV and other hepatotropic viruses was associated with greater elevation of aspartate and alanine aminotransferases.     

Outcomes of Living Donor Liver Transplantation for Patients with Preoperative Portal Vein Problems

Background

Portal vein thrombosis (PVT) is a common complication for patients with end-stage liver disease. The presence of PVT used to be a contraindication to living donor liver transplantation (LDLT). The aim of this study is to evaluate the influence of preoperative PVT on perioperative and long-term outcomes of the recipients after LDLT.

Methods

We reviewed the data of patients who underwent LDLT during the period between 2004 till 2017.

Results

During the study period, 500 cases underwent LDLT. Patients were divided into three groups. Group I included non-PVT, 446 patients (89.2%); group II included attenuated PV, 26 patients (5.2%); and group III included PVT, 28 patients (5.6%). Higher incidence of hematemesis and encephalopathy was detected in PVT (p?=?0.001). Longer anhepatic phase was found in PVT (p?=?0.013). There were no significant differences between regarding operation time, blood loss, transfusion requirements, ICU, and hospital stay. The 1-, 3-, and 5-year overall survival (OS) rates of non-PVT were 80.5%, 77.7%, and 75%, and for attenuated PV were 84.6%, 79.6%, and 73.5%, and for PVT were 88.3%, 64.4%, and 64.4%, respectively. There was no significant difference between the groups regarding OS rates (logrank 0.793).

Conclusion

Preoperative PVT increases the complexity of LDLT operation, but it does not reduce the OS rates of such patients.