Fine needle aspiration cytology of ovarian sex cord tumor with annular tubules

The clinical and cytopathologic features of a case of ovarian sex cord tumor with annular tubules are presented. To the best of our knowledge, this is the first report describing the cytologic features in a fine needle aspirate. Aspiration cytology cannot distinguish this tumor with certainty from a granulosa-cell tumor.     

Fine needle aspiration biopsy of Hashimoto's thyroiditis. Sources of diagnostic error.

OBJECTIVE: To determine the accuracy of cytologic interpretation in the diagnosis of Hashimoto's thyroiditis (HT). STUDY DESIGN: At Ottawa Hospital from 1987 to 1994, 1,638 fine needle aspiration biopsies (FNABs) from thyroid were performed. HT was suggested in 184 FNAB samples taken from 157 patients. Of the 184 aspirates diagnosed with HT, 39 had corresponding surgical specimens taken from 31 patients. A retrospective review of these FNABs and surgical pathology slides formed the basis of this study. RESULTS: In 27 (69%) aspirates, HT was diagnosed on both the FNAB and surgical specimens. In 10 of 27 FNABs an associated lesion was not sampled by FNAB. In four of these 10 aspirates some of the cellular features of HT were misinterpreted, and the possibility of an associated neoplasm could not be ruled out. This resulted in four false positive diagnoses. In 12 (31%) FNABs from nine patients, the cytologic diagnosis of HT was not confirmed histologically. These cases included five Hürthle cell adenomas and one case each of follicular adenoma, nodular goiter, macrofollicular adenoma and malignant lymphoma. This resulted in five false negative diagnoses. CONCLUSION: These results support the value of FNAB in the diagnosis of HT. The presence of hyperplastic follicular cells on FNAB samples from HT may mimic a follicular neoplasm and result in a false positive interpretation. Adequate sampling of the thyroid is important, particularly when there is an associated lesion. The diagnosis of lymphocytic thyroiditis should not be made when only a few lymphocytes are present. Finally, pleomorphic Hürthle cells may be present in aspirates from Hürthle cell neoplasms and underdiagnosed as HT, especially when they are associated with a few lymphocytes.     

Is miR-144 an effective inhibitor of PTEN mRNA: a controversy in breast cancer

Breast cancer is the first common cancer among women worldwide. One of the major signaling pathways playing a role in the onset and progression of this disease is PI3K/Akt/mTOR, which can be inhibited by PTEN. miRNAs are small non-coding molecules that regulate the expression of their targets by inhibition or suppression, and thus, their dysregulated expression results in the development of cancer. Using various software applications predicting miRNAs and evaluating GEO microarray data, miR-144 was selected as an inhibitor of PTEN. The expression of miR-144 and PTEN was evaluated in 18 triple negative breast cancer (TNBC) clinical samples and cell lines including 4T1, MDA-MB-231, MDA-MB-468, SK-BR-3, and MCF-7 in comparison with normal cells. PTEN and miR-144 expression analysis revealed their elevated expression in MCF-7 cells. MDA-MB-468, SK-BR-3, and MDA-MB-231 cells showed decreased levels of PTEN and increased levels of miR-144. In contrast, 4T1 cells had an increased expression of PTEN and decreased expression of miR-144. In clinical samples, miR-144 was up-regulated in 22% of the cases and PTEN was down-regulated in 78% of the cases. The results showed that the expression of PTEN and miR-144 was inversely correlated in metastatic breast cancer cell lines. However, in TNBC clinical samples, there was no correlation between the expression of miR-144 and PTEN. Literature shows that there are other influencing factors affecting the expression of miRNAs. Therefore, care should be taken in interpreting the results of gene expression studies and its relation with cancer diagnosis/prognosis.     

Cloning,Expression, and Assessment of Cytotoxic Effects of A-NGR Fusion Protein

Targeted drug delivery is an attractive field in cancer studies. In this study, a novel fusion protein consisting of Shiga toxin A subunit and NGR peptide has been constructed. The cytotoxic Shiga toxin A subunit has the ability to kill cancer cells while NGR is a well-known peptide that targets the whole molecule to cancer cells. Two forms of this novel fusion protein, one without linker (A-NGR) and one with linker (A-GGGGS-NGR) were studied. 3D structure prediction of the two forms carried out by I-TASSER and their validation and analysis were performed by ProSA web and RAMPAGE. Results showed that A-NGR is a better model than the one with linker. A-NGR was constructed by PCR method and cloned in pBAD/gIII A vector. Then, it was successfully expressed in Escherichia coli by induction with arabinose and subsequently purified by affinity chromatography under denaturing condition. Ultimately, the cytotoxic effect of the purified protein was evaluated on U937 cancer cells and MRC-5 normal cells by MTT assay. Conclusively, the fusion protein was successfully cloned and expressed and evaluated for its cytotoxic effects. The IC50 value of A-NGR fusion protein for U937 cell was about 26.86 µg/ml while no cytotoxic effect was observed on MRC-5 cells. Therefore, considering the promising cytotoxic effects of the fusion protein, further in vitro evaluations of this fusion protein on different cell lines are underway.     

Regulation of autophagy by polyphenols: Paving the road for treatment of neurodegeneration

In the present paper, we will discuss on the importance of autophagy in the central nervous system, and outline the relation between autophagic pathways and the pathogenesis of neurodegenerative disorders. The potential therapeutic benefits of naturally occurring phytochemicals as pharmacological modulators of autophagy will also be addressed. Our findings provide renewed insight on the molecular modes of protection by polyphenols, which is likely to be at least in part mediated not only by their potent antioxidant and anti-inflammatory effects, but also through modulation of autophagic processes to remove the aberrant protein aggregates.     

Electrochemical CO2 Reduction with Atomic Iron‐Dispersed on Nitrogen‐Doped Graphene

Electrochemical reduction of CO₂ provides an opportunity to reach a carbon‐neutral energy recycling regime, in which CO₂ emissions from fuel use are collected and converted back to fuels. The reduction of CO₂ to CO is the first step toward the synthesis of more complex carbon‐based fuels and chemicals. Therefore, understanding this step is crucial for the development of high‐performance electrocatalyst for CO₂ conversion to higher order products such as hydrocarbons. Here, atomic iron dispersed on nitrogen‐doped graphene (Fe/NG) is synthesized as an efficient electrocatalyst for CO₂ reduction to CO. Fe/NG has a low reduction overpotential with high Faradic efficiency up to 80%. The existence of nitrogen‐confined atomic Fe moieties on the nitrogen‐doped graphene layer is confirmed by aberration‐corrected high‐angle annular dark‐field scanning transmission electron microscopy and X‐ray absorption fine structure analysis. The Fe/NG catalysts provide an ideal platform for comparative studies of the effect of the catalytic center on the electrocatalytic performance. The CO₂ reduction reaction mechanism on atomic Fe surrounded by four N atoms (Fe–N₄) embedded in nitrogen‐doped graphene is further investigated through density functional theory calculations, revealing a possible promotional effect of nitrogen doping on graphene.     

Gold and Female Reproductive Organs: an Ultrastructural Study

Gold, a heavy yellow-colored metal, is usually found in nature as a metallic element or as salts. This noble metal historically had a reputation as an anti-inflammatory medicine for rheumatoid arthritis, a nervine, and a remedy for nervous disorders, as well as a potential anticancer agent. It has also been used as component in dental restorations and in implant materials. The present study was undertaken to point out histological and ultrastructural effects of gold, administered by intraperitoneal route, in pregnant female reproductive organs (ovary and uterus), in order to clarify its side effects on the reproductive function. Using the transmission electron microscopy (TEM), the ultrastructural investigations of both ultrathin ovarian and uterine sections of treated pregnant rats revealed the existence of numerous heterogeneous clusters with very electron-dense inclusions characterized by various aspects in the lysosomes of granulosa, theca interna cells, and theca externa cells. Degeneration of these tissues, like cell vacuolization, marked expansion of the endoplasmic reticulum, mitochondrial alterations, and necrotic foci, were also highlighted. Moreover, huge phagolysosomes and high numbers of eosinophils as signs of inflammation were also identified especially in endometrial and myometrial cells of gold-treated rats. The ultrastructural investigations of reproductive organ sections of control pregnant rats showed a normal ultrastructural aspect and no loaded lysosomes. These results speculated the toxicity of gold at the used dose. The observed signs of toxicity allowed concluding that the important role of lysosome in the sequestration of this element under an insoluble form in all categories of cells in the studied tissues does not seem to be efficient.