The prognostic significance of HER2 expression in urothelial carcinoma.

INTRODUCTION: Urothelial carcinoma poses a great challenge in disease management due to the high recurrence rate and a greater likelihood of disease progression. HER2 (human epidermal growth factor receptor 2) is one of the proteins variably expressed in urothelial carcinoma, prompting its investigation as a potential predictive marker. The aim of this study was to assess the HER2 status in urothelial carcinoma, its correlation with tumour grade, tumour stage, recurrence and progression. MATERIALS AND METHODS: We retrospectively analysed 69 specimens of transurethral resection or cystectomy in patients with urothelial carcinoma. Immunohistochemistry for HER2 was performed and the expressions were correlated with tumour grade, tumour stage, presence of recurrence and tumour progression. Staining was evaluated according to the same criteria of breast cancer. Scores of 2+ and 3+ were considered positive. The data were analysed using the chi-square test with statistical significance set at P <0.05. RESULTS: Positive HER2 expression was found in 13 cases (18.8%). HER2 positivity was significantly associated with high-grade tumours (P=0.005). However, there is no significant association with tumour stage, recurrence or progression. CONCLUSION: HER2 is potentially a good immunohistochemical marker for identifying patients with higher-grade urothelial carcinoma and stratifying patients for future targeted therapy.

Mitigation of doxorubicin-induced cardiotoxicity by dichloroacetate: potential roles of restoration of PGC-1α/SIRT3 signaling and suppression of oxidative stress and apoptosis.

OBJECTIVE: Doxorubicin (DOX) is an effective chemotherapeutic agent used in the treatment of various neoplasms. Nevertheless, its therapeutic efficacy is hampered by life-threatening heart failure. Therefore, the current study was undertaken to investigate whether dichloroacetate (DCA), a metabolic and mitochondrial modulator, when administered at a therapeutically feasible dose could potentially reverse acute DOX cardiotoxicity. Furthermore, the possible underlying mechanisms of cardioprotection were also assessed. MATERIALS AND METHODS: Different techniques were performed to assess cardiac injury like echocardiography, histopathology, transmission electron microscope, biomarkers of cardiac injury, and oxidative stress markers. Further, the expression levels of mRNA and protein were quantified by PCR and immunohistochemistry, respectively. RESULTS: Echocardiography showed that mice that received DOX/DCA combination were protected against heart failure. Additionally, histopathology and transmission electron microscopy revealed structural damage alleviation by DOX/DCA combination, which was confirmed biochemically via significant suppression of elevated CK-MB and AST levels. Mechanistically, DOX dysregulated the expression of PGC-1α and SIRT-3 genes which are key to normal mitochondrial functioning. Of note, co-treatment with DCA effectively restored PGC-1α/SIRT-3 signaling and normalized the mitochondrial DNA index. Moreover, events downstream of DOX-triggered mitochondrial dysfunction such as oxidative stress and p53-dependent apoptosis were all abrogated by combination with DCA. CONCLUSIONS: The present study is the first to provide in vivo evidence that DCA is effective in protecting against acute DOX cardiotoxicity. Additionally, the study highlights the potential of administering metabolic modulators to safeguard against DOX cardiotoxicity.

Expression of oestrogen-α receptor in papillary thyroid carcinoma and its association with metastasis.

INTRODUCTION: Papillary thyroid carcinoma (PTC) is the ninth most common malignancy among women. Although the disease prognosis is good, less favourable outcomes are predicted in those with higher disease stages and nodal metastasis. Oestrogen- α (ER-α) expression has been associated with aggressive presentation and greater disease progression and has been proposed as a predictor for lymph node metastases. The objective of this study was to evaluate the association between ER expression and clinicopathological features i.e. lymph node metastasis, tumour size, extrathyroidal extension, histological variants of PTC , age groups , ethnic and gender. METHODS: We studied ER-α expression in 84 cases of PTC obtained within an eight-year period (2011-2018) by immunohistochemical technique (IHC). Associations between ER-α expression and clinicopathological features were evaluated using Fisher's exact test. The statistical significance was set at p < 0.05. RESULTS: ER-α was expressed in 13.1% of all the PTC cases examined (n=11/84). There were no associations observed between ER-α expression and lymph node metastasis (p=1.000), tumour size (p=0.970), extrathyroidal extension (p=0.677), variants of PTC (p=1.000), age groups (p=0.188), gender (p=0.725) or race (p=0.920). CONCLUSION: There was no evidence in this study to support the application of ER-α as prediction marker for lymph node metastasis or disease aggressiveness in PTC. Given that the scope of this study was limited to the protein expression of ER- α, we also propose the inclusion of molecular analysis of ESR1 gene expression, as well as inclusion of detailed clinical and radiological findings in future research investigating the role of ER-α in prognostication of PTC.

CD56 expression in benign and malignant thyroid lesions.

INTRODUCTION: Thyroid cancer is the most common endocrine malignancy with more than 95% originating from follicular epithelial cells. Diagnostic dilemma may arise in occasional cases such as when an encapsulated nodule with a follicular growth pattern exhibits clear nuclei with grooves making it difficult to distinguish a follicular adenoma from encapsulated follicular variant papillary thyroid carcinoma. This study aimed to evaluate the diagnostic utility of an immunohistochemical marker, CD56, to distinguish between benign and malignant thyroid lesions. MATERIALS AND METHODS: We retrospectively studied CD56 expression in 54 benign and 54 malignant thyroid lesions using archival formalin fixed paraffin-embedded tissue blocks for the study period from January 2010 to December 2015, diagnosed in a tertiary hospital. RESULTS: CD56 was expressed in 52/54 (96.3%) of benign specimens and only 24/54 (44.4%) of malignant ones. The malignant specimens comprised 31 (57.4%) papillary thyroid carcinomas (PTC), 11 (20.3%) follicular carcinomas (FC), seven (13%) medullary thyroid carcinomas (MC), one (1.9%) poorly differentiated carcinoma (PC) and four (7.4%) anaplastic carcinomas (AC). CD56 was not expressed in 28/31 (90.3%) of the PTCs, 1/11 (9.1%) FCs, 1/4 (25%) of ACs while all MCs and the PD were positive. The benign group comprised nodular hyperplasias (29/54), lymphocytic thyroiditis (10/54), follicular adenomas (FA) (14/54) and one hyalinising trabecular tumour. CD56 was expressed in all the benign cases except one FA and one nodular hyperplasia. Thirteen of the 14 FAs were CD56 positive. The difference in expression between benign and malignant tumours was statistically significant as the p value was <0.01. CONCLUSION: CD56 is a potentially good immunohistochemical marker for differentiating papillary thyroid carcinoma from other benign follicular lesions of the thyroid especially in differentiating follicular variant PTC from FA in equivocal cases.

Use of the channel fill level in defining a design space for twin screw wet granulation.

Twin screw wet granulation is a key process in the continuous manufacture of oral solid dosage forms. Previous research has qualitatively suggested that the channel fill level influences the granules produced. In this paper a quantitative measure of the total volumetric fraction of the conveying element channels of the screw filled with powder (φ) was used. Experimental results are shown which demonstrate that very similar particle size distributions can be obtained at the same φ with the same material and screw configuration but radically different solids feed rates and screw speeds. Morphology of the granules also correlates with φ. This is consistent with previous observations in the literature correlating granule attributes with powder feed rate and screw speed but also considers the two parameters in combination. A process design space approach based on φ is proposed. This can be determined empirically, and potentially has value in setting process control strategies, assuring process robustness and allowing process flexibility during the product lifecycle.

Femtosecond nonlinear fiber optics in the ionization regime.

By using a gas-filled kagome-style photonic crystal fiber, nonlinear fiber optics is studied in the regime of optically induced ionization. The fiber offers low anomalous dispersion over a broad bandwidth and low loss. Sequences of blueshifted pulses are emitted when 65 fs, few-microjoule pulses, corresponding to high-order solitons, are launched into the fiber and undergo self-compression. The experimental results are confirmed by numerical simulations which suggest that free-electron densities of ∼10(17) cm(-3) are achieved at peak intensities of 10(14) W/cm(2) over length scales of several centimeters.