Trichinella spiralis larvae have very special characters that make them able to completely transform the function of the affected muscle cells towards a self-serving environment, offering them nourishment and protection via what is known as “nurse cells”. This setting may be affected by drugs that are used for the treatment of co-morbidities and co-infections as calcium channel blockers, which are widely used in clinical practice. In the present study, the effects of verapamil, ivermectin (IVM), and their combined administration on the parasitic burden, immuno-pathology and angiogenesis were investigated during experimental trichinellosis. Estimation of intestinal adult parasitic stages and muscle larvae was done. VEGF gene expression and CD31 immunohistochemical local expression were measured to investigate angiogenesis, in addition to histopathological examination to explore the extent of inflammation. Although verapamil did not have an effect on the adult worm count during the intestinal phase, it induced an anti-inflammatory effect on intestinal pathology. During the muscle phase, it was very effective in reducing the larval count by 93.78%. IVM effectively reduced the worm count by 85.34%, and the muscle larval count by 97.84%, while combined verapamil and IVM administration resulted in a significant reduction in both adult parasites by 69.5% and larval stages by 99%. Both verapamil and IVM and their combination induced a potent decrease in local CD31 protein expression and VEGF gene expression. The important role of calcium and calcium channels during the pathology of trichinellosis, in addition to the pivotal role of calcium on biological processes such as immunity and angiogenesis, make calcium-channel blockers promising candidates for drug repurposing in the management of helminthic infection.

Background: Thyroid cancer (TC) is a common malignant tumor, however the role of total vitamin D: 25(OH)D, Platelet Derived Growth Factor (PDGF) and Insulin Like Growth Factor 1 (IGF-1) in the development of TC is still unclear. Aim: To assess the roles of 25(OH)D, PDGF and IGF-1 in the progression of thyroid diseases. METHODS: The serum levels of 25(OH)D, PDGF and IGF-1 were assessed in 70 patients with papillary thyroid cancer (PTC), 60 patients with benign thyroid nodules (BN) compared to 60 normal controls (NC) using ELISA technique. Results: There was a significant decrease in the serum level of 25(OH)D in TC patients compared to NC (P<0.001) and BN patients (P=0.006). There was a significant increase in the serum levels of PDGF and IGF-1 in TC patients (P<0.001), and BN patients (P<0.001) compared to NC, while there were no significant differences between TC and BN (P=0.087, and 0.258; respectively). PDGF correlated significantly with IGF-1 (r=0.412, P<0.001), TSH (r=0.146, P=0.045), and inversely correlated with 25(OH)D (r= -0.156, P=0.013) and FT4 (r=-0.178, P=0.014). There was a significant inverse correlation between the serum levels of IGF-1 and FT4 (r=-0.172, P=0.017). Sensitivity and specificity for assessment of TC patients were (65.7% and 58.3%, P= 0.001) for 25(OH)D, (65.7% and 58.3%, P=0.021) for IGF-1, and (68.6% and 61.7%, P=0.006) for PDGF. Multivariate analysis demonstrated that serum 25(OH)D (OR=0.578, 95%CI= 0.426-0.783), IGF-1 (OR=1.019, 95%CI= 1.010-1.029) and PDGF (OR=1.007, 95%CI= 1.004-1.009) were considered independent risk factors for thyroid cancer (P<0.001, for all). Conclusion: 25(OH) D, IGF-1 and PDGF are significantly different in TC and BN cases compared to control. They have an important role in the progression of TC. However, these data should be validated on a larger sample size.

Background Although a minority of the thyroid nodules is malignant, usually the invasive diagnostic procedures are warranted. This prospective study aims to assess the diagnostic performance of the US criteria in addition to the TI-RADS score and the SWE for the differentiation between the benign and malignant thyroid nodules as a potential surrogate for the invasive procedures. Results Ninety-nine patients with thyroid nodules (79 females and 20 males, with a mean age of 45.9 ± 7.7 years; 30–69 years) were enrolled in this study and underwent conventional ultrasound, color Doppler, TI-RADS scoring, and shear wave elastography (SWE); the findings were correlated to the histopathological results. Our results revealed a significant increase in SWE elasticity indices (EIs) and presence of color Doppler signals in malignant nodules as compared with the benign ones (ρ < 0.05). Combined TI-RADS and SWE as well as TI-RADS and color Doppler imaging had given a better sensitivity for detection of malignancy. Conclusion Elasticity indices had shown a significantly high diagnostic performance that is almost approaching the histopathological results. Combined SWE, color Doppler and TI-RADS, as a sum of findings, could effectively differentiate between benign and malignant thyroid nodules. Furthermore, it had offered a non-invasive tool for accurate risk stratification of malignant nodules.

Background: Obesity has an important role in the pathogenesis of cancer; however, there are no clear mechanisms explaining the association between obesity and risk of thyroid cancer (TC). Methods: It is a cross-sectional study including 184 patients with benign thyroid nodules (BN) and 19 patients with TC. Body mass index (BMI), waist circumference (WC), hip circumference (HC), waist/hip (W/H) ratio were assessed and correlated to relevant clinico-pathological features of the patients, different ultra-sonographic (U/S) criteria and risk of malignancy. Results: There was a significant increase in BMI, WC and W/H ratio in TC patients compared to BN group (P=0.001, 0.011 and 0.003). Increased BMI, WC and HC were associated significantly with solid nodules (P<0.05). WC increased in hypoechoic (103.1 ±15.4cm) and heterogeneous (103.8±16.7cm) nodules, compared to isoechoic (97.3±15.5cm) and hyperechoic (96.1±10cm) nodules (P=0.046). It also increased with lymph nodes enlargement (P=0.04). There was a significant association between WC and TIRADS classification (P=0.032), as it increased with TR4b (118.5 ± 12.9 cm) and TR5 (117.3 ± 13.9 cm) compared to TR2 (114.1 ± 15.7 cm, P=0.025 and 0.008, respectively). WC is an independent predictor for TC [OR: 1.092, CI: 1.020-1.170, P=0.012]. It achieved sensitivity, specificity and AUC (71.4%, 68.7% and 0.750; respectively), at a cutoff value of 108.5 cm (P=0.003), and when combined with BMI at a cutoff value of 32.59 (77.8% and 68.4%, respectively, AUC: 0.780, P<0.001). Conclusion: Central adiposity is strongly associated with the risk of TC. WC is more superior to BMI when correlated with TIRADS classification and also is an independent predictor for TC.

Background: Tumor cell autophagy can influence cellular immunity by participation in the recognition and modification of tumor-related antigens. Objectives: The objective of this study was to evaluate the immunohistochemical expression of the autophagy-related marker; light chain 3B (LC3B) in tumor cells and the assessment of T lymphocytes by a cluster of differentiation 3 (CD3) in gliomas, and to correlate them with the available clinic-pathological variables in glioma patients. Materials and methods: Immunohistochemical staining for LC3B and CD3 was performed on 60 paraffin-embedded glioma tissue. LC3B immunoreactivity score of 0-6 was designated negative, and those scoring 7-12 were considered positive. The median level of CD3 positive T lymphocytes was calculated for both high and low-grade gliomas. In low-grade gliomas, the CD3 expressing T lymphocytes equal to or more than 2.6, were considered positive while in high-grade gliomas, those equal to or more than 16 were considered positive. Results: LC3B expression in tumor cells was detected in 24/60 (40%) of gliomas. Expression of LC3B was significantly more frequent in high-grade gliomas (23/33, 69.7%) compared to low grade ones (1/27, 5%), (p value= 0.000). LC3B expression was correlated with the patients age (P value= 0.047) & histological variants (P value= 0.000). CD3 positive T lymphocytes were significantly more prominent in high-grade gliomas (25/33 , 41.7%) than low-grade ones (2/27, 3.3%), (P value= 0.001). A significant association was noted between CD3 expression and the patients age (P value= 0.003), sex (P value: 0.035) and histological variants (P value= 0.001). LC3B expression in tumor cells was significantly correlated with CD3 positive T lymphocytes (P value: 0.000). Conclusion: Autophagic activity of tumor cells and T lymphocyte infiltrates were reported more in high-grade gliomas compared to low-grade ones, giving high-grade gliomas the chance in autophagy target therapy & immunotherapy.

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BACKGROUND: Maspin (a tumor suppressor gene) is down-regulated in breast, prostate, gastric, and melanoma. Although it is not detected in normal pancreatic tissue, it is over-expressed in pancreatic cancer suggesting that maspin may play different activities in different cell types. Pancreatic ductal adenocarcinoma (PC) acquires maspin expression through hypomethylation of its promoter. AIM: Because the discrimination between ampullary and periampullary carcinomas is challenging in advanced cases, this inspired us to search for the use of maspin expression to discriminate between ampullary carcinoma (AC), PC, duodenal adenocarcinoma (DC), and other confusing benign and inflammatory pancreatic lesions. METHODS: Immunostaining for maspin was performed for 80 pancreaticoduodenal lesions. Sixty cases were malignant: 48 cases of pancreatic epithelial tumor (41 PC and 7 solid pseudopapillary neoplasm), 9 AC, and 3 DC. Twenty cases were non-malignant: 12 inflammatory (chronic pancreatitis), 5 benign neoplastic (serous cystadenomas), and 3 normal pancreatic tissue. Cytoplasmic and/or nuclear staining was considered positive as: Focally positive (5–50% of tumor cells), diffusely positive (>50% of tumor cells), or negative (<5% tumor cells). RESULTS: Maspin expression (positive/negative), distribution (focal/diffuse), and nuclear expression are significantly different between PC, solid pseudopapillary neoplasm, AC, and DC. PC shows significantly higher expression with more diffuse positivity and more nuclear expression than other malignant groups. Forty cases of PC (40/41) (97.6%) showed positive expression; 28 of them (28/40) (70%) showed diffuse expression and 82.5% (33 cases) showed nuclear and cytoplasmic expression. Only one case (14.3%) (1/7) of solid pseudopapillary neoplasm showed positive focal cytoplasmic expression. Three AC cases (3/9) (33.3%) showed positive focal cytoplasmic expression. Two cases of DC (2/3) (66.7%) showed positive focal cytoplasmic expression. Maspin expression shows significant positive correlation with poor prognostic variables as tumor grade, lymphovascular invasion, T stage of PC. Minority of chronic pancreatitis and benign lesions are maspin positive with significant difference from the malignant groups. CONCLUSION: Our results suggest that maspin can be of value in differentiating pancreatic adenocarcinoma from ampullary carcinoma, duodenal adenocarcinoma, and other confusing lesions as chronic pancreatitis.

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