The incidence of primary liver tumors, hepatocellular carcinoma (HCC), intrahepatic cholangiocellular carcinoma (ICC), and combined HCC/ICC (cHCC/CC) is increasing. For ICC, targeted therapy exists only for a small subpopulation of patients, while for HCC, Sorafenib and Lenvatinib are in use. Diagnosis of cHCC/CC is a great challenge and its incidence is underestimated, bearing the risk of unintended non-treatment of ICC. Here, we investigated effects of targeted inhibitors on human ICC cell lines (HUH28, RBE, SSP25), in comparison to extrahepatic (E)CC lines (EGI1, CCC5, TFK1), and HCC/hepatoblastoma cell lines (HEP3B, HUH7, HEPG2). Cells were challenged with: AKT inhibitor MK-2206; multikinase inhibitors Sorafenib, Lenvatinib and Dasatinib; PI3-kinase inhibitors BKM-120, Wortmannin, LY294002, and CAL-101; and mTOR inhibitor Rapamycin. Dosage of the substances was based on the large number of published data of recent years. Proliferation was analyzed daily for four days. All cell lines were highly responsive to MK-2206. Thereby, MK-2206 reduced expression of phospho(p)-AKT in all ICC, ECC, and HCC lines, which mostly corresponded to reduction of p-mTOR, whereas p-ERK1/2 was upregulated in many cases. Lenvatinib showed inhibitory effects on the two HCC cell lines, but not on HEPG2, ICCs and ECCs. Sorafenib inhibited proliferation of all cells, except the ECC line CCC5. However, at reduced dosage, we observed increased cell numbers in some ICC experiments. Dasatinib was highly effective especially in ICC cell lines. Inhibitory effects were observed with all four PI3-kinase inhibitors. However, cell type-specific differences were also evident here. Rapamycin was most effective in the two HCC cell lines. Our studies show that the nine inhibitors differentially target ICC, ECC, and HCC/hepatoblastoma lines. Caution should be taken with Lenvatinib and Sorafenib administration in patients with cHCC/CC as the drugs may have no effects on, or might even stimulate, ICC.

No abstract

The research include methodology consisted of conducting the Survey based research with different awareness campaign. Special Survey Campaign of which quantitative survey was a part involved conscientious background research, discussion, and survey formation. The motive of the campaign was to collect information about the troubles, help, or advice people needed through Google forms. According to our survey, 61.29% of people have faced the core symptoms of the virus, out of the total population 62.9% people have been taking immunity boosters including Zinc and Vitamin C. The people hit by the Delta variant were more likely to show symptoms and were affected more as compared to the other variants of the virus. Overuse of Chemical Immunity boosters should be prevented as they have many side effects, and hence, can lead to Diarrhoea, Vomiting, loss of appetite and many more. The best measures such as eating well, adopt physical activity, yoga and especially prone position in their daily routine, following official guidelines of the government and their doctors' advice and lastly staying strong, happy and healthy would help the people to overcome and defeat this Pandemic. Key words: Zoonotic, Quantitative Survey, Symptoms, Immunity boosters, Yoga, Side Effects, Pandemic.