Metastasis is the most lethal hallmark of esophageal squamous cell carcinoma (ESCC). The aim of the study is to identify key signaling pathways that control metastasis in ESCC. Highly invasive ESCC sublines (designated I3 cells) were established through three rounds of selection of cancer cells invading through matrigel-coated chambers. Gene expression profile of one of the I3 sublines was compared with that of its parental cell line using cDNA microarray analysis. Gene ontology and pathway analyses of the differentially expressed genes (both upregulated and downregulated) indicated that genes associated with cellular movement and the AKT pathway were associated with increased cancer cell invasiveness. Western blot analysis confirmed increased phosphorylated AKT (p-AKT), N-cadherin and decreased E-cadherin expression in the I3 cells. Immunohistochemistry was used to evaluate the clinical significance of p-AKT expression in ESCC, and the results showed higher p-AKT nuclear expression in lymph node metastases when compared with primary carcinoma. Inactivation of the PI3K/AKT pathway with specific inhibitors, or with PTEN overexpression, resulted in reversed cadherin switching and inhibited cancer cell motility. Inhibition of the pathway by treatment with wortmannin markedly suppressed experimental metastasis in nude mice. Our data demonstrated the importance of the PI3K/AKT signaling pathway in ESCC metastasis and support PI3K/AKT as a valid therapeutic target in treatment of metastatic ESCC.

The aim of this systematic review is to study the features of cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) by analysing the 129 documented cases in the English literature. The disease occurred almost exclusively in women. The median age of presentation for CMV-PTC was 24 years. Slightly over half of the patients with CMV-PTC had familial adenomatous polyposis (FAP). CMV-PTC presented before the colonic manifestations in approximately half of the patients with FAP. Patients with FAP often have multifocal tumours in the thyroid. Microscopic examination of CMV-PTC revealed predominately cribriform and morular pattern of cancer cells with characteristic nuclear features of papillary thyroid carcinoma. Psammoma body is rare. On immunohistochemical studies, β-catenin is diffusely positive in CMV-PTC. The morular cells in CMV-PTC are strongly positive for CD10, bcl-2 and E-cadherin. Pre-operative diagnosis of CMV-PTC by fine-needle aspiration biopsy could be aided by cribriform architecture, epithelial morules and β-catenin immunostaining. Mutations of APC gene are found in the patients with CMV-PTC associated with FAP. In addition, mutations in CTNNB1, RET/PTC rearrangement and PI3K3CA mutations have been reported. BRAF mutation is negative in all CMV-PTC tested. Compared to conventional papillary thyroid carcinoma, CMV-PTC had a lower frequency of lymph node metastases at presentation (12%) and distant metastases (3%) as well as lower recurrence rates (8.5%) and patients' mortality rates (2%). To conclude, patients with CMV-PTC have distinctive clinical, pathological and molecular profiles when compared to conventional papillary thyroid carcinoma.

BackgroundThe infodemiological analysis of queries from search engines to shed light on the status of various noncommunicable diseases has gained increasing popularity in recent years.ObjectiveThe aim of the study was to determine the international perspective on the distribution of information seeking in Google regarding “cancer” in major English-speaking countries.MethodsWe used Google Trends service to assess people’s interest in searching about “Cancer” classified as “Disease,” from January 2004 to December 2015 in Australia, Canada, New Zealand, the United Kingdom, and the United States. Then, we evaluated top cities and their relative search volumes (SVs) and country-specific “Top searches” and “Rising searches.” We also evaluated the cross-country correlations of SVs for cancer, as well as rank correlations of SVs from 2010 to 2014 with the incidence of cancer in 2012 in the abovementioned countries.ResultsFrom 2004 to 2015, the United States (relative SV [from 100]: 63), Canada (62), and Australia (61) were the top countries searching for cancer in Google, followed by New Zealand (54) and the United Kingdom (48). There was a consistent seasonality pattern in searching for cancer in the United States, Canada, Australia, and New Zealand. Baltimore (United States), St John’s (Canada), Sydney (Australia), Otaika (New Zealand), and Saint Albans (United Kingdom) had the highest search interest in their corresponding countries. “Breast cancer” was the cancer entity that consistently appeared high in the list of top searches in all 5 countries. The “Rising searches” were “pancreatic cancer” in Canada and “ovarian cancer” in New Zealand. Cross-correlation of SVs was strong between the United States, Canada, and Australia (>.70, P<.01).ConclusionsCancer maintained its popularity as a search term for people in the United States, Canada, and Australia, comparably higher than New Zealand and the United Kingdom. The increased interest in searching for keywords related to cancer shows the possible effectiveness of awareness campaigns in increasing societal demand for health information on the Web, to be met in community-wide communication or awareness interventions.

We aim to investigate the expression profiles of galectin family genes (galectins-1, 2, 3, 4, 7, 8, 9, 10, and 11) in colorectal carcinomas. Messenger RNA (mRNA) expression of galectin family members (1, 2, 3, 4, 7, 8, 9, 10, and 12) was analyzed by real-time polymerase chain reaction in colorectal tissues from 201 patients (54 noncancer colorectal tissues, 49 adenomas, and 98 adenocarcinomas). Galectin-1 and galectin-3 protein expressions were determined by immunohistochemistry. In general, high galectin mRNA expression was noted in colorectal carcinomas in early stages of their pathogenesis. Significant differences in galectins-2, 3, 7, 8, and 10 mRNA expression were associated with pathologic stages (P<.05). Increased prevalence of galectins-2, 7, 8, and 10 mRNA overexpression was noted in nonmetastatic colorectal carcinomas (P<.05). Galectin-1 and galectin-3 proteins were present in the nucleus and cytoplasm of the colorectal tissues and expressed significantly higher in colorectal carcinomas when compared to colorectal adenomas (61% and 95%, respectively). Patients with colorectal carcinoma with high levels of galectin-3 mRNA and protein expression showed better prognosis (P=.052). To conclude, many novel correlations between the deregulation of galectin family genes and various clinicopathological features in colorectal adenocarcinoma were noted. Overexpression of galectins at the mRNA level and proteins were predominant in earlier stages of colorectal carcinomas. These altered expression patterns of galectin genes suggest the multifunctional role of galectin genes in the regulation of colorectal cancer development, progression, and metastasis.

Tissue microarray technology could allow immunohistochemical staining or in situ hybridization on hundreds of different tissue samples simultaneously. It allows faster analysis and considerably reducing costs incurred in staining. The technique also provides a high-throughput analysis of multiple tissues for the different types of research. In the literature, many researches of esophageal adenocarcinoma use tissue microarray to enhance the output. In this chapter, we have a brief overview of tissue microarray technologies, the advantages and disadvantages of tissue microarray, and related troubleshootings.