Carcinogenesis ; pathology ; Colitis ; pathology ; Humans

BACKGROUND AND OBJECTIVES: It is known that a part of laryngeal premalignant lesions progresses to an invasive carcinoma. Despite many previous reports, conventional histology is not sufficient to predict such tumor progression. Herein, the authors investigated the role of CD44v3 as a biomarker in predicting the progression of laryngeal premalignant lesion to an inavasive cancer. SUBJECTS AND METHOD: Paraffin-embedded tissue specimens from 40 patients were diagnosed accordingly as laryngeal invasive squamous cell carcinoma (n=10), Carcinoma in situ (n=10), dysplasia (n=10), and hyperkeratosis (n=10) between 1993 and 2002. They were immunohistochemically stained for CD44v3 protein. RESULTS: In invasive squamous cell carcinoma, the expression of CD44v3 was diffused and gave a strong positive stain, and in carcinoma in situ, it was diffused and gave 3+-2+ stain. However, in dysplasia and hyperkeratosis, the proportion of CD44v3 expression was decreased by 2+-1+, and 1+-0, respectively. CONCLUSION: These results suggest that the expression of CD44v3 in laryngeal premalignant and malignant lesions can be associated with tumorigenesis and invasion. Those strong positive expressions of CD44v3 may represent more aggressive pathology of the larynx.
Carcinogenesis ; Carcinoma in Situ ; Carcinoma, Squamous Cell ; Humans ; Larynx* ; Pathology

Aberrant oxidative metabolism in cells is one of the hallmarks of cancer. Overproduction of reactive species promotes carcinogenesis by inducing genetic mutations and activating oncogenic pathways, and thus, antioxidant therapy is considered as an important strategy for cancer prevention and treatment. Caveolin-1 (Cav-1), a constituent protein of caveolae, is involved in not only the formation of the caveolae, vesicular transport, maintaining cholesterol homeostasis directly, but also many cellular physiological and pathological processes including growth, regulation of mitochondrial antioxidant level, apoptosis and carcinomas by interacting with a lot of signaling molecules through caveolin scaffolding domain. Cav-1 has also been shown to mediate tumor genesis and progression through oxidative stress modulation, while Cav-1-targeted treatment could scavenge the reactive species. Intracellular reactive species could modulate the expression, degradation, post-translational modifications and membrane trafficking of Cav-1. More importantly, emerging evidence has indicated that multiple antioxidants could exert antitumor activities in cancer cells by modulating the signaling of Cav-1. This paper reviewed the research progresses on the roles of Cav-1 and oxidative stress in tumorigenesis and development, and would provide new insights on designing strategies for cancer prevention or treatment.
Antioxidants ; Apoptosis ; Carcinogenesis ; Carcinoma ; pathology ; Caveolin 1 ; Humans ; Mitochondria ; Neoplasms ; pathology ; Oxidative Stress ; Signal Transduction

Lung cancer is a major medical problem. Despite advances in molecular biology and pharmacology, the outcome of lung cancer treatment is unsatisfactory. Clinically, inflammation and cancer are closely associated, and, genetically, these two processes are regulated by the same gene loci. Inflammation promotes cancer formation. Increasing evidence shows that neuroimmune interaction involving inflammatory disease and the vagus nerves are crucial in the interaction. Airway sensory receptors are biosensors that detect the lung inflammatory process through various mediators and cytokines. This information is transmitted through vagal afferents to the brain and produces a host of responses that regulate the extent and intensity of inflammation. Tumor cells express receptors for neurotransmitters and provide a substrate for direct interaction with neurons. Thus, neural regulation of the immune response is targeted towards inflammation as well as tumors. The airway sensors can detect cancer-related cytokines, which provides a direct pathway to inform the brain of tumor growth. The knowledge of how these sensors may monitor tumor progression and provide neuroimmune interaction in the control of tumor development and metastasis will improve our treatment of lung cancer.
Carcinogenesis ; Cytokines ; physiology ; Humans ; Inflammation ; pathology ; Lung ; innervation ; pathology ; Lung Neoplasms ; pathology ; Sensory Receptor Cells ; physiology ; Vagus Nerve ; physiology

Ulcerative colitis is a non-specific colorectal inflammation of unknown causes. It is now known to complicate the dangers of colorectal cancer more than was previously thought. Macrophages are an important part of immune system and play a positive role in immune reaction. But it has been shown that the phenotype and the function of macrophages change in the tumor microenvironment. Through their interaction with colorectal cancer cells and by releasing large quantities of cytokines, macrophages promote colorectal cancer cells by inhibiting angiogenesis and inhibit apoptosis. But the macrophages are also affected by cancer, interact with other inflammatory cells, and become immune suppressed. Thus the changes of macrophages are inseparable with colitis-associated colorectal carcinogenesis.
Carcinogenesis ; Cell Transformation, Neoplastic ; immunology ; Colitis, Ulcerative ; complications ; immunology ; pathology ; Colorectal Neoplasms ; etiology ; immunology ; pathology ; Disease Progression ; Humans ; Macrophages ; pathology

OBJECTIVETo identify specific serum glycoprotein profiles that correspond to the carcinogenic process of primary liver cancer (PLC) by analyzing a population with high-incidence of PLC using lectin affinity microarray.

METHODSSerum samples were collected from individuals classified as high risk for PLC (including patients with liver cirrhosis and hepatitis B) and development of PLC was recorded. Healthy individuals served as normal controls. The serum samples were subjected to glycoprotein profling by using lectin microarrays and the results were confirmed by lectin blot. Between-group differences were statistically analyzed.

RESULTSPLC carcinogenesis was found to be correlated with enhanced affinity for AAL, ACL, ConA, LCA, MPL, NML, PHA-E, PHA-L, PSA, RCA-I, STL, VAL,WGA, and SNA (P less than 0.05). These data implied that changes in specific glycan structures, such as aFuc, GlcNAc, GalNAc, mannose, bisecting GlcNAc and terminal beta1-4 Gal, may be involved in PLC carcinogenesis . The PLC group showed significantly different results for all detected lectins, except SNA (P less than 0.05). However, among the PLC group, the SNA affinity was not significantly different for the hepatitis B group (P =0.443, P more than 0.05).

CONCLUSIONGlycans may be associated with the carcinogenic process of PLC and may be developed as diagnostic and prognostic biomarkers of PLC in the future.

Carcinogenesis ; Chromatography, Affinity ; Cohort Studies ; Glycoproteins ; blood ; Humans ; Lectins ; blood ; Liver Neoplasms ; blood ; pathology

As a member of the sirtuins family, also called Class III histone deacetylases (HDACs), SIRT6 has many catalytic enzyme activities and plays a pivotal role in biological processes including anti-aging, chromatin regulation, transcriptional control, glucose and lipid metabolism, and DNA damage repair. Recently, increasing evidences indicated that SIRT6 was related to initiation and development of tumors, such as hepatic cancer, lung cancer, breast cancer and genital system tumors. However, SIRT6 might play a dual role in tumorigenesis and progression. SIRT6 often acted as a tumor suppressor, but might play an oncogenic role. Based on our current study, we depicted the essential roles of SIRT6 in the initiation and progression of various tumors, and summarized its mode of actions, which might provide clues for cancer therapy.
Carcinogenesis ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Neoplasms ; genetics ; pathology ; Oncogenes ; Sirtuins ; genetics ; metabolism

The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.
Carcinogenesis ; metabolism ; pathology ; Disease Progression ; Epithelial-Mesenchymal Transition ; physiology ; Humans ; Neoplasm Metastasis

Excess iron is tightly associated with tumorigenesis in multiple human cancer types through a variety of mechanisms including catalyzing the formation of mutagenic hydroxyl radicals, regulating DNA replication, repair and cell cycle progression, affecting signal transduction in cancer cells, and acting as an essential nutrient for proliferating tumor cells. Thus, multiple therapeutic strategies based on iron deprivation have been developed in cancer therapy. During the past few years, our understanding of genetic association and molecular mechanisms between iron and tumorigenesis has expanded enormously. In this review, we briefly summarize iron homeostasis in mammals, and discuss recent progresses in understanding the aberrant iron metabolism in numerous cancer types, with a focus on studies revealing altered signal transduction in cancer cells.
Carcinogenesis ; genetics ; metabolism ; Homeostasis ; Humans ; Iron ; metabolism ; Neoplasms ; genetics ; metabolism ; pathology ; Signal Transduction

BACKGROUND AND OBJECTIVES: Gap junctional intercellular communication (GJIC) is a mechanism for direct cell to cell signalling and is mediated by gap junctions, which consist of transmembrane proteins called connexins (Cxs). The authors investigated the role of connexin 26 as a biomarker that helps diagnose laryngeal squamous cell lesions. SUBJECTS AND METHOD: Paraffin-embedded tissue specimens from 50 patients, who were diagnosed with laryngeal invasive squamous cell carcinoma (n=15), carcinoma in situ (n=10), dysplasia (n=15), and non-neoplastic epithelial hyperplasia (n=10) between 1993 and 2005, were immunohistochemically stained for connexin 26 protein. RESULTS: Intracytoplasmic positive expression of connexin 26 was found in 100% of invasive squamous cell carcinoma and in 20% of carcinoma in situ. However, in dysplasia and hyperplasia, there were no positive expressions. Moreover, the majority of intercellular or membranous staining tended to decline in dysplasia, carcinoma in situ, and squamous cell carcinoma. CONCLUSION: These results suggest that aberrant expression of connexin 26 in laryngeal squamous cell lesions can be associated with tumorigenesis and invasion. Further studies are needed to investigate these expressions of connexin 26 and that it may represent more aggressive pathology of the larynx.
Carcinogenesis ; Carcinoma in Situ ; Carcinoma, Squamous Cell ; Connexins ; Gap Junctions ; Humans ; Hyperplasia ; Larynx* ; Neoplasms, Squamous Cell ; Pathology