Expression of lectin-specific cellular glycoconjugates during oral carcinogenesis

The binding pattern of two lectins, concanavalin A (ConA) and peanut agglutin (PNA), in various phases of tumour progression in the oral epithelium was studied. These included non-dysplastic, dysplastic and neoplastic lesions as well as normal tissue. ConA and PNA showed intense staining in the basement membrane of all types of lesions. Little difference was observed in the staining patterns between different stages of oral carcinogenesis, either with ConA or PNA. ConA showed mild cytoplasmic and membrane staining in all types of lesions while PNA showed moderate to intense staining in both the cytoplasm and membrane of lower-layer cells in all histological groups. The present study therefore shows that these lectins have limited value in the elucidation of oral carcinogenesis and are of insignificant diagnostic value.Abbreviations ConA concanavalin A - PNA peanut agglutinin S. Kannan was supported by a research fellowship from the Council for Scientific and Industrial Research, India.     

Transplanted bone marrow stromal cells are not cellular origin of hepatocellular carcinomas in a mouse model of carcinogenesis

AIM：To investigate the malignant potential of hepatic stem cells derived from the bone marrow stromal cells （BMSCs） in a mouse model of chemical hepatocarcinogenesis.
METHODS：BMSCs from male BALB/c mice were harvested and cultured, then transplanted into female syngenic BALB/ c mice via portal vein. Hepato-carcinogenesis was induced by 6 mo of treatment with diethylnitrosamine （DEN）. Six months later, the liver was removed from each treated mouse and evaluated by immunohistochemistry and fluorescence in situ hybridization （FISH）.
RESULTS：Twenty-six percent of recipient mice survived and developed multiple hepatocellular carcinomas （HCCs）. Immunohistochemically, HCC expressed placental form of glutathione-S-transferase （GST-P） and α-fetoprotein, but did not express cytokeratin 19. Y chromosome positive hepatocytes were detected by fluorescent in situ hybridization （FISH） in the liver of mice treated with DEN after BMSCs transplantation while no such hepatocytes were identified in the liver of mice not treated with DEN. No HCC was positive for the Y chromosome by FISH.
CONCLUSION：Hepatic stem cells derived from the bone marrow stromal cells have a low malignant potential in our mouse model of chemical hepatocarcingenesis.     

The multihit model of carcinogenesis: Etiologic implications for colon cancer

A new multihit model of carcinogenesis is developed for use in evaluating age-specific cancer incidence rates in human populations. The model allows for some heterogeneity in both risk (perhaps genetic) and pathway (number of hits). Fitting the model yields estimates of (1) levels of effect of background exposure to environmental agents, (2) tumor growth times after initiation of a malignant cell, and (3) relative sizes of high-risk groups in a human population. Maximum likelihood procedures are used to fit the model to the polyposis coli data of Veale and the colon cancer incidence data from the Third National Cancer Survey. Model estimates may be verified in some cases by review of independent data in the literature and results have both theoretical and practical implications. Findings are generally consistent with the adenoma-carcinoma etiologic sequence postulated by Hill, Morson and Bussey with one exception. A large proportion of the population may be at risk of four-hit colon tumors following a non-adenoma etiologic sequence.     

胃干细胞与弥漫型胃癌的发生

随着发病率的增高,弥漫型胃癌对人类的健康造成了较大危害。研究表明,此类胃癌的发生与胃黏膜增殖区有关,而这一区域也正是胃干细胞定居的部位。因此胃干细胞可能在弥漫型胃癌的发生过程中扮演了重要角色。这方面的研究将加深我们对弥漫型胃癌发生机制的认识,并有助于实现早期防治的目标。     

Establishing a prognostic model for metachronous second squamous cell lung cancer in patients with resected squamous cell lung cancer

BackgroundFor metachronous second pulmonary squamous cell carcinoma (msPSC) in patients with resected PSC, the method to distinguish tumour clonality has not yet been well established, which makes it difficult to determine accurate staging and predict prognosis.MethodsPatients who underwent surgery for first PSC and encountered msPSC were recruited from the Surveillance, Epidemiology, and End Results (SEER) database. We extracted overall survival 1 (OS1) for the first PSC, overall survival 2 (OS2) for msPSC, and interval survival for the time interval between the first and second PSC. The nomogram was calibrated for OS2, and recursive partitioning analysis (RPA) was performed for risk stratification.ResultsA total of 617 patients were identified. Several independent prognostic factors were identified and integrated into the nomogram for OS2, including gender, age (2^nd), nodal status (1^st), node metastasis (2^nd), and extrapulmonary metastasis (2^nd). The calibration curves showed optimal agreement between the predictions and actual observations, and the c-index was 0.678. Surgery was associated with longer survival for msPSC patients. The prognosis of sublobectomy was comparable and inferior to that of lobectomy in the low- and moderate-risk groups, respectively. Radiotherapy was associated with better outcomes in patients who did not undergo surgery.ConclusionsThe RPA-based clinical nomogram appears to be suitable for the prognostic prediction and risk stratification of OS2 in msPSC. This practical system may help clinicians make decisions and design clinical studies.     

Human embryonic stem cells as a cellular model for human disorders

Human embryonic stem cells (HESCs) are pluripotent cell lines derived from the inner cell mass (ICM) of embryos at the blastocyst stage. These cells possess self renewal capacity and differentiation potential to all three embryonic germ layers. These unique characters made HESCs an attractive research tool for studying early human developmental processes as well as a potential therapeutic tool for various human diseases. Here, we focus on HESCs as a cellular model for human disorders. The advantages of such models as well as the various methodologies to achieve HESCs carrying a genetic defect will be discussed.     

ATM in oral carcinogenesis: association with clinicopathological features

PURPOSE: The ataxia telangiectasia mutated (ATM) gene plays a critical role in DNA damage response. Our aim here was to investigate the expression profile and loss of heterozygosity (LOH) of ATM, as well as their relationships to clinicopathological parameters in oral premalignant lesions (leukoplakia) and primary oral squamous cell carcinoma (OSCC). METHODS: Immunohistochemical assay and PCR were performed to detect the expression profile and LOH at D11S2179 of ATM. The association between clinicopathological parameters and the changes of ATM was statistically analyzed. RESULTS: ATM protein levels were higher in oral leukoplakia than those in normal controls, while the expressions of ATM protein had a versatile tendency in OSCC: 10 samples (31.25%) showed increased ATM protein levels than those observed in normal tissues, 12 samples (37.50%) had the same protein levels as the normal tissues, and 10 samples (31.25%) showed reduced or absent ATM levels. The patients with reduced/absent ATM expression had more poorly-differentiated situation as well as the tendency for lymph node metastasis. Most interestingly, 50% of these reduced cases were younger than 50 years old. PCR for LOH assay displayed that none of the samples from oral leukoplakia had abnormal changes in D11S2179, while three samples (9.38%) of OSCC showed loss of heterozygosity, and two samples (6.25%) with microsatellite instability. CONCLUSIONS: These findings suggest that overexpression of ATM may be one of the early events in the carcinogenesis of OSCC. ATM might be a candidate biomarker for diagnosis and prognosis in OSCC, as well as a possible genetic marker for early-onset OSCC.     

Molecular and cellular features of esophageal cancer cells

More than 70 cell lines were established from esophageal cancer, including 15 TE-series cell lines established by the authors. This article reviews molecular and cellular features of esophageal cancer cells from studies using these cell lines as well as primary tumors. The subjects reviewed include primary cultures of normal epithelium of the esophagus and of esophageal tumors, their growth and differentiation properties, chromosomal aberrations, protein kinase C, growth factors and their receptors, oncogenes, and tumor-suppressor genes. Lesions of genetic loci in esophageal cancer include the absence of mutations inras genes in primary tumors, amplification and overexpression of the c-erbB gene, co-amplification ofhst-1 andint-2 genes, mutations, and allelic loss of tumor suppressor genes, p53, Rb, APC, and MCC. Future clinical improvement will be achieved on the basis of the understanding of molecular and cellular features of esophageal cancer cells.Abbreviations PKC protein kinase C - PCR polymerase chain reaction - O⁶-MedG O⁶-methyldeoxyguanosine The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest editorials on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author The EditorsThis work was supported by grants-in-aid from the Ministry of Health and Welfare (1978–1982) and the Ministry of Education (1991)     

Fusion of renal epithelial cells: a model for studying cellular mechanisms of ion transport.

The investigation of epithelial ion transport at the cellular level by means of electrophysiological techniques is hampered by the small size of epithelial cells. Moreover, interpretation of experiments is complex due to poorly defined and highly variable paracellular leaks (shunt pathways). In search of a new experimental approach we developed a technique to isolate renal epithelial cells (diameter approximately equal to 10 micron) from diluting segments of the frog kidney and to fuse them to "giant" cells (diameter approximately equal to 100 micron). These cells generate membrane potentials of -54.1 +/- 1.6 mV (mean +/- SEM; n = 40). They are sensitive to the diuretic drugs furosemide and amiloride and to the K+- and Cl- -permeability blockers Ba2+ and anthracene-9-carboxylic acid. The experiments demonstrate membrane potential measurements in cells isolated from renal epithelium and fused to giant cells. The cells retain their specific membrane properties and could serve as a valuable experimental model in epithelial research.     

Stem cells in squamous head and neck cancer

The initiation and metastasis of head and neck squamous cell carcinomas (HNSCC) and other cancers have recently been related to the presence of cancer stem cells (CSC). CSC are cancer initiating, sustaining and are mostly quiescent. Specific markers that vary considerably depending on tumor type or tissue of origin characterize putative CSC. Compared to the bulk tumor mass, CSC are less sensitive to chemo- and radiotherapy and may also have low immunogenicity. Therapeutic targeting of CSC may improve clinical outcome of HNSCC which has two distinct etiologies: infection of epithelial stem cells by high-risk types of the human papillomavirus, or long-term tobacco and alcohol abuse. Recent knowledge on the role of CSC in HNSCC is reviewed and where necessary parallels to CSC of other origin are drawn to give a more comprehensive picture.     

Colorectal cancer： Pathways,pathology and practice： From the editor

This review explores the chief genetic and epigenetic events that promote pathological progression in colorectal carcinogenesis. This article discusses the molecular and pathological basis for classifying colorectal neoplasia into suppressor, mutator and methylator pathways. These differing mechanisms of genomic instability are associated with specific cancer characteristics, and may provide the opportunity for more effective prevention and surveillance strategies in the future. This is the first review in a series of five topics outlining important and developing aspects of colorectal cancer.     

羟基喜树碱诱导口腔鳞癌细胞凋亡的作用机制探讨

目的探讨羟基喜树碱（HcPT）对人口腔鳞癌细胞株KB细胞的凋亡诱导作用及其机制。方法体外培养KB细胞,MTT试验检测HCPT的细胞毒性作用;Hoechst33258染色和流式细胞术对细胞凋亡进行定性和定量分析;蛋白印迹检测Caspase-3和Bcl-2蛋白表达情况。结果HCPT能诱导KB细胞凋亡,且具有剂量依赖关系;随凋亡率增高,Caspase-3蛋白表达显著增强,Bcl-2蛋白表达显著减弱（P均〈0．05）。结论HCPT可促进口腔鳞癌细胞凋亡,其可能机制是诱导Caspase-3蛋白表达和抑制Bcl-2蛋白表达。     

Gene-amplification model of carcinogenesis.

A two-stage model of carcinogenesis is proposed based on recent evidence for the occurrence of proto-oncogenes in the vertebrate genome, evidence for gene amplification during carcinogenesis, and studies of the action of tumor promoters. The model is baed on the view that an increase in the level of gene product from such proto-oncogenes is sufficient to induce neoplastic transformation. It proposes that the initial step in carcinogenesis (initiation) is a mutation producing a tandem duplication of a proto-oncogene. Gene amplification can then occur by successive unequal sister chromatid crossing-over events in several cell cycles until sufficient gene product is produced to transform the cell.     

Selenoprotein deficiency accelerates prostate carcinogenesis in a transgenic model

Considerable animal and human data have indicated that selenium is effective in reducing the incidence of several different types of cancer, including that of the prostate. However, the mechanism by which selenium inhibits carcinogenesis remains unknown. One possibility is that dietary selenium influences the levels of selenium-containing proteins, or selenoproteins. Selenoproteins contain selenium in the form of selenocysteine and perform a variety of cellular functions, including antioxidant defense. To determine whether the levels of selenoproteins can influence carcinogenesis independent of selenium intake, a unique mouse model was developed by breeding two transgenic animals: mice with reduced selenoprotein levels because of the expression of an altered selenocysteine-tRNA (i6A-) and mice that develop prostate cancer because of the targeted expression of the SV40 large T and small t oncogenes to that organ [C3(1)/Tag]. The resulting bigenic animals (i6A-/Tag) and control WT/Tag mice were assessed for the presence, degree, and progression of prostatic epithelial hyperplasia and nuclear atypia. The selenoprotein-deficient mice exhibited accelerated development of lesions associated with prostate cancer progression, implicating selenoproteins in cancer risk and development and raising the possibility that selenium prevents cancer by modulating the levels of these selenoproteins.