In recent years, an intelligent noninvasive endoscope has been felt necessary for early diagnosis of malignant tumor in gastrointestine (GI). It is our purpose to develop a microwireless robotic endoscope to examine the human GI. The presented robot's diameter and length is 10 and 190 mm, respectively. A locomotion principle based on biomimetic earthworm is adopted for a higher adaptability to the GI. The robot is composed of three linear driving cells. A micromotor, a reducer, and a microscrew pair mechanism are integrated into each cell. Multijoints are used to connect every two driving cells for robot's high flexibility. The robot's energy is continuously supplied in real time by an energy transmitting system based on electromagnetic coupling. Experiments on the energy transmission and locomotion are performed to test the power transferring volume and locomotion effect in GI. The experiments indicate that the minimum received power, 400 mW, is obtained in a cylindrical space with 200 mm diameter and 200 mm length. In vitro experiments in a pig intestine indicate that this robot can move forward or backward effectively. This paper provides a good prototype for the deeper research on locomotion theory and energy transferring technology in vivo in future.

A Wireless Robotic Endoscope for Gastrointestine

Although inorganic arsenic (iAs) is a well-known human carcinogen recognized by the World Health Organization (2001) and the International Agency for Research on Cancer (1987), the mechanism of carcinogenicity are not clear. Because of significant differences in arsenic (As) metabolism between experimental animals and humans, the use of animal models to evaluate the carcinogenic effects iAs has not been established successfully (Goering et al. 1999). For decades, As has been considered a nongenotoxic carcinogen because it is only weakly active or, more often, completely inactive in bacterial and mammalian cell mutation assays (Hei and Filipic 2004). Recently, increasing evidence has shown that As is a strong, dose-dependent gene and chromosomal mutagen that is capable of inducing mostly multilocus deletions (Hei et al. 1998). Experiments in mammalian cells have also shown that this induction was significantly reduced in the presence of antioxidant enzymes (Liu et al. 2002).

As early as 1976, villagers from Guizhou province in southwestern China were reported to be suffering severe symptoms of arsenicosis (Zhou et al. 1993), which was attributed to exposure to high levels of As in food, especially in corn and chili peppers, and to a lesser extent by breathing As-laden air (Finkelman et al. 2003). Villagers mined local low-grade As-containing coal from abundant, small local coal pits, with As-coal concentrations mostly in the range of hundreds of milligrams per kilogram (Finkelman et al. 1999; Zheng et al. 1999). Corn and chili peppers were dried over unventilated indoor stoves used for every day cooking and for heating during the winter months. Repeated surveys of As-coal and medical examinations have identified nine towns in four counties in southwest Guizhou province as having high levels of As in food and air (Zhang et al. 2000a). Approximately 200,000 people within the four counties were at risk of exposure to high levels of As; 3,000 cases of arsenicosis were diagnosed in the late 1990s, with approximately 2,000 of these cases in Xinren county alone (Liu et al. 2002). Over the years, various measures adopted by local governments, such as shutting down the coal pits containing high levels of As and installation of ventilated stoves, have been only minimally effective until a health education campaign was implemented in 2005 (An et al. 2005).

New cases of arsenicosis have been identified each year since 1990, although there was evidence of reduction in exposure as early as 1998. Between 1998 and 2004, collected coal samples had As concentrations of 92–816 mg/kg (Huang et al. 2002). The average concentration in indoor air during that time was 0.087 ± 0.045 mg/m3 (n = 22), which is lower than that in indoor air in 1991 [0.46 ± 0.30 mg/m3 (n = 18); Zhang et al. 2000a; Zhou et al.1993]. Urinary As concentrations declined from 130.6 ± 121.2 μg/L (n = 167) in 1998 to 97.0 ± 76.1 μg/L (n = 43) in 2004. This finding coincided with the decrease of As concentrations in indoor air. In the exposed population, skin lesions were common. Other damage included lung dysfunction, neuropathy, and nephrotoxicity. The prevalence of hepatomegaly was 20%. Approximately 200 people have died from the effects of the most severe As poisoning, which included liver cirrhosis, ascites, and liver and skin cancers. Treatment of individuals who have arsenicosis was difficult because of a long exposure time of more than 30 years (Zhou et al.1993) and the high level of As exposure in the population.

In this article, we report the results of a series of investigations between 1998 and 2004, which included a large number of individuals with arsenicosis. To look for cellular and molecular biomarkers of exposure, we collected blood and skin samples from villagers who had been exposed to As. We analyzed the effects of As exposure on chromosome and DNA damage, DNA synthesis and repair, and tumor suppressor gene mutations. One of our goals was to identify molecular biomarkers for early diagnosis that may be applicable to populations exposed to much lower levels of As, usually found in drinking water.

Unventilated indoor coal-fired stoves in Guizhou province, China: cellular and genetic damage in villagers exposed to arsenic in food and air

Knowing the status of molecules involved in cell cycle control in cancer is vital for therapeutic approaches aiming at their restoration. The p27KIP1 and p57KIP2 cyclin-dependent kinase inhibitors are nodal factors controlling normal cell cycle. Their expression in normal lung raises the question whether they have a mutual exclusive or redundant role in nonsmall cell lung cancer (NSCLC). A comparative comprehensive analysis was performed in a series of 70 NSCLCs. The majority of cases showed significantly reduced expression of both members compared to normal counterparts. Low KIP protein levels correlated with increased proliferation, which seems to be histological subtype preponderant. At mechanistic level, degradation by SKP2 was demonstrated, in vivo and in vitro, by siRNA-methodology, to be the most important downregulating mechanism of both KIPs in NSCLC. Decreased p57KIP2-transcription complements the above procedure in lowering p57KIP2-protein levels. Methylation was the main cause of decreased p57KIP2-mRNA levels. Allelic loss and imprinting from LIT1 mRNA contribute also to decreased p57KIP2 transcription. In vitro recapitulation of the in vivo findings, in A549 lung cells (INK4A-B(−/−)), suggested that inhibition of the SKP2-degradation mechanism restores p27KIP1 and p57KIP2 expression. Double siRNA treatments demonstrated that each KIP is independently capable of restraining cell growth. An additional demethylation step is required for complete reconstitution of p57KIP2 expression in NSCLC. © 2006 Wiley-Liss, Inc.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.22214

Downregulation of the KIP family members p27(KIP1) and p57(KIP2) by SKP2 and the role of methylation in p57(KIP2) inactivation in nonsmall cell lung cancer.

Evaluation of cell cycle protein expression in gastric cancer: cyclin B1 expression and its prognostic implication.

Background and Objectives

The p16INK4a (p16), cyclin D1, cyclin-dependent kinase (CDK) 4 and retinoblastoma (Rb) genes are components of the Rb pathway that controls the G1-S checkpoint of the cell cycle. The aim of this study was to assess the relationship between their abnormalities and clinicopathological features in gastric carcinomas.



Mehtods

Immunohistochemical analysis of the encoded proteins was performed on a series of 158 cases.



Results

Loss of p16/Rb protein (pRb) expression and overexpression of cyclin D1/CDK4 were observed in 49%/40% and 37%/37% of gastric carcinomas, respectively. At least 1 of these abnormalities was found in 86% of the cases and a positive correlation was noted between p16 and pRb (P = 0.009). Cyclin D1 (P = 0.042) and CDK4 (P = 0.008) overexpession was inversely associated with lymph node metastasis and depth of invasion, respectively. Loss of pRb expression was more frequently in diffuse type lesions than in the intestinal type (P = 0.022). The patients with p16+/pRb−/cyclin D1−/CDK4− or p16−/pRb+/cyclin D1−/CDK4− tumors demonstrated particularly poor survival. With multivariate survival analysis, only depth of invasion and TNM stage could be proven as independent predictors.



Conclusions

The Rb pathway is disrupted in the vast majority of gastric carcinomas. This study also identified specific immunohistochemical marker profiles for prognosis. J. Surg. Oncol. 2008;98:60–66. © 2008 Wiley-Liss, Inc.

Abnormal expression of p16(INK4a), cyclin D1, cyclin-dependent kinase 4 and retinoblastoma protein in gastric carcinomas.

AIM: To investigate the relationship between inactivation of p16 gene and gastric carcinoma, and the mechanism of inactivation of p16 gene in gastric carcinogenesis.

METHODS: 40 fresh tumor tissue specimens were taken from primary gastric cancer patients. Expression of p16 protein was detected by immunohistochemical method. Deletion and point mutation of p16 gene were analyzed by polymerase chain reaction (PCR) and DNA sequencing, respectively.

RESULTS: The frequency of loss of p16 protein expression in the gastric cancer tissue, adjacent nontumor tissue, and distal normal tissue was 77.5% (31/40), 55.0% (22/40), and 17.5% (7/40), respectively (P < 0.005). Homozygous deletion of exon 1 and exon 3 was observed in two and three cases, respectively, giving an overall frequency of homozygous deletion of 12.5%. All five cases had diffuse type gastric carcinoma. No p16 gene point mutation was detected.

CONCLUSION: These findings suggest a close correlation between inactivation of p16 gene and gastric carcinoma. Further investigations are needed to testify the mechanism of inactivation of p16 gene in gastric carcinogenesis.

Relationship between inactivation of p16 gene and gastric carcinoma.

Tumour budding (TB) activity, cell nest size (CNS), and desmoplastic reaction (DR) have been confirmed to be significantly correlated with prognosis in oesophageal squamous cell cancer (ESCC) recently. However, there are limited data on the prognostic significance of combined assessment of cellular dissociation and tumour stroma in ESCC.

Wen-Bin Huang

Papers

Relationship between inactivation of p16 gene and gastric carcinoma.

Combined assessment of tumour cell nest size and desmoplastic reaction as an excellent prognostic predictor in oesophageal squamous cell carcinoma