MicroRNA-92a regulates the development of cutaneous malignant melanoma by mediating FOXP1.

OBJECTIVE: MicroRNAs are noncoding RNAs which are involved in the occurrence and progression of tumors. This study aims to explore the role of microRNA-92a in cutaneous malignant melanoma (CMM) and its underlying mechanism. PATIENTS AND METHODS: The expression level of microRNA-92a in 75 pairs of CMM tissues and paracancerous tissues was determined using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between microRNA-92a expression with clinical data of CMM patients was analyzed. Besides, microRNA-92a expression in CMM cells and primary epidermal melanocytes (PEM) was determined by qRT-PCR as well. After transfection of si-microRNA-92a in CMM cells, biological performances of CMM were determined using cell counting kit-8 (CCK-8), colony formation and transwell assay, respectively. FOXP1 expression in CMM cells and tissues was determined using Western blot. Kaplan-Meier survival curves were drawn to explore the correlation between the FOXP1 expression and prognosis of CMM patients. RESULTS: MicroRNA-92a was highly expressed in CMM tissues compared with that of paracancerous tissues. Compared with CMM patients with lower expression of microRNA-92a, those with higher expression of microRNA-92a presented higher tumor stage, higher incidences of lymph node metastasis and distant metastasis, as well as lower overall survival. The knockdown of microRNA-92a remarkably decreased proliferative, invasive and metastatic capacities of CMM cells. Western blot results elucidated that microRNA-92a knockdown in CMM cells upregulates FOXP1 expression. Additionally, rescue experiments showed that mi-croRNA-92a regulates biological performances of CMM cells by regulating FOXP1. CONCLUSIONS: MicroRNA-92a is highly expressed in CMM, which is remarkably correlated to tumor stage and poor prognosis of CMM patients. We found that microRNA-92a pro-motes malignant progression of CMM by regulating FOXP1.

TLR4 promotes liver inflammation by activating the JNK pathway.

OBJECTIVE: Drug-induced liver injury has become a serious public health problem that cannot be ignored. Although the mechanism of acetaminophen (APAP)-induced liver injury has been investigated for several decades, there are still many deficiencies. However, only a deeper study of its mechanism can provide more effective measures of prevention and treatment for APAP-induced liver injury. The aim of this study was to investigate whether toll-like receptor 4 (TLR4) participates in and regulates APAP-induced liver injury, which may provide a new direction for the prevention and treatment of clinical drug-induced hepatitis. MATERIALS AND METHODS: WT mice were treated with APAP (300 mg/kg) or equivalent PBS. The livers of mice were taken at 1 h, 3 h, 6 h and 12 h after treatment. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect TLR4 mRNA expression level in the liver. After TLR4 involving in APAP-induced liver injury was confirmed, we investigated the relationship between TLR4 expression and hepatic inflammation. WT and TLR4-/- mice received APAP (3000 mg/kg) intraperitoneal injection after 16 h of fasting; serum was collected after 8 h and 24 h, and serum alanine aminotransferase (ALT) and reduced glutathione (GSH) activity were measured. Rat liver tissue was observed for histological changes by hematoxylin and eosin (H&E) staining. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) assay were performed to analyze proinflammatory cytokines expression (such as TNF-α, IL-1ß, MCP-1, IL-6). After isolating mononuclear cells (MNCs) in the liver of mice, flow cytometry was used to detect cell activation level and infiltration of macrophages and neutrophils. Western blotting was used to analyze the activation of phosphorylated JNK and p38 signaling pathways in livers of WT and TLR4-/- mice. In addition, after stimulated with APAP, the silence of TLR4 in RAW264.7 cells could activate phosphorylated JNK and p38 signaling pathways. RESULTS: After APAP stimulation, WT mice exhibited more severe liver injury than TLR4-/- mice, with higher ALT levels, lower GSH levels, and more necrotic or apoptotic cells. TLR4-/- mice have lower levels of inflammatory cytokines including MCP-1 and IL-6; at the same time, the number of infiltrating macrophages and neutrophils in liver tissue of TLR4-/- mice was significantly lower than that of WT mice. The activation of JNK signaling pathway was strikingly enhanced in WT mice treated with APAP, but no significant difference was observed in the activation of JNK phosphorylation in TLR4-/- mice after the same dose of APAP stimulation. Similarly, in RAW264.7 cells, the activation of phosphorylated JNK and p38 was remarkably inhibited by TLR4-siRNA, but was activated in the control group, which was consistent in vivo. CONCLUSIONS: APAP-treated TLR4-/- mice showed milder liver injury compared to WT mice. It was confirmed that TLR4 could activate the JNK signaling pathway to induce the secretion of inflammatory factors and the infiltration of macrophages to promote APAP-induced liver injury. This finding might provide a new prevention and treatment idea for clinical drug-induced hepatitis.

[Clinical effects of application of antibiotic bone cement in wounds of diabetic foot ulcers].

Objective: To explore the clinical effects of antibiotic bone cement in the treatment of diabetic foot ulcers. Methods: According to the treatment methods, 18 patients with diabetic foot ulcers (11 males and 7 females, aged 53-79 years), who were conformed to the study criteria and admitted to our hospital from January 2016 to January 2017, were enrolled in traditional group; 18 patients with diabetic foot ulcers (11 males and 7 females, aged 55-80 years), who were conformed to the study criteria and admitted to our hospital from February 2017 to February 2018, were enrolled in bone cement group. Wounds of patients in traditional group were treated with vacuum sealing drainage after conventional debridement. Wounds of patients in bone cement group were covered with antibiotic bone cement after conventional debridement. The number of patients with positive bacterial culture in wound exudate in the 2 groups on admission and 3, 6, 9, and 15 days after surgery, the length of hospital stay, the number of operation, and the wound complete healing time were retrospectively recorded. Data were processed with Fisher's exact probability test and independent sample t test. Results: Compared with (29±10) d and (4.6±1.2) times of patients in traditional group, the length of hospital stay [(9±3) d] of patients was obviously shortened, the number of operation [(1.3±0.6) times] of patients was obviously reduced, the number of patients with positive bacterial culture in wound exudate at each time point post surgery was obviously reduced (t=8.177, 9.896, P<0.05 or P<0.01) in bone cement group. There were no statistically significant differences in the number of patients with positive bacterial culture in wound exudate on admission and wound complete healing time between patients in the 2 groups (t=0.175, P>0.05). Conclusions: The antibiotic bone cement treatment of diabetic foot ulcers can reduce the number of patients with positive bacterial culture in wound exudate and the number of operation, as well as shorten the length of hospital stay.

Commentary on "A novel treatment strategy for newly diagnosed high-grade T1 bladder cancer: Gemcitabine and cisplatin adjuvant chemotherapy-A single-institution experience."

BACKGROUND: Management of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as "T1G3." OBJECTIVE: To evaluate the characteristics and the long-term outcome of GC adjuvant chemotherapy in T1G3 bladder cancer after transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: We, retrospectively, reviewed 48 patients who were newly diagnosed with T1G3 bladder cancer between January 2009 and December 2012. A total of 48 patients received 4 cycles of GC adjuvant chemotherapy after TURBT. One month after 4 cycles of GC adjuvant chemotherapy, response was evaluated by re-TURBT. Median follow-up was 59.5 (range: 18-70) months, all patients have been observed for more than 3 years. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response. RESULT: Complete response was achieved in 44 (91.7%) patients. Of complete responders, 5 patients experienced recurrence and 5 patients showed progression. The progression rate and disease-specific survival rate were 10.4% and 91.7% at 3 years, respectively. More than 80% of survivors preserved their bladder. Kaplan-Meier curves showed that concomitant carcinoma in situ (CIS) was the only factor that had an influence on progression-free survival (P = 0.022) and disease-specific survival (P = 0.017). Concomitant CIS was the prognostic factor for progression rate and disease-specific survival rate at 3 years (P = 0.008 and P = 0.035). CONCLUSION: GC adjuvant chemotherapy is a safe conservative treatment for T1G3 bladder cancer, but effective is really a phase II study. Patients with T1G3 bladder cancer with concomitant CIS should be treated more aggressively because of the high risk of progression.

[Concepts of "urinary bladder" and "vesicles (bao)" , "jin ye" (fluid and humor) and "urine" and other associated issues].

In the Huang di nei jing(Huangdi's Internal Classic), jin ye (fluid and humor) is described in two senses, broad and narrow, though not so strictly.Sometimes, jin ye is explained ambiguously as "sweat" and "urine" , as in the phrase "the bladder, being a house of jin ye" , here "jin ye" refers to the urine. In the Qi jue lun pian of Su wen (Chapter on Qi-Syncope of Plain Questions) , the "bao" in the sentence "heat of bao moved to bladder" refersto the uterus. In the Shi cong rong lun pian (Chapter of Readily Inspecting) of Plain Questions, the "bladder" in the phrase "gallbladder, stomach, large intestine, small intestine, spleen, bao and bladder" , which, being an annotation of "bao" originally, is mistakenly incorporated into the text of the Classic. In the Wu wei lun of Ling shu (On Five Tastes in Miraculous Pivot) , the "bao" in "bao of bladder" refers to the external hou (external manifestation) of the bladder, that is the scrotum. In the Bei ji qian jin yao fang (Essential Prescriptions Worth a Thousand Gold for Emergencies) , the short sentence "pang guang zou bao" is an error in itself. In the sentence of "settled in the bao and zhi causing to dream of defecation and urination" in the Yin xie fa meng (Dreams due to Evils) of Miraculous Pivot, "bao" refers to uterus, and "zhi" to anus. In Bi lun pian(Chapter on Impediment) of Plain Questions, "the man suffered bao bimight feel internal pain when the lesser abdomen and bladder are pressed" , here, "bao" refers to the bladder. In the Wu yin wu wei(Chapter on Five Sound and Five Tastes) of Miraculous Pivot, the "bao" in the sentence "thoroughfare vessel and conception vessel all starts from bao" , again, "bao" here refers to the bladder, rather than to the uterus. From the above descriptions of "bladder" and "bao" in the Huangdi's Internal Classic, the "bladder" in ancient medical books refers to the substantial bladder, an anatomical organ, and "bao" refers to cystiform organs, including the bladder, uterus, scrotum etc.

Effects of dietary DL-2-hydroxy-4(methylthio)butanoic acid supplementation on growth performance, indices of ascites syndrome, and antioxidant capacity of broilers reared at low ambient temperature.

This study examined the effects of dietary DL-2-hydroxy-4(methylthio)butanoic acid (DL-HMTBA) supplementation on growth performance, antioxidant capacity, and ascites syndrome (AS) in broilers reared at low ambient temperature (LAT) from 7 to 28 days of age. Eight hundred 7-day-old broilers were randomly assigned to two ambient temperatures (LAT and normal ambient temperature [NAT]), four supplemental DL-HMTBA levels (0.17, 0.34, 0.51, and 0.68 %) of the basal diet in a 2 × 4 factorial arrangement (ten replicate pens; ten birds/pen). LAT and NAT indicate temperatures of 12-14 and 24-26 °C in two chambers, respectively, and broilers were reared at these temperatures from 7 to 28 days of age. LAT significantly decreased body weight gain (P < 0.001), serum glutathione (GSH) content (day 14, P = 0.02; day 28, P = 0.045), glutathione peroxidase (GSH-Px) activity, and total antioxidant capacity (T-AOC) at 21 days (P = 0.001, 0.015) and 28 days (P = 0.017, 0.010) and increased feed conversion ratio (FCR) (P < 0.001), serum malondialdehyde (day 21, P = 0.000) and protein carbonyl Level (day 14, P = 0.003; day 21, P = 0.035). As for incidence of AS, there were significant effects of LAT on red blood cell (RBC) count (P < 0.05), hematocrit (HCT) (P < 0.05), and the right to total ventricular weight ratio (RV/TV) at 21 days (P = 0.012) and 28 days (P = 0.046). Supplementation of DL-HMTBA markedly decreased RV/TV at day 28 (P = 0.021), RBC (day 21, P = 0.008), HCT (day 21, P < 0.001), mean cell hemoglobin (day 14, P = 0.035; day 21, P = 0.003), and serum protein carbonyl level (day 21, P = 0.009), while significantly increased serum GSH content (day 14, P = 0.022; day 28, P = 0.001), SOD and GSH-Px activities at 21 days of age (P < 0.001 and P = 0.037). The optimal supplemental DL-HMTBA levels in basal diet of broilers aged from 7 to 28 days under low or normal temperatures were similar, so the authors recommended supplemental of DL-HMTBA level was 0.46 %.

High expression of P53-induced Ring-h2 protein is associated with poor prognosis in clear cell renal cell carcinoma.

PURPOSE: This study was carried out to examine P53-induced Ring-h2 protein (Pirh2) expression and investigate its clinical and prognostic significance in patients with clear cell renal cell carcinoma (ccRCC). METHODS: Pirh2 mRNA and protein expressions were detected by quantitative reverse-transcription polymerase chain reaction (Q-RT PCR) and Western blotting in 35 frozen renal cancer tissue specimens and 35 adjacent normal renal tissue specimens of the same patients. Pirh2 protein expression was assessed by immunohistochemical analysis in 92 paraffin-embedded specimens of human ccRCC and 30 specimens of adjacent normal renal tissue. Correlations between Pirh2 and clinicopathologic features and prognosis were analyzed statistically. RESULTS: Pirh2 mRNA and protein levels in ccRCC samples were increased significantly as compared with the adjacent normal renal tissues (P < 0.001). Pirh2 mRNA overexpression correlated with high stage and grade of the renal cancer (P < 0.001 and P < 0.001 respectively). Pirh2 protein expression was negative in most normal renal tissue specimens (23/30) but positive in 52.2% (48/92) of ccRCC specimens (P = 0.006). Pirh2 protein expression correlated with tumor grade and stage (P < 0.001 and P < 0.001 respectively). The median follow-up interval was 42.0 months. Overexpression of Pirh2 protein in ccRCC was significantly associated with shorter overall survival and recurrence-free survival (P = 0.001 and P = 0.003, respectively). Multivariate analysis showed that Pirh2 expression was an independent prognostic factor for ccRCC patients (P = 0.037). CONCLUSIONS: Pirh2 was up-regulated in ccRCC at both transcriptional and translational levels compared with normal renal tissues, suggesting that Pirh2 may be a potential prognostic marker for ccRCC.

Overexpression of HMGA2 in bladder cancer and its association with clinicopathologic features and prognosis HMGA2 as a prognostic marker of bladder cancer.

PURPOSE: To examine HMGA2 expression and investigate its clinical and prognostic significance in human urothelial bladder cancer (BUC). METHODS: We detected HMGA2 mRNA and protein expression by quantitative reverse-transcription polymerase chain reaction and western blotting, respectively in 44 frozen bladder cancer tissues and 18 adjacent normal bladder tissues. HMGA2 protein expression was assessed by immunohistochemical analysis of 148 paraffin-embedded specimens of human BUC and 30 specimens of adjacent normal bladder tissue. Correlations between HMGA2 and clinicopathologic features and prognosis were tested by statistical analyses. RESULTS: HMGA2 mRNA and protein levels in bladder cancer samples were significantly increased compared with adjacent normal bladder tissues (P < 0.001). mRNA overexpression correlated with high stage and grade of the bladder cancer (P < 0.001 and P = 0.002 respectively). HMGA2 protein expression was negative in all normal urothelial tissue samples, but positive in 52% (77/148) of bladder cancers (P < 0.001). HMGA2 expression correlated with tumor grade and stage (P < 0.001 and P = 0.003 respectively), Overexpression of HMGA2 protein in non-muscle-invasive bladder cancer was significantly associated with shorter recurrence-free survival (P < 0.001), and progression-free survival (P = 0.0004). Multivariate analysis showed that HMGA2 expression was an independent prognostic factor for both tumor recurrence (P < 0.001) and tumor progression (P = 0.006). CONCLUSIONS: HMGA2 is up-regulated in bladder cancer at both the transcriptional and translational levels compared with normal bladder tissue, HMGA2 protein is thus a potential prognostic marker for predicting tumor recurrence and progression.

Early bone response to sandblasted, dual acid-etched and H2O2/HCl treated titanium implants: an experimental study in the rabbit.

The aim of this study was to evaluate the influence of a roughened H(2)O(2)/HCl heat-treated titanium surface on peri-implant bone formation at an early stage in vivo. 24 Ti(6)Al(4)V alloy implants were used; half were treated by sandblasted and dual acid-etched treatments (control group), while the others were treated by sandblasted, dual acid-etched and H(2)O(2)/HCl heat treatments (test group). The morphology and roughness were analyzed by field emission SEM and atomic force microscopy. The implants were inserted into the femora of 12 adult white rabbits. After 2 and 4 weeks, femora block specimens were prepared for histological and histomorphometric analysis. SEM micrographs showed that multilevel and different sized pits were formed on both surfaces. New bone formation was observed on both implant surfaces. Test implants demonstrated a greater mean percentage of bone-implant contact as compared with controls at 2 (46.84 vs. 41.81, p=0.000) and 4 weeks (49.43 vs. 44.87, p=0.006) of healing. It is concluded that the H(2)O(2)/HCl heat-treated rough titanium surface promoted enhanced bone apposition during the early stages of new bone formation around the implant.

The application of C12 biochip in the diagnosis and monitoring of colorectal cancer: systematic evaluation and suggestion for improvement.

BACKGROUND: The 12 tumor markers' (TMs) biochip diagnostic (C12) system has been proven useful in some previous studies but its value for colorectal cancer (CRC) only was not systematically investigated. AIMS: To evaluate the value of C12 system for CRC. SETTINGS AND DESIGN: The associations between TMs and clinicopathological characteristics were evaluated. The most relevant TMs, the most useful combinations, and the correlations between TM levels were assessed. MATERIALS AND METHODS: The TMs detected by the C12 system in the sera of 170 pathologically confirmed CRC patients were analyzed. One or more TMs higher than or equal to reference value were defined as positive. STATISTICAL ANALYSIS: Chi-square test, Spearman rank correlation test and Receiver-operating characteristic (ROC) curves were used for the analysis. RESULTS: The overall positive rate was 41.76%, and was low in stage 0-I (12.90%). Carcinoembryonic cantigen (CEA) had the highest positive rate of 36.47%. The positive rates were significantly correlated to clinical stages and lymph node status, but not to age, sex, tumor location and pathological types. Any combinations of the five highest positive TMs did not have significantly improvements. The levels of three most related TMs (CEA, CA19-9, CA242) of CRC had positive correlation with each other. CA242 and beta-HCG levels were associated with lymph node metastasis. CONCLUSIONS: C12 system has some value in advanced CRC, but not in early CRC.

Neuroradiology imaging database: using picture archive and communication systems for brain tumour research.

INTRODUCTION: Disease registries and databases form an important component of research in clinical medicine, and can be useful to support retrospective studies and prospective clinical trials. However, analysis of radiological imaging databases has not been explored: imaging and clinical data often exist as separate silos of information, even in modern digital-enabled hospitals in Singapore. We describe a computerised method for creating a radiological research database using data from the picture archive and communication system (PACS) and hospital information system (HIS). METHODS: Using a relational database and Java programming language, we created the neuroradiology imaging database (NRID). A web-interface for keyword searches were tested with the clinical data from PACS of a tertiary referral hospital for neurological diseases. Keyword and wildcard searches were conducted for various brain neoplasms and compared to HIS discharge diagnosis. RESULTS: The NRID was deployed successfully and keyword search could be completed in real time. Lists of patients with meningioma, oligodendroglial tumour, neurocytomas, cerebral abscess, and neurocysticercosis could be exported and compared with the HIS discharge diagnosis. Patients with neurological diseases could be obtained by manually combining lists. CONCLUSION: An imaging database can be created using clinical PACS data, which can enable keyword search functions to support brain tumour research. Radiological databases can help support clinical research, but further work needs to be done in order to take full advantage of the potential of digital health information.

Computer-aided stereotactic functional neurosurgery enhanced by the use of the multiple brain atlas database.

This paper introduces a computer-aided atlas-based functional neurosurgery methodology and describes NeuroPlanner, a software system which supports it. NeuroPlanner provides four groups of functions: 1) data-related for data reading, interpolation, reformatting, and image processing; 2) atlas-related for multiple atlases reading, atlas-to-data global and local registrations, two-way anatomical indexing, and multiple labeling in two and three dimensions; 3) atlas-data exploration-related for three-dimensional (3-D) display and real-time manipulation of cerebral structures, continuous navigation, two-dimensional (2-D), triplanar, 3-D presentations, and 2-D interaction in four views; and 4) neurosurgery-related for targeting, trajectory planning, mensuration, simulating the insertion of microelectrode, and simulating therapeutic lesioning. All operations, excluding atlas and data reading, are real time. The combined anatomical index of the multiple brain atlas database containing complementary 2-D and 3-D atlases has about 1000 structures per hemisphere, and over 400 sulcal patterns. Neurosurgical planning with mutually preregistered multiple brain atlases in all three orthogonal orientations is novel. The approach is validated with 24 intraoperative and postoperative datasets for thalamotomies, thalamic stimulations, pallidotomies, and pallidal stimulations. Its potential benefits include increased accuracy of target definition, reduced time of the surgical procedure by decreasing the number of tracts, facilitated planning of more sophisticated trajectories, lowered cost by reducing the number of microelectrodes used, reduced surgical complications, and the extra degree of confidence given to the neurosurgeon.

Ultrastructural cytochemical study of enzymes expressed by signet ring cells in gastric cancer.

AIM: To study the ultrastructural localization of five marker enzymes (ALPase, ACPase, G6Pase, TPPase and CCOase) in gastric cancer signet ring cells to demonstrate their biologic behaviors. METHODS: Five marker enzymes were examined in signet ring cells of seven gastric cancer patients by ultrastructural enzyme cytochemical techniques. RESULTS: The number of corresponding organelles and the activities of marker enzymes, especially ACPase and TPPase, increased, leading to stronger mucus synthesis, secretion and digestion in gastric cancer signet ring cells. There was a lack of collagenous fibers in the stroma around the cancer nests. CONCLUSION: Signet ring cell carcinoma is very invasive with metastasis rates due to the secretion of proteolytic enzymes.

Significance of monoclonal antibody SC3A expression in gastric carcinoma and precancerous lesion.

AIM: To study the significance of monoclonal antibody SC3A expression in gastric carcinoma and precancerous lesions. METHODS: Immunohistochemical staining and mucin histochemical staining were performed on paraffin-embedded sections from gastric benign and malignant lesions from 101 patients. RESULTS: SC3A positive rate was 80.3% (57/71) in lesions of gastric carcinoma. The expression of SC3A was not related to the classification, differentiation, metastasis and or survival rates. The positive rate of SC3A in cancers secreting acid mucin (90.2%) or sulphomucin (91.3%) was higher than that in cancers without acid mucin (20.0%) or sulphomucin (60.0%) (P < 0.01). The positive rate of sulphomucin was higher in cases of intestinal metaplasia with cancer (88.9%) than that of cases of intestinal metaplasia with a benign lesion (35.3%) (P < 0.01). Additionally, the positive rate of SC3A with sulphomucin in intestinal metaplasia (60.9%) was higher than that without sulphomucin (31.3%) (P < 0.05). CONCLUSION: SC3A monoclonal antibody might be helpful in the diagnosis of gastric cancer and the discernment of histogenesis.

[Light and electron microscopic histochemical studies of alkaline phosphatase (ALP) isoenzymes in gastric cancer].

By using light and electron microscopic histochemical techniques, the activities and distributions of ALP isoenzymes in gastric cancers and benign gastric diseases were examined. The results showed: Nagao, Regan and Kasahara isoenzymes, which were not expressed in normal gastric mucosae and non-malignant lesions, may be considered as the tumor markers of gastric cancer. The epithelium of intestinal metaplasia exhibited intestinal-type ALP only, which was one of the markers of well-differentiated intestinal metaplasia. In the view-point of the gene expression of ALP isoenzymes, two mutation hypothesis and recessive-gene mutation hypothesis may be proper for gastric cancer.

Cell survival probability under ionizing radiation.

The survival probability of a living cell exposed to ionizing radiation in an experimental setup is derived. The survival of a cell depends on the severity of the radiation damage and efficiency of the cellular repair. The formula of the survival probability is expressed as a function of dose, nonlinear rate of lesion induction, nonlinear rate of cellular repair, and a key experimental parameter--the holding time. The result is an extension of the Markovian dose-response model developed by Yang and Swenberg.

A stochastic two-stage carcinogenesis model: a new approach to computing the probability of observing tumor in animal bioassays.

A new definition of probability of observing tumor in animal bioassay is developed. It is derived from a two-stage stochastic model for carcinogenesis with time-dependent birth and death rates for cell proliferation. The model takes into account the method of collecting data on preneoplastic and neoplastic lesions. The new definition is appropriate for analyzing the presence or absence of tumors in animal bioassays.

[Distribution and ultrastructural localization of carcino-embryonic antigen (CEA) in signet-ring cells of gastric cancer].

The distribution and ultrastructural localization of CEA in signet-ring cells of 15 gastric cancer specimens were observed by PAP and immunoelectron microscopic methods. The mechanism of abnormal distribution of CEA in the signet-ring cell and its biological significance are discussed. The results showed that the CEA positive rate in signet-ring cells was 100% with the polarity lost in distribution. Under the light microscope, the CEA stain patterns were of two types-cytoplasmic and membranous types. The former was predominant. Under the electron microscope, most of the CEA was distributed on the cell membrane and cytoplasm. CEA was found in intracellular membranous structure of the cancer cells, especially in protein synthesis and transport organellae (RER, Golgi Complex etc). The synthesis of CEA in cancer cells increased, yet its elimination was somewhat hampered. The result was that the RER became extended and were full of CEA (+) material. In the free signet-ring cell, there was a small and short contact plane. The tight junction was severed as the cell junction was reduced. The antigenic determinant of CEA was glycoprotein. The abnormal distribution of CEA in signet-ring cells might be the morphologic reflection of the glycosylation of surface glycoprotein of tumor cells. These abnormal changes would lead to mal-functions and biologic misbehavior in the cells. It may even lead to disturbances in connection and recognition, loss of contact inhibition and decrease in the adhesion between tumor cells and therefore may easily give rise to infiltration and metastasis.