Asymptomatic colorectal cancer detected by screening

PURPOSE: Colorectal cancer screening has become prevalent. To discuss the efficacy of screening, we studied the characteristics of asymptomatic Colorectal cancer detected by screening. METHODS: This is a retrospective review of patients with colorectal cancer treated at our institution. During the past 20 years, 96 of 1,046 cases of colorectal cancer were asymptomatic and detected by screening. Sixty-one of these cases were detected in the recent five years. The initial screening procedures were fecal occult blood test in 51 cases, sigmoidoscopy or colonoscopy in 18, barium enema in 9, and other tests in 18. RESULTS: Thirteen lesions (14 percent) were smaller than 1.0 cm and 32 (33 percent) were 1–2 cm in size. There were 34 Tis, 21 T1, and 8 T2 tumors. Of the 55 Tis or T1 lesions, 14 showed nonpolypoid growth (5 flat-elevated, 7 flat-elevated with depression, 1 flat, 1 depressed), and 12 of these were detected on endoscopy. Thirty-four cases were TNM Stage 0, 25 were Stage I, 16 were Stage II, 12 were Stage III, and 9 were Stage IV. Sixty-one percent of those detected by screening were in either Stage 0 or Stage I compared with 16 percent in the symptomatic group. Cumulative five-year disease-free survival rates were 100 percent for both Stage 0 and Stage I, 94 percent for Stage II, and 52 percent for Stage III. Overall cumulative five-year survival rate was 87 percent for those detected by screening, compared with 57 percent in symptomatic patients. CONCLUSIONS: Asymptomatic cancers detected by screening were at a less advanced stage. In particular, many nonpolypoid early cancers were detected by endoscopic screening.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995.     

Calcium transient dynamics and the mechanisms of ventricular vulnerability to single premature electrical stimulation in Langendorff-perfused rabbit ventricles.

BACKGROUND: Single strong premature electrical stimulation (S(2)) may induce figure-eight reentry. We hypothesize that Ca current-mediated slow-response action potentials (APs) play a key role in the propagation in the central common pathway (CCP) of the reentry. METHODS: We simultaneously mapped optical membrane potential (V(m)) and intracellular Ca (Ca(i)) transients in isolated Langendorff-perfused rabbit ventricles. Baseline pacing (S(1)) and a cathodal S(2) (40-80 mA) were given at different epicardial sites with a coupling interval of 135 +/- 20 ms. RESULTS: In all 6 hearts, S(2) induced graded responses around the S(2) site. These graded responses propagated locally toward the S(1) site and initiated fast APs from recovered tissues. The wavefront then circled around the refractory tissue near the site of S(2). At the side of S(2) opposite to the S(1), the graded responses prolonged AP duration while the Ca(i) continued to decline, resulting in a Ca(i) sinkhole (an area of low Ca(i)). The Ca(i) in the sinkhole then spontaneously increased, followed by a slow V(m) depolarization with a take-off potential of -40 +/- 3.9 mV, which was confirmed with microelectrode recordings in 3 hearts. These slow-response APs then propagated through CCP to complete a figure-eight reentry. CONCLUSION: We conclude that a strong premature stimulus can induce a Ca(i) sinkhole at the entrance of the CCP. Spontaneous Ca(i) elevation in the Ca(i) sinkhole precedes the V(m) depolarization, leading to Ca current-mediated slow propagation in the CCP. The slow propagation allows more time for tissues at the other side of CCP to recover and be excited to complete figure-eight reentry.     

Augmentation of tumor necrosis factor family-induced apoptosis by E3330 in human hepatocellular carcinoma cell lines via inhibition of NFκB

AIM: To investigate the reduction of cell viability in human hepatocellular carcinoma (HCC) cell lines induced by inhibition of nuclear factor κB (NFκB).METHODS: HLE, SKHep1, and HepG2 were incubated and E3330 was used to compare the stimulation of some chemotherapeutic drugs with that of TNF family, Fas ligand, TNFα and TNF-related apoptosis-inducing ligand (TRAIL) at the point of the reduction of cell viability by inhibiting NFκB.RESULTS: E3330 decreased NFκB levels in HLE cells stimulated by TNF and TRAIL. The cytotoxicity of the combination of TRAIL, TNFα, Fas ligand, and E3330increased synergistically in a dose-dependent manner compared to either E3330 alone in all HCC cell lines by MTT assay. However, the combination of some chemotherapeutic drugs and E3330 did not decrease the cell viability.CONCLUSION: Inhibition of NFκB sensitizes human HCC cell lines to TNF-mediated apoptosis including TRAIL, and TRAIL-based tumor therapy might be a powerful potential therapeutic tool in the treatment of human HCC.     

Changes in the prevalence of intestinal parasites among Japanese expatriates in developing countries]

In order to study the prevalence of intestinal parasites among Japanese expatriates of developing countries, we conducted fecal specimen examinations annually from 1995 to 2000. Fecal specimens were collected from Japanese expatriates of each area: Asia, the Middle East, East Europe, Africa and Latin America. The specimens were fixed with 10% formalin in the local area, and then examined in Japan. We used the formalin-ether sedimentation method to find protozoan cysts or helminth eggs. In 1995, the infection ratio was 3.0% (N = 981), decreasing to 2.4% (N = 1,275) in 1996, 2.3% (N = 1,620) in 1997 and 1.6% (N = 1,574) in 1998. However, the ratio began to increase in 1999 (2.0%, N = 1,713) and 2000 (2.5%, N = 1,806). The ratio in Africa was the highest in each year, followed by Asia and Latin America. Heterophyidae (51 cases), Giardia lamblia (42) and Trichuris trichiura (30) were detected most frequently. In Egypt, the ratio of Heterophyidae rose by 28.8% in 2000. This was the prime reason for the increase in the overall ratio of infections worldwide. Most of the Japanese infected with Heterophyidae in Egypt had ingested dried mullet roe. This may explain the reason for the increase in the infection ratio there. Although the prevalence of intestinal parasites among Japanese expatriates in developing countries is decreasing, those who eat fish in these areas are still at risk. In order to eradicate intestinal parasitosis from this group, we must continue preventive measures such as health education.     

Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce cell cycle progression through the synthesis of c-Myc protein by internal ribosome entry site-mediated translation via phosphatidylinositol 3-kinase pathway in human factor-dependent leukemic cells

To investigate the roles of c-myc during hematopoietic proliferation induced by growth factors, we used factor-dependent human leukemic cell lines (MO7e and F36P) in which proliferation, cell cycle progression, and c-Myc expression were strictly regulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3). In these cell lines, both c-myc mRNA and c-Myc protein stability were not affected by GM-CSF and IL-3, suggesting a regulation of c-Myc protein at the translational level. However, rapamycin, an inhibitor of cap-dependent translation, did not block c-myc induction by GM-CSF and IL-3. Thus, we studied the cap-independent translation, the internal ribosome entry site (IRES), during c-Myc protein synthesis using dicistronic reporter gene plasmids and found that GM-CSF and IL-3 activated c-myc IRES to initiate translation. c-myc IRES activation, c-Myc protein expression, and cell cycle progression were all blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. In another factor-dependent cell line, UT7, we observed the cell cycle progression and up-regulation of c-Myc protein, c-myc mRNA, and c-myc IRES simultaneously, which were all inhibited by LY294002. Results indicate that hematopoietic growth factors induce cell cycle progression via IRES-mediated translation of c-myc though the PI3K pathway in human factor-dependent leukemic cells.