Role of MAP kinase in the enhanced cell proliferation of long term estrogen deprived human breast cancer cells

Women with estrogen receptor (ER) positive breast cancers frequently respond initially to inhibition of estrogen action but later relapse with re-growth of tumor. Previously, we have utilized MCF-7 human breast cancer cells deprived of estradiol long term (LTED cells) as the model system to study the regrowth phenomenon and have demonstrated that these cells exhibited increased cell proliferation rate and increased ER functionality during the adaptive processes. In this report, we examined the hypothesis that the mitogen-activated protein kinase (MAP kinase) signal was involved. We found that activated MAP kinase was elevated in LTED cells and that the MAP kinase specific inhibitor PD98059 was able to inhibit the elevated MAP kinase and [³H]thymidine uptake in LTED cells, suggesting mediation of DNA synthesis and proliferation by the MAP kinase pathway. Other MAP kinase upstream inhibitors, including genestein, RG13022, and mevastatin were also able to inhibit the [³H]thymidine uptake in LTED cells. Interestingly, the antiestrogen, ICI 182,780 was able to block the activated MAP kinase in LTED cells. Treatment with PD98059 did not block elevated basal ERE-CAT activity while at the same time inhibiting [³H]thymidine uptake in LTED cells. Furthermore, treatment with PD98059 partially blocked the E₂-stimulated ERE-CAT activity and [³H]thymidine uptake in both LTED and in wild type cells, indicating that both MAP kinase-dependent and MAP kinase-independent pathways are involved in the transactivation function of ER. Taken together, our data suggest that the MAP kinase pathway is, in part, involved in the adaptive process which results in enhanced DNA synthesis and cell proliferation in the absence of exogenous estrogen in LTED 3ptcells.     

Fixation of lung apex in spontaneous pneumothorax is safe and efficient in decrease recurrences

Background

Video-assisted thoracoscopic bullectomy with pleurodesis is widely used to treat spontaneous pneumothorax. However, 1%–3% of patients experience postoperative complications that may require reoperation, such as bleeding or prolonged air leaks, and 3%–7% of patients require a repeat thoracoscopic bullectomy due to recurrence. Therefore, a modified procedure with improved outcomes is required.

Teleconsultation with the mobile camera-phone in remote evaluation of replantation potential

BACKGROUND: The purpose of the present study was to investigate the feasibility of teleconsultation with the mobile camera-phone to transfer clinical images and communicate on line for evaluation of replantation potential in completely amputated fingers. METHODS: Teleconsultations including clinical images of the amputated portion and stump as well as patient information were transmitted between the physicians in the emergency room and the consultant phlstic surgeon through Panasonic camera-phones, which had a built-in 110,000-pixel digital camera and a 65,536 colors display. The digital images displayed on the screen were further evaluated by three remote plastic surgeons individually and the evaluations were compared with the decision made according to onsite inspection by the consultant surgeon. RESULTS: The study population consisted of 35 patients with a total of 60 digital injures occurring between January to October 2003. The ability to identify the amputation location and status of amputation kwel from remote diagnosis was demonstrated by all three surgeons in 90% and 87% of these sixty amputated digits respectively. Of the 42 digits that were considered to have replantation potential during onsite evaluation, 38 (90%) digits were considered to be so by all three surgeons in group agreement during remote diagnosis. Of the 18 digits that were not considered to be replantable during onsite evaluation, 15 (83%) digits were also deemed without replantation potential, thus making the sensitivity and specificity of recognizing digital replantation potential, 90% and 83_'O re,_1pectively. CONCLUSIONS: The camera-phone is a feasible tool for remote evaluation regarding the replantation potential of completely amputated fingers and it holds significant promise in avoiding unnecessary patient transfer by providing useful information.     

Unexpected rapid progression of metastatic adenoid cystic carcinoma during treatment with imatinib mesylate

BACKGROUND: There is a lack of effective treatment for metastatic adenoid cystic carcinoma (ACC), a usually indolent tumor. We studied the efficacy of imatinib mesylate, a potent inhibitor of KIT tyrosine kinase, in patients with KIT-positive metastatic ACC. METHOD: Five patients with lung metastasis were treated in a pilot study with imatinib 400 mg by mouth twice a day. Mutations of c-kit and platelet-derived growth factor receptor (PDGFR)-alpha in tumors from these patients were analyzed. RESULTS: Disease progression was noted in three of five patients during the short treatment periods, ranging from 2 to 3 weeks. Three patients died of disease within 6 months. No detectable mutations were found in c-kit and PDGFR-alpha. CONCLUSION: We observed an unexpected high progression rate of metastatic ACC within short periods during imatinib treatment. Use of imatinib to treat cancers without c-kit or PDGFR-alpha mutation should be approached with caution.     

Effects of acoustic noise on the auditory nerve compound action potentials evoked by electric pulse trains

This study investigated the effects of acoustic noise on the auditory nerve compound action potentials in response to electric pulse trains. Subjects were adult guinea pigs, implanted with a minimally invasive electrode to preserve acoustic sensitivity. Electrically evoked compound action potentials (ECAP) were recorded from the auditory nerve trunk in response to electric pulse trains both during and after the presentation of acoustic white noise. Simultaneously presented acoustic noise produced a decrease in ECAP amplitude. The effect of the acoustic masker on the electric probe was greatest at the onset of the acoustic stimulus and it was followed by a partial recovery of the ECAP amplitude. Following cessation of the acoustic noise, ECAP amplitude recovered over a period of approximately 100-200 ms. The effects of the acoustic noise were more prominent at lower electric pulse rates (interpulse intervals of 3 ms and higher). At higher pulse rates, the ECAP adaptation to the electric pulse train alone was larger and the acoustic noise, when presented, produced little additional effect. The observed effects of noise on ECAP were the greatest at high electric stimulus levels and, for a particular electric stimulus level, at high acoustic noise levels.     

Serum insulin-like growth factor-II as a serologic marker of small hepatocellular carcinoma

OBJECTIVE: Alpha-fetoprotein (AFP) is not a useful tumor marker for diagnosis of small hepatocellular carcinoma (HCC). There is over-expression of insulin-like growth factor (IGF)-II in HCC tissue. This study investigates the diagnostic application of IGF-II in small HCC. MATERIAL AND METHODS: Serum levels of IGF-II and AFP were determined in 41 patients with small cirrhotic HCC (< or = 3 cm), 41 sex- and age-matched patients with cirrhosis alone (LC), and 41 healthy adults. The optimal cut-off values for diagnosing HCC were determined with receiver operating characteristics (ROC) curve. RESULTS: Both IGF-II and AFP levels in HCC were higher than those in LC patients or controls (each p = 0.0001). The IGF-II levels in LC patients were lower than those in controls (p = 0.001). In HCC patients, multivariate analysis indicated that that both IGF-II (odds ratio, 4.54; 95% confidence interval, 2.15-9.55; p = 0.0001) and AFP (odds ratio, 1.05; 95% confidence interval, 1.01-1.08; p = 0.003) were found to be associated with an increased risk of presence of HCC. The optimal cut-off values of IGF-II (4.1 mg/g prealbumin) and AFP (50 ng/ml) were determined with ROC curves. The sensitivity, specificity, and diagnostic accuracy values for IGF-II were 63%, 90%, and 70%, respectively. Those for AFP were 44%, 95%, and 70%, respectively. Determination of both markers in parallel significantly increase the diagnostic accuracy (88%) and sensitivity (80%), with a high specificity (90%). CONCLUSIONS: Serum IGF-II level can be used as an independent serologic marker or a complementary tumor marker to AFP for diagnosis of small HCC.     

Differential integration rates of hepatitis B virus DNA in the liver of children with chronic hepatitis B virus infection and hepatocellular carcinoma

BACKGROUND AND AIM: Integration of hepatitis B virus-DNA (HBV-DNA) into the host genome, a phenomenon found frequently in hepatocellular carcinomas (HCC) and causally linked to oncogenesis, has not been well characterized in children. The aim of the present study was to determine the prevalence of HBV integration more accurately and to decide whether the integration rate varies at different stages of chronic HBV infection in children. METHODS: Of 13 children with chronic hepatitis, 14 liver biopsy tissues were analyzed. One liver tissue with pure liver cirrhosis, nine non-tumor, and nine tumor liver tissues from children with HCC were analyzed by a very sensitive method, inverse polymerase chain reaction (IPCR). RESULTS: Thirteen genuine viral-host junctional sequences from 23 patients were successfully isolated and proved that IPCR is a useful method in this context. The results also indicated that the detection rate of HBV-DNA integration increased in parallel with the progress of liver histology towards the neoplastic transformation, with 0% in the liver of chronic hepatitis, 22.2% in non-tumor livers of HCC patients, and 66.7% in tumor liver tissues of HCC patients. CONCLUSION: The present results indicate that integration of HBV-DNA into the host genome was rarely confirmed at the early stage of chronic hepatitis in children until the stage of HCC formation.