Growth inhibitory effect of paradicsompaprika in cancer cell lines

We investigated whether components of paradicsompaprika have direct antitumor effects or inhibitory effects on cancer growth, using its water extract. We applied collagen gel droplet embedded culture drug sensitivity test (CD-DST) as a screening method, which was developed based on the characteristics of cell culture on collagen matrix. Colon adenocarcinoma cells, epithelial cells of lung cancer, and cervical cancer cells were used. Paradicsompaprika is classified as Capsiucum annume L. var. grossum of Solanaceae. It is the first of the Hungarian species that was planted in Japan. It is available as TOMA-P in Japan. TOMA-P contains abundant carotenoids including capsanthin and beta-carotene. Water extract of paradicsompaprika was added to each cell at each concentration, and the mixture was cultured for 24 h and 7 days. The inhibitory effects against lung cancer and cervical cancer were observed concentration- and time-dependently. The effect was more prominent against lung cancer. The growth of bowel cancer cells was observed after the 7-day exposure of paradicsompaprika at the concentrations below the highest concentration compared to the control. At the highest concentration, the growth inhibition was not different between the 24-h exposure and the 7-day exposure, which suggests that tumor dormancy was induced. Results of the present study suggest that the water extract of paradicsompaprika can be a candidate of a new anticancer agent. Fat soluble component of paradicsompaprika, capsanthin is regarded as an anti-promoter of cancer. Thus, paradicsompaprika possesses chemopreventive and inhibitory effects on cancer cells.     

Prediction of cell kill kinetics of anticancer agents using the collagen gel droplet embedded-culture drug sensitivity test

A vital component of chemotherapy is selecting effective anticancer agents for the patient and determining an appropriate dose and administration regimen. Prediction of the drug sensitivity of each patient and cell kill kinetics of the drug may improve the outcome of treatment and avoid unnecessary dosing of the drug. For this reason, the development and clinical application of anticancer drug sensitivity tests and cell kill kinetics tests which successfully reflect clinical outcomes are required. In the present study, we tried to establish a cell kill kinetics test through the use of new anticancer agents: paclitaxel, docetaxel, SN-38, vinorelbine, and gemcitabine. These agents were studied at concentrations close to their clinical doses using a collagen gel droplet embedded-culture drug sensitivity test (CD-DST). It is thought that the mechanism, by which the anticancer agents used in this study exert their effects is dependent on the cell cycle; however, the cell kill kinetics of these agents at clinical concentrations has not yet been clarified in vitro. We investigated the drug sensitivity and cell kill kinetics of these new anticancer agents against a human colon cancer strain. Results of this study suggest that the test method established by us can predict drug sensitivity and cell kill kinetics of the agents, and can be a useful tool in deciding appropriate treatment regimen for individual patients.     

The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress

Various key cell cycle components, especially G0/G1 regulators, have effects not only on cell proliferation but also on cell differentiation. Cdh1, one of the co-activators that maintain anaphase-promoting complex/cyclosome activity, plays a crucial role in the mitotic phase, but has recently been identified as a G0/G1 regulator, suggesting that the role of Cdh1 in cell differentiation. Here, we generated Cdh1 conditional gene-trap mice to examine Cdh1 functions in adult tissues by overcoming the embryonic lethality of Cdh1 homozygous gene-trap mice. We focused on the hematopoietic system and found that Cdh1-deficient mice exhibited a general decrease in mature lineage progenitor cells and a significant increase in short-term hematopoietic stem cells. This phenomenon became conspicuous by irradiation shortly after Cdh1 downregulation, suggesting that Cdh1 regulates the pool sizes of the hematopoietic stem cells and mature lineage progenitor cells by protecting cells from genotoxic stress. We also found that the irradiation-induced G2/M checkpoint was defective in Cdh1-deficient BM cells, causing the loss of stem/progenitor cells. This is the first report revealing Cdh1 function in adult hematopoiesis and showing a role of Cdh1 in a G2/M checkpoint regulation in vivo.     

A review of lasers and light sources in the treatment of acne vulgaris.

There are various treatment modalities for acne vulgaris including topical and oral therapy as well as microdermabrasion and chemical peels. Recently, there has been an emergence of novel laser and light sources as a means for treating acne vulgaris. This article will review the advances of laser and light sources in the treatment of acne vulgaris.     

The action of Amagasaki City Health Center to the train derailment accident on the Japan Railway Fukuchiyama Line

OBJECTIVES: To examine and describe the reactions of Amagasaki City Health Center to the train derailment accident that occurred on April 25th, 2005 on the Japan Railway (JR) Fukuchiyama Line in order to provide useful information for health centers to help them deal with such catastrophic disasters in the future. METHODS: Each day after the accident reactions and actions were examined and described. They included mental health care provided by the health center for the inhabitants of the condominium building into which the derailed train had crashed, as well as the volunteers who participated in the rescue work. Health checkups were also provided for the latter. RESULTS: Actions directly related to the rescue were continued by the health center for four days after the accident. The mainly consisted of the following. The health center asked hospitals to input information concerming their ability to respond to the emergency situation into the Hyogo Emergency Medical Information System. A relief party was organized by the health center staff and engaged in the rescue and on-site rescue triage. The health center slso coordinated the mortuary work. Two days after the accident, "postmortem triage," to insure that bodies were taken directly to a mortuary after death certification by a physician was needed on site after rescue triage was concluded. The health center confirmed all information for the passengers' safety. The rescue volunteers and the nearby inhabitants who were affected consulted with the person in charge of mental health care provided by the health center from immediately after the accicent for a period of five months to September 30. Health checkups for rescue volunteers were conducted for infections and post-traumatic stress disorder. CONCLUSIONS: This JR accident was characterized by many civilian volunteers engaged in rescue over the relatively long period of rescue of four days.Mental health care and health checkups were needed for civililian volunteers and were therefore provided by the health center. During the four days of rescue, triage was begun immediately after the accident and subsequent postmortem triage was also required.     

Effects of adrenaline on circulatory dynamics and cardiac function in rats administered chlorpromazine

We aimed to elucidate changes in circulatory dynamics and cardiac function during concomitant use of chlorpromazine (CPZ) and adrenaline (AD). An arterial line and left intraventricular pressure–volume measurement catheter were inserted in rats. CPZ 10 mg/kg was administered to the left great adductor muscle, followed by normal saline (NS) or AD 50 μg/kg through the tongue 20 min later. End-diastolic volume (V _ed), end-systolic pressure (P _es), stroke volume (SV), stroke work (SW), end-systolic volume elastance (E _es), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate (PR) were measured. Following AD administration, V _ed significantly decreased at 2–4 and 10 min than that in control rats; P _es significantly decreased at 1 min; E _es significantly increased from 2 to 10 min; SV did not change significantly, and SW significantly reduced at 1 and 2 min; SBP and DBP were lower at 1–3 min than in the control; and PR increased at 10 min. These findings suggest that when AD-containing local anesthetics are administered during dental treatment of patients taking CPZ, there is a risk of a temporary drop in blood pressure. However, the blood pressure is recovered a few minutes later by the increase in afterload and the myocardial contractile force.     

PKC/MEK inhibitors suppress oxaliplatin‐induced neuropathy and potentiate the antitumor effects

Oxaliplatin is a key drug commonly used in colorectal cancer treatment. Despite high clinical efficacy, its therapeutic application is limited by common, dose‐limiting occurrence of neuropathy. As usual symptomatic neuropathy treatments fail to improve the patients' condition, there is an urgent need to advance our understanding of the pathogenesis of neuropathy to propose effective therapy and ensure adequate pain management. Oxaliplatin‐induced neuropathy was recently reported to be associated with protein kinase C (PKC) activation. It is unclear, however, whether PKC inhibition can prevent neuropathy. In our current studies, we found that a PKC inhibitor, tamoxifen, inhibited oxaliplatin‐induced neuropathy via the PKC/extracellular signal‐regulated kinase (ERK)/c‐Fos pathway in lumbar spinal cords (lumbar segments 4–6). Additionally, tamoxifen was shown to act in synergy with oxaliplatin to inhibit growth in tumor cells‐implanted mice. Moreover, mitogen‐activated protein kinase kinase (MEK) 1/2 inhibitor, PD0325901, suppressed oxaliplatin‐induced neuropathy and enhanced oxaliplatin efficacy. Our results indicate that oxaliplatin‐induced neuropathy is associated with PKC/ERK/c‐Fos pathway in lumbar spinal cord. Additionally, we demonstrate that disruption of this pathway by PKC and MEK inhibitors suppresses oxaliplatin‐induced neuropathy, thereby suggesting that PKC and MEK inhibitors may be therapeutically useful in preventing oxaliplatin‐induced neuropathy and could aid in combination antitumor pharmacotherapy.